title: Amelioration of brain damage by lidoflazine after prolonged ventricular fibrillation cardiac arrest in dogs.
abstract: 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.
mesh_terms: 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
chemical_list: D010879:Piperazines; D008013:Lidoflazine; D009638:Norepinephrine