The role of cromakalim and a nitric oxide synthase blocker in cardiac arrhythmia in the intact baboon model.
The arrhythmogenic effect of adenosine triphosphate (ATP)-sensitive potassium channel openers is controversial and may be dependent on the type of animal model used. Information on the effect of these drugs in the normal primate model is limited. The purpose of this study was first to determine the arrhythmogenic properties of cromakalim in the baboon and second to determine whether N-omega-nitro-L-arginine methyl ester (L-NAME) has any effect on the induced arrhythmia. Adult (2-4 years old) baboons (Papio ursinus) were anesthetized with a continuous i.v. infusion of ketamine (100 mg/ ml), diazepam (5 mg/ml), and saline (ratio 2:2:50) at a rate of 40-60 ml/h. Sympathetic responses were inhibited by administration of propranolol (1 mg/kg) before the start of the experiments. Cromakalim (30 microg/kg) was administered before and after L-NAME (7.5 mg/kg), and the parameters were monitored for 15 min after each intervention. A Millar double-tipped microcatheter was used to record left ventricular and aortic pressures. Lead II of the ECG was monitored. During a 15-min period after administration of cromakalim, 22.3 +/- 6.0 abnormal ventricular complexes were recorded. L-NAME administration significantly reduced these abnormal complexes to 4.5 +/- 2 (paired t test, p < or = 0.05). We therefore conclude that cromakalim has arrhythmogenic properties in the baboon and that these can be attenuated by L-NAME.
Hay
L
L
Department of Physiology, Medical University of Southern Africa, Medunsa. lhay@medunsa.ac.za
Schutte
P J
PJ
Du Plooy
W J
WJ
Kahler
C P
CP
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000517:prevention & control*; D002404:Catheterization; D019806:Cromakalim / Q000494:pharmacology*; D004195:Disease Models, Animal; D004562:Electrocardiography / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010215:Papio; D011433:Propranolol / Q000494:pharmacology; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D004791:Enzyme Inhibitors; D019806:Cromakalim; D011433:Propranolol; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester