Electrophysiological mechanisms of cocaine-induced cardiac arrest. A possible cause of sudden cardiac death.
The hypothesis that cocaine intoxication results in cardiac arrest by producing a block of the propagation of the action potential, without loss of pacemaker function, was tested in rat cardiac tissues. In spontaneously active sinoatrial preparations, cocaine exerted a dose-dependent negative chronotropic action, which was not modified by atropine or propranolol. Sinus node arrest was never observed. Instead, cocaine produced sinoatrial block. The mechanism of this block involved a fall in the resting potential and a decrease in the amplitude and Vmax of phase 0 of the action potential of atrial fibers. In sinoatrial preparations and papillary muscles driven at 5 Hz., cocaine depressed the resting potential, the total amplitude, the overshoot of the action potential, and the Vmax of phase 0. Cocaine had a biphasic effect on the atrial action potential duration. The initial shortening was muscarinic. The prolongation was alpha-adrenergic mediated and probably the result of the inhibition of the transient outward current Ito. In papillary muscles, only the prolongation of the action potential occurred. In conclusion, the electrophysiological actions of cocaine can explain cardiac sudden death. The fall in the resting potential associated with the decrease in the amplitude of the action potential of contractile fibers will result in a block of the propagation of the action potential. Quiescence of the contractile fibers will occur while the sinus node is still generating action potentials at a rate compatible with life.
Sherief
H T
HT
Department of Physiology and Biophysics, College of Medicine, Howard University, Washington, DC 20059.
Carpentier
R G
RG
D000818:Animals; D003042:Cocaine; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D004594:Electrophysiology; D006323:Heart Arrest / Q000139:chemically induced / Q000503:physiopathology*; D006325:Heart Atria / Q000187:drug effects / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials; D051381:Rats; D011919:Rats, Inbred Strains; D012848:Sinoatrial Block / Q000139:chemically induced / Q000503:physiopathology
D003042:Cocaine