EFFECT OF COCAINE ON LEFT-VENTRICULAR FUNCTION - RELATION TO INCREASED WALL STRESS AND PERSISTENCE AFTER TREATMENT

Background To determine whether alterations in left ventricular (LV) f unction after a cocaine infusion are due to reduced myocardial contrac tility or changes in loading conditions, we examined LV function in 30 morphine-sedated, closed-chest dogs. We also wanted to determine the time course of the effects of cocaine on LV function after the infusio n was stopped. Methods and Results Two-dimensional echocardiography an d hemodynamics provided LV fractional shortening and end-systolic wall stress data. Radionuclide ventriculography was also performed. Four g roups of dogs received saline or cocaine infusions of 10, 30, or 100 m u g . kg(-1). min(-1). Cocaine was infused for 90 minutes with ECG and arterial pressure monitoring. Animals were monitored for an additiona l 120 minutes after the infusion ended. Arterial pressure rose over th e course of the experiment in all four groups, but saline and cocaine 10 mu g . kg(-1). min(-1) did not significantly change ejection fracti on. Cocaine 30 and 100 mu g . kg(-1)min(-1) acutely increased arterial pressure and heart rate but decreased ejection fraction from 0.64 +/- 0.06 to 0.45 +/- 0.08 and from 0.65 +/- 0.10 to 0.46 +/- 0.11, respec tively. Additionally, cocaine 100 mu g . kg(-1). min(-1) decreased fra ctional shortening from 36 +/- 9% to 23 +/- 12%. However, cocaine 30 a nd 100 mu g . kg(-1). min(-1) also increased wall stress from 42 +/- 1 5 to 65 +/- 11 g/cm(2) and from 37 +/- 15 to 90 +/- 33 g/cm(2), respec tively. These results were analyzed by use of the relation between wal l stress and fractional shortening as an index of contractility. Fract ional shortening after cocaine infusion was displaced downward as a re sult of increased wall stress rather than changes in contractility. In addition, alteration of afterload with phenylephrine (6 mu g/kg) and sodium nitroprusside (10 mu g/kg) before and during infusion of cocain e 100 mu g . kg(-1). min(-1) showed similar regression lines for wall stress to fractional shortening. Conclusions Ejection-phase indexes of LV function were reduced by cocaine in this model of conscious, sedat ed dogs, but effects were attributable to increased wall stress rather than to reduced myocardial contractility. These effects persisted for at least 2 hours after the infusion was stopped.