Abstract 21087: Coronary Reperfusion Ameliorates the Deleterious Effect of Mechanical Unloading on Infarct Size and Interstitial Fibrosis After Acute Myocardial Infarction

Abstract

Background: Contemporary studies show that myocardial fibrosis worsens after mechanical unloading with left ventricular assist devices (LVADs). The exact mechanism underlying this phenomenon remains unknown. Mechanical unloading has however been associated with a reduction in microvascular lumenal diameter in the failing heart, suggesting a link with negative auto-regulatory effects on the collateral circulation. We hypothesise that coronary reperfusion after myocardial infarction ameliorates the deleterious effect of mechanical unloading on infarct size and interstitial fibrosis. Methods: Syngeneic male Lewis rats weighing 200 to 300g were studied. Myocardial infarction – acute (AMI) and chronic (CMI) - was induced by LAD ligation. Two groups were generated: a permanent ligation group (AMI and CMI) and a reperfusion - coronary circulation restored after 90 minutes - group (AMI/R and CMI/R). In each group hearts were either loaded (L) or unloaded (U). In the loaded subgroup, rats were recovered after coronary ligation. In the unloaded subgroup, the infarcted hearts were explanted after 90 minutes and transplanted into the abdomen of healthy recipients via heterotopic abdominal heart transplantation. Hearts were explanted on day 2, day 7, and 16wks. The recipient’s heart acted as control. Histological analysis and western blotting for αSMA and TGF-β1 (markers of fibrosis) were completed. Results: Ninety rats were studied. There was a significant increase in infarct ratio (IR) - infarct size/area at risk-, and interstitial fibrosis (IF) after mechanical unloading in the permanent ligation group at day 2 (AMI-L vs AMI-U p = 0.0073 (IR) and p = 0.0012 (IF)) and day 7 (AMI-L vs AMI-U p = 0.0166 (IR) and p = 0.0363 (IF)). After coronary reperfusion, there was no increase in IR or IF with mechanical unloading. At 16wks however, this protective effect of reperfusion was lost (CMI/R-L vs CMI/R-U p = 0.004 (IR) and p = 0.0024 (IF)). The expression profiles of αSMA and TGF-β1 correlated with the results above. Conclusion: These data suggest an association between the revascularisation of a less auto-regulated vessel and amelioration of the deleterious effect of mechanical unloading on the extracellular matrix with implications for LVAD induced recovery.