Flow-function dissociation following an acute dose of cocaine: effect of captopril on coronary flow.
BACKGROUND
Acute administration of cocaine leads to left ventricular dysfunction and a decrease in coronary blood flow. This experiment studied the relationship between function and flow over time in cocaine heart disease and examined the effects of captopril on this relationship.


METHODS
Dogs anesthetized with pentobarbital (n = 13) were given a 3 mg/kg body weight intravenous bolus of cocaine followed by a 7 mg/kg infusion over 10 minutes. Animals were then randomly assigned to receive either captopril (0.5 mg/kg infused over 5 minutes, followed by 0.5 mg/kg/h) or an equivalent volume of saline beginning 15 minutes after cocaine administration. Coronary blood flow (radioactive microspheres and Doppler flow probes) and left ventricular function (two-dimensional echocardiogram and dP/dt) were monitored for 2 hours.


RESULTS
Within 15 minutes, cocaine caused a drop in dP/dt by 39% to 42% and in coronary blood flow by 35%. Cocaine also caused an increase in left ventricular end-diastolic pressures in both groups. Cocaine resulted in prolongation of an index of end-diastolic isovolumic relaxation time (tau) from a baseline of 34 milliseconds to 56 milliseconds at 15 minutes after cocaine administration in the control group and from a baseline of 35 milliseconds to 49 milliseconds in the captopril group (P < 0.05). By 2 hours after therapy, the tau in the control group remained elevated, whereas in the captopril group it returned toward baseline. At 2 hours of observation, systolic function recovered while coronary flow remained depressed. There was no difference between the captopril and control groups in coronary blood flow or systolic cardiac function at any time during the study.


CONCLUSIONS
Cocaine caused left ventricular systolic and diastolic dysfunction as well as reduced coronary blood flow. At 2 hours there is a dissociation of systolic function, which recovers, and of coronary blood flow, which does not. Captopril had no effect on coronary blood flow or systolic left ventricular function following cocaine administration.
Rezkalla
S
S
Marshfield Clinic, WI 54449-5777.
Hale
S
S
Alker
K
K
Kloner
R A
RA
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology*; D003042:Cocaine / Q000633:toxicity*; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
D002216:Captopril; D003042:Cocaine