Aprotinin improves functional outcome but not cerebral infarct size in an experimental model of stroke during cardiopulmonary bypass.
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.
Homi
H Mayumi
HM
Department of Anesthesiology, Division of Pediatric Anesthesia, Duke University, Durham, North Carolina, USA.
Sheng
Huaxin
H
Arepally
Gowthami M
GM
Mackensen
G Burkhard
GB
Grocott
Hilary P
HP
D000818:Animals; D000990:Antithrombin III / Q000378:metabolism; D007611:Aprotinin / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D001777:Blood Coagulation; D001786:Blood Glucose / Q000378:metabolism; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D002544:Cerebral Infarction / Q000473:pathology*; D016207:Cytokines / Q000097:blood; D006439:Hemodynamics / Q000187:drug effects; D007610:Kallikreins / Q000037:antagonists & inhibitors; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*; D020521:Stroke / Q000209:etiology / Q000523:psychology / Q000628:therapy*; D013917:Thrombin / Q000378:metabolism; D016896:Treatment Outcome
D001786:Blood Glucose; D016207:Cytokines; D015842:Serine Proteinase Inhibitors; D000990:Antithrombin III; D007611:Aprotinin; D007610:Kallikreins; D013917:Thrombin