Abstract P1047: Imatinib Attenuates Reperfusion Injury In A Rat Model Of Acute Myocardial Infarction

Background: Reperfusion of an occluded coronary artery is often accompanied by injury of the microvasculature (MVI), which portends a worse long term prognosis after an acute myocardial infarction (AMI). In previous experimental studies, the tyrosine-kinase inhibitor imatinib has shown to reduce vascular leakage and therefore could have a potential role to prevent MVI. This study aims to provide a potential therapeutic approach using imatinib to attenuate reperfusion injury. Methods: First, 16 isolated male Wistar rat hearts were randomly assigned to 10 μM imatinib or placebo and subjected to 40 min of global ischemia followed by 120 min of reperfusion ex vivo in a Langendorff setup. Global infarct size and mechanical function were assessed. Second, 25 male Wistar rats were randomly assigned to 30 mg/kg imatinib or placebo intravenously and subjected to 45 min of left anterior descending coronary artery ligation followed by 180 min of reperfusion in vivo. Cardiovascular magnetic resonance imaging was performed to assess infarct size and cardiac function. Subsequently, hearts were perfused ex vivo with a fluorescent vascular leakage tracer and used for fluorescence- and electron microscopy. Results: In isolated hearts, imatinib reduced global infarct size (imatinib 36.2±7.9 vs placebo 50.0±8.0% infarcted area/total area, p<0.01), improved end diastolic pressure (imatinib 44.2±8.0 vs placebo 59.5±13.5 mmHg, p<0.05) and rate pressure product recovery (imatinib 39.0±6.8 vs placebo 26.2±7.6% of baseline, p<0.05). In vivo, imatinib reduced infarct size (imatinib 12.6±8.8 vs placebo 25.6±9.3% infarcted area/left ventricle, p<0.01), but did not improve global cardiac function. At the end of reperfusion, imatinib showed lower vascular resistance, higher coronary flow and less microvascular leakage (all p<0.05). At the ultrastructural level, imatinib showed better preserved microvascular integrity compared to placebo. Conclusion: This study provides evidence that imatinib attenuates reperfusion injury in an ex vivo and in vivo AMI rat model, mainly by protection of the coronary microcirculation. These data warrant future work to examine the potential of imatinib to reduce reperfusion injury in patients with AMI.