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Increased Lung Water and Ascites after Massive Cocaine Overdosage in Mice and Improved Survival Related to Beta-Adrenergic Blockage

Eugene D. Robin, MD; Ronald J. Wong, BS; and Kay A. Ptashne, PhD
[+] Article, Author, and Disclosure Information

Grant Support: Partial support by a grant from the Samuel and Leah Osher Medical Education Fund.

Requests for Reprints: Eugene D. Robin, MD, United Indian Health Services, P.O. Box Drawer 0, Trinidad, CA 95570.

Current Author Addresses: Dr. Robin: United Indian Health Services, P. O. Box Drawer 0, Trinidad, CA 95570.

Dr. Ptashne and Mr. Wong: Department of Medicine, Anatomy-HRP Building, Stanford University, Stanford, CA 94305-5070.

© 1989 American College of PhysiciansAmerican College of Physicians

Ann Intern Med. 1989;110(3):202-207. doi:10.7326/0003-4819-110-3-202
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Study 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.

Design: 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.

Interventions: 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 µg per mouse) before cocaine.

Measurements and Main Results: Intravenous cocaine hydrochloride resulted in an increase in lung water (saline controls, 4. 17 it 1.3 [standard deviation] mg water per mouse; cocaine hydrochloride, 5.94 + 0.9 mg water per g mouse; P < 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 µg 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 < 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.


ascites ; cocaine ; lung ; mice





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