The Potential Protective Effect of Carvedilol on Induced Myocardial Ischemia-Reperfusion Injury in Rats: A Histological and Immunohistochemical Study

Abstract

Reperfusion injury is a paradoxical response following ischemic heart disease that exacerbates myocardial damage, resulting in ischemia reperfusion (IR) injury. This study explored the protective effect of carvedilol (CAR) on cardiac tissue in myocardial IR injury. Forty Wistar rats were randomly allocated into control, IR, and CAR + IR groups. Myocardial IR injury was surgically induced for 45 min followed by 120 min of reperfusion. CAR (2 mg/kg/day) was administered orally for 7 days prior to IR induction. Cardiac effects were assessed via physiological measurements, serum biomarkers of creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI), immunohistochemical detection of Bcl-2-associated X-protein (Bax) and B cell lymphoma 2 (Bcl-2), light and electron microscopy, histopathological grading, and morphometric and statistical analysis. CAR pretreatment markedly preserved cardiac function in IR-injured rats by significantly reducing QTc and ST-segment elevations and suppressing ventricular arrhythmias. Biochemically, serum CK-MB and cTnI levels were significantly lowered, while Bax expression decreased and Bcl-2 increased. Histologically, CAR mitigated necrosis, hemorrhage, and cellular degeneration. Ultrastructurally, myocardial integrity, capillary patency, and telocyte morphology were preserved. CAR pretreatment effectively mitigated myocardial IR injury through multifaceted mechanisms including improving cardiac electrical stability, reducing biochemical and apoptotic damage, and preserving histological and ultrastructural integrity.