Increased lung water and ascites after massive cocaine overdosage in mice and improved survival related to beta-adrenergic blockage.
OBJECTIVE
To determine the effect of massive cocaine intoxication on lung water and ascites accumulation and the effect of beta- and alpha-adrenergic blockade on survival in massive cocaine intoxication in the mouse.


METHODS
The effect of massive cocaine intoxication on lung water, ascitic fluid accumulation, and survival following LD 100 doses of intravenous cocaine with and without alpha- and beta-adrenergic blockade was determined.


METHODS
Cocaine hydrochloride (0.15 mg/g body weight) was administered intravenously with no other interventions; with propranolol hydrochloride intravenously (0.5 mg per mouse) before and after cocaine; and with phentolamine intravenously (10.5 micrograms per mouse) before cocaine.


RESULTS
Intravenous cocaine hydrochloride resulted in an increase in lung water (saline controls, 4.17 +/- 1.3 [standard deviation] mg water per g mouse; cocaine hydrochloride, 5.94 +/- 0.9 mg water per g mouse; P less than 0.002). Cocaine hydrochloride always resulted in the accumulation of transudative ascitic fluid (saline controls, no measurable ascitic fluid; cocaine administration, 20.2 +/- 12.9 micrograms per mouse; ascitic fluid protein concentration, 23.5 +/- 8.5 g/L). Propranolol hydrochloride administered before or after intravenous cocaine hydrochloride resulted in a striking reduction in mortality (84 of 84 mice without propranolol died [mortality = 100%]; 7 of 39 mice with propranolol died [mortality = 18%]; P less than 0.001).


CONCLUSIONS
Massive cocaine intoxication is associated with increased lung water and transudative ascites. Fluid accumulation is not prevented by either alpha- or beta-adrenergic blockers. Propranolol, administered either before or after cocaine, sharply reduces mortality. The results should be extrapolated to treatment in humans with caution.
Robin
E D
ED
Stanford University School of Medicine, California.
Wong
R J
RJ
Ptashne
K A
KA
D000818:Animals; D001201:Ascites / Q000139:chemically induced / Q000188:drug therapy*; D003042:Cocaine / Q000633:toxicity*; D005110:Extracellular Space / Q000187:drug effects*; D008168:Lung / Q000187:drug effects*; D008297:Male; D051379:Mice; D010646:Phentolamine / Q000627:therapeutic use*; D011433:Propranolol / Q000627:therapeutic use*; D011654:Pulmonary Edema / Q000139:chemically induced / Q000188:drug therapy
D011433:Propranolol; D003042:Cocaine; D010646:Phentolamine