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Transient time course of cocaine-induced cardiac depression versus sustained peripheral vasoconstriction
1Department of Internal Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Objectives:
The goal of this study was to define in vivo the magnitude and temporal course of cocaine-induced cardiac depression separate from peripheral vascular loading changes.
Background:
Cocaine administration immediately alters arterial pressure, ventricular filling, contractility and heart rate. These combined changes have complicated previous analyses of the cardiac effects of cocaine, because routine measures of function are influenced by all these factors.
Methods:
Pressure-volume loops and relations were measured by conductance catheter technique in 10 intact chest anesthetized dogs before and up to 30 min after administration of cocaine (3 mg/kg intravenously). Heart rate was kept constant by atrial pacing, and data were obtained before and after ganglionic blockade.
Results:
Cocaine decreased ejection fraction, cardiac output and maximal rate of rise of left ventricular pressure (dP/dtmax) and increased arterial vascular resistance (all p < 0.05). The maximal change occurred by 2 min and was fully sustained for the next 30 min. In contrast, contractile indexes based on pressure-volume analysis (e.g., end-systolic pressure-volume relation) decreased only briefly at 2 min (by -19%) and returned to control value after 5 to 10 min. Reflex blockade with hexamethonium eliminated cocaine-induced vasoconstriction, but the magnitude and brevity of cardiac depression were unaltered. Ejection fraction, dP/dtmax and cardiac output now also decreased transiently, suggesting that the sustained changes observed before blockade in these variables were load related. Analogous load effects also explained changes in peak filling rate.
Conclusions:
Cocaine induces brief direct cardiac depression that is temporally dissociated from more sustained peripheral vasoconstriction. This dissociation is not measured by traditional left ventricular function analysis because of simultaneous load change. The transience of cardiac depression suggests that it probably does not play a major role in late adverse sequelae of cocaine administration.