Aprotinin improves functional outcome but not cerebral infarct size in an experimental model of stroke during cardiopulmonary bypass.

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2010-07

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Abstract

Background

Aprotinin, a nonspecific serine protease inhibitor, has been used to decrease bleeding and reduce the systemic inflammatory response after cardiopulmonary bypass (CPB). Studies have variably linked aprotinin administration with both improved as well as adverse cerebral consequences after cardiac surgery. We designed this study to determine whether an antiinflammatory dose of aprotinin could improve the histologic and functional neurologic outcome in a rat model of focal cerebral ischemia during CPB.

Methods

After surgical preparation, the animals were randomized into 2 groups: an aprotinin group (60,000 kIU/kg IV) and a control group (0.9% NaCl IV). Normothermic CPB was performed for 60 minutes during which time a partial overlapping 60 minutes of right middle cerebral artery occlusion was induced. Cytokines (tumor necrosis factor-alpha, interleukin [IL]-1beta, IL-6, and IL-10) were measured at baseline, the end of CPB, then 2 and 24 hours after CPB. On postoperative day 3, the animals underwent functional neurologic testing and histologic assessment of cerebral infarct volume.

Results

There was a reduction in systemic inflammation in the aprotinin group compared with the control group, demonstrated by lower levels of IL-1beta (P = 0.035) and IL-6 (P = 0.047). The aprotinin group also had a better functional neurologic performance (median [interquartile range]: aprotinin 27 [8] vs control 32 [6]; P = 0.042). However, there was no difference in cerebral infarct volume (aprotinin 306 [27] mm(3) vs control 297 [52] mm(3); P = 0.599).

Conclusions

In this experimental model of stroke occurring during CPB, aprotinin decreased the systemic inflammatory response to CPB. Although there was no difference in the cerebral infarct volume, there was a small improvement in the short-term functional neurologic outcome in the aprotinin group.

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10.1213/ane.0b013e3181e0549f

Publication Info

Homi, H Mayumi, Huaxin Sheng, Gowthami M Arepally, G Burkhard Mackensen and Hilary P Grocott (2010). Aprotinin improves functional outcome but not cerebral infarct size in an experimental model of stroke during cardiopulmonary bypass. Anesthesia and analgesia, 111(1). pp. 38–45. 10.1213/ane.0b013e3181e0549f Retrieved from https://hdl.handle.net/10161/23298.

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Scholars@Duke

Homi

Hercilia Mayumi Homi

Assistant Professor of Anesthesiology
Sheng

Huaxin Sheng

Associate Professor in Anesthesiology

We have successfully developed various rodent models of brain and spinal cord injuries in our lab, such as focal cerebral ischemia, global cerebral ischemia, head trauma, subarachnoid hemorrhage, intracerebral hemorrhage, spinal cord ischemia and compression injury. We also established cardiac arrest and hemorrhagic shock models for studying multiple organ dysfunction.  Our current studies focus on two projects. One is to examine the efficacy of catalytic antioxidant in treating cerebral ischemia and the other is to examine the efficacy of post-conditioning on outcome of subarachnoid hemorrhage induced cognitive dysfunction.

Arepally

Gowthami Morey Arepally

Professor of Medicine

Gowthami M. Arepally, M.D. is a Professor of Medicine in the Division of Hematology at Duke University Medical Center.  Her clinical interests are in immune thrombocytopenias, thrombotic disorders, and complement-mediated diseases.  Dr. Arepally’s long-standing research program investigates the immune pathogenesis of heparin induced thrombocytopenia (HIT).  Current laboratory efforts focus on the role of complement activation in antibody production and thrombosis in HIT, studies of complement inhibitors for immune-complex mediated diseases and diagnostic biomarkers of platelet activation.  


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