Chronic Exposure to Cocaine Binging Predisposes to an Accelerated Course of Dilated Cardiomyopathy in Conscious Dogs following Rapid Ventricular Pacing

摘要

Despite extensive study,the extent to which cocaine use predisposes to cardiac injury remains unknown.We hypothesized that chronic cocaine binging would increase susceptibility to a subsequent cardiac insult,even in the absence of demonstrable effects on baseline hemodynamics.We studied progression of dilated cardiomyopathy (DCM) induced by rapid ventricular pacing (240 beats per minute) in five conscious,chronically instrumented dogs,after exposure to repetitive cocaine binging (COC) in the form of four consecutive 1 mg/kg i.v.boluses daily for 8 days,to simulate human cocaine abuse.We compared the results with nine control dogs (CON) undergoing the exact pacing protocol,without prior cocaine exposure.Baseline hemodynamics were not significantly altered by chronic cocaine exposure.Following 2 weeks of pacing,COC dogs exhibited accelerated progression to DCM,depressed plasma nitric oxide levels (CON,17 +- 2 muM;COC,10 +- 2 muM,p < 0.05),and a significantly greater increase in plasma epinephrine (CON,33 +- 6 pg/ml;COC,104 +- 24 pg/ml).After only 2 weeks of pacing,COC dogs demonstrated progressive DCM of a magnitude comparable with end-stage pacing-induced DCM.Chronic cocaine binging increases susceptibility to a subsequent myocardial insult and accelerates progression of DCM in conscious dogs following rapid pacing.These data suggest that although chronic cocaine use alone may not affect myocardial function,it predisposes to greater susceptibility to a superimposed insult.