EFFECT OF DILTIAZEM ON BRAIN RESUSCITATION IN A RAT CIRCULATORY ARREST MODEL (CALCIUM BLOCKERS, CEREBRAL ISCHEMIA)
Abstract
Intracellular calcium intoxication of brain and vascular smooth muscle cells has been hypothesized to be a major contributor to brain damage following cardiopulmonary arrest and resuscitation. I have measured the effects of diltiazem, a calcium entry blocker, on survival and neurological deficit (ND) following an average of 12 min of experimental cardio-respiratory arrest and resuscitation in rats. There was no statistically significant improvement in survival or ND, but there was significant amelioration of the incidence of motor seizures. There was a definite accumulation of calcium in the brain and heart following 12-15 min of ischemia and 60 min of reperfusion. Diltiazem significantly decreased brain calcium content after 12 min of ischemia but had no effect after 15 min. Brain blood flow was severely diminished to less than 20% of non-ischemic control flow following 12 min ischemia and 60 min reperfusion. Diltiazem did not improve brain blood flow in this setting. Thus, calcium does appear to be involved in post-ischemic encephalopathy perhaps directly on neurons and/or indirectly via a hypoperfusion effect. Diltiazem provided only a modest overall benefit, indicating it may not be the drug of choice in cerebral resuscitation of humans.
Degree
Ph.D.
Subject Area
Surgery
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