Nitric oxide fails to confer endogenous antiarrhythmic cardioprotection in the primate heart in vitro.
OBJECTIVE
The role of nitric oxide (NO) in cardiac pathophysiology remains controversial. According to data from several studies using rat and rabbit isolated hearts, NO is an endogenous cardioprotectant against reperfusion-induced ventricular fibrillation (VF). Thus, if cardiac NO production is abolished by perfusion with L-N(G)-nitro-L-arginine methylester (L-NAME) (100 microM) there is a concomittant increase in the incidence of reperfusion-induced VF, with L-NAME's effects on NO and VF prevented by L- (but not D-) arginine co-perfusion. To make a better estimate of the clinical relevance of these findings, 100 microM L-NAME was tested in primate hearts under similar conditions.


METHODS
Marmoset (Callithrix jaccus) hearts, isolated and perfused, were subjected to 60 min left regional ischaemia followed by 10 min reperfusion in vitro. The ECG was recorded and NO in coronary effluent measured by chemiluminescence.


RESULTS
L-NAME (100 micro M) decreased NO in coronary effluent throughout ischaemia and reperfusion (e.g. from 3720+/-777 pmol min(-1) g(-1) in controls to 699+/-98 pmol min(-1) g(-1) after 5 min of ischaemia) and, during ischaemia, lowered coronary flow and reduced heart rate, actions identical to those seen in rat and rabbit hearts. However, the incidence of reperfusion-induced VF was unchanged (20%, with or without L-NAME).


CONCLUSIONS
A species difference exists in the effectiveness of endogenous NO to protect hearts against reperfusion-induced VF. The present primate data, which presumably take precedence over rat and rabbit data, cast doubt on the clinical relevance of NO as an endogenous, antiarrhythmic, cardioprotectant.
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Cardiovascular Division, Rayne Institute, St Thomas' Hospital, London, UK.
Curtis
M J
MJ
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000378:metabolism*; D002144:Callithrix; D003326:Coronary Circulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester