No involvement of endogenous nitric oxide in classical ischemic preconditioning in swine.
Endogenous nitric oxide (NO) is involved in the protection by classical ischemic preconditioning (IP) against ischemia-induced arrhythmias in anesthetized dogs. Furthermore, NO triggers and mediates protection against infarction and stunning in delayed IP in conscious rabbits. Up to now it is unclear whether or not endogenous NO is also involved in the protection against infarction by classical IP in vivo. In 45 enflurane-anesthetized swine, severe left anterior descending coronary artery hypoperfusion for 90 min followed by 2 h of reperfusion resulted in an infarct size (IS, triphenyl tetrazolium chloride-staining) of 20.5+/-5.4% (S.E.M.) of the area at risk. Inhibition of NO synthase by l -nitro arginine (l -NA, 30 mg/kg i.v.) increased left ventricular (LV) peak pressure from 93+/-3 to 120+/-1 mmHg (P<0.05), but did not alter IS (22.4+/-5. 6%). With aortic constriction to match the increase in LV peak pressure with l -NA, IS was unchanged (18.1+/-5.1%). IP by 10 min ischemia and 15 min reperfusion preceding the 90 min target ischemia reduced IS to 2.0+/-0.8% (P<0.05 v. non-preconditioned groups). This reduction of IS by IP was not affected by l -NA (1.3+/-0.9%, P<0.05 v. non-preconditioned groups). Area at risk and myocardial blood flow (microspheres) during ischemia were not different among groups. Relationships between IS and subendocardial blood flow with l -NA or aortic constriction, respectively, were not different from that with placebo, but were significantly shifted downwards by IP with and without l -NA. Thus, endogenous NO does not alter infarct size development per se and is not involved in the protection against infarction by classical IP in pigs in vivo.
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Abteilung für Pathophysiologie, Zentrum für Innere Medizin, Universitätsklinikums Essen, Hufelandstr. 55, Essen, 45122, Germany.
Schulz
R
R
Behrends
M
M
Gres
P
P
Umschlag
C
C
Heusch
G
G
D000818:Animals; D006321:Heart / Q000503:physiopathology*; D006439:Hemodynamics; D019157:Ischemic Preconditioning, Myocardial; D009203:Myocardial Infarction / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism*; D013552:Swine; D013556:Swine, Miniature
D009569:Nitric Oxide