Amelioration of brain damage by lidoflazine after prolonged ventricular fibrillation cardiac arrest in dogs.
Calcium entry blockers can ameliorate postischemic cerebral hypoperfusion, protect the myocardium against ischemia, and may protect against early postischemic neurologic deficit. This study documents that a calcium entry blocker, given after cardiac arrest, can ameliorate late postischemic neurologic deficit (ND). Thirty-four dogs received 10 min of ventricular fibrillation, restoration of spontaneous circulation by external cardiopulmonary resuscitation, and standard postarrest intensive care. Eleven of these dogs were given lidoflazine, 1 mg/kg body weight, within 10 min postarrest and again at 8 h and 16 h. Pupillary light reflexes, EEG activity, arterial-cerebrovenous oxygen gradients (O2 demand/supply ratios) and intracranial pressure were the same in both groups. After weaning from controlled ventilation at 24 h, ND scores improved consistently through the 96-h observation period in the lidoflazine-treated dogs. In the control group, ND scores were significantly higher than in the lidoflazine-treated dogs. In the lidoflazine-treated group, 5/11 dogs achieved normal overall performance and none remained comatose, whereas all control dogs had some deficit and 4/11 remained comatose. Delayed neurologic deterioration occurred in 6/11 control and 0/11 lidoflazine-treated dogs. Total mean cerebral histopathologic damage (HD) scores at 96 h were not significantly different between the two groups; however, individual HD scores and maximum cerebro-spinal fluid (brain-specific) creatine-phosphokinase activity--which increases after brain insults--correlated well with 96-h ND scores. In the lidoflazine group, life-threatening dysrhythmias were less frequent and the norepinephrine requirement for blood pressure maintenance was the same as in the control group. Cardiac output remained at prearrest levels in the lidoflazine-treated dogs, but decreased in the control group, particularly during the first 4 h postarrest.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000209:etiology; D002302:Cardiac Output / Q000187:drug effects; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D004569:Electroencephalography; D006324:Heart Arrest, Induced; D006439:Hemodynamics / Q000187:drug effects*; D008013:Lidoflazine / Q000627:therapeutic use*; D009638:Norepinephrine / Q000627:therapeutic use; D010879:Piperazines / Q000627:therapeutic use*; D011897:Random Allocation; D012025:Reflex, Pupillary / Q000187:drug effects; D012151:Resuscitation; D014693:Ventricular Fibrillation / Q000150:complications
D010879:Piperazines; D008013:Lidoflazine; D009638:Norepinephrine