DEPRESSANT EFFECTS OF QUINIDINE GLUCONATE ON LEFT-VENTRICULAR FUNCTION IN CONSCIOUS DOGS WITH AND WITHOUT VOLUME OVERLOAD

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 increase (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 β-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±0.10 to 0.62±0.10 lengths at onset of ejection (LOE)/sec (p<0.01), and dP/dt 40 decreased from 2140±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 β-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.