Effects of the antianginal drug trapidil on atrioventricular conduction disturbances during acute myocardial ischemia.

Adenosine and related compounds have been shown to produce atrioventricular (AV) conduction block during acute myocardial ischemia. We investigated the effects of the antianginal drug trapidil, which has been shown to inhibit phosphodiesterase, on AV conduction disturbances in a canine model of acute myocardial ischemia. In 35 anesthetized dogs, the AV node artery was cannulated and perfused with arterial blood. Adenosine (300 µg, 650 µg, or 1000 µg) was injected into the AV node artery. With administration of adenosine at 300 µg, 650 µg, or 1000 µg, the atrio-His (AH) interval was increased by 14.6 ms, 22.3 ms, and 29.7 ms, respectively. The effects of adenosine were potentiated by pretreatment with intravenous dipyridamole (250 µg/kg), an inhibitor of adenosine uptake, but the effects of adenosine were attenuated with intravenous trapidil (3 mg/kg), an inhibitor of phosphodiesterase. AV node artery occlusion resulted in prolongation of the AH interval in 4 of 12 dogs. The ischemia-induced AH prolongation was potentiated with intravenous dipyridamole and attenuated with intravenous trapidil. AV conduction disturbances associated with inferior myocardial infarction may be related in part to endogenously released adenosine, and trapidil may be useful in treating AV block associated with acute AV node ischemia.

Effect of the ATP-sensitive K⁺ channel opener nicorandil in a canine model of proarrhythmia.

Increased action potential duration (APD) induces early afterdepolarization (EAD) in vitro and torsade de pointes in vivo, and ATP-sensitive K(+) channel openers decrease APD in cardiac tissue. We tested whether the ATP-sensitive K(+) channel opener nicorandil has antiarrhythmic effects on class III antiarrhythmic drug-induced ventricular arrhythmia. In 10 anesthetized dogs with chronic atrioventricular block, we recorded monophasic action potentials (MAPs) from the left and right ventricular (LV and RV) endocardium. The class III antiarrhythmic drug nifekalant (1 mg/kg, IV) was administered at 5 minute intervals (total doses; 2-6 mg/kg) until the appearance of EADs, premature ventricular contractions (PVCs), or polymorphic ventricular tachycardias (PVTs). Five minutes after the end of nifekalant administration, nicorandil (1.0 mg/kg) was administered over 5 minutes. Nifekalant decreased the ventricular escape rate from 75 ± 5 beats/minute to 45 ± 10 beats/minute and increased RV-MAP duration (MAPD) from 217 ± 32 msec to 308 ± 2 msec (P < 0.01) and LV-MAPD from 232 ± 32 msec to 353 ± 82 msec (P < 0.01). EADs were recorded in 9 dogs, frequent premature ventricular contractions (PVCs) developed in 10 dogs, incessant PVTs developed in 3 dogs, and monomorphic ventricular tachycardia developed in 3 dogs after nifekalant administration. Nicorandil decreased RV-MAPD to 267 ± 57 msec and LV-MAPD to 279 ± 44 msec. It suppressed EADs, decreased the incidence of PVCs, and abolished PVT. Nicorandil may be clinically useful for treatment of PVCs and PVTs accompanying acquired long QT syndrome.