Thrombolysis using plasminogen activator and heparin reduces cerebral no-reflow after resuscitation from cardiac arrest: an experimental study in the cat.
OBJECTIVE
Successful resuscitation of the brain requires complete microcirculatory reperfusion, which, however, may be impaired by activation of blood coagulation after cardiac arrest. The study addresses the question of whether postischemic thrombolysis is effective in reducing cerebral no-reflow phenomenon.


METHODS
14 adult normothermic cats were submitted to 15-min cardiac arrest, followed by cardiopulmonary resuscitation (CPR) and 30 min of spontaneous recirculation. The CPR protocol included closed-chest cardiac massage, administration of epinephrine 0.2 mg/kg, bicarbonate 2 mEq/kg per 30 min, and electrical defibrillation shocks.


METHODS
During CPR, animals in the treatment group (n = 6) received intravenous bolus injections of 100 U/kg heparin and 1 mg/kg recombinant tissue type plasminogen activator (rt-PA), followed by an infusion of rt-PA 1 mg/kg per 30 min.


RESULTS
Microcirculatory reperfusion of the brain was visualized by labeling the circulating blood with 300 mg/kg of 15% fluorescein isothiocyanate albumin at the end of the recirculation period. Areas of cerebral no-reflow--defined as the absence of microvascular filling--were identified by fluorescence microscopy at eight standard coronal levels of forebrain, and expressed as the percentage of total sectional area. One animal in the treatment group was excluded from further analysis because of intracerebral hemorrhage due to brain injury during trepanation. Autopsy revealed the absence of intracranial, intrathoracic, or intra-abdominal bleeding in all the other animals. In untreated animals (n = 8), no-reflow affected 28 +/- 13% of total forebrain sectional areas, and only 1 out of 8 animals showed homogenous reperfusion (i.e., no-reflow < 15% of total forebrain sectional areas). Thrombolytic therapy (n = 5) significantly reduced no-reflow to 7 +/- 5% of total forebrain sectional areas and all treated animals showed homogenous reperfusion at the microcirculatory level.


CONCLUSIONS
The present data demonstrate that thrombolytic therapy improves microcirculatory reperfusion of the cat brain when administered during reperfusion after cardiac arrest.
Fischer
M
M
Max-Planck-Institute for Neurological Research, Department of Experimental Neurology, Köln, Germany.
Böttiger
B W
BW
Popov-Cenic
S
S
Hossmann
K A
KA
D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D016887:Cardiopulmonary Resuscitation / Q000379:methods; D002415:Cats; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D004569:Electroencephalography; D006323:Heart Arrest / Q000150:complications / Q000188:drug therapy / Q000628:therapy*; D006439:Hemodynamics; D006493:Heparin / Q000627:therapeutic use*; D008833:Microcirculation / Q000187:drug effects; D010960:Plasminogen Activators / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D015912:Thrombolytic Therapy / Q000379:methods*; D013997:Time Factors
D000925:Anticoagulants; D006493:Heparin; D010960:Plasminogen Activators