Acute morphological effects of cocaine on rat cardiomyocytes.
The cardiovascular actions of cocaine in vivo are varied and often antagonistic. Cocaine produces excitatory sympathomimetic effects by interfering with re-uptake of norepinephrine at adrenergic nerve terminals. However, the local anaesthetic properties of cocaine exert depressant effects on the myocardium. In an attempt to differentiate the direct effects of cocaine from the indirect sympathomimetic effects on the myocardium, primary cultures of neonatal rat cardiomyocytes were established under serum-free conditions and exposed to cocaine and/or norepinephrine. After 36-48 h in culture, spontaneously contracting cells were treated with cocaine (10-1,000 micrograms/ml) and contractile rate (beats/min) quantitated, after which the cells were processed for ultrastructural examination. The contractile rate was reduced at all dosages with nearly 80% reduction at the highest concentration studied. Recovery of beating rate was observed 24 h after removal of cocaine. Pronounced cytoplasmic vacuolation of the cells occurred at concentrations > or = 100 micrograms/ml. Ultrastructural examination revealed extensive myofibrillar disruption, membrane damage, and a near complete loss of organized sarcomeres. Nuclear morphology remained unaffected. Within 24 h after removal of cocaine from the medium, myocytes recovered their characteristic cytoplasmic architecture, indicative of sarcomere reassembly. The results observed in response to cocaine were distinctly different from the response to norepinephrine. In these myocytes, the contractile rate was enhanced twofold and morphological damage was not observed. These findings suggest that cocaine can directly alter myocardial morphology independent of its sympathomimetic effects.
Vitullo
J C
JC
Division of Anesthesiology, Cleveland Clinic Foundation, Ohio 44195-5154.
Mekhail
N A
NA
Estafanous
F G
FG
Khairallah
P A
PA
Engelmann
G L
GL
D000818:Animals; D002374:Catalase; D002478:Cells, Cultured; D003042:Cocaine / Q000494:pharmacology*; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology; D008297:Male; D008854:Microscopy, Electron; D009206:Myocardium / Q000166:cytology* / Q000648:ultrastructure; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012518:Sarcomeres / Q000187:drug effects / Q000648:ultrastructure; D013482:Superoxide Dismutase; D013997:Time Factors
D016895:Culture Media, Serum-Free; D002374:Catalase; D013482:Superoxide Dismutase; D003042:Cocaine; D009638:Norepinephrine