Effect of selective A1 adenosine receptor antagonism of postdefibrillation cardiovascular depression: evidence for an antiadrenergic role of endogenous adenosine.
OBJECTIVE
The aim was to examine the effect of a selective A1 adenosine receptor antagonist (N-0861) on postdefibrillation cardiovascular depression to determine whether antagonist mediated enhanced postdefibrillation haemodynamic recovery is due to reversal of the antiadrenergic action of adenosine, an A1 receptor mediated effect.


METHODS
Halothane-nitrous oxide anaesthetised Duroc pigs of either sex, weight 22-25 kg, were subjected to sequential episodes of induced ventricular fibrillation lasting either 15 s (terminated by a suprathreshold shock at 60-70 A) or 35 s (subjected to a subthreshold shock at 20 A followed by a suprathreshold shock at 60-70 A) during intravenous placebo infusion (n = 10), N-0861 infusion (0.1 mg.kg-1.min-1, n = 10), and N-0861 infusion plus propranolol (2 mg.kg-1, n = 6).


RESULTS
N-0861 significantly enhanced immediate postdefibrillation electrophysiological and haemodynamic recovery compared to placebo for ventricular fibrillation episodes lasting 35 s. Over the first 15 s postdefibrillation, N-0861 significantly (p < 0.05) shortened mean cycle length by 55%, increased mean arterial pressure by 33%, and increased the first derivative of left ventricular pressure (an indirect measure of cardiac contractility) by 100% compared to placebo. At 60 s postdefibrillation, when other variables were equal, the first derivative of left ventricular pressure in the presence of N-0861 remained 26% greater than placebo. This effect was completely antagonised by propranolol.


CONCLUSIONS
(1) Cardiac contractility in the immediate postdefibrillation period is suppressed by the antiadrenergic action of endogenous adenosine. (2) Selective A1 adenosine receptor antagonism can markedly enhance postdefibrillation contractility. (3) These results support an antiadrenergic role of endogenous adenosine under pathophysiological conditions.
Wesley
R C
RC
Division of Cardiology, Long Beach VA Medical Center, CA 90822.
Porzio
D
D
Sadeghi
M
M
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D004554:Electric Countershock; D005260:Female; D006321:Heart / Q000187:drug effects*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009636:Norbornanes / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D058914:Purinergic Antagonists; D011941:Receptors, Adrenergic / Q000187:drug effects*; D013552:Swine
D009636:Norbornanes; D058914:Purinergic Antagonists; D011941:Receptors, Adrenergic; C073387:N 0861; D011433:Propranolol; D000225:Adenine; D000241:Adenosine