PROTECTIVE EFFECT OF CLORICROMENE, A COUMARINE DERIVATIVE, IN HYPOVOLEMIC HEMORRHAGIC-SHOCK IN THE RAT

Hypovolemic hemorrhagic shock was induced in male anesthetized rats by intermittently withdrawing blood from an iliac catheter over a period of 20 min until mean arterial pressure (MAP) fell to 30 mm Hg. Survival rate, MAP, plasma myocardial depressant factor (MDF) activity and plasma levels of both TxB2 and 6-keto PGF-1-alpha were then evaluated. Cloricromene (0.5, 1, and 2 mg/kg) or an equal volume of vehicle (0.9% NaCl solution) were injected intravenously 5 min after the end of the bleeding. Hemorrhagic shocked rats showed enhanced plasma levels of MDF, TxB2 and 6-keto PGF1-alpha. All vehicle-treated rats died within 25 min. Cloricromene (1 and 2 mg/kg) given curatively significantly increased survival rate and blunted the rise in plasma MDF and TxB2. Moreover, cloricromene reversed the severe hypotension and the ST-segment elevation occurring during hemorrhagic shock. The data suggest that cloricromene exerts beneficial effects in experimental hypovolemic shock, probably reversing myocardial failure.