Intensive Care Medicine

, Volume 22, Issue 11, pp 1214–1223 | Cite as

Thrombolysis using plasminogen activator and heparin reduces cerebral no-reflow after resuscitation from cardiac arrest: An experimental study in the cat

  • M. Fischer
  • B. W. Böttiger
  • K. -A. Hossmann
  • S. Popov-Cenic



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 noreflow phenomenon.


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 2mEq/kg per 30 min, and electrical defibrillation shocks.


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 1mg/kg per 30 min.

Measurements and 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 noreflow — 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 homogeneous 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 homogeneous reperfusion at the microcirculatory level.


The present data demonstrate that thrombolytic therapy improves microcirculatory reperfusion of the cat brain when administered during reperfusion after cardiac arrest.

Key words

Brain resuscitation Cardiac arrest Cerebral ischemia Microcirculation Thrombolytic therapy 


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Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • M. Fischer
    • 1
  • B. W. Böttiger
    • 1
  • K. -A. Hossmann
    • 1
  • S. Popov-Cenic
    • 2
  1. 1.Department of Experimental NeurologyMax-Planck-Institute for Neurological ResearchKölnGermany
  2. 2.Department of Experimental Hematology and Transfusion MedicineUniversity of BonnGermany
  3. 3.Department of Anesthesiology and Intensive Care MedicineBonnGermany
  4. 4.Department of AnesthesiologyUniversity of HeidelbergGermany

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