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 Ca(2+) homeostasis. The aim of this study was to examine the effects of dantrolene, a blocker of sarcoplasmic reticulum (SR) Ca(2+) 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.
Hall
S R R
SR
Department of Anesthesiology, Queen's University, Kingston, Ontario, Canada.
Wang
L
L
Milne
B
B
Hong
M
M
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D009202:Cardiomyopathies / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D002395:Catecholamines / Q000097:blood; D003620:Dantrolene / Q000494:pharmacology*; D004234:Diuretics, Osmotic / Q000494:pharmacology*; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D019586:Intracranial Hypertension / Q000150:complications* / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008353:Mannitol / Q000494:pharmacology*; D009125:Muscle Relaxants, Central / Q000494:pharmacology*; D011654:Pulmonary Edema / Q000209:etiology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D014019:Tissue Donors; D016277:Ventricular Function, Left / Q000187:drug effects
D002395:Catecholamines; D004234:Diuretics, Osmotic; D009125:Muscle Relaxants, Central; D008353:Mannitol; D008315:Malondialdehyde; D003620:Dantrolene; D002118:Calcium