The Protective Effect of Cx43 Protein-Mediated Phosphocreatine on Myocardial Ischemia/Reperfusion Injury

Objectives. To verify the protective effect of phosphocreatine on myocardium in an ischemic model and the possible mechanism of action. Methods. The model of myocardial ischemia/reperfusion (I/R) was established by the ligation balloon method. 30 SD rats were randomly divided into three groups, n = 10 in each group. Sham operation group: the coronary artery was not blocked and observed for 120 minutes. The ischemia/reperfusion (I/R) group was given ischemia for 30 minutes and ischemia reperfusion for 90 minutes. Phosphocreatine (PCr) group: after 30 minutes of ischemia, the rats were intraperitoneally injected with PCr (200 mg/kg) for 90 minutes. The animal groups of myocardial ischemia/reperfusion model in vitro were the same as those in vivo. The heart was removed by thoracotomy and washed immediately in H-K buffer solution. Then, the heart was installed on the Langendorff instrument. The concentration of PCr perfusion fluid in the PCr group was 10 mmol/L. The changes in coronary blood flow in isolated myocardium were recorded. The heart rate and electrocardiogram were recorded by RM6240BT. At the end of the experiment, myocardial pathological sections and Cx43 immunofluorescence staining were made, and the contents of malondialdehyde (MDA) in myocardial tissue were detected. Results. Phosphocreatinine treatment improved the myocardial ischemia model, performance in electrocardiogram (ECG) changes (ST segment apparent), and histological changes (decrease in necrotic myocardial cells, inflammatory cell infiltration, and a reduction in myocardial edema). At the same time, MDA decreased, while coronary blood flow and Cx43 expression significantly improved. Conclusions. Phosphocreatine can improve the electrocardiogram and restore histologic changes in ischemic myocardium and coronary blood flow. The postulated mechanism is by inhibiting the generation of free oxygen radicals and restoring the expression of Cx43 protein.

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Astragaloside attenuates cardiotoxicity effects of Doxorubicin by inhibiting TLR4/NF-кB signaling pathway

American Journal of BioMedicine ◽

10.18081/2333-5106/017-78-92 ◽

2017 ◽

Vol 5 (1) ◽

pp. 78-92

Author(s):

Najah R. Hadi ◽

Fadhil G. Al-Amran

Keyword(s):

Blood Flow ◽

Coronary Artery ◽

Myocardial Ischemia ◽

Protective Effect ◽

Ischemia Reperfusion ◽

Cardiac Injury ◽

Ischemic Tissue ◽

Tnf Α ◽

Myocardial Ischemia Reperfusion ◽

Significant Protective Effect

Myocardial Ischemia-Reperfusion (I/R) injury refers to myocardial, vascular or electrophysiological dysfunction of heart induced by the restoration of blood flow to previously ischemic tissue. In this study, we investigated the effects of Telmisartan in I/R injury and apoptosis. Mice are subjected to 30 min ischemia followed by 120 min reperfusion through ligation of descending coronary artery (LAD). Mice treated with Telmisartan (0.5mg/kg, via IP injection) significantly attenuated I/R-induced increases of myocardial TNF-α, IL-1β, IL-6 and markedly increased myocardial Bcl-2 protein expression. Furthermore, Telmisartan significant protective effect against myocardial I/R injury. These results demonstrated that Telmisartan reduces inflammatory reaction associated with I/R injury induced by LAD ligation in addition to its reduction for cardiac injury and apoptosis induced by ischemia reperfusion.

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Natriuretic Peptide Receptor-C Regulates Coronary Blood Flow and Prevents Myocardial Ischemia/Reperfusion Injury

Circulation ◽

10.1161/01.cir.0000141802.29945.34 ◽

2004 ◽

Vol 110 (10) ◽

pp. 1231-1235 ◽

Cited By ~ 94

Author(s):

Adrian Hobbs ◽

Paul Foster ◽

Craig Prescott ◽

Ramona Scotland ◽

Amrita Ahluwalia

Keyword(s):

Blood Flow ◽

Myocardial Ischemia ◽

Reperfusion Injury ◽

Coronary Blood Flow ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Natriuretic Peptide Receptor ◽

Peptide Receptor ◽

Myocardial Ischemia Reperfusion Injury ◽

Myocardial Ischemia Reperfusion

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A3adenosine receptor agonist IB-MECA reduces myocardial ischemia-reperfusion injury in dogs

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01001.2002 ◽

2003 ◽

Vol 285 (2) ◽

pp. H607-H613 ◽

Cited By ~ 42

Author(s):

John A. Auchampach ◽

Zhe-Dong Ge ◽

Tina C. Wan ◽

Jeannine Moore ◽

Garrett J. Gross

Keyword(s):

Blood Flow ◽

Myocardial Ischemia ◽

Infarct Size ◽

Reperfusion Injury ◽

Coronary Blood Flow ◽

Coronary Occlusion ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Myocardial Ischemia Reperfusion Injury ◽

Myocardial Ischemia Reperfusion

We examined the effect of the A3adenosine receptor (AR) agonist IB-MECA on infarct size in an open-chest anesthetized dog model of myocardial ischemia-reperfusion injury. Dogs were subjected to 60 min of left anterior descending (LAD) coronary artery occlusion and 3 h of reperfusion. Infarct size and regional myocardial blood flow were assessed by macrohistochemical staining with triphenyltetrazolium chloride and radioactive microspheres, respectively. Four experimental groups were studied: vehicle control (50% DMSO in normal saline), IB-MECA (100 μg/kg iv bolus) given 10 min before the coronary occlusion, IB-MECA (100 μg/kg iv bolus) given 5 min before initiation of reperfusion, and IB-MECA (100 μg/kg iv bolus) given 10 min before coronary occlusion in dogs pretreated 15 min earlier with the ATP-dependent potassium channel antagonist glibenclamide (0.3 mg/kg iv bolus). Administration of IB-MECA had no effect on any hemodynamic parameter measured including heart rate, first derivative of left ventricular pressure, aortic pressure, LAD coronary blood flow, or coronary collateral blood flow. Nevertheless, pretreatment with IB-MECA before coronary occlusion produced a marked reduction in infarct size (∼40% reduction) compared with the control group (13.0 ± 3.2% vs. 25.2 ± 3.7% of the area at risk, respectively). This effect of IB-MECA was blocked completely in dogs pretreated with glibenclamide. An equivalent reduction in infarct size was observed when IB-MECA was administered immediately before reperfusion (13.1 ± 3.9%). These results are the first to demonstrate efficacy of an A3AR agonist in a large animal model of myocardial infarction by mechanisms that are unrelated to changes in hemodynamic parameters and coronary blood flow. These data also demonstrate in an in vivo model that IB-MECA is effective as a cardioprotective agent when administered at the time of reperfusion.

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