Effects of Milrinone on Atrioventricular Conduction in the Canine Heart Under Normal Conditions, During Atrial Flutter and After Ligation and Reperfusion of the Septal Artery

Abstract

Milrinone and AV Conduction. Milrinone, in addition to its vasodilatory and inotropic actions, has been shown to enhance or restore electrical activity in depolarized tissues and to improve conduction in isolated cardiac tissues depressed by exposure to an ischemic environment. These electrophysiological actions of the drug are thought to be secondary to milrinone's ability to enhance the transmembrane calcium current (ICa). The present study was designed to evaluate the effectiveness of milrinone (10–100 μg/kg, IV bolus) to modulate atrioventricular (AV) nodal conduction in anesthetized dogs under normal conditions, after ligation and reperfusion of the septal coronary arteries and during atrial flutter. All dosage regimens (10–100 μg/kg milrinone) produced a positive inotropic effect with no significant changes in blood pressure. Under normal conditions, 100 jig/kg of milrinone significantly reduced the PR interval, Wenckebach cycle length and AV nodal refractory period without causing a significant change in heart rate. The improvement in AV conduction and decrease in AV nodal refractoriness led to significant dose‐dependent increases in ventricular rate during atrial flutter. Low doses of milrinone also accelerated the flutter rate. Ligation of the septal coronary arteries for 2 to 6 hours produced stable atrioventricular conduction disturbances in six of the 11 dogs studied: complete AV block (n = 1), second‐degree AV block (n= 2) and first‐degree AV block (n= 3). Milrinone (100 μg/kg) improved AV conduction in five of the six dogs. Reperfusion of the septal arteries following 6 hours of ligation produced a sustained high degree AV block in two out of five dogs. Milrinone promptly restored 1:1 conduction in both cases. Our results suggest that milrinone may be of benefit in the treatment of some cases of AV conduction disturbance and that the drug, through its effects to facilitate AV conduction and abbreviate AV refractoriness, can lead to a significant and perhaps dangerous increase in ventricular rate in patients with atrial flutter or fibrillation. (J Cardiovasc Electrophysiol, Vol 1. pp. 93–102. 1990)