CORONARY ENDOTHELIAL DYSFUNCTION AFTER ISCHEMIA AND REPERFUSION IN THE DOG - A FUNCTIONAL AND MORPHOLOGICAL INVESTIGATION

Coronary endothelial dysfunction is characterized by a lower response to endothelium-dependent vasodilators such as acetylcholine (ACh) and serotonin (5HT), but by an unaltered response to endothelium-independe nt vasodilators such as nitroglycerin (NTG). In the present study, we investigated the vasoreactivity of the coronary bed in vivo, in a dog model of ischemia and reperfusion (I/R). We also assessed the morpholo gy of the subepicardial arterioles and capillary bed by means of scann ing electron microscopy (SEM). Anesthetized, instrumented dogs were di vided in two groups. One group (N = 27) was submitted to ischemia (60 min) and reperfusion (180 min) of the left circumflex coronary artery, the second group (N = 8) was sham-operated. Prior to and following I/ R, ACh, 5-HT, and NTG were given intracoronarily. At the end of the ex periment a 1 cm(3) myocardial biopsy was processed for SEM. The sham-o perated dogs showed a reduction of basal coronary flow of 11 %, but th e vasoreactivity to ACh and 5-HT remained constant. In the I/R group, basal coronary flow was reduced by 35 % (p < 0.05), and the vasoreacti vity to ACh and 5-HT, but not to NTG, was significantly blunted. At SE M the arterioles of the dogs submitted to I/R showed a marked adhesion of leukocytes associated with holes on the endothelial surface, while the capillary bed was free of changes and patent. Thus, following I/R , coronary endothelial dysfunction could be demonstrated in vivo by th e blunting of the vasoreactive responses to two different endothelium- dependent vasodilators. The responses to NTG were not affected, probab ly because the function of the smooth muscle cell was preserved, and t he capillary bed was patent.