title: Contrastive effects of prostaglandin F2 alpha on normal cardiac rhythm and ouabain-induced cardiac arrhythmias in cats: possible neural basis.
abstract: The effects of prostaglandin F2 alpha (PGF2 alpha) on normal cardiac rhythm and ouabain-induced cardiac arrhythmias were investigated in chloralose-anaesthetized cats. PGF2 alpha (1-16 micrograms/kg i.v. bolus) produced ventricular arrhythmias and few incidences of AV conduction disturbances in normal cats. Changes in heart rate and blood pressure caused by PGF2 alpha in normal cats were complex, namely a decrease, an increase, or an initial decrease followed by an increase. Bilateral vagotomy antagonized the ventricular arrhythmias, AV conduction disturbances and hemodynamic changes produced by 16 micrograms/kg i.v. PGF2 alpha. On the other hand, atropine (2 mg/kg i.v.) pretreatment blocked the AV conduction disturbances and the reduction in heart rate and blood pressure, but not the ventricular arrhythmias or the increase in heart rate and blood pressure caused by 16 micrograms/kg i.v. PGF2 alpha. The ventricular arrhythmogenic effect of PGF2 alpha was prevented by propranolol (1 mg/kg i.v.). Intervention with cardiotoxic doses of ouabain augmented the PGF2 alpha-induced AV conduction disturbances, sinus bradycardia and hypotension, and attenuated the ventricular arrhythmias. Subsequent bilateral vagotomy prevented the ouabain-potentiated PGF2 alpha-induced AV block and sinus bradycardia, attenuated the hypotension and further reduced the ventricular arrhythmias. PGF2 alpha (2-16 micrograms/kg i.v.), contrary to its arrhythmogenic effect in normal cats, mainly suppressed ouabain-induced ventricular and supraventricular arrhythmias in ouabain-intoxicated cats, but aggravated the same in few cats. PGF2 alpha (16 micrograms/kg), prior to ouabain administration, produced ventricular arrhythmias in a group of 8 cats and later, in the same group of animals, when tested on ouabain-induced arrhythmias, it mainly antagonized them. These results suggest that PGF2 alpha evokes an arrhythmogenic effect on cardiac rhythm of normal hearts and mainly an antiarrhythmic effect on ouabain-induced arrhythmias largely through the mediation of two functionally opposing excitatory and inhibitory autonomic neural reflex pathways, respectively. The afferents of these pathways are of vagal origin. The efferent pathways of the inhibitory and excitatory reflexes involve in part increased vagal activity and increased sympathetic activity to the heart, respectively. Alteration by ouabain of the arrhythmogenic nature of PGF2 alpha on normal heart to its antiarrhythmic effect on the arrhythmic heart may be due to its selective potentiating effect on the inhibitory reflex pathway.
authors.affiliation: Department of Pharmacology, All-India Institute of Medical Sciences, New Delhi.
authors.forename: T S
authors.initials: TS
authors.lastname: Rao
authors.forename: S D
authors.initials: SD
authors.lastname: Seth
authors.forename: S C
authors.initials: SC
authors.lastname: Manchanda
authors.forename: U
authors.initials: U
authors.lastname: Nayar
mesh_terms: D000758:Anesthesia; D000818:Animals; D000889:Anti-Arrhythmia Agents; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D001283:Atrioventricular Node / Q000187:drug effects; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D015237:Dinoprost / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects*; D006329:Heart Conduction System / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D010042:Ouabain; D011433:Propranolol / Q000494:pharmacology; D014628:Vagotomy
chemical_list: D000889:Anti-Arrhythmia Agents; D010042:Ouabain; D001285:Atropine; D011433:Propranolol; D015237:Dinoprost