Mannitol but not dantrolene prevents myocardial dysfunction following intra-cranial hypertension in rats

Cardiac complications stemming from intra-cranial hypertension may result from impaired intra-cellular Ca²⁺ homeostasis. The aim of this study was to examine the effects of dantrolene, a blocker of sarcoplasmic reticulum (SR) Ca²⁺ release, on myocardial dysfunction associated with intra-cranial hypertension in rats. Dantrolene (10 mg) with and without 15% mannitol was administered to halothane-anesthetized rats prior to induction of intra-cranial hypertension by subdural balloon inflation. Its effects were compared to 3% and 15% mannitol and 5% Pentaspan^®. Dantrolene with mannitol or 15% mannitol alone prevented the transient intra-cranial hypertension-induced hyperdynamic response and ensuing circulatory collapse that was found in animals pre-treated with 3% mannitol solution or pentaspan. Moreover, hemodynamic function was preserved irrespective of TnI cleavage. However, only animals treated with high dose 15% mannitol exhibited lower lipid peroxidation content in the heart. In contrast, pre-treatment with dantrolene alone did not prevent the cardiac complications associated with intra-cranial hypertension. In conclusion, 15% mannitol attenuated the cardiopulmonary complications associated with intra-cranial hypertension. Dantrolene without mannitol was without effect. Since mannitol exhibits free radical scavenging properties, protection could be the result of a decrease in oxidative stress after intra-cranial hypertension.