THROMBOLYSIS USING PLASMINOGEN-ACTIVATOR AND HEPARIN REDUCES CEREBRALNO-REFLOW AFTER RESUSCITATION FROM CARDIAC-ARREST - AN EXPERIMENTAL-STUDY IN THE CAT

Objective: Successful resuscitation of the brain requires complete mic rocirculatory reperfusion, which, however, may be impaired by activati on of blood coagulation after cardiac arrest. The study addresses the question of whether postischemic thrombolysis is effective in reducing cerebral no-reflow phenomenon. Design: 14 adult normothermic cats wer e submitted to 15-min cardiac arrest, followed by cardiopulmonary resu scitation (CPR) and 30 min of spontaneous recirculation. The CPR proto col included closed-chest cardiac massage, administration of epinephri ne 0.2 mg/kg, bicarbonate 2 mEq/kg per 30 min, and electrical defibril lation shocks. Interventions: During CPR, animals in the treatment gro up (n = 6) received intravenous bolus injections of 100 U/kg heparin a nd 1 mg/kg recombinant tissue type plasminogen activator (rt-PA), foll owed by an infusion of rt-PA 1 mg/kg per 30 min. Measurements and resu lts: Microcirculatory reperfusion of the brain was visualized by label ing the circulating blood with 300 mg/kg of 15% fluorescein isothiocya nate albumin at the end of the recirculation period. Areas of cerebral no-reflow - defined as the absence of microvascular filling - were id entified by fluorescence microscopy at eight standard coronal levels o f forebrain, and expressed as the percentage of total sectional area. One animal in the treatment group was excluded from further analysis b ecause of intracerebral hemorrhage due to brain injury during trepanat ion. Autopsy revealed the absence of intracranial, intrathoracic, or i ntra-abdominal bleeding in all the other animals. In untreated animals (n = 8), no-reflow affected 28 +/- 13% of total forebrain sectional a reas, and only 1 out of 8 animals showed homogenous reperfusion (i.e., no-reflow < 15% of total forebrain sectional areas). Thrombolytic the rapy (n = 5) significantly reduced no-reflow to 7 +/- 5% of total fore brain sectional areas and all treated animals showed homogeneous reper fusion at the microcirculatory level. Conclusions: The present data de monstrate that thrombolytic therapy improves microcirculatory reperfus ion of the cat brain when administered during reperfusion after cardia c arrest.