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)