Impact of Ischemia and Reperfusion Times on Myocardial Infarct Size in Mice In Vivo

Abstract

The murine in vivo model of acute myocardial infarction is increasingly used to study signal transduction pathways. However, methodological details of this model are rarely published, and durations of ischemia and reperfusion (REP) time vary considerably among different laboratories. In this study, we tested the hypothesis that infarct size (IS) is dependent on both duration of ischemia and REP time. Pentobarbital-anesthetized male C57BL/6 mice were intubated, mechanically ventilated, and instrumented for continuous monitoring of mean arterial blood pressure and heart rate. After left fourth thoracotomy, the left anterior descending coronary artery was ligated. Mice were randomly assigned to receive 30, 45, or 60 mins of coronary artery occlusion (CAO) and 120, 180, or 240 mins of REP, respectively. IS was determined with triphenyltetrazolium chloride and area at risk (AAR) with Evans blue, respectively. Arterial blood gas analysis and hemodynamics were not different among groups. Prolongation of CAO from 30 to 60 mins significantly (*P<0.05) increased IS from 18% +/- 5% to 69% +/- 3%*, from 20% +/- 2% to 69% +/- 6%* and from 42% +/- 10% to 75% +/- 2%* after 120, 180, and 240 mins REP, respectively. Moreover, IS was increased from 18% +/- 5% to 42% +/- 10%* (30 mins CAO) and from 40% +/- 3% to 72% +/- 6%* (45 mins CAO) when REP time was prolonged from 120 to 240 mins. IS was not increased when REP was prolonged from 120 to 240 mins at 60 mins CAO (69% +/- 3% vs. 75% +/- 2%). In the present study, we describe important methodological aspects of the murine in vivo model of acute myocardial infarction and provide evidence that, in this model, IS depends both on duration of ischemia and on REP time.