Effects of regional ischaemia, with or without reperfusion, on endothelium dependent coronary relaxation in the dog.

Abstract:

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.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Winn MJ,Ku DD

doi

10.1093/cvr/26.3.250

subject

Has Abstract

pub_date

1992-03-01 00:00:00

pages

250-5

issue

3

eissn

0008-6363

issn

1755-3245

journal_volume

26

pub_type

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