Direct delivery of neuronal nitric oxide synthase into myocardium improves heart failure after acute myocardial infarction in rats

Abstract

We previously reported that the direct delivery of nNOS induced the infracted area after acute myocardial infarction (AMI). We investigated the hemodynamics effect of targeted, direct delivery of nNOS and the hemagglutinating virus of Japan envelope (HVJ-E) vector transduced into rat cardiomyocytes after AMI. AMI induced to ligate the left anterior descending coronary artery of Wistar rat. And then 90 minutes later, we injected nNOS with the HVJ-E vector (NV group, n=8), β-galactosidase with HVJ-E vector (BV group, n=8), nNOS alone (N group, n=8) or HVJ-E vector alone (V group, n=8) into the hearts and continued to measure left ventricular pressure in order to calculate the value of dp/dt. We removed them at 3 hours later and evaluated the infarcted area by a colormetry. The infarcted areas in sections from the NV group were significantly narrower than those from the other groups (p<0.05). The value of dp/dt at the end point in the NV group was significantly higher than those from the other groups (p<0.05). Our findings suggest that direct nNOS transduction into cardiomyocytes rapidly diminished the size of infarcted areas after AMI. This type of targeted delivery should have wide application in terms of delivering therapeutic nNOS to the heart, and provide a powerful therapeutic tool with which to treat ischemic heart disease. [J Physiol Sci. 2008;58 Suppl:S59]