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ABSTRACT Aim: This study aimed to investigate the combined effects of magnesium (Mg) and high dose ascorbic acid on cardiac ischemia- reperfusion (IR) injury. Material and Method: This study was performed on 45 patients that were scheduled for coronary artery bypass graft (CABG) operations. The patients were divided into three equal groups. Group C received 50 mg/kg ascorbic acid; Group CM received the same dose of ascorbic acid plus 30 mg/kg Mg; Group K received neither ascorbic acid nor Mg. At various times during the operation, the blood levels of malondialdehyde (MDA), serum creatine kinase MB (CK-MB), and lactate dehydrogenase (LDH) levels were analyzed. Results: There were statistically significant decreases in arrhythmia requiring intervention in Group CM compared to Group K (P=0.026). MDA levels increased in all groups but MDA 2 and MDA 3 levels were found to be statistically significantly lower in Group C and Group CM than in Group K (P=0.009, P=0.012, P=0.009 and P=0.006 respectively). However, inhibition of lipid peroxidation in both Group C and Group CM was not parallel to cardiac enzymes and hemodynamic measurements. There was no significant statistical difference in the cardiac enzyme levels between Group K, Group C, and Group CM (p>0.05). Conclusion: To reduce the IR, Mg with a high dose of ascorbic acid may be efficacious in patients undergoing cardiac surgery. A larger population group is needed to prove the results of this study.

ABSTRACT Aim: This study aimed to investigate the combined effects of magnesium (Mg) and high dose ascorbic acid on cardiac ischemia- reperfusion (IR) injury. Material and Method: This study was performed on 45 patients that were scheduled for coronary artery bypass graft (CABG) operations. The patients were divided into three equal groups. Group C received 50 mg/kg ascorbic acid; Group CM received the same dose of ascorbic acid plus 30 mg/kg Mg; Group K received neither ascorbic acid nor Mg. At various times during the operation, the blood levels of malondialdehyde (MDA), serum creatine kinase MB (CK-MB), and lactate dehydrogenase (LDH) levels were analyzed. Results: There were statistically significant decreases in arrhythmia requiring intervention in Group CM compared to Group K (P=0.026). MDA levels increased in all groups but MDA 2 and MDA 3 levels were found to be statistically significantly lower in Group C and Group CM than in Group K (P=0.009, P=0.012, P=0.009 and P=0.006 respectively). However, inhibition of lipid peroxidation in both Group C and Group CM was not parallel to cardiac enzymes and hemodynamic measurements. There was no significant statistical difference in the cardiac enzyme levels between Group K, Group C, and Group CM (p>0.05). Conclusion: To reduce the IR, Mg with a high dose of ascorbic acid may be efficacious in patients undergoing cardiac surgery. A larger population group is needed to prove the results of this study.

This article is from Cardiovascular Diabetology , volume 12 . Abstract Background: Diabetic patients, through incompletely understood mechanisms, endure exacerbated ischemic heart injury compared to non-diabetic patients. Intermedin (IMD) is a novel calcitonin gene-related peptide (CGRP) superfamily member with established cardiovascular protective effects. However, whether IMD protects against diabetic myocardial ischemia/reperfusion (MI/R) injury is unknown. Methods: Diabetes was induced by streptozotocin in Sprague–Dawley rats. Animals were subjected to MI via left circumflex artery ligation for 30 minutes followed by 2 hours R. IMD was administered formally 10 minutes before R. Outcome measures included left ventricular function, oxidative stress, cellular death, infarct size, and inflammation. Results: IMD levels were significantly decreased in diabetic rats compared to control animals. After MI/R, diabetic rats manifested elevated intermedin levels, both in plasma (64.95 ± 4.84 pmol/L, p 

This article is from Cardiovascular Diabetology , volume 12 . Abstract Background: Diabetic patients, through incompletely understood mechanisms, endure exacerbated ischemic heart injury compared to non-diabetic patients. Intermedin (IMD) is a novel calcitonin gene-related peptide (CGRP) superfamily member with established cardiovascular protective effects. However, whether IMD protects against diabetic myocardial ischemia/reperfusion (MI/R) injury is unknown. Methods: Diabetes was induced by streptozotocin in Sprague–Dawley rats. Animals were subjected to MI via left circumflex artery ligation for 30 minutes followed by 2 hours R. IMD was administered formally 10 minutes before R. Outcome measures included left ventricular function, oxidative stress, cellular death, infarct size, and inflammation. Results: IMD levels were significantly decreased in diabetic rats compared to control animals. After MI/R, diabetic rats manifested elevated intermedin levels, both in plasma (64.95 ± 4.84 pmol/L, p 

artykuł w: Annales Universitatis Mariae Curie-Skłodowska. Sectio D, Medicina. Vol. 58/2, 131 (2003), 247-252. ; Bibliografia na stronie 251.

This article is from Journal of Biomedical Research , volume 26 . Abstract The present study investigated the effect of garlic (Allium sativum Linn.) aqueous extracts on ischemic preconditioning and ischemia-reperfusion induced cardiac injury, as well as adenosine involvement in ischemic preconditioning and garlic extract induced cardioprotection. A model of ischemia-reperfusion injury was established using Langendorff apparatus. Aqueous extract of garlic dose was standardized (0.5%, 0.4%, 0.3%, 0.2%, 0.1%, 0.07%, 0.05%, 0.03%, 0.01%), and the 0.05% dose was found to be the most effective. Higher doses (more than 0.05%) were highly toxic, causing arrhythmia and cardiodepression, whereas the lower doses were ineffective. Garlic exaggerated the cardioprotective effect of ischemic preconditioning. The cardioprotective effect of ischemic preconditioning and garlic cardioprotection was significantly attenuated by theophylline (1,000 µmol/L) and 8-SPT (10 mg/kg, i.p.) and expressed by increased myocardial infarct size, increased LDH level, and reduced nitrite and adenosine levels. These findings suggest that adenosine is involved in the pharmacological and molecular mechanism of garlic induced cardioprotection and mediated by the modulation of nitric oxide.

This article is from PLoS ONE , volume 9 . Abstract Background: Acupuncture exerts cardioprotective effects on several types of cardiac injuries, especially myocardial ischemia (MI), but the mechanisms have not yet been well elucidated. Angiogenesis mediated by VEGF gene expression and its modification through histone acetylation has been considered a target in treating myocardial ischemia. This study aims to exam whether modulation of angiogenesis through H3K9 acetylation regulation at VEGF gene is one possible cardioprotective mechanism of acupuncture. Results: We generated rat MI models by ligating the left anterior descending coronary artery and applied electroacupuncture (EA) treatment at the Neiguan (PC6) acupoint. Our results showed that acupuncture reversed the S-T segment change, reduced Q-wave area, decreased CK, CK-MB, LDH levels, mitigated myocardial remodeling, and promoted microvessel formation in the MI heart. RNA-seq analysis showed that VEGF-induced angiogenesis signaling was involved in the modulation of EA. Western blot results verified that the protein expressions of VEGF, Ras, phospho-p44/42 MAPK, phospho-p38 MAPK, phospho-SAPK/JNK and Akt, were all elevated significantly by EA treatment in the MI heart. Furthermore, increased H3K9 acetylation was also observed according with the VEGF. ChIP assay confirmed that EA treatment could notably stimulate the recruitment of H3K9ace at the VEGF promoter. Conclusions: Our study demonstrates for the first time that acupuncture can effectively up-regulate VEGF expression through H3K9 acetylation modification directly at the VEGF promoter and hence activate VEGF-induced angiogenesis in rat MI models. We employed high throughput sequencing in this study and, for the first time, generated genome-wide gene expression profiles both in the rat MI model and in acupuncture treatment.

This article is from Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease , volume 2 . Abstract Background: We reported previously that Brown Norway (BN) rats are more resistant to myocardial ischemia/reperfusion (I/R) injury than are Dahl S (SS) rats. To identify the unique genes differentially expressed in the hearts of these rats, we used DNA microarray analysis and observed that enoyl coenzyme A hydratase–containing domain 2 (ECHDC2) is highly expressed (≈18‐fold) in the SS hearts compared with the BN hearts. Methods and Results: RT‐PCR, Western blot, and immunohistochemistry analyses verified that ECHDC2 was highly expressed in SS hearts compared with the BN hearts. ECHDC2 gene locates at chromosome 5 of rat and is expressed in mitochondria of the heart, mainly in cardiomyocytes but not in cardiofibroblasts. Overexpression of ECHDC2 in cells increased susceptibility to I/R injury while knockdown of ECHDC2 enhanced resistance to I/R injury. Furthermore, we observed that left anterior descending coronary artery ligation–induced myocardial infarction was more severe in the SS hearts than in the BN hearts or SSBN5 hearts, which was built on SS rats but had the substitution of chromosome 5 from BN rats. We also demonstrated that ECHDC2 did not alter mitochondrial O2 consumption, metabolic intermediates and ATP production. By gas chromatography–mass spectrometry, we found that ECHDC2 overexpression increased the levels of the cellular branched chain amino acids leucine and valine. Conclusion: ECHDC2, a mitochondrial protein, may be involved in regulating cell death and myocardial injury. Its deficiency in BN rats contributes to their increased resistance to myocardial I/R compared with SS rats. ECHDC2 increases branched chain amino acid metabolism and appears to be a novel regulator linking cell metabolism with cardiovascular disease.

This article is from Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease , volume 2 . Abstract Background: We reported previously that Brown Norway (BN) rats are more resistant to myocardial ischemia/reperfusion (I/R) injury than are Dahl S (SS) rats. To identify the unique genes differentially expressed in the hearts of these rats, we used DNA microarray analysis and observed that enoyl coenzyme A hydratase–containing domain 2 (ECHDC2) is highly expressed (≈18‐fold) in the SS hearts compared with the BN hearts. Methods and Results: RT‐PCR, Western blot, and immunohistochemistry analyses verified that ECHDC2 was highly expressed in SS hearts compared with the BN hearts. ECHDC2 gene locates at chromosome 5 of rat and is expressed in mitochondria of the heart, mainly in cardiomyocytes but not in cardiofibroblasts. Overexpression of ECHDC2 in cells increased susceptibility to I/R injury while knockdown of ECHDC2 enhanced resistance to I/R injury. Furthermore, we observed that left anterior descending coronary artery ligation–induced myocardial infarction was more severe in the SS hearts than in the BN hearts or SSBN5 hearts, which was built on SS rats but had the substitution of chromosome 5 from BN rats. We also demonstrated that ECHDC2 did not alter mitochondrial O2 consumption, metabolic intermediates and ATP production. By gas chromatography–mass spectrometry, we found that ECHDC2 overexpression increased the levels of the cellular branched chain amino acids leucine and valine. Conclusion: ECHDC2, a mitochondrial protein, may be involved in regulating cell death and myocardial injury. Its deficiency in BN rats contributes to their increased resistance to myocardial I/R compared with SS rats. ECHDC2 increases branched chain amino acid metabolism and appears to be a novel regulator linking cell metabolism with cardiovascular disease.

This article is from SpringerPlus , volume 3 . Abstract Purpose: The purpose of this study was to investigate the utility incremental diagnostic value of combined assessment with coronary CT angiography (CCTA) and myocardial CT perfusion imaging (CTP) using dual-energy technology with an Adenosine Triphosphate (ATP) load technique. Materials and methods: Twenty-one patients underwent ATP-provocation dual-energy CT and CAG. We compared the diagnostic accuracy with CAG, for ischemic region due coronary stenosis by CCTA alone and CCTA combined with CTP (Combined CCTA/CTP). Results: All of 21 patients CTP images could be evaluated, however 8 CCTA images could not be evaluated by calcification and motion artifact, so assessability was 61.9% (13/21) for CCTA alone, and 100% for Combined CCTA/CTP. With CAG results as a comparison, the sensitivity, specificity, positive predictive value, and negative predictive value were, respectively, 83.3% (20/24), 74.4% (29/39), 66.7% (20/30), and 87.8% (29/33) for CCTA alone, and 66.7% (16/24), 92.3% (36/39), 84.2% (16/19), and 81.8% (36/44) for combined CCTA/CTP. The diagnostic accuracy of the two methods were 77.8% (49/63) and 82.5% (52/63). Conclusion: Dual-energy CT may be a useful modality for perfusion assessment and correlated well with the severity of stenosis on CAG. This technique may even be of use in cases of severe calcification in the coronary artery wall.

This article is from PLoS ONE , volume 9 . Abstract G-protein-coupled receptors (GPCRs) are the most abundant receptors in the heart and therefore are common targets for cardiovascular therapeutics. The activated GPCRs transduce their signals via heterotrimeric G-proteins. The four major families of G-proteins identified so far are specified through their α-subunit: Gαi, Gαs, Gαq and G12/13. Gαi-proteins have been reported to protect hearts from ischemia reperfusion injury. However, determining the individual impact of Gαi2 or Gαi3 on myocardial ischemia injury has not been clarified yet. Here, we first investigated expression of Gαi2 and Gαi3 on transcriptional level by quantitative PCR and on protein level by immunoblot analysis as well as by immunofluorescence in cardiac tissues of wild-type, Gαi2-, and Gαi3-deficient mice. Gαi2 was expressed at higher levels than Gαi3 in murine hearts, and irrespective of the isoform being knocked out we observed an up regulation of the remaining Gαi-protein. Myocardial ischemia promptly regulated cardiac mRNA and with a slight delay protein levels of both Gαi2 and Gαi3, indicating important roles for both Gαi isoforms. Furthermore, ischemia reperfusion injury in Gαi2- and Gαi3-deficient mice exhibited opposite outcomes. Whereas the absence of Gαi2 significantly increased the infarct size in the heart, the absence of Gαi3 or the concomitant upregulation of Gαi2 dramatically reduced cardiac infarction. In conclusion, we demonstrate for the first time that the genetic ablation of Gαi proteins has protective or deleterious effects on cardiac ischemia reperfusion injury depending on the isoform being absent.

This article is from PLoS ONE , volume 9 . Abstract Objective: Coronary artery disease (CAD) is associated with abdominal obesity and metabolic syndrome. Adipocytes secrete adipokines, including the newly discovered adipocyte fatty acid binding protein (A-FABP) and chemerin. Adipokines contribute to the pathogenesis of CAD. In patients with CAD, the presence of significant ischemia predicts adverse outcomes. It is unknown whether adipokines can be better predictors of the presence of significant myocardial ischemia than conventional risk factors. This study aimed to compare adipokines with clinical risk factors and abdominal obesity as predictive factors for significant myocardial ischemia. Methods: One hundred and ninety-six adults with suspected, but unproven, CAD were consecutively enrolled. The main measures were clinical and biochemical parameters and stress myocardial perfusion imaging with gated myocardial perfusion single-photon emission computed tomography (SPECT), with computed tomography (CT) attenuation correction. The abdominal visceral fat area was examined using a hybrid SPECT/CT scanner. Serum levels of high-sensitivity C-reactive protein (hs-CRP) and adipokines (adiponectin, A-FABP, and chemerin) were evaluated. Results: A-FABP levels correlated significantly with adiponectin, hs-CRP, body mass index, waist circumference, and visceral fat area. A-FABP was significantly associated with metabolic syndrome (OR 3.2, 95% CI 1.6–6.4, p = 0.001), significant myocardial ischemia (OR 1.9, 95% CI 1.0–3.4, p = 0.05), and stress lung-to-heart ratio (β = 0.03, p = 0.03) on SPECT. Chemerin was significantly associated with serum triglyceride levels but not with metabolic syndrome, significant ischemia, or stress lung-to-heart ratio on SPECT. A-FABP was better at detecting significant inducible ischemia than other biomarkers, although this was a modest improvement (area under ROC curve 0.579, 95% CI 0.46–0.69). Conclusions: Serum A-FABP concentrations correlate significantly with visceral fat area, metabolic syndrome, and predicted significant myocardial ischemia on SPECT. This may help to more accurately assess CAD risk, especially in patients with metabolic syndrome.

This article is from Nutrition Research and Practice , volume 8 . Abstract BACKGROUND/OBJECTIVE: Myocardial cell death due to occlusion of the coronary arteries leads to myocardial infarction, a subset of coronary heart disease (CHD). Dietary fiber is known to be associated with a reduced risk of CHD, the underlying mechanisms of which were suggested to delay the onset of occlusion by ameliorating risk factors. In this study, we tested a hypothesis that a beneficial role of dietary fiber could arise from protection of myocardial cells against ischemic injury, manifested after occlusion of the arteries. MATERIALS/METHODS: Three days after rats were fed apple pectin (AP) (with 10, 40, 100, and 400 mg/kg/day), myocardial ischemic injury was induced by 30 min-ligation of the left anterior descending coronary artery, followed by 3 hr-reperfusion. The area at risk and infarct area were evaluated using Evans blue dye and 2,3,5-triphenyltetrazolium chloride (TTC) staining, respectively. DNA nicks reflecting the extent of myocardial apoptosis were assessed by TUNEL assay. Levels of cleaved caspase-3, Bcl-2, and Bax were assessed by immunohistochemistry. RESULTS: Supplementation of AP (with 100 and 400 mg/kg/day) resulted in significantly attenuated infarct size (IS) (ratio of infarct area to area at risk) by 21.9 and 22.4%, respectively, in the AP-treated group, compared with that in the control group. This attenuation in IS showed correlation with improvement in biomarkers involved in the apoptotic cascades: reduction of apoptotic cells, inhibition of conversion of procaspase-3 to caspase-3, and increase of Bcl-2/Bax ratio, a determinant of cell fate. CONCLUSIONS: The findings indicate that supplementation of AP results in amelioration of myocardial infarction by inhibition of apoptosis. Thus, the current study suggests that intake of dietary fiber reduces the risk of CHD, not only by blocking steps leading to occlusion, but also by protecting against ischemic injury caused by occlusion of the arteries.

This article is from Korean Circulation Journal , volume 42 . Abstract Background and Objectives: Fragmented QRS complexes (fQRS) are associated with increased morbidity and mortality. The causative relationship between fQRS and cardiac fibrosis has been shown, but whether the presence and the number of fQRS on admission of electrocardiogram (ECG) predicts ST segment resolution in patients undergoing primary percutaneous coronary intervention (p-PCI) has not been investigated until now. Subjects and Methods: This study included one hundred and eighty-four consecutive patients with ST elevation myocardial infarction (STEMI) who underwent p-PCI. The presence or absence of fQRS on pre and post-PCI ECG and their relation with myocardial infarction and reperfusion parameters were investigated. Results: Patients with fQRS on admission of ECG or newly developed fQRS after p-PCI had increased inflammatory markers, higher cardiac enzyme levels, increased pain to balloon time, prolonged QRS time, more extended coronary involvement and more frequent Q waves on ECG in comparison to patients with absence or resolved fQRS. The presence and higher number of fQRS on admission or post-PCI ECGs were significantly related with low percent of ST resolution and myocardial reperfusion parameters. The area under the receiver operating characteristics curve values for the presence and number of fQRS to detect Thrombolysis in Myocardial Infarction Blush Grade 0 and 1, were 0.682 and 0.703. Conclusion: In our study, fQRS was significantly related to infarction and myocardial reperfusion parameters before and after p-PCI. Successful myocardial reperfusion by p-PCI caused the reduction in number of fQRS and QRS time with higher ST resolution. fQRS may be useful in identifying the patients at higher cardiac risk with increased ischemic jeopardized or infarcted myocardium, and persistent or newly developed fQRS may predict low percent of ST segment resolution in patients undergoing p-PCI.

The purpose of this study was to conduct controlled human trichloroethylene (TCE) inhalation studies to support physiologically-based pharmacokinetic (PB-PK) modeling of TCE exposure in healthy men and women. TCE is a volatile liquid used in degreasing operations, industrial cleaning, paint strippers, rug cleaners, spot removers, and typewriter correction fluid with widespread industrial and military use. Eight female and nine male subjects willing to provide informed consent were medically qualified for participation, then were exposed to 4 hours of 50 ppm or 100 ppm TCE at rest in a controlled environmental chamber. Following exposure, subjects remained in the chamber breathing clean air at rest and during sleep for an additional 18 hours. Periodically during and after exposure, blood samples were taken via venous catheter and urine samples were collected via specimen containers. The blood and urine samples were partitioned and treated with reagents, and the subsamples flash-frozen. Frozen samples were shipped to designated laboratories for chemical analysis, and the resulting TCE and TCE-metabolite data transmitted to the Tri-Service Toxicology group at Wright-Patterson Air Force Base (WPAFB) for PB-PK model analysis. Results of the TCE PB-PK model analyses are to be reported elsewhere by the WPAFB investigators.

This article is from Brazilian Journal of Medical and Biological Research , volume 46 . Abstract Quercetin (Que), a plant-derived flavonoid, has multiple benefical actions on the cardiovascular system. The current study investigated whether Que postconditioning has any protective effects on myocardial ischemia/reperfusion (I/R) injury in vivo and its potential cardioprotective mechanisms. Male Sprague-Dawley rats were randomly allocated to 5 groups (20 animals/group): sham, I/R, Que postconditioning, Que+LY294002 [a phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway inhibitor], and LY294002+I/R. I/R was produced by 30-min coronary occlusion followed by 2-h reperfusion. At the end of reperfusion, myocardial infarct size and biochemical changes were compared. Apoptosis was evaluated by both TUNEL staining and measurement of activated caspase-3 immunoreactivity. The phosphorylation of Akt and protein expression of Bcl-2 and Bax were determined by Western blotting. Que postconditioning significantly reduced infarct size and serum levels of creatine kinase and lactate dehydrogenase compared with the I/R group (all P

This article is from Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease , volume 3 . Abstract Background: We have demonstrated that tumor necrosis factor (TNF) receptor‐associated factor 2 (TRAF2), a scaffolding protein common to TNF receptors 1 and 2, confers cytoprotection in the heart. However, the mechanisms for the cytoprotective effects of TRAF2 are not known. Methods/Results: Mice with cardiac‐restricted overexpression of low levels of TRAF2 (MHC‐TRAF2LC) and a dominant negative TRAF2 (MHC‐TRAF2DN) were subjected to ischemia (30‐minute) reperfusion (60‐minute) injury (I/R), using a Langendorff apparatus. MHC‐TRAF2LC mice were protected against I/R injury as shown by a significant ≈27% greater left ventricular (LV) developed pressure after I/R, whereas mice with impaired TRAF2 signaling had a significantly ≈38% lower LV developed pressure, a ≈41% greater creatine kinase (CK) release, and ≈52% greater Evans blue dye uptake after I/R, compared to LM. Transcriptional profiling of MHC‐TRAF2LC and MHC‐TRAF2DN mice identified a calcium‐triggered exocytotic membrane repair protein, dysferlin, as a potential cytoprotective gene responsible for the cytoprotective effects of TRAF2. Mice lacking dysferlin had a significant ≈39% lower LV developed pressure, a ≈20% greater CK release, and ≈29% greater Evans blue dye uptake after I/R, compared to wild‐type mice, thus phenocopying the response to tissue injury in the MHC‐TRAF2DN mice. Moreover, breeding MHC‐TRAF2LC onto a dysferlin‐null background significantly attenuated the cytoprotective effects of TRAF2 after I/R injury. Conclusion: The study shows that dysferlin, a calcium‐triggered exocytotic membrane repair protein, is required for the cytoprotective effects of TRAF2‐mediated signaling after I/R injury.

Carbon monoxide is of continuing interest to the military community. The transient nature of weapons firing, the spatial distribution of CO concentration, and differences in individual physiology will cause the CO dose to vary significantly among crewmembers. Continuous and noninvasive ambulatory monitoring of cardiopulmonary measurements in situ may provide an understanding of the effects of CO exposure among crewmembers in the field environment. This project evaluates the utility of combined impedance and electrocardiographic estimators of cardiac function during exercise in air and with exposure to CO. Treadmill exercise is included on test subjects for comparison with the existing body of data on exercise performance in asymptomatic patients and the body of data which reflects performance decrements with exercise and CO in normals. Upper body exercise is included to test the hypothesis that this form of exercise places a greater strain on the cardiovascular system than lower body exercise, both with and without CO exposure. All of the accomplished work to date has involved preparatory tasks, therefore no experimental results are reported. The midterm report does discuss the literature review, the experiment plan, and the development of a human exposure facility for executing the planned experiments. RA 3; Carbon monoxide; Exercise; ECG; Impedance cardiography

Carbon monoxide is of continuing interest to the military community. The transient nature of weapons firing, the spatial distribution of CO concentration, and differences in individual physiology will cause the CO dose to vary significantly among crewmembers. Continuous and noninvasive ambulatory monitoring of cardiopulmonary measurements in situ may provide an understanding of the effects of CO exposure among crewmembers in the field environment. This project evaluates the utility of combined impedance and electrocardiographic estimators of cardiac function during exercise in air and with exposure to CO. Treadmill exercise is included on test subjects for comparison with the existing body of data on exercise performance in asymptomatic patients and the body of data which reflects performance decrements with exercise and CO in normals. Upper body exercise is included to test the hypothesis that this form of exercise places a greater strain on the cardiovascular system than lower body exercise, both with and without CO exposure. All of the accomplished work to date has involved preparatory tasks, therefore no experimental results are reported. The midterm report does discuss the literature review, the experiment plan, and the development of a human exposure facility for executing the planned experiments. RA 3; Carbon monoxide; Exercise; ECG; Impedance cardiography

Carbon monoxide is of continuing interest to the military community. The transient nature of weapons firing, the spatial distribution of CO concentration, and differences in individual physiology will cause the CO dose to vary significantly among crewmembers. Continuous and noninvasive ambulatory monitoring of cardiopulmonary measurements in situ may provide an understanding of the effects of CO exposure among crewmembers in the field environment. This project evaluates the utility of combined impedance and electrocardiographic estimators of cardiac function during exercise in air and with exposure to CO. Treadmill exercise is included on test subjects for comparison with the existing body of data on exercise performance in asymptomatic patients and the body of data which reflects performance decrements with exercise and CO in normals. Upper body exercise is included to test the hypothesis that this form of exercise places a greater strain on the cardiovascular system than lower body exercise, both with and without CO exposure. All of the accomplished work to date has involved preparatory tasks, therefore no experimental results are reported. The midterm report does discuss the literature review, the experiment plan, and the development of a human exposure facility for executing the planned experiments. RA 3; Carbon monoxide; Exercise; ECG; Impedance cardiography

Infant mortality for Pulmonary Atresia with Intact Ventricular Septum (PAIVS) remains high (up to 20-30%), often in relation to development of myocardial ischemia in the presence of a diminutive right ventricle (RV) and single ventricle physiology. Although coronary artery anatomy is recognized as a major predictor of poor outcomes, its predictive value varies widely among studies and does not comprehensively determine mortality risk. This scoping review aims to characterize the breadth and strength of association between anatomical and pathophysiological risk factors and myocardial ischemia, use of mechanical circulatory support, and early mortality in infants with Pulmonary Atresia with Intact Ventricular Septum (PAIVS).

Infant mortality for Pulmonary Atresia with Intact Ventricular Septum (PAIVS) remains high (up to 20-30%), often in relation to development of myocardial ischemia in the presence of a diminutive right ventricle (RV) and single ventricle physiology. Although coronary artery anatomy is recognized as a major predictor of poor outcomes, its predictive value varies widely among studies and does not comprehensively determine mortality risk. This scoping review aims to characterize the breadth and strength of association between anatomical and pathophysiological risk factors and myocardial ischemia, use of mechanical circulatory support, and early mortality in infants with Pulmonary Atresia with Intact Ventricular Septum (PAIVS).

This article is from Journal of Korean Medical Science , volume 27 . Abstract Sauchinone has been known to have anti-inflammatory and antioxidant effects. We determined whether sauchinone is beneficial in regional myocardial ischemia/reperfusion (I/R) injury. Rats were subjected to 20 min occlusion of the left anterior descending coronary artery, followed by 2 hr reperfusion. Sauchinone (10 mg/kg) was administered intraperitoneally 30 min before the onset of ischemia. The infarct size was measured 2 hr after resuming the perfusion. The expression of cell death kinases (p38 and JNK) and reperfusion injury salvage kinases (phosphatidylinositol-3-OH kinases-Akt, extra-cellular signal-regulated kinases [ERK1/2])/glycogen synthase kinase (GSK)-3β was determined 5 min after resuming the perfusion. Sauchinone significantly reduced the infarct size (29.0% ± 5.3% in the sauchinone group vs 44.4% ± 6.1% in the control, P < 0.05). Accordingly, the phosphorylation of JNK and p38 was significantly attenuated, while that of ERK1/2, Akt and GSK-3β was not affected. It is suggested that sauchinone protects against regional myocardial I/R injury through inhibition of phosphorylation of p38 and JNK death signaling pathways.

This article is from BMC Cardiovascular Disorders , volume 13 . Abstract Background: In recent decades, several studies have assessed the value of cardiac rehabilitation as secondary prevention and have reported substantial reductions in readmissions. However, conclusive evidence is scarce. The present study aims to evaluate the efficacy of a supervised exercise training program for improving percentages of hospital readmission for cardiac causes in patients with myocardial ischemia in the first year after a cardiac event. The effect on all-cause readmission, all-cause mortality, functional capacity, quality of life and adherence to regular exercise is also discussed. Methods/Design: This study will be conducted as a randomized controlled trial. Eligible patients will be randomly assigned to a control group receiving standard care or to an intervention group which, in addition to standard care, will take part in a supervised exercise training program consisting of three hours a week (spread over three alternate days) of supervised exercise training for 10 weeks. Both groups will perform an exercise stress test and a blood test during the first and third month after hospital discharge. The follow-up period will be 12 months after hospital discharge. The primary outcome measures will be the percentage of patients readmitted, total number of readmissions and length of hospitalization for cardiac disease during the first year after hospital discharge, and time to first hospital admission for cardiac disease. Discussion: A representative group of hospitalized patients after myocardial ischemia will be studied in order to provide comprehensive data on the potential impact of a supervised exercise training program on hospital readmission rates. Trial registration: Current Controlled Trials ISRCTN57634424.

This study used automated physical activity monitors to objectively examine the relationship between heightened physical activity levels and the occurrence of daily life ischemia in patients with coronary artery disease (CAD). A total of S4 ischemic episodes were recorded in 21 CAD patients (2.6 +/- 2.3 episodes/person) during 883 hours of continuous ECG and activity monitoring. The results of this study indicated that episodes of activity-induced ischemia occurred throughout the day, but tended to peak in the early morning hours due to dramatic shifts in activity and heart rate concomitant to the initiation of morning activities upon arising. In general, gradual increases in physical activity and heart rate were observed during the hour before the onset of ischemia. The findings of this study provide objective corroboration of previous self-report investigations of activity-induced ambulatory ischemia and highlight the potency of increased myocardial oxygen demand as a trigger of daily life ischemia.

This article is from Journal of Stem Cells & Regenerative Medicine , volume 8 . Abstract Introduction. Amniotic membrane contains a multipotential stem cell population and is expected to possess the machinery to regulate immunological reactions. We investigated the safety and efficacy of allogeneic amniotic membrane-derived mesenchymal stromal cell (AMSC) transplantation in a porcine model of chronic myocardial ischemia as a preclinical trial.Methods. Porcine AMSCs were isolated from amniotic membranes obtained by cesarean section just before delivery and were cultured to increase their numbers before transplantation. Chronic myocardial ischemia was induced by implantation of an ameroid constrictor around the left circumflex coronary artery. Four weeks after ischemia induction, nine swine were assigned to undergo either allogeneic AMSC transplantation or normal saline injection. Functional analysis was performed by echocardiography, and histological examinations were carried out by immunohistochemistry 4 weeks after AMSC transplantation.Results. Echocardiography demonstrated that left ventricular ejection fraction was significantly improved and left ventricular dilatation was well attenuated 4 weeks after AMSC transplantation. Histological assessment showed a significant reduction in percentage of fibrosis in the AMSC transplantation group. Injected allogeneic green fluorescent protein (GFP)-expressing AMSCs were identified in the immunocompetent host heart without the use of any immunosuppressants 4 weeks after transplantation. Immunohistochemistry revealed that GFP colocalized with cardiac troponin T and cardiac troponin I.Conclusions. We have demonstrated that allogeneic AMSC transplantation produced histological and functional improvement in the impaired myocardium in a porcine model of chronic myocardial ischemia. The transplanted allogeneic AMSCs survived without the use of any immunosuppressants and gained cardiac phenotype through either their transdifferentiation or cell fusion.

This article is from Western Journal of Emergency Medicine , volume 12 . Abstract Penetrating trauma is a rare cause of myocardial infarction. Our report describes a 47-year-old female who presented with a gunshot wound from a shotgun and had an ST-elevation myocardial infarction. The patient received emergent coronary angiography, which demonstrated no evidence of coronary atherosclerotic disease but did show occlusion of a marginal vessel secondary to a pellet. The patient was managed medically for the myocardial infarction without cardiac sequelae. Patients with penetrating trauma to the chest should be evaluated for myocardial ischemia. Electrocardiography, echocardiography and cardiac angiography play vital roles in evaluating these patients and helping to guide management.

A computer model-based approach is presented to characterize hemodynamic consequences of myocardial ischemia in terms of depressed ventricular elastance and delayed and reduced ischemic regional cardiac muscle shortening, as well as relaxation time constants. The model is shown to be versatile in quantifying the severity of myocardial ischemia.

This article is from Journal of Cardiovascular Magnetic Resonance , volume 15 . Abstract Many investigators have speculated that hyperintense plaques (HIPs) of the carotid artery on noncontrast T1-weighted imaging (T1WI) in cardiovascular magnetic resonance indicate the presence of mural or intraplaque hemorrhage containing methemoglobin. However, coronary plaque imaging with T1WI is challenging, and the clinical significance of coronary HIPs on T1WI remains unknown. Incidentally, it is very rare to find an intracoronary thrombus at the culprit lesion site in patients in stable condition. This article reports the case of a lesion containing an intracoronary thrombus, detected as HIP on T1WI associated with the filter no-reflow phenomenon in a patient with silent myocardial ischemia.

Impaired autonomic-cardiac regulation, as defined by reduced levels of heart rate variability (HRV), is an independent predictor of death in patients with coronary artery disease (CAD) and a history of myocardial infarction. Moreover, transient shifts in HRV have been observed before the acute onset of ambulatory myocardial ischemia in CAD patients. The present study investigated whether or not changes in autonomic-cardiac regulation: (1) were associated with altered hemodynamic regulation in CAD patients; (2) could identify CAD patients at-risk for ambulatory myocardial ischemia; or (3) were related to changes in physical exertion and heart rate levels before the onset of ambulatory myocardial ischemia. Fifty-three patients with documented CAD (44 men; mean age 65 years) participated in 48-hours of ambulatory electrocardiographic (Holter), physical activity, and blood pressure monitoring. Holter tapes were analyzed for evidence of myocardial ischemia and were used to generate several indices of HRV, including markers for sympathetic and parasympathetic tone, and their ratio, sympathovagal tone. Results indicated that CAD patients with lower levels of HRV (n = 26) had significantly higher levels of heart rate than did patients with preserved levels of HRV (n = 27; p .05), whereas HRV was found to be unrelated to patients blood pressure levels (p s .05). Contrary to predictions, ischemic CAD patients (n = 9) were found to have significantly higher levels of HRV and significantly lower levels of heart rate when compared to non-ischemic patients (n = 44; p s .05). These differences were not related to patients medication regimens, ejection fraction, or history of reperfusion procedures (p s 05). Ischemic and non-ischemic CAD patients did not differ in terms of their HRV, heart rate, or blood pressure levels during prescribed non-ischemic periods of keepi

This article is from Particle and Fibre Toxicology , volume 11 . Abstract Background: Clinical studies have now confirmed the link between short-term exposure to elevated levels of air pollution and increased cardiovascular mortality, but the mechanisms are complex and not completely elucidated. The present study was designed to investigate the hypothesis that activation of pulmonary sensory receptors and the sympathetic nervous system underlies the influence of pulmonary exposure to diesel exhaust particulate on blood pressure, and on the myocardial response to ischemia and reperfusion. Methods & Results: 6 h after intratracheal instillation of diesel exhaust particulate (0.5 mg), myocardial ischemia and reperfusion was performed in anesthetised rats. Blood pressure, duration of ventricular arrhythmia, arrhythmia-associated death, tissue edema and reperfusion injury were all increased by diesel exhaust particulate exposure. Reperfusion injury was also increased in buffer perfused hearts isolated from rats instilled in vivo, excluding an effect dependent on continuous neurohumoral activation or systemic inflammatory mediators. Myocardial oxidant radical production, tissue apoptosis and necrosis were increased prior to ischemia, in the absence of recruited inflammatory cells. Intratracheal application of an antagonist of the vanilloid receptor TRPV1 (AMG 9810, 30 mg/kg) prevented enhancement of systolic blood pressure and arrhythmia in vivo, as well as basal and reperfusion-induced myocardial injury ex vivo. Systemic β1 adrenoreceptor antagonism with metoprolol (10 mg/kg) also blocked enhancement of myocardial oxidative stress and reperfusion injury. Conclusions: Pulmonary diesel exhaust particulate increases blood pressure and has a profound adverse effect on the myocardium, resulting in tissue damage, but also increases vulnerability to ischemia-associated arrhythmia and reperfusion injury. These effects are mediated through activation of pulmonary TRPV1, the sympathetic nervous system and locally generated oxidative stress.

This article is from The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology , volume 17 . Abstract This study was designed to evaluate the protective effect of Korean red ginseng (KRG) against ischemia/reperfusion (I/R) injury in isolated guinea pig heart. KRG has been shown to possess various ginsenosides, which are the major components of Panax ginseng. These components are known naturally occurring compounds with beneficial effects and free radical scavenging activity. The heart was induced to ischemia for 60 min, followed by 120 min reperfusion. The hearts were randomly allocated into five groups (n=8 for each group): normal control (N/C), KRG control, I/R control, 250 mg/kg KRG group and 500 mg/kg KRG group. KRG significantly increased hemodynamics parameters such as aortic flow, coronary flow and cardiac output. Moreover, KRG significantly increased left ventricular systolic pressure (LVSP), the maximal rate of contraction (+dP/dtmax) and maximal rate of relaxation (-dP/dtmax). Also, treatment of KRG ameliorated electrocardiographic index such as the QRS, QT and RR intervals. Moreover, KRG significantly suppressed the lactate dehydrogenase, creatine kinase-MB fraction and cardiac troponin I and ameliorated the oxidative stress markers such as malondialdehyde and glutathione. KRG was standardized through ultra performance liquid chromatograph analysis for its major ginsenosides. Taken together, KRG has been shown to prevent cardiac injury by normalizing the biochemical and oxidative stress.

This article is from Journal of Advanced Pharmaceutical Technology & Research , volume 5 . Abstract Globally, the rate of development of myocardial diseases and hypertension is very common, which is responsible for incremental morbidity and mortality statistics. Treatment of ischemic hypertensive patients with diuretics such as hydrochlorothiazide (HCTZ) can precipitate myocardial infarction due to hypokalemia. This study was undertaken to evaluate the pharmacodynamic interaction of green tea extract (GTE) with HCTZ against ischemia-reperfusion induced myocardial toxicity. Wistar albino rats of either sex were taken and pretreated with high (500 mg/kg, p.o.) and low (100 mg/kg, p.o.) dose of GTE for 30 days. Standard, high and low dose of interactive groups received HCTZ (10 mg/kg, p.o.) for last 7 days. Ischemia-reperfusion injury was induced by modified Lagendorff apparatus, and the effect of different treatments was evaluated by percentage recovery in terms of heart rate and developed tension, serum biomarkers, and heart tissue antioxidant levels. Prophylactic treatment groups, such as high and low dose of GTE and their interactive groups with HCTZ, exhibited significant percentage recovery in terms of heart rate and developed tension. Apart from that, significant increase in superoxide dismutase and catalase, decrease in thiobarbituric acid reactive species in heart tissue, as well as significant decrease in serum lactate dehydrogenase, creatinine phosphokinase-MB and N-acetylcysteine levels have also been documented. The present findings clearly suggest that GTE dose-dependently reduces myocardial toxicity due to ischemia, and combination with HCTZ can reduce the associated side-effects and exhibits myocardial protection.

This article is from PLoS ONE , volume 9 . Abstract Aim: Myocardial infarction (MI) remains a major cause of death and disability worldwide, despite available reperfusion therapies. Inflammatory signaling is considered nodal in defining final infarct size. Activation of the innate immune receptor toll-like receptors (TLR) 9 prior to ischemia and reperfusion (I/R) reduces infarct size, but the consequence of TLR9 activation timed to the onset of ischemia is not known. Methods and Results: The TLR9-agonist; CpG B was injected i.p. in C57BL/6 mice immediately after induction of ischemia (30 minutes). Final infarct size, as well as area-at-risk, was measured after 24 hours of reperfusion. CpG B injection resulted in a significant increase in circulating granulocytes and monocytes both in sham and I/R mice. Paradoxically, clear evidence of reduced cardiac infiltration of both monocytes and granulocytes could be demonstrated in I/R mice treated with CpG B (immunocytochemistry, myeloperoxidase activity and mRNA expression patterns). In addition, systemic TLR9 activation elicited significant alterations of cardiac inflammatory genes. Despite these biochemical and cellular changes, there was no difference in infarct size between vehicle and CpG B treated I/R mice. Conclusion: Systemic TLR9-stimulation upon onset of ischemia and subsequent reperfusion does not alter final infarct size despite causing clear alterations of both systemic and cardiac inflammatory parameters. Our results question the clinical usefulness of TLR9 activation during cardiac I/R.

To evaluate the efficacy and safety of Neiguan electroacupuncture in the treatment of myocardial ischemia-reperfusion in rats.

This article is from Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease , volume 3 . Abstract Background: Women are more likely than men to develop resistant hypertension, which is associated with excess risk of major adverse outcomes; however, the impact of resistant hypertension in women with ischemia has not been explicitly studied. In this Women's Ischemia Syndrome Evaluation (WISE) analysis, we assessed long‐term adverse outcomes associated with apparent treatment‐resistant hypertension (aTRH) among women with suspected myocardial ischemia referred for coronary angiography. Methods and Results: Women (n=927) were grouped according to baseline blood pressure (BP): normotensive (no hypertension history, BP

This article is from Experimental and Therapeutic Medicine , volume 5 . Abstract Honokiol, a potent radical scavenger, has been demonstrated to ameliorate cerebral infarction following ischemia/reperfusion (I/R) injury. However, its effects on myocardial I/R injury remain unclear. The present study aimed to examine the effects of honokiol on myocardial I/R injury and to investigate its potential cardioprotective mechanisms. Sprague-Dawley rats were pretreated with honokiol and exposed to a 30-min myocardial ischemia followed by 2-h coronary reperfusion. Myocardial I/R-induced infarct size and biochemical and histological changes were compared. The expression of nuclear factor κB(NF-κB; p65) was assessed by western blotting. Pretreatment with honokiol significantly reduced infarct size, and serum creatine kinase (CK) and lactate dehydrogenase (LDH) release compared with those in the I/R group following a 2-h reperfusion. The malondialdehyde (MDA) level, myeloperoxidase (MPO) activity, concentrations of tumor necrosis factor (TNF)-α and interleukin (IL)-6 and expression level of NF-κB were all reduced by honokiol pretreatment, while honokiol inhibited the decreases in superoxide dismutase (SOD) and catalase (CAT) activities. In addition, less neutrophil infiltration and histopathological damage in the myocardium were observed in the honokiol-pretreated group. These findings indicate that honokiol pretreatment diminished myocardial I/R injury through attenuation of oxidative stress and inflammation.

This study investigated the effects of carbon monoxide (CO) exposure on cardiac function during exercise. Subjects had their blood COHb level raised to 5%, 10%, 15%, and 20% COHb by inhaling air and CO mixtures from Douglas bags and by breathing air and CO chamber mixtures to maintain COHb level during exercise. AH subjects performed both multistage treadmill (to 10 METS) and hand- crank (to 5 MEETS) exercise at each CO exposure level. Sixteen subjects ranging from 21 to 29 years of age (mean of 24.6 years) completed the study. The results indicate that young, apparently healthy males can perform submaximal upper and lower-body exercise without adverse health effects after CO exposures attaining 20% COHb. The data also show that the cardiovascular system compensates for the reduced oxygen-carrying capacity of the blood by augmenting heart rate, cardiac contractility, and cardiac output for both types of exercise. The enhanced response begins to fail at higher levels of CO exposure and exercise, and although not tested in this study, must ultimately result in reduced maximal exercise capacity. Carbon monoxide, Carboxyhemoglobin, Cardiac output, Contractility, COHb

This study investigated the effects of carbon monoxide (CO) exposure on cardiac function during exercise. Subjects had their blood COHb level raised to 5%, 10%, 15%, and 20% COHb by inhaling air and CO mixtures from Douglas bags and by breathing air and CO chamber mixtures to maintain COHb level during exercise. AH subjects performed both multistage treadmill (to 10 METS) and hand- crank (to 5 MEETS) exercise at each CO exposure level. Sixteen subjects ranging from 21 to 29 years of age (mean of 24.6 years) completed the study. The results indicate that young, apparently healthy males can perform submaximal upper and lower-body exercise without adverse health effects after CO exposures attaining 20% COHb. The data also show that the cardiovascular system compensates for the reduced oxygen-carrying capacity of the blood by augmenting heart rate, cardiac contractility, and cardiac output for both types of exercise. The enhanced response begins to fail at higher levels of CO exposure and exercise, and although not tested in this study, must ultimately result in reduced maximal exercise capacity. Carbon monoxide, Carboxyhemoglobin, Cardiac output, Contractility, COHb

This article is from PLoS ONE , volume 9 . Abstract Background: Oxidative stress plays a key role in exacerbating diabetes and cardiovascular disease. Heme oxygenase-1 (HO-1), a stress response protein, is cytoprotective, but its role in post myocardial infarction (MI) and diabetes is not fully characterized. We aimed to investigate the protection and the mechanisms of HO-1 induction in cardiomyocytes subjected to hypoxia and in diabetic mice subjected to LAD ligation. Methods: In vitro: cultured cardiomyocytes were treated with cobalt-protoporphyrin (CoPP) and tin protoporphyrin (SnPP) prior to hypoxic stress. In vivo: CoPP treated streptozotocin-induced diabetic mice were subjected to LAD ligation for 2/24 h. Cardiac function, histology, biochemical damage markers and signaling pathways were measured. Results: HO-1 induction lowered release of lactate dehydrogenase (LDH) and creatine phospho kinase (CK), decreased propidium iodide staining, improved cell morphology and preserved mitochondrial membrane potential in cardiomyocytes. In diabetic mice, Fractional Shortening (FS) was lower than non-diabetic mice (35±1%vs.41±2, respectively p

This article is from PLoS ONE , volume 9 . Abstract Rationale: During the past 30 years, myocardial ischemia/reperfusion injury in rodents became one of the most commonly used model in cardiovascular research. Appropriate pain-prevention appears critical since it may influence the outcome and the results obtained with this model. However, there are no proper guidelines for pain management in rats undergoing thoracic surgery. Accordingly, we evaluated three analgesic regimens in cardiac ischemia/reperfusion injury. This study was strongly focused on 3R’s ethic principles, in particular the principle of Reduction. Methods: Rats undergoing surgery were treated with pre-surgical tramadol (45 mg/kg intra-peritoneal), or carprofen (5 mg/kg sub-cutaneous), or with pre-surgical administration of carprofen followed by 2 post-surgery tramadol injections (multi-modal group). We assessed behavioral signs of pain and made a subjective evaluation of stress and suffering one and two hours after surgery. Results: Multi-modal treatment significantly reduced the number of signs of pain compared to carprofen alone at both the first hour (61±42 vs 123±47; p

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During the early phase of myocardial ischemia, extracellular K+ accumulation is considered pivotal in the genesis of reentrant arrhythmias Despite the importance of this phenomenon, the causes of cellular K+ loss are still unknown. Because of their ability to simulate the electrical activity of cardiomyocytes, action potential (AP) models provide an alternative for exploring their behavior under normoxic or pathological conditions. Our goal was to investigate, with the aid of computer simulations, the mechanisms responsible for the ischemic increase of extracellular K+ concentration (K+(sub o)). The electrophysiological behavior of one single cardiomyocyte has been simulated during 14 minutes in the absence of coronary flow, using a modified version of Luo Rudy phase II AP model, The activation of the ATP-sensitive K+ current, as well as other possible causes of the ischemic increase of K+(sub o) such as inhibition of Na+/K+ pump current and altered Na+ fluxes, have been taken into account in the simulations. Our results show that the concomitant effect of these three mechanisms in the absence of coronary flow leads to an increase of K+(sub o) quantitative and qualitatively similar to the experimentally observed during acute myocardial ischemia.

During the early phase of myocardial ischemia, extracellular K+ accumulation is considered pivotal in the genesis of reentrant arrhythmias Despite the importance of this phenomenon, the causes of cellular K+ loss are still unknown. Because of their ability to simulate the electrical activity of cardiomyocytes, action potential (AP) models provide an alternative for exploring their behavior under normoxic or pathological conditions. Our goal was to investigate, with the aid of computer simulations, the mechanisms responsible for the ischemic increase of extracellular K+ concentration (K+(sub o)). The electrophysiological behavior of one single cardiomyocyte has been simulated during 14 minutes in the absence of coronary flow, using a modified version of Luo Rudy phase II AP model, The activation of the ATP-sensitive K+ current, as well as other possible causes of the ischemic increase of K+(sub o) such as inhibition of Na+/K+ pump current and altered Na+ fluxes, have been taken into account in the simulations. Our results show that the concomitant effect of these three mechanisms in the absence of coronary flow leads to an increase of K+(sub o) quantitative and qualitatively similar to the experimentally observed during acute myocardial ischemia.

This article is from Experimental and Therapeutic Medicine , volume 8 . Abstract High mobility group box 1 protein (HMGB1) has an important role in myocardial ischemia/reperfusion (I/R) injury. Sodium butyrate, an inhibitor of histone deacetylase, has been shown to inhibit HMGB1 expression. In the present study, the effect of sodium butyrate on myocardial I/R injury in rats was investigated. Anesthetized male rats were intraperitoneally administered sodium butyrate (100 or 300 mg/kg) 30 min prior to the induction of ischemia. The rats were then subjected to ischemia for 30 min followed by reperfusion for 4 h. Infarct size, lactate dehydrogenase (LDH), creatine kinase (CK) and superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels were then measured. The expression of HMGB1 was assessed using western blot analysis. The results demonstrated that pretreatment with sodium butyrate (300 mg/kg) significantly reduced the infarct size, as well as the levels of LDH and CK (P

This article is from Journal of Veterinary Science , volume 13 . Abstract Akt/protein kinase B is a well-known cell survival factor and activated by many stimuli including mechanical stretching. Therefore, we evaluated the cardioprotective effect of a brief mechanical stretching of rat hearts and determined whether activation of Akt through phosphatidylinositol 3-kinase (PI3K) is involved in stretch-induced cardioprotection (SIC). Stretch preconditioning reduced infarct size and improved post-ischemic cardiac function compared to the control group. Phosphorylation of Akt and its downstream substrate, GSK-3β, was increased by mechanical stretching and completely blocked by wortmannin, a PI3K inhibitor. Treatment with lithium or SB216763 (GSK-3β inhibitors) before ischemia induction mimicked the protective effects of SIC on rat heart. Gadolinium (Gd3+), a blocker of stretch-activated ion channels (SACs), inhibited the stretch-induced phosphorylation of Akt and GSK-3β. Furthermore, SIC was abrogated by wortmannin and Gd3+. In vivo stretching induced by an aorto-caval shunt increased Akt phosphorylation and reduced myocardial infarction; these effects were diminished by wortmannin and Gd3+ pretreatment. Our results showed that mechanical stretching can provide cardioprotection against ischemia-reperfusion injury. Additionally, the activation of Akt, which might be regulated by SACs and the PI3K pathway, plays an important role in SIC.

This article is from Journal of Visualized Experiments : JoVE . Abstract Ischemia-reperfusion (IR) was surgically performed in murine hearts which were then subjected to repeated imaging to monitor temporal changes in functional parameters of key clinical significance. Two-dimensional movies were acquired at high frame rate (8 kHz) and were utilized to estimate high-quality myocardial strain. Two-dimensional elastograms (strain images), as well as strain profiles, were visualized. Results were powerful in quantitatively assessing IR-induced changes in cardiac events including left-ventricular (LV) contraction, LV relaxation and isovolumetric phases of both pre-IR and post-IR beating hearts in intact mice. In addition, compromised sector-wise wall motion and anatomical deformation in the infarcted myocardium were visualized. The elastograms were uniquely able to provide information on the following parameters in addition to standard physiological indices that are known to be affected by myocardial infarction in the mouse: internal diameters of mitral valve orifice and aorta, effective regurgitant orifice, myocardial strain (circumferential as well as radial), turbulence in blood flow pattern as revealed by the color Doppler movies and velocity profiles, asynchrony in LV sector, and changes in the length and direction of vectors demonstrating slower and asymmetrical wall movement. This work emphasizes on the visual demonstration of how such analyses are performed.

http://uf.catalog.fcla.edu/uf.jsp?st=UF002642291&ix=pm&I=0&V=D&pm=1

This article is from International Journal of Preventive Medicine , volume 5 . Abstract Background:: Type-D personality has been identified as a risk factor for general and cardiac mortality in patients with coronary artery disease (CAD). Dobutamine-atropine stress echocardiography (DASE) is an established method for non-invasive evaluation of myocardial ischemia in patients with CAD. The objective of this study was to evaluate the prevalence of type-D personality and its association with the occurrence of myocardial ischemia as assessed by DASE. Methods:: This case-control study enrolled 306 patients (61 ± 9.6 years, 57.8% female) who were referred by physicians to assessment of myocardial ischemia. Before undergoing DASE, the patients answered the type-D scale, which identifies type-D personality. Results:: Type-D personality was identified in 106 patients (34.6%). DASE was positive for myocardial ischemia in 32.4% (99) of 306 participants there was no significant association between type-D personality and ischemic changes on DASE (P = 0.941; odds ratio: 0.98; confidence interval 95%: 0.57-1.69). Chest pain was the only clinical variable with statistically significant prevalence in type-D personality patients (77.4% vs. 57.0%; P < 0.001). Conclusions:: Type-D personality was not a significant risk factor for the presence of ischemic changes on DASE. Patients with type-D personality tended to complain more frequently of chest pain than non-type-D patients.

This article is from PLoS ONE , volume 9 . Abstract The Rho/Rho-kinase pathway plays an important role in many cardiovascular diseases such as hypertension, atherosclerosis, heart failure, and myocardial infarction. Although previous studies have shown that Rho-kinase inhibitors reduce ischemia/reperfusion (I/R) injury and cytokine production, the role of Rho-kinase in leukocytes during I/R injury is not well understood. Mice were subjected to 30-min ischemia and reperfusion. Rho-kinase activity was significantly greater in leukocytes subjected to myocardial I/R compared to the sham-operated mice. Administration of fasudil, a Rho-kinase inhibitor, significantly reduced the I/R-induced expression of the proinflammatory cytokines interleukin (IL)-6, C-C motif chemoattractant ligand 2 (CCL2), and tumor necrosis factor (TNF)-α, in leukocytes, compared with saline as the vehicle. Furthermore, fasudil decreased I/R-induced myocardial infarction/area at risk (IA) and I/R-induced leukocyte infiltration in the myocardium. Interestingly, IA in fasudil-administered mice with leukocyte depletion was similar to that in fasudil-administered mice. I/R also resulted in remarkable increases in the mRNA expression levels of the proinflammatory cytokines TNF-α, IL-6, and CCL2 in the heart. Inhibition of Rho-kinase activation in leukocytes has an important role in fasudil-induced cardioprotective effects. Hence, inhibition of Rho-kinase may be an additional therapeutic intervention for the treatment of acute coronary syndrome.