Exacerbation of systemic inflammation and increased cerebral infarct volume with cardiopulmonary bypass after focal cerebral ischemia in the rat.
OBJECTIVE
Stroke remains a significant contributor to morbidity and mortality after cardiac surgery. Cardiopulmonary bypass is known to induce a significant inflammatory response, which could adversely influence outcomes. We hypothesized that cardiopulmonary bypass, through an enhanced systemic inflammatory response, might affect outcomes after focal cerebral ischemia.


METHODS
Wistar rats (275-300 g) were anesthetized, surgically prepared for cardiopulmonary bypass and right middle cerebral artery occlusion, and randomly allocated to 2 groups: focal cerebral ischemia alone (n = 9) and focal cerebral ischemia combined with normothermic cardiopulmonary bypass (n = 8). Serum cytokines (tumor necrosis factor alpha and interleukins 1beta, 6, and 10) were measured at baseline, at end of bypass, and at 2, 6, and 24 hours after bypass. On postoperative day 3, animals underwent neurologic testing, after which the brains were prepared for assessment of cerebral infarct volume. Data were compared between groups by Mann-Whitney U test.


RESULTS
Compared with the ischemia-alone group, the ischemia plus bypass group had significantly higher levels of circulating tumor necrosis factor alpha and interleukins 1beta and 10 at the end of bypass and 2 hours after bypass. In addition, the ischemia plus bypass animals had larger total cerebral infarct volumes (286 +/- 125 mm(3)) than did those with ischemia alone (144 +/- 85 mm(3), P = .0124).


CONCLUSIONS
Cardiopulmonary bypass increased cerebral infarct size after focal cerebral ischemia in rats. This worsening of outcome may in part be related to an augmented inflammatory response that accompanies cardiopulmonary bypass.
Division of Cardiothoracic Anesthesiology and Critical Care Medicine, Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA.
H Mayumi
HM
Homi
Wilbert L
WL
Jones
Fellery
F
de Lange
G Burkhard
GB
Mackensen
Hilary P
HP
Grocott
D000818:Animals; D001522:Behavior, Animal; D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000150:complications* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery / Q000209:etiology* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D018836:Inflammation Mediators / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D009043:Motor Activity; D051381:Rats; D017208:Rats, Wistar; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology* / Q000276:immunology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015854:Up-Regulation
D015415:Biomarkers; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10