Depressant effects of quinidine gluconate on left ventricular function in conscious dogs with and without volume overload.
Authors: R L Engler, M M Le Winter, J S Karliner
Journal: Circulation (1979)

To assess the effects of quinidine gluconate on left ventricular (LV) performance, sonomicrometer length gauges and micromanometer catheters were implanted in 17 conscious dogs.Studies were carried out before and after the development of volume overload LV hypertrophy induced by an aortocaval fistula.Quinidine gluconate was given intravenously in two successive doses of 6 mg/kg, yielding serum levels in the usual therapeutic range.In eight normal dogs, the heart rate increased (p < 0.01), LV enddiastolic pressure (EDP) fell (p < 0.01), and peak LV systolic pressure (SP) was unchanged 15 minutes after the second dose.Mean normalized shortening rate (MNSR) decreased (p < 0.05) and dP/dt at 40 mm Hg of developed pressure (dP/dt 40) was unchanged.When the heart rate was held constant by atrial pacing during B3-adrenergic blockade induced by propranolol 0.5 mg/kg, quinidine resulted in a fall of LVSP from 123.7 ± 6.1 to 106.7 ± 2.2 mm Hg (p < 0.05) and LVEDP was unchanged.MNSR decreased from 0.85 i 0.10 to 0.62 i 0.10 lengths at onset of ejection (LOE)/sec (p < 0.01), and dP/dt 40 decreased from 2140 i 99 to 1725 102 mm Hg/sec (p < 0.01).In 11 dogs with volume overload hypertrophy, LV performance was unchanged or increased after quinidine.However, when the heart rate was held constant by atrial pacing during #-adrenergic blockade, quinidine produced a fall in LVSP from 121.4 ± 3.5 to 106.2 ± 2.3 mm Hg (p < 0.01), no change in LVEDP, a decrease in MNSR from 1.52 ± 0.22 to 1.35 ± 0.19 LOE/sec (p < 0.01) and a decrease in dP/dt 40 from 2331 ± 94 to 1989 ± 143 mm Hg/sec (p < 0.01) 15 minutes after the second dose.We conclude that quinidine causes depression of LV performance in normal dogs and in dogs with LV hypertrophy due to volume overload.Augmented sympathetic tone during quinidine administration may mask these depressant effects.This study may serve as a pharmacologic model to study the effects of drugs on LV performance.QUINIDINE IS WIDELY USED to treat cardiac arrhythmias in patients with coexistent myocardial disease,' but its effects on myocardial performance are poorly defined.Studies in isolated heart muscle have shown a dose-dependent depression of contrac- tility.5The results of studies in the intact heart have been conflicting, some having shown no change in in- dices of left ventricular (LV) performance9' 1 and others depression of LV function."'Further, changes in loading conditions, which may alter indices of myocardial performance independently of changes in inotropic state, have usually not been well characterized in previous investigations, or anesthetic agents that may alter both autonomic tone and myocardial performance have been used.'6Because quinidine is an arteriolar vasodilator"' 17 and a venodilator,18 both due to its direct action on vascular smooth muscle and to its a-adrenergic blocking properties,'17' ' changes in loading conditions and autonomic tone are to be expected after administration of the drug and must be considered in evaluating