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

Abstract

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<O.O5) increased in liver (Li), intestine (I). kidney (K), and lung (Lu), suggesting that FL increased flow in these tissues. Hypo Li, I, Lu, muscle (M), and brain (B) and Rew Li exhibited greater than predicted Eb concentrations suggesting endothelial damage. In Rew tissues, FL increased Eb in Li, Lu, heart (H) and M (35.O plus or minus 8.O vs. 28.3 plus or minus 6.5, 47.9 plus or minus 24.8 vs. 19.5 plus or minus 9.1, 19.0 plus or minus 6.3 vs. 13.4, 4.4 plus or minus 1.8 vs. 3.0 plus or minus 1.2, ug/gm dry wt of tissue, respectively) compared to CRew, with no difference in cooling or rewarming rates suggesting increased perfusion of these tissues. FL-induced increased extravasation was due to increased perfusion of rewarmed tissues thus potentially reducing ischemic damage resulting from hypothermia and rewarming.

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Document Details

Document Type
Technical Report
Publication Date
May 01, 2003
Accession Number
ADA414632

Entities

People

  • Amy M. Bastille
  • Candace B. Matthew
  • Ingrid V. Sils

Organizations

  • United States Army Research Institute of Environmental Medicine

Tags

DTIC Thesaurus Topics

  • Abstracts
  • Anatomy
  • Azo Compounds
  • Biological Sciences
  • Blood Flow
  • Cells
  • Department Of Defense
  • Endothelial Cells
  • Endothelium
  • Hypothermia
  • Information Operations
  • Military Research
  • Perfusion
  • Tissues

Fields of Study

  • Biology

Readers

  • Cardiovascular Physiology
  • Exercise and Sports Science.
  • Materials Science and Engineering.