Myocardial salvage in acute myocardial infarction - challenges in clinical translation.

摘要

In 2001, the Mochly-Rosen laboratory published the first evidence that inhibition of delta protein kinase C (6PKC) at the onset of reperfusion reduced tissue injury in preclinical models of acute myocardial infarction (AMI). In various models of cardiac ischemia and reperfusion (I/R) including cultured neonatal cardiac myocytes [1], ex vivo whole rat heart [2], and in vivo porcine heart [3], we demonstrated that delivering a rationally designed peptide allosteric inhibitor of 6PKC (8V1-1) at reperfusion reduced infarct size by about 70% [3]. 5V1-1 treatment reduced necrosis and apoptosis, accelerated ATP regeneration, preserved mitochondrial structure, and preserved organization of contractile elements [3-6]. We also found that treatment with 6V1-1 protected the vascular endothelium, leading to improved microvasculature flow and rapid recovery of coronary flow reserve [5].