Abstract 11360: Augmentation of Connexin-43 Conductance Reduces Ischemia-Reperfusion Injury and Myocardial Infarct Size
Rotigaptide augments endothelium-derived hyperpolarization by enhancing connexin-43 conductance. We hypothesized that rotigaptide would reduce both endothelial ischemia-reperfusion injury (IRI) and myocardial infarction (MI) in response to ischemia. IRI of the human forearm (cuff inflated to 200 mmHg for 20 min) was induced in the presence or absence of intra-arterial rotigaptide (25 nmol/min). Using venous occlusion plethysmography, bilateral forearm arterial blood flow was measured at rest and during intra-arterial infusion of acetylcholine (n=11) ([ACh] 5-20 µg/min) or sodium nitroprusside (n=10) ([SNP] 2 - 8 mg/min) before and after intra-arterial infusion of placebo/Rotigaptide and IRI. Experimental MI was achieved by 40 min of catheter-induced occlusion of the left anterior descending artery (LAD) in pigs. Rotigaptide (n=9) or placebo (n=10) was infused intravenously as a bolus (1000 ng/kg) 10 min prior to reperfusion and continuously (10 µg/kg/hr) during 2 hours of reperfusion. Before euthanization and excision of the heart Evans blue dye was injected intra-atrial with a ligature around the LAD at the site of occlusion to determine the area at risk (AAR). Triphenyltetrazoliumchloride (TTC) staining was used to assess the extent of myocardial infarction size (IS) as a proportion of the AAR. Both protocols were randomized and blinded. In the human study, rotigaptide prevented IRI induced endothelial dysfunction (P=0.007, figure 1). In the animal study Rotigaptide protected the myocardium against IR injury (P=0.006, figure 2). Our experimental data support the theory that Rotigaptide protects against IRI and reduce injury following MI.
- © 2012 by American Heart Association, Inc.