Flunarizine Attenuates Hypothermia/Rewarming-Induced Changes in Protein and Water Movement Across the Endothelium of Rats

摘要

Severe hypothermia damages endothelial cell cytoskeleton and significantly reduces tissue perfusion that is only partially restored on rewarming. The calcium channel blocker flunarizine (FL) was administered to examine the mechanisms and possible attenuation of hypothermia-induced changes in extravasation and perfusion. Blood and tissue samples were taken from 6 groups of 12 male rats: CN (control, normothermic). FLN (N rats given 1 mg/kg of FL by gavage), CHypo and FLHypo (cooled to and maintained at a Tc of 25 degrees C for 1 hr following vehicle control or FL) and CRew and FLRew (rewarmed to a Tc of 35 degrees C following Hypo). Recovery of Evans blue (Eb) bound albumin was used as a marker of protein extravasation. Because blood flow to most organs is significantly reduced during hypothermia, values for expected Eb were predicted from previously reported reduced flow and measured N extravasation, for Hypo and Rew tissues. In FLN rats, Eb was scientifically (p