Disease-modifying antirheumatic drugs and remote ischemic postconditioning ameliorate the myocardial injury in rats under cerebral stroke

Abstract

Objective: Currently, there is uncertainty about the increased risk of myocardial infarction following ischemic stroke or transient ischemic attack and the method of risk management after the stroke. In this experimental study, we aimed to evaluate myocardial injury after inducing global cerebral ischemia in rats and assess their responses to the treatments with diseasemodifying antirheumatic drugs (DMARDs) and ischemic postconditioning (PC). Materials and Methods: Global cerebral ischemia was induced by occluding the bilateral common carotid arteries for 20 minutes and subsequently reperfusing them. Thirty-two Wistar rats were divided into 4 treatment groups (n=8 for each group). Group I received 7 mg/kg/day infliximab immediately and at 6 hours after the stroke and group II received 10 mg/ kg/day leflunomide immediately and at 6 hours after the stroke. In group III, the skeletal muscle in the limbs was clamped for 180 minutes immediately after the stroke and was reperfused for 120 minutes. Group IV was sham-operated and received saline immediately and at 6 hours after the stroke. Myocardium tissue samples were collected for histopathologic assays and to create hypoxia-induced tissue oxidative markers. Results: We found that apoptosis and nucleus loss in the myocardium were significantly decreased after the administration of infliximab, leflunomide, and remote ischemic PC. Necrosis in the myocardium and cardiac malondialdehyde (MDA) level were also significantly decreased after treatment with remote skeletal muscle PC. Conclusion: Our findings demonstrated that remote ischemic PC and DMARDs were protective against cerebral ischemia/ reperfusion injury. They acted by mobilizing the endogenous adaptive mechanisms in the myocardium and inhibited oxidative stress by increasing the activity of antioxidant enzymes.