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.
Martorana
P A
PA
Hoechst Marion Roussel, Disease Group Cardiovascular Agents, Frankfurt/Main.
Goebel
B
B
Ruetten
H
H
Koehl
D
D
Keil
M
M
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