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Nicorandil (N) increases potassium conductance in vascular smooth muscle and so induces vasodilation; N also dose-dependently reduces action potential duration (APD). However, it is unclear whether increased potassium conductance, and concomitant APD shortening, might be arrhythmogenic, particularly when myocardial ischemia (where potassium efflux is increased) concurs. Data on the anti-arrhythmic effectiveness of N have also been published: N reduced the spontaneous discharge of sino-atrial node and so reduced heart rate, both in vitro and man. On the other hand, among other vasodilators, cicletanine (C) has been reported to increase potassium conductance, an effect which was advocated to explain its antiarrhythmic potency. In the present investigation the direct myocardial effects of N were compared to those following C in 63 experiments (from 13 Guinea-pigs), using atrial strips (containing sino-atrial node) superfused in 1-compartment bath with normal Tyrode's solution. Using glass microelectrodes, standard electrophysiologic variables were recorded (APA, RMP, APD50%, Vmax) in spontaneously beating atrial tissue, either in Tyrode, dimethyl-sulfoxide (DMSO 1:100, as solvent), C 10(-5) M (in DMSO 1:100), and N 10(-3) M (in DMSO 1:100), whose respective perfusion periods (15 min) were randomized, always following 15 min of washout with Tyrode. Only N was tested in experiments of both 15 and 30 min duration.(ABSTRACT TRUNCATED AT 250 WORDS)

We have investigated (multivariate Cox's model) the relative risk of stable excitation-conduction block (ECB) in right ventricular myocardial strips (2 x 5 x 1 mm) from 26 female guinea-pigs, bathed in a 2-compartment chamber (3 ml) on the anterior side of which modified Tyrode's solution (K+ 12 mM, HCO3- 9 mM, pH 7 +/- 0.05, pO2 80 +/- 10 mmHg and absence of glucose) is supraperfused (stimulation rate: 450 ms; wire in the posterior compartment), thus enabling simulation of electrophysiologic changes seen during acute myocardial ischemia. Using glass microelectrodes, action potential amplitude (APA), durations (APD50 and 90%), resting membrane potential (RMP) and upstroke velocity (Vmax) are investigated. The hypothesis was tested of prostacyclin and histamine involvement in the genesis of ischemia-induced ECB in this model. Either a weak prostacyclin stimulator (cicletanine 10(-5) M, IPSEN, Paris, F, in DMSO 1:100; n = 16) or a potent prostacyclin generation blocker (indomethacin 10(-5) M, Sigma, in DMSO 1:100; n = 10) and either DMSO alone (1:100; n = 16) or a specific histaminergic H1 receptor antagonist (terfenadine 10(-5) M, Sigma, in DMSO 1:100; n = 10) were supraperfused using a randomization scheme. Each animal was used twice and either a first or a second occlusion (supraperfusing the modified Tyrode's solution for 30 min) period was performed and the randomized substances were supraperfused, thus enabling obtention of n = 52 experiments for analysis.(ABSTRACT TRUNCATED AT 250 WORDS)