Background: Brief episodes of ischemia followed by reperfusion adversely affect endothelial vasomotor function. We hypothesized that heparin may impart a protective effect on the coronary endothelium during ischemia-reperfusion injury possibly via the nitric oxide pathway.
Methods: Eighteen anesthetized dogs were randomly assigned to one of two treatment groups: saline solution or bovine heparin (6.0 mg x kg intravenously). A flow probe and cannula were placed in the left anterior descending artery. Functional recovery of the coronary endothelium was assessed after 15 minutes of ischemia and during 120 minutes of reperfusion after acetylcholine and nitroprusside challenge. In a separate group (n = 10), nitric oxide activity was measured as nitrate/nitrite levels and cyclic guanosine monophosphate levels in the left anterior descending artery.
Results: Control dogs displayed a significant decrease in percent change of left anterior descending artery flow at 15, 30, and 60 minutes of reperfusion (67%+/-8%, 76% +/-11%, and 84%+/-8%) when compared with preischemic values (108+/-6; p < 0.01). Heparinized dogs, however, showed preservation of coronary endothelial function after acetylcholine challenge throughout reperfusion. Heparin-treated dogs also displayed a significant increase in nitrate/nitrite levels during reperfusion (37.3+/-4.1 micromol/L) when compared with the saline group (24.3+/-0.8 micromol/L; p < 0.03). Left anterior descending artery levels of cyclic guanosine monophosphate were also significantly increased after heparin administration (3.0+/-0.3 pmol/mg) when compared with ischemia-reperfusion alone (0.7+/-0.1 pmol/mg; p < 0.03).
Conclusions: Heparin preserves the vasoregulatory function of the coronary endothelium during brief episodes of ischemia-reperfusion injury, in part, via the nitric oxide pathway. Administration of heparin may have important therapeutic implications in the prevention of coronary endothelial dysfunction associated with reperfusion injury.