Aprotinin improves cerebral protection: Evidence from a survival porcine model

Aprotinin is a serine protease inhibitor used during cardiac surgery to reduce blood loss and preserve platelet function. It has also been shown to reduce leukocyte activation during and after cardiopulmonary bypass. The goal of the study was to test the hypothesis that aprotinin could reduce cerebr...

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Published in:The Journal of thoracic and cardiovascular surgery 2006-10, Vol.132 (4), p.948-953
Main Authors: Anttila, Vesa, Hagino, Ikuo, Iwata, Yusuke, Mettler, Bret A., Lidov, Hart G.W., Zurakowski, David, Jonas, Richard A.
Format: Article
Language:English
Subjects:
Animals
Aprotinin - therapeutic use
Biological and medical sciences
Brain Diseases - etiology
Brain Diseases - mortality
Brain Diseases - prevention & control
Cardiopulmonary Bypass - adverse effects
Circulatory Arrest, Deep Hypothermia Induced - adverse effects
Medical sciences
Serine Proteinase Inhibitors - therapeutic use
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
Surgery of the heart
Survival Rate
Swine
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Summary:Aprotinin is a serine protease inhibitor used during cardiac surgery to reduce blood loss and preserve platelet function. It has also been shown to reduce leukocyte activation during and after cardiopulmonary bypass. The goal of the study was to test the hypothesis that aprotinin could reduce cerebral injury after low-flow cardiopulmonary bypass and deep hypothermic circulatory arrest. Sixteen piglets (mean weight, 13.6 ± 1.3 kg) were randomly assigned to receive aprotinin or placebo (8 animals per group) before a 120-minute period of deep hypothermic circulatory arrest (15°C) or 25 mL · kg −1 · min −1 low-flow cardiopulmonary bypass (25°C or 34°C). Piglets had a cranial window placed over the parietal cerebral cortex for direct examination of the microcirculation by means of intravital microscopy. Rhodamine-stained leukocytes were observed in postcapillary venules, with analysis for adhesion and rolling. Plasma was labeled with fluorescein isothiocyanate–dextran for assessment of functional capillary density. Neurologic and histologic scores were used as the primary outcome measures. During rewarming, the mean number of both rolling and adherent leukocytes was significantly lower after aprotinin administration ( P < .05). At 5 and 15 minutes of rewarming, functional capillary density recovered faster with aprotinin treatment ( P < .05). Functional outcome (neurologic deficit score) on postoperative day 1 was significantly improved in aprotinin-treated piglets ( P < .05). Aprotinin reduces inflammation and improves neurologic outcome after a prolonged period of deep hypothermic circulatory arrest or low-flow cardiopulmonary bypass.
ISSN:0022-5223
1097-685X
DOI:10.1016/j.jtcvs.2006.06.017