CARDIAC VENOUS ENDOTHELIAL DYSFUNCTION AFTER MYOCARDIAL-ISCHEMIA AND REPERFUSION IN DOGS

Endothelial dysfunction is a prominent occurrence in coronary arteries after myocardial ischemia and reperfusion. However, this has not been studied in coronary veins. Endothelium-dependent vasorelaxation was studied in cardiac venous rings obtained from dogs subjected to 60 min of coronary artery occlusion followed by 270 min of reperfusion, as well as from dogs subjected to sham ischemia-reperfusion. Myocardial ischemia resulted in a 96 +/- 2% decrease in coronary flow to the ischemic area 60 min after occlusion of the left anterior descending (LAD) coronary artery, which led to a significant degree of cardiac necrosis (i.e., 32.9 +/- 3.9% of area at risk). Cardiac venous rings isolated from sham ischemia-reperfusion dogs relaxed 68 +/- 3% to 200 muM ADP, 65 +/- 3% to 2 muM A23187, and 76 +/- 4% to 200 muM sodium nitrite (NaNO2). Corresponding values for cardiac venous rings isolated from ischemic-reperfused dogs were 32 +/- 3% for 200 muM ADP (P < 0.01 vs. sham), 31 +/- 3% for 2 muM A23187 (P < 0.01 vs. sham), and 74 +/- 3% for 200 muM NaNO2 (NS from sham). In rings from control dogs, vasorelaxation to ADP and A23187 was markedly inhibited by 4 mM N(G)-methyl-L-arginine (L-NMMA) and 10 methylene blue and restored after N(G)-nitro-L-arginine by 3 mM L-arginine. These results demonstrate that a significant degree of endothelial dysfunction occurred in cardiac venous rings after ischemia and reperfusion. Moreover, adherence of dog neutrophils to cardiac veins obtained from dogs 2 h after reperfusion was significantly greater than adherence to either ischemic-reperfused dog coronary arteries or dog cardiac veins not subjected to ischemia-reperfusion. This increased neutrophil adherence correlated with a significant endothelial dysfunction of cardiac veins 2 h after reperfusion. Thus cardiac venous endothelial dysfunction may be involved in neutrophil adherence to cardiac venous endothelium and the migration of neutrophils across the vessel wall into the myocardium contributing to reperfusion injury.