Complement factor 1 inhibitor improves cardiopulmonary function in neonatal cardiopulmonary bypass.
BACKGROUND
The inflammatory insult associated with cardiopulmonary bypass (CPB) continues to result in morbidity for neonates undergoing complex repair of congenital cardiac defects. Complement and contact activation are important mediating processes involved in this injury. Complement factor 1 esterase inhibitor (C1-inh), a natural inhibitor of complement, kallikrein, and coagulation pathways, may be decreased in children undergoing cardiac operations requiring CPB. We tested the hypothesis that C1-inh supplementation will ameliorate the cardiac and pulmonary dysfunction in a model of neonatal CPB.


METHODS
Fifty-two neonatal pigs were randomly assigned to receive 0 IU (n = 22), 500 IU (n = 15), 1,000 IU (n = 8), or 1,500 IU (n = 7) of C1-inh. Doses were delivered 5 minutes before starting 90 minutes of normothermic CPB. Pulmonary and cardiovascular measures were taken before and 5, 30, and 60 minutes after CPB.


RESULTS
Five animals did not survive CPB. The C1-inh concentration post-CPB increased monotonically with increasing dose (p < 0.001). Weight gain was significantly less in the 1,500 IU group (0.24 +/- 0.10 kg versus 0.38 +/- 0.09 kg, p = 0.001). Dynamic compliance increased with C1-inh dose from 0 to 500 IU by 23% +/- 4% (p < 0.001), but the increase leveled off at the higher doses. Alveolar-arterial O2 gradient decreased with C1-inh dose (p = 0.009). Time derivative of left ventricular pressure (dP/dt(max)) increased significantly with increasing dose (p = 0.016). At the highest dose of C1-inh, the time constant of isovolumic relaxation was increased (p = 0.018).


CONCLUSIONS
The C1-inh supplementation results in improved pulmonary and systolic cardiac function in a model of neonatal CPB. The negative effect on diastolic function requires further investigation.
Baig
Kamran
K
Department of Surgery, Kings College Hospital, London, England.
Nassar
Rashid
R
Craig
Damian M
DM
Quick
George
G
Jiang
Hai Xiang
HX
Frank
Michael M
MM
Lodge
Andrew J
AJ
Anderson
Page A W
PA
Jaggers
James
J
D000818:Animals; D000831:Animals, Newborn; D002315:Cardiopulmonary Bypass / Q000379:methods / Q000401:mortality*; D050718:Complement C1 Inhibitor Protein / Q000378:metabolism* / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006334:Heart Function Tests; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D008297:Male; D011300:Preoperative Care; D011897:Random Allocation; D012016:Reference Values; D012129:Respiratory Function Tests; D012307:Risk Factors; D012680:Sensitivity and Specificity; D013318:Stroke Volume; D013552:Swine
D050718:Complement C1 Inhibitor Protein