Mechanisms of Cellular Alterations Due to Ischemia-Reperfusion Injury in the Heart

Temsah, Rana M.; Netticadan, Thomas; Dhalla, Naranjan S.

doi:10.1007/978-1-4615-0355-2_11

Cited by 5 publications

(6 citation statements)

References 113 publications

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“…However, many post-myocardial infarction patients suffer from long QT interval syndrome, characterized by the prolongation of action potential duration and bradyarrhythmias, which often lead to myocardial stunning and cardiac sudden death. Myocardial stunning refers to a continuous low-functioning state of the ischemic myocardium and it is observed in myocardial systolic and diastolic dysfunction induced by impaired ventricular function [25][26][27]. Our results demonstrated that SXSM significantly ameliorated bradyarrhythmias induced by I/R injury, indicating a possible anti-arrhythmic action of SXSM in myocardial I/R, which makes SXSM a unique pharmacological agent from other drugs with anti-I/R injury effects.…”

Section: Discussionsupporting

confidence: 51%

Shenxian-Shengmai Oral Liquid Reduces Myocardial Oxidative Stress and Protects Myocardium from Ischemia-Reperfusion Injury

Zhao

Zhang

Luan

et al. 2018

Cell Physiol Biochem

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Background/Aims: Shenxian-shengmai (SXSM) oral liquid, a Chinese patent compound medicine, has been used to treat sinus bradyarrhythmias induced by mild sick sinus syndrome in clinical practice. Myocardial ischemia, in particular in serious or right coronary-related heart diseases, can cause bradyarrhythmias and cardiac dysfunction. Moreover, reperfusion of ischemic myocardium is associated with additional myocardial damage known as myocardial ischemia-reperfusion (I/R) injury. This study was designed to evaluate the effects of SXSM on bradyarrhythmias and cardiac dysfunction induced by myocardial I/R injury, and to explore the underlying mechanisms. Methods: Administration of SXSM to adult male Sprague Dawley (SD) rats was achieved orally by gavage and control rats were given equivalent deionized water every day for 14 days. After the last administration, the heart was connected with the Langendorff perfusion apparatus and both groups were subjected to ischemia for 20 min followed by reperfusion for 40 min to induce myocardial I/R injury. Heart rate (HR), left ventricular developed pressure (LVDP), the maximal increase rate of left ventricular pressure (+dp/dt_max) and the maximal decrease rate of left ventricular pressure (-dp/dt_max) were recorded by a physiological signal acquisition system. The heart treated with ischemic preconditioning (IPC) for 3 times at a range of 5 min/time before ischemia served as a positive control group. The hearts without I/R injury served as control group. After reperfusion, superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-Px) activities in the myocardium were determined by appropriate assay kits. Myocardial SOD1 and glutamate cysteine ligase catalytic subunit (GCLC) expression were assessed by western blot analysis. For the in vitro study, SXSM serum was prepared according to the serum pharmacological method and neonatal rat cardiomyocytes were isolated from the heart of new born SD rats. Neonatal rat cardiomyocytes were pretreated with SXSM serum and subjected to H₂O₂ or anoxia/ reoxygenation (A/R) treatment to induce oxidative damage. Cell viability was evaluated using a Cell Counting Kit-8 (CCK8) assay. Levels of reactive oxygen species (ROS), SOD, GSH and GSH-Px in cardiomyocytes were determined by appropriate assay kits. SOD1 and GCLC expression were assessed by western blot analysis. Buthionine-[S, R]-sulfoximine (BSO), a GCLC inhibitor, and SOD1 siRNA were also used for identifying the cardiac protective targets of SXSM. Results: SXSM and ischemic preconditioning (IPC) significantly increased heart rate during myocardial reperfusion and protected cardiac function against myocardial I/R injury, including an increase in left ventricular diastolic pressure (LVDP), the maximal increase rate of left ventricular pressure (+dp/dt_max) and the maximal decrease rate of left ventricular pressure (-dp/dt_max). We also found that SXSM and IPC improved the expansion of myocardial interstitium, t...

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Section: Discussionsupporting

confidence: 51%

Shenxian-Shengmai Oral Liquid Reduces Myocardial Oxidative Stress and Protects Myocardium from Ischemia-Reperfusion Injury

Zhao

Zhang

Luan

et al. 2018

Cell Physiol Biochem

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“…The precise mechanisms underlying the myocardial ischaemia‐reperfusion injury are incompletely understood. Several studies have suggested that development of intracellular calcium overload, enhanced formation of reactive oxygen species and other oxidants as well as enhanced synthesis and release of endothelin during ischaemia‐reperfusion contribute to microvascular injury leading to ‘no reflow’ and ultimately myocardial damage (Temsah et al 2003).…”

mentioning

confidence: 99%

Cardioprotective Effects of Bosentan, a Mixed Endothelin Type A and B Receptor Antagonist, during Myocardial Ischaemia and Reperfusion in Rats

Singh

Sehrawat

Kumar

et al. 2006

Basic Clin Pharma Tox

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The present study evaluated the cardioprotective potential of bosentan, a mixed endothelin type A and B receptor antagonist, in the myocardial ischaemia-reperfusion model of myocardial infarction. Adult male wistar rats (175-225 g) were divided into three groups: sham operated, non-myocardial ischaemia-reperfusion (SHAM); saline-treated myocardial ischaemia-reperfusion control (CON); bosentan-treated myocardial ischaemia-reperfusion (BOS). All animals were anaesthetized and subjected to 40 min. occlusion of left anterior descending coronary artery followed by 120 min. of reperfusion. Saline or drug was administered to the CON or BOS group, respectively, 20 min. after the left anterior descending coronary artery occlusion. Haemodynamic parameters viz. systolic arterial pressure, diastolic arterial pressure and heart rate were recorded throughout the experimental period. Hearts were subsequently excised and processed for histopathological and infarct size evaluation and for biochemical estimation of cardiac specific enzyme creatine kinase-MB (CK-MB) and myocardial malondialdehyde, a lipid peroxidation marker. Myocardial ischaemic reperfusion resulted in severe myocardial injury, depression of haemodynamic function, significant increase in malondialdehyde levels and decline in CK-MB isoenzyme activity in the heart tissue. Administration of bosentan (3 mg/kg, intravenously) slightly improved haemodynamic effects, decreased myocardial oxygen consumption, significantly (PϽ0.01) attenuated the rise in malondialdehyde levels and loss of myocardial CK-MB isoenzyme activity compared to the CON group, whereas bosentan administration significantly reduced the percentage area of fiber loss and infarct area. It is therefore concluded that endothelin-1 may mediate myocardial damage produced by ischaemia and reperfusion and that dual blockade of endothelin A and endothelin B receptors may have potential as a mode of therapy for myocardial infarction.

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“…It should be mentioned that formation of Ang II due to the activation of the rennin-angiotensin system may produce oxidative stress through its action on NADP/NADPH oxidase, whereas excessive amounts of catecholamines may produce oxyradicals during the process of For reprint orders, please contact: reprints@futuremedicine.com Future Cardiol. (2008) 4(4) future science group future science group oxidation [24][25][26]. Furthermore, nitric oxide produced by the endothelium upon combination with superoxide radicals will generate peroxynitrite, a highly reactive oxidant [26].…”

Section: Mechanisms Of Ischemic-reperfusion Injurymentioning

confidence: 99%

“…Although oxidative stress can be seen to produce cardiac dysfunction and myocardial cell damage by affecting different subcellular organelles directly, most of its effects (which simulate the ischemic-reperfusion injury) are considered to be mediated through the occurrence of an excessive amount of Ca 2+ (intracellular Ca 2+ overload) in the myocardium [27][28]. In fact, intracellular Ca 2+ overload has been shown to produce activation of proteases and phospholipases, impair energy production, alter gene expression and induce myocardial cell damage and dysfunction [24,28,29].…”

Section: Mechanisms Of Ischemic-reperfusion Injurymentioning

confidence: 99%

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Strategies for the Regulation of Intracellular Calcium in Ischemic Heart Disease

2008

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Mechanisms of Cellular Alterations Due to Ischemia-Reperfusion Injury in the Heart

Cited by 5 publications

References 113 publications

Shenxian-Shengmai Oral Liquid Reduces Myocardial Oxidative Stress and Protects Myocardium from Ischemia-Reperfusion Injury

Shenxian-Shengmai Oral Liquid Reduces Myocardial Oxidative Stress and Protects Myocardium from Ischemia-Reperfusion Injury

Cardioprotective Effects of Bosentan, a Mixed Endothelin Type A and B Receptor Antagonist, during Myocardial Ischaemia and Reperfusion in Rats

Strategies for the Regulation of Intracellular Calcium in Ischemic Heart Disease

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