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Cerebral ischemia and reperfusion: prevention of brain mitochondrial injury by lidoflazine.

Abstract
Mitochondrial degradation is implicated in the irreversible cell damage that can occur during cerebral ischemia and reperfusion. In this study, the effects of 10 min of ventricular fibrillation and 100 min of spontaneous circulation on brain mitochondrial function was studied in dogs in the absence and presence of pretreatment with the Ca2+ antagonist lidoflazine. Twenty-three beagles were separated into four experimental groups: (i) nonischemic controls (ii) those undergoing 10-min ventricular fibrillation, (iii) those undergoing 10-min ventricular fibrillation pretreated with 1 mg/kg lidoflazine i.v., and (iv) those undergoing 10-min ventricular fibrillation followed by spontaneous circulation for 100 min. Brain mitochondria were isolated and tested for their ability to respire and accumulate calcium in a physiological test medium. There was a 35% decrease in the rate of phosphorylating respiration (ATP production) following 10 min of complete cerebral ischemia. Those animals pretreated with lidoflazine showed significantly less decline in phosphorylating respiration (16%) when compared with nontreated dogs. Resting and uncoupled respiration also declined following 10 min of fibrillatory arrest. One hundred minutes of spontaneous circulation following 10 min of ventricular fibrillation and 3 min of open-chest cardiac massage provided complete recovery of normal mitochondrial respiration. Energy-dependent Ca2+ accumulation by isolated brain mitochondria was unimpaired by 10 min of complete cerebral ischemia. However, by 100 min after resuscitation, there was a small, but significant rise in the capacity for mitochondrial Ca2+ sequestration when compared to either control or fibrillated groups.(ABSTRACT TRUNCATED AT 250 WORDS)
AuthorsR E Rosenthal, F Hamud, G Fiskum, P J Varghese, S Sharpe
JournalJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (J Cereb Blood Flow Metab) Vol. 7 Issue 6 Pg. 752-8 (Dec 1987) ISSN: 0271-678X [Print] United States
PMID3693430 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Piperazines
  • Adenosine Triphosphate
  • Lidoflazine
  • Calcium
Topics
  • Adenosine Triphosphate (biosynthesis)
  • Animals
  • Brain (drug effects, ultrastructure)
  • Calcium (antagonists & inhibitors, metabolism)
  • Cerebrovascular Circulation
  • Dogs
  • Ischemic Attack, Transient (etiology, metabolism)
  • Lidoflazine (pharmacology, therapeutic use)
  • Mitochondria (drug effects, metabolism)
  • Oxygen Consumption (drug effects)
  • Piperazines (pharmacology)
  • Ventricular Fibrillation (complications)

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