Bax deficiency reduces infarct size and improves long-term function after myocardial infarction

We have previously found that, following myocardial ischemia/reperfusion injury, isolated hearts from bax gene knockout mice [Bax(−/;−)] exhibited higher cardioprotection than the wild-type. We here explore the effect of Bax(−/−), following myocardial infarction (MI) in vivo. Homozygotic Bax(−/−) and matched wild-type were studied. Mice underwent surgical ligation of the left anterior descending coronary artery (LAD). The progressive increase in left-ventricular end diastolic diameter, end systolic diameter, in Bax(−/−) was significantly smaller than in Bax(+/+) at 28 d following MI (p<0.03) as seen by echocardiography. Concomitantly, fractional shortening was higher (35±4.1% and 27±2.5%, p<0.001) and infarct size was smaller in Bax(−/−) compared to the wild-type at 28days following MI (24±3.7% and 37±3.3%, p<0.001). Creatine kinase and lactate dehydrogenase release in serum were lower in Bax(−/−) than in Bax(+/+) 24h following MI. Caspase 3 activity was elevated at 2 h after MI only in the wild-type, but reduced to baseline values at 1 and 28 d post-MI. Bax knockout mice hearts demonstrated reduced infarct size and improved myocardial function following permanent coronary artery occlusion. The Bax gene appears to play a significant role in the post-MI response that should be further investigated.