Exaggerated cardiovascular effects of cocaine in conscious dogs with pacing-induced dilated cardiomyopathy.
BACKGROUND
The aim of this study was to explore the characteristics and mechanisms of the cardiovascular effects of cocaine in dilated cardiomyopathy.


RESULTS
We studied the cardiovascular responses to acute intravenous cocaine (1 mg/kg) in 8 conscious, chronically instrumented dogs before and after the development of dilated cardiomyopathy induced by rapid ventricular pacing. To help elucidate the role of altered baroreflex function in mediating the cardiovascular effects of cocaine, we also studied responses in 3 conscious, chronically instrumented dogs that had undergone surgical sinoaortic baroreceptor denervation. Cocaine produced greater increases in heart rate (+57 +/- 8% from 112 +/- 5 beats/min versus +28 +/- 3% from 100 +/- 4 beats/min; P <.01), first derivative of left ventricular pressure (+30 +/- 5% from 1,714 +/- 147 mm Hg/sec versus +15 +/- 3% from 3,032 +/- 199 mm Hg/sec; P <.01), coronary vascular resistance (+28 +/- 5% from 2.3 +/- 0.3 mm Hg/mL/min versus +11 +/- 5% from 2.2 +/- 0.3 mm Hg/mL/min; P <.05) and plasma norepinephrine concentration (+130 +/- 31% from 462 +/- 102 pg/mL versus +86 +/- 32% from 286 +/- 77 pg/mL; P <.05) in dogs with dilated cardiomyopathy as compared to controls. In addition, responses were much more rapid in onset following the development of dilated cardiomyopathy. Chronotropic and inotropic responses to cocaine were similarly rapid and exaggerated in dogs after baroreceptor denervation.


CONCLUSIONS
Cocaine produces rapid and exaggerated chronotropic, inotropic, and coronary vasoconstrictor responses in conscious dogs with pacing-induced dilated cardiomyopathy. Alterations in arterial baroreflex function may play a role in these observations, which in turn may underlie the clinically observed association between cocaine and heart failure.
Mathier
Michael A
MA
Cardiovascular Institute of the University of Pittsburgh Health System, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Shen
You-Tang
YT
Shannon
Richard P
RP
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D017704:Baroreflex / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D002304:Cardiac Pacing, Artificial / Q000009:adverse effects*; D002311:Cardiomyopathy, Dilated / Q000097:blood / Q000209:etiology* / Q000503:physiopathology*; D002319:Cardiovascular System / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D003714:Denervation; D004195:Disease Models, Animal; D004280:Dobutamine / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007275:Injections, Intravenous; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008955:Models, Cardiovascular; D005996:Nitroglycerin / Q000494:pharmacology; D009638:Norepinephrine / Q000097:blood; D010656:Phenylephrine / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects / Q000293:injuries / Q000601:surgery; D012849:Sinoatrial Node / Q000187:drug effects / Q000293:injuries / Q000601:surgery; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D015415:Biomarkers; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D004280:Dobutamine; D005996:Nitroglycerin; D003042:Cocaine; D007545:Isoproterenol; D009638:Norepinephrine