Heparin And Nonanticoagulant Heparin Preserve Regional Myocardial Contractility After Ischemia-Reperfusion Injury: Role Of Nitric Oxide

AbstractObjectives: These studies were performed to determine the effect of heparin and nonanticoagulant heparin on myocardial function after ischemia-reperfusion and to further evaluate the role that the nitric oxide–cyclic guanosine monophosphate pathway plays in mediating the effect of heparin.Methods: Fifteen dogs were subjected to 15 minutes ischemia followed by 120 minutes reperfusion and pretreated with either saline solution, bovine heparin (6.0 mg/kg intravenously), or N-acetyl heparin (6.0 mg/kg intravenously), a heparin derivative without anticoagulant properties. The left anterior descending artery was occluded for 15 minutes and regional systolic shortening, a unitless measure of myocardial contractility, assessed during reperfusion. To evaluate the role of nitric oxide, the inhibitor Nω-nitro-l-arginine, 1.5 mg/kg intracoronary, was given before heparin administration. Myocardial levels of cyclic guanosine monophosphate, the second messenger of nitric oxide, were also measured in the N-acetyl heparin group using radioimmunoassay.Results: Regional systolic shortening was significantly decreased in the saline group during 60 and 120 minutes compared with before ischemia (9.2 ± 1.0 and 9.0 ± 0.9 vs 12.2 ± 1.2, p 0.0003). Heparin and N-acetyl heparin–treated dogs, however, showed preservation of systolic shortening throughout reperfusion. Administration of nitro-l-arginine significantly attenuated the protective effect of heparin (9.2 ± 1.2 vs 12.7 ± 1.1, p ≤0.0001) and N-acetyl heparin (9.3 ± 0.3 vs 12.8 ± 0.4, p≤0.0001) during 120 minutes reperfusion. Myocardial levels of cyclic guanosine monophosphate were also significantly increased in the N-acetyl heparin group compared with saline (199.1 ± 7.1 vs 103.5 ± 4.5 pmol/mg, p ≤0.0001).Conclusions: Heparin preserves myocardial contractility after ischemia-reperfusion independent of its anticoagulant properties. Furthermore, the protective effects of heparin during ischemia-reperfusion are mediated, at least in part, through a nitric oxide–cyclic guanosine monophosphate pathway. (J Thorac Cardiovasc Surg 1998;115:440-9