Effects of regional ischaemia, with or without reperfusion, on endothelium dependent coronary relaxation in the dog.
OBJECTIVE
The aim was to establish whether the duration of coronary ischaemia and coronary ischaemia with reperfusion selectively reduced the magnitude of relaxation mediated by endothelium dependent relaxing factor (EDRF) in response to thrombin, compared with relaxation produced by acetylcholine and calcimycin.


METHODS
Adult male dogs, anaesthetised with sodium pentobarbitone (30 mg.kg-1 intravenously) were used. Coronary artery occlusions were maintained for either 15 or 45 min; in half the dogs from each timepoint, occlusion was followed by 60 min reperfusion. At the end of each in situ period, coronary arteries were removed from both ischaemic and non-ischaemic regions, cut into rings, and hung in isolated organ baths. Dose-response relationships to the EDRF dependent vasodilators thrombin, acetylcholine, and calcimycin, and to the EDRF independent vasodilator isoprenaline, were then established.


RESULTS
Thrombin (0.003-0.3 units.ml-1) caused dose dependent relaxation in all tissues. Relaxant responses (E(max)) in the non-ischaemic vessels from both 15 and 45 min treatment groups were used as control data for the responses in ischaemic vessels. Maximum responses were not different in the non-ischaemic groups from either 15 or 45 min studies, at 82.7 (SEM 3.7)% after 15 min, and 82.1(2.4)% after 45 min. There was a small but significant reduction in E(max) after 15 min and 45 min ischaemia, to 74.4(3.2)% and 74.4(3.0)% respectively. Sixty minutes reperfusion provoked a further reduction in E(max) to 64.9(3.8)% after 45 min ischaemia, but not after 15 min ischaemia [70.3(4.2)%]. Neither 15 nor 45 min interventions altered E(max) of relaxation to acetylcholine or calcimycin (greater than 88.0% in each group). Similarly there were no significant differences between groups to the relaxation stimulated by isoprenaline (E(max) greater than 90.0%).


CONCLUSIONS
The data suggest that loss of EDRF dependent relaxation to thrombin is more sensitive to ischaemia than the relaxation produced by either acetylcholine or calcimycin, and appears to be manifested early in the onset of ischaemic injury.
Winn
M J
MJ
Department of Pharmacology, University of Alabama, Birmingham 35294.
Ku
D D
DD
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D003327:Coronary Disease / Q000378:metabolism* / Q000503:physiopathology; D003331:Coronary Vessels / Q000187:drug effects; D046508:Culture Techniques; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D009200:Myocardial Contraction / Q000187:drug effects*; D015425:Myocardial Reperfusion / Q000379:methods; D009569:Nitric Oxide / Q000378:metabolism*; D013917:Thrombin / Q000494:pharmacology; D013997:Time Factors
D009569:Nitric Oxide; D000001:Calcimycin; D013917:Thrombin; D000109:Acetylcholine