Effects of Protective Controlled Coronary Reperfusion on Left Ventricular Remodeling in Dogs With Acute Myocardial...

Coronary artery obstruction causes ischemia of cardiac tissue, leading to acute myocardial infarction (AMI). The treatment of choice for reducing acute myocardial ischemic injury is early, effective vascular reperfusion using thrombolytic therapy or primary percutaneous coronary intervention. However, reperfusion can cause cardiomyocyte injury. Currently, there is no effective therapy to prevent cardiac reperfusion-related tissue damage. This study evaluated whether Protective Controlled Coronary Reperfusion (PCCR), selectively delivered to ischemic tissue, is associated with decreased myocardial scarring, contractile deterioration and reperfusion-associated myocardial edema.

Three hours of cardiac ischemia was induced in 10 mongrel dogs, and followed by either 30-minute PCCR or sham treatment. Cardiac performance was evaluated 2, 4 and 6 months later. Trichrome staining was used to distinguish collagen from viable myocardial tissue and to evaluate mean scar area.

One hour following reperfusion, PCCR significantly attenuated the relative increase (edema) in left ventricular end diastolic posterior wall thickness compared with sham treatment. At 6 months follow-up, the PCCR group showed a modest corrected increase in left ventricular ejection fraction (c∆LVEF) in comparison to the sham group where it deteriorated (2.3 ± 10.5% vs. -16.4 ± 10.3%, respectively, p = 0.043). Histomorphometric assessments of the hearts showed the PCCR group had smaller area of scarring, as compared to sham-treated animals (9.0 ± 2.4% vs. 14.0 ± 3.3%, p = 0.047).

In this pilot study, PCCR reduced myocardial edema, modestly increased in c∆LVEF and resulted in a smaller scar area. Further studies are needed to fully ascertain the mechanisms that underlie the potential benefits of PCCR therapy prior to initiating clinical trials in human subjects with AMI.