Prostaglandins inhibit efferent cardiac sympathetic nerve effects by acting at presynaptic sites and may act to suppress some arrhythmias. In the present study, the effects of intravenous administration of prostacyclin (PGI2) and prostaglandin E2 (PGE2) on early afterdepolarization and ventricular tachycardia induced by cesium chloride (0.5 mmol/liter per kg body weight intravenously) combined with stimulation of bilateral ansae subclaviae in anesthetized dogs were examined. The right atrium was paced at a constant cycle length of 600 ms. A left ventricular endocardia! monophasic action potential catheter was used to detect early afterdepolarizations. Prostacyclin (0.2 μg/kg per min) reduced the amplitude of the early afterdepolarizations (39.2 ± 8.4% of the monophasic action potential amplitude during control study to 28.7 ± 5.5%, n = 10; p < 0.001) as well as the prevalence of ventricular tachycardia (11 of 14 dogs during control study to 5 of 14 dogs; p = 0.031). Prostaglandin E2 (0.2 to 0.6 μg/kg per min) did not significantly reduce the early afterdepolarization amplitude (34.7 ± 8.9% to 25.1 ± 10.7%, n = 8; p = 0.085) or the prevalence of ventricular tachycardia (8 of 10 versus 6 of 10 dogs; p = 0.50). Alpha- and beta-adrenoceptor blockade with combined intravenous administration of propranolol (0.5 mg/kg) and phentolamine (0.3 mg/kg) decreased the amplitude of the early afterdepolarizations induced by cesium chloride and bilateral ansae subclaviae stimulation from 38.6 ± 11.2% to 18.8 ± 3.3% (n = 6; p = 0.005). Additional administration of PGI2 further reduced the early afterdepolarization amplitude from 18.8 ± 3.3% to 9.8 ± 4.8% (n = 6; p = 0.001). In control dogs, the amplitude of the early afterdepolarizations and the prevalence of ventricular tachycardia did not change over time with repeated doses of cesium chloride and bilateral ansae subclaviae stimulation. Thus, exogenous PGI2 suppresses early afterdepolarization amplitude and reduces the prevalence of ventricular tachycardia induced by cesium chloride combined with bilateral ansae subclaviae stimulation in dogs, even after alpha- and beta-adrenoceptor blockade. A direct action on the cesium chloride-induced repolarization abnormality, unrelated or in addition to sympathetic neural modulation, is likely to be involved in the PGI2 effect.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine