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-independent 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 morphology of the subepicardial arterioles and capillary bed by means of scanning electron microscopy (SEM). Anesthetized, instrumented dogs were divided 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 experiment a 1 cm3 myocardial biopsy was processed for SEM. The sham-operated dogs showed a reduction of basal coronary flow of 11%, but the 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 vasoreactivity to ACh and 5-HT, but not to NTG, was significantly blunted. At SEM 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 patient. Thus, following I/R, coronary endothelial dysfunction could be demonstrated in vivo by the blunting of the vasoreactive responses to two different endothelium-dependent vasodilators. The responses to NTG were not affected, probably because the function of the smooth muscle cell was preserved, and the capillary bed was patent.
Hoechst Marion Roussel, Disease Group Cardiovascular Agents, Frankfurt/Main.
P A
PA
Martorana
B
B
Goebel
H
H
Ruetten
D
D
Koehl
M
M
Keil
D000818:Animals; D003331:Coronary Vessels / Q000503:physiopathology; D004285:Dogs; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D008297:Male; D008855:Microscopy, Electron, Scanning; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D009206:Myocardium / Q000648:ultrastructure; D014655:Vascular Resistance