Myocardial ischemia/reperfusion in rats: characterization of cardiac injuries

Abstract

Coronary reperfusion is an important tool to limit infarct size and preserve cardiac function after acute myocardial infarction. However, the reperfusion of acutely ischemic myocardium can induce arrhythmias and cardiomyocyte death, a phenomenon known as myocardial reperfusion injury. The study of the mechanisms and the search for therapies to protect the heart from reperfusion injury is an important field of research. The aim of this study was to evaluate mophofunctional and molecular aspects involved in a rat model of acute myocardial ischemia followed by reperfusion (IR). Male Wistar rats (N=47) were anesthetized with ketamine and xylazine (50 and 10 mg/kg, ip) and subjected to myocardial IR by temporary (30 min) ligation of left descending coronary artery. Control rats (N=7) underwent the same surgery without coronary ligation. After 4 weeks 45% of the rats subjected to IR showed no cardiac lesion (NL) while 38% presented mild (ML) and 17% large (LL) lesion of the heart. Cardiac function, evaluated by echocardiography, was impaired in all rats subjected to IR, independently of the degree of cardiac lesion. Interstitial fibrosis, quantified in non‐infarcted myocardium, was 11±0.8% in control rats and was found increased in rats with IR (19.7±1.4, 19.4±1.2 and 21.6±1.2% in rats with NL, ML and LL, respectively). Activity of matrix‐metalloproteinase‐2 was higher in the myocardium of rats subjected to IR (0,44 to 0.48 AU) as compared to their control counterparts (0.22 AU). Moreover, concentration of superoxide anion in the myocardium of rats subjected to IR was higher (176±44, 127±13 and 108±30 RLU/mg of protein in rats with NL, ML and LL, respectively) as compared to their controls (50±5 RLU/mg of protein). Finally, hydrogen peroxide was measured 86±29 nmol/mg of protein in myocardium of control rats and was found markedly higher (1077±192, 1194±238 and 639±117 nmol/mg of protein in IR rats with NL, ML and LL, respectively) in the animals subjected to IR. These results show that IR leads to distinct degrees of myocardial injury in a rat model, which contributes to cardiac dysfunction over time. Reactive oxygen species (O2− and H2O2) and MMP‐2 seems to be involved in cardiac dysfunction and heart failure development after reperfusion.Support or Funding InformationFinancial support: CNPq (870308/1997‐1) e FAPESP (2013/20549‐7).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.