The effect of chronic cocaine administration on hemodynamic stability and neurohumoral mediators during isoflurane anesthesia and shock in rats.
BACKGROUND
The aim of this investigation was to determine whether chronic cocaine administration altered endogenous vasoconstrictor secretion in response to hypotension from isoflurane anesthesia and blood loss in rats.


METHODS
Rats received continuous intravenous infusions of saline (n=11), or cocaine 6 mg kg(-1) d(-1) (n=13) or 18 mg kg(-1) d(-1) (n=12) for 13 days. On day 14, rats were anesthetized with intraperitoneal ketamine and xylazine and a femoral artery catheter and a tracheotomy performed to allow lung ventilation (PaCO2, 30-40 mmHg). After baseline parameters were noted, isoflurane was introduced to end-tidal concentrations of 0.7% for 10 min (1/2 MAC), 1.4% for 10 min (MAC) and again 0.7% for 10 min (1/2 MAC-2) when 5 ml of blood was withdrawn (SHOCK). Blood samples were drawn to assess arterial blood gas indices at various time points as well as plasma epinephrine, angiotensin II and vasopressin at MAC, 1/2 MAC-2 and SHOCK.


RESULTS
Rats administered cocaine had higher oxygen extraction, required higher minute ventilation and had lower PaO2 values than rats administered saline despite similar body temperatures and hematocrits. Isoflurane administration resulted in significant dose dependent but similar blood pressure decreases in all study groups. Plasma epinephrine, angiotensin II and vasopressin concentrations were not different in saline or cocaine treated animals at any time point.


CONCLUSIONS
These data suggest that chronic cocaine treatment in rats does not impair endogenous vasoconstrictor secretion nor alter the heart rate and blood pressure response to isoflurane and blood loss.
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Department of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, NY 10032-3784, USA. bm446columbia.edu
Pantuck
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Diaz
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Soo
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D000758:Anesthesia; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood; D003042:Cocaine / Q000494:pharmacology*; D004837:Epinephrine / Q000097:blood; D006439:Hemodynamics / Q000187:drug effects*; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000097:blood; D051381:Rats; D012769:Shock / Q000503:physiopathology*; D014662:Vasoconstrictor Agents / Q000378:metabolism*
D018685:Anesthetics, Inhalation; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D001127:Arginine Vasopressin; D007530:Isoflurane; D003042:Cocaine; D009638:Norepinephrine; D004837:Epinephrine