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BackgroundTargeting the mitochondria during ischemia/reperfusion (IR) can confer cardioprotection leading to improved clinical outcomes. The cardioprotective potential of (-)-epicatechin (EPI) during IR via modulation of mitochondrial function was evaluated.Methods and resultsIschemia was induced in rats via a 45 min occlusion of the left anterior descending coronary artery followed by 1 h, 48 h, or 3 week reperfusion. EPI (10 mg/kg) was administered IV 15 min prior to reperfusion for the single dose group and again 12 h later for the double dose group. Controls received water. Experiments also utilized cultured neonatal rat ventricular myocytes (NRVM) and myoblasts. A single dose of EPI reduced infarct size by 27% at 48 h and 28% at 3 week. Double dose treatment further decreased infarct size by 80% at 48 h, and 52% by 3 weeks. The protective effect of EPI on mitochondrial function was evident after 1h of reperfusion when mitochondria demonstrated less respiratory inhibition, lower mitochondrial Ca2+ load, and a preserved pool of NADH that correlated with higher tissue ATP levels. Mechanistic studies in NRVM revealed that EPI acutely stimulated maximal rates of respiration, an effect that was blocked by inhibitors of the mitochondrial pyruvate carrier, nitric oxide synthase, or soluble guanylyl cyclase. In myoblasts, knockdown of components of the mitochondrial pyruvate carrier blocked EPI-induced respiratory stimulation.ConclusionsIV EPI confers cardioprotection via preservation of mitochondrial function potentially through enhanced substrate provision. These provocative results document a novel mechanism of a natural product with potential clinical utility.

Myocardial ischemia and reperfusion-evoked spinal reflexes involve nociceptive signals that trigger neuronal excitation through cardiac afferents, projecting into the thoracic spinal cord. Ischemic preconditioning (IPC) involves brief episodes of sublethal ischemia and reperfusion enhances the resistance of the myocardium to subsequent ischemic insults. This study investigated the effects of IPC on ischemia-reperfusion (I/R) stimulation-induced activation in the thoracic spinal cord of rats. A new remotely controlled I/R model was established. The infarct size was determined as a percentage of area at risk (IS/AAR) and arrhythmia scores were evaluated. Non-invasive in vivo fMRI was used for signal quantitative analysis of thoracic spinal spatiotemporal. The role of IPC on the excitability of substantia gelatinosa (SG) neurons was assessed by spinal patch clamp recording technique. The altered expressions of c -Fos, SP, and CGRP in T 4 segment were detected by immunohistochemical staining. The novel I/R model was induced successfully and reliably utilized, and IPC treatment markedly reduced the myocardial infarct size. fMRI analysis revealed that IPC reduced the increased BOLD signals induced by prolonged ischemia-reperfusion. Patch clamp recording showed that IPC treatment reversed the enhanced excitability of SG neurons during I/R treatment. The results of immunofluorescent staining indicated that IPC mitigated the I/R-induced dramatic increase of c -Fos, and reduced the release of SP and CGRP in dorsal horns of spinal cord. These results suggested that IPC suppressed neuronal activation induced by I/R stimuli in rat thoracic spinal cord using spinal cord fMRI and patch clamp recording techniques. • A novel remotely controlled ischemia-reperfusion model was proposed for fMRI study. • Spinal fMRI was used to detect the efficiency of ischemic preconditioning. • IPC suppressed neuronal activation induced by IR stimuli in spinal cord. • Modulation of SP and CGRP release response to cardiac ischemia-reperfusion; • Inhibitive effect of IPC on the excitability of SG neurons [ABSTRACT FROM AUTHOR]

Background Myocardial ischemia/reperfusion injury represents a clinically critical problem associated with coronary artery bypass graft surgery (CABG). The degree of oxidative stress, inflammation and apoptosis are increased during the reperfusion of the heart muscles following ischemia. The present study aims to examine the protective role of melatonin in ameliorating the degree of cardiac injury in patients undergoing bypass surgery, and whether this effect is a dose related. Methods A total of forty-five patients who were undergoing elective CABG in (Al-Najaf Cardiac Center, Al-Najaf, Iraq) were included in this study for the period between January, 2015 and November, 2015. Participants were randomly allocated into 3 study groups: Placebo-controlled group (C), low dose melatonin treatment group, 10 mg capsule once daily (M1) and high dose melatonin treatment group 20 mg capsule once daily (M2). Results Compared to the control group, there was a significant increase in the ejection fraction (EF%) associated with a significant decline in heart rate (HR) among the M1 and M2 groups compared to the C group (P < 0.05). In addition, there was a significant reduction in plasma levels of cardiac Troponin-I (CTnI), interleukin-1beta (IL-1β), Inducible nitric oxide synthase (iNOS) and caspase-3 enzymes in the melatonin groups (group M1 and M2) compared to the control group, (P < 0.05) in Melatonin-treated groups. Comparing the two melatonin study groups, the changes in the parameters mentioned above were more significant in the M2 group compared to the M1 group (P < 0.05). Conclusion These findings suggested that melatonin supplementation can ameliorate the degree of myocardial ischemic–reperfusion injury, dose dependent effects. [ABSTRACT FROM AUTHOR]

Background Targeting the mitochondria during ischemia/reperfusion (IR) can confer cardioprotection leading to improved clinical outcomes. The cardioprotective potential of (-)-epicatechin (EPI) during IR via modulation of mitochondrial function was evaluated. Methods and results Ischemia was induced in rats via a 45min occlusion of the left anterior descending coronary artery followed by 1h, 48h, or 3week reperfusion. EPI (10mg/kg) was administered IV 15min prior to reperfusion for the single dose group and again 12h later for the double dose group. Controls received water. Experiments also utilized cultured neonatal rat ventricular myocytes (NRVM) and myoblasts. A single dose of EPI reduced infarct size by 27% at 48h and 28% at 3week. Double dose treatment further decreased infarct size by 80% at 48h, and 52% by 3weeks. The protective effect of EPI on mitochondrial function was evident after 1h of reperfusion when mitochondria demonstrated less respiratory inhibition, lower mitochondrial Ca2+ load, and a preserved pool of NADH that correlated with higher tissue ATP levels. Mechanistic studies in NRVM revealed that EPI acutely stimulated maximal rates of respiration, an effect that was blocked by inhibitors of the mitochondrial pyruvate carrier, nitric oxide synthase, or soluble guanylyl cyclase. In myoblasts, knockdown of components of the mitochondrial pyruvate carrier blocked EPI-induced respiratory stimulation. Conclusions IV EPI confers cardioprotection via preservation of mitochondrial function potentially through enhanced substrate provision. These provocative results document a novel mechanism of a natural product with potential clinical utility. [ABSTRACT FROM AUTHOR]

Background: Targeting the mitochondria during ischemia/reperfusion (IR) can confer cardioprotection leading to improved clinical outcomes. The cardioprotective potential of (-)-epicatechin (EPI) during IR via modulation of mitochondrial function was evaluated., Methods and Results: Ischemia was induced in rats via a 45 min occlusion of the left anterior descending coronary artery followed by 1 h, 48 h, or 3 week reperfusion. EPI (10 mg/kg) was administered IV 15 min prior to reperfusion for the single dose group and again 12 h later for the double dose group. Controls received water. Experiments also utilized cultured neonatal rat ventricular myocytes (NRVM) and myoblasts. A single dose of EPI reduced infarct size by 27% at 48 h and 28% at 3 week. Double dose treatment further decreased infarct size by 80% at 48 h, and 52% by 3 weeks. The protective effect of EPI on mitochondrial function was evident after 1h of reperfusion when mitochondria demonstrated less respiratory inhibition, lower mitochondrial Ca2+ load, and a preserved pool of NADH that correlated with higher tissue ATP levels. Mechanistic studies in NRVM revealed that EPI acutely stimulated maximal rates of respiration, an effect that was blocked by inhibitors of the mitochondrial pyruvate carrier, nitric oxide synthase, or soluble guanylyl cyclase. In myoblasts, knockdown of components of the mitochondrial pyruvate carrier blocked EPI-induced respiratory stimulation., Conclusions: IV EPI confers cardioprotection via preservation of mitochondrial function potentially through enhanced substrate provision. These provocative results document a novel mechanism of a natural product with potential clinical utility., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)