Nonanticoagulant Heparin Prevents Coronary Endothelial Dysfunction After Brief Ischemia-Reperfusion Injury in the Dog

• DOI: 10.1161/01.cir.99.8.1062
• Publication Date: 2012-06-12T00:42:29Z
• Authors: Peter C. Kouretas; Young D. Kim; Paul A. Cahill; Adam K. Myers; Lam N. To; Yi-Ning Wang; James V. Sitzmann; Robert L. Hannan
• Keywords: Endothelial Dysfunction

Background —Coronary endothelial dysfunction after brief ischemia-reperfusion (IR) remains a clinical problem. We investigated the role of heparin and N -acetylheparin, nonanticoagulant derivative, in modulating coronary function IR injury, with an emphasis on defining nitric oxide (NO)–cGMP pathway heparin-mediated effect. Methods Results —Male mongrel dogs were surgically instrumented, effects both bovine -acetylheparin vasomotor function, expressed as percent change from baseline flow acetylcholine challenge, studied 15 minutes regional ischemia left anterior descending artery (LAD) followed by 120 reperfusion. In treated placebo (saline), was significantly ( P ≤0.03) decreased 30 reperfusion (65±12% 73±12%) compared preischemia (103±6%). contrast, vasodilatory response to endothelium-independent vasodilator sodium nitroprusside maintained during Preischemic administration (6.0 mg/kg IV) preserved throughout parallel group dogs, nitrate/nitrite (NOx) cGMP levels LAD measured treatment 15-minute caused significant increase basal NOx saline controls. Pretreatment also alone. Conclusions —These results suggest that preserves injury mechanism independent its anticoagulant activity effect may be mediated part activation NO-cGMP pathway.