Role of blood doping in the coronary vasoconstrictor response to cocaine.
BACKGROUND
The mechanism by which cocaine induces myocardial ischemia remains controversial. Most prior studies have postulated that cocaine-induced coronary vasoconstriction limits myocardial oxygen delivery during times of increased myocardial oxygen demand.


RESULTS
To determine the contribution of altered myocardial metabolic demands to the coronary vasoconstrictor effects of intravenous cocaine (COC 1 mg/kg), we studied 13 conscious, chronically instrumented dogs in the intact state and with heart rate held constant with atrial pacing in the presence and absence of beta-adrenergic blockade with propranolol (2 mg/kg) to limit the inotropic and chronotropic effects of cocaine on associated increases in myocardial oxygen consumption. In the intact state, COC caused a prompt increase in coronary blood flow (+30 +/- 3%, P < .01) that returned rapidly to baseline within 10 minutes, whereas coronary vascular resistance did not increase significantly (+17 +/- 6%, P < .05) until 15 minutes after COC. Notably, myocardial oxygen consumption increased (+57 +/- 4%, P < .01) to a greater extent than oxygen delivery (+42 +/- 3%, P < .01) during the first 2.5 minutes, requiring increased oxygen extraction (from 75 +/- 1% to 80 +/- 1%, P < .01), although only transiently. Thereafter, enhanced oxygen delivery matched the required oxygen consumption without further need to extract additional oxygen. Surprisingly, the enhanced oxygen delivery associated with COC in conscious dogs did not depend on persistent increases in coronary blood flow but rather was due to enhanced arterial oxygen content (+22 +/- 4%, P < .01) as a result of a significant "blood doping" effect with associated increases in circulating hemoglobin from 12.1 +/- 0.4 to 14.2 +/- 0.6 g/dL (P < .01), which persisted for 60 minutes.


CONCLUSIONS
The myocardial oxygen requirements associated with COC administration have a significant impact on both the magnitude and the mechanism of the coronary vasoconstrictor effects of COC in conscious dogs. Furthermore, the enhanced myocardial oxygen delivery associated with COC administration is not dependent solely on coronary blood flow responses but is due to a significant "blood doping" effect associated with COC.
Shannon
R P
RP
Department of Medicine, Harvard Medical School, Brigham & Women's Hospital, Boston, MA, USA.
Manders
W T
WT
Shen
Y T
YT
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects*
D003042:Cocaine