Failure of flunarizine to improve cerebral blood flow or neurologic recovery in a canine model of complete cerebral ischemia.
Ten minutes of cerebral ischemia was produced in 12 dogs by temporary ligation of the venae cavae and aorta. After reperfusion the dogs received the calcium entry blocker, flunarizine, 6 micrograms/kg infused over a ten minute period. Cerebral blood flow (CBF) and metabolism (CMRO2) were measured pre-ischemia and for 2 h post-ischemia in 6 dogs. At the end of the study brain biopsies were analyzed for cerebral metabolites. Neurologic recovery was evaluated for up to 48 h post-ischemia in an additional 6 dogs. The results of each study were compared to those previously obtained in untreated animals. The cerebral blood flows (when expressed as a percent of the pre-ischemic control value) of the flunarizine-treated and untreated groups were similar throughout the post-ischemic period. Following an initial hyperemia, the CBF fell to significantly less than the pre-ischemic control values, and remained approximately 26% of control during the final 90 min in both groups. The CMRO2 was also the same for both groups. Cerebral metabolites were similar although abnormal in both groups. Flunarizine produced pulmonary edema in 5 of 6 dogs studied for neurologic recovery. Four of these dogs died within 12 h and another dog demonstrated severe neurologic damage. None of the untreated dogs developed pulmonary edema, but 6 of 7 dogs evidenced severe neurologic damage or were dead at 48 h. Thus, flunarizine failed to improve either cerebral blood flow or neurologic outcome when given after complete cerebral ischemia in the dog. A cardiodepressive effect of flunarizine might have contributed to the poor neurologic outcome.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D002936:Cinnarizine / Q000031:analogs & derivatives / Q000627:therapeutic use*; D004285:Dogs; D004734:Energy Metabolism / Q000187:drug effects; D005444:Flunarizine; D009539:Nicotinic Acids / Q000627:therapeutic use; D009553:Nimodipine; D010101:Oxygen Consumption / Q000187:drug effects; D010879:Piperazines / Q000627:therapeutic use*
D002121:Calcium Channel Blockers; D009539:Nicotinic Acids; D010879:Piperazines; D002936:Cinnarizine; D009553:Nimodipine; D005444:Flunarizine