Blood hibernation: a novel strategy to inhibit systemic inflammation and coagulation induced by cardiopulmonary bypass.
BACKGROUND
Inflammation and coagulation are two intimately cross-linked defense mechanisms of most, if not all organisms to injuries. During cardiopulmonary bypass (CPB), these two processes are activated and interact with each other through several common pathways, which may result in subsequent organ dysfunction. In the present study, we hypothesized that the addition of nitric oxide, prostaglandin E1 (PGE1), and aprotinin to the systemic circulation, hereby referred to as blood hibernation, would attenuate the inflammation and coagulation induced by CPB.


METHODS
Thirty adult mongrel dogs were equally divided into five groups, anesthetized and placed on hypothermic CPB (32 degrees C). Each group received respectively the following treatments: (1) inhalation of 40 ppm nitric oxide; (2) intravenous infusion of 20 ng x kg(-1) x min(-1) of PGE1; (3) 80,000 kallikrein inhibitor units (KIU)/kg of aprotinin; (4) the combination of all three agents (blood hibernation group); and (5) no treatment (control group) during CPB. Activation of leukocyte, platelet, endothelial cell, and formation of thrombin were assessed after CPB.


RESULTS
As compared with the other four groups, leukocyte counts were higher, while plasma elastase, interleukin-8, CD11b mRNA expression, myeloperoxidase activities and lung tissue leukocyte counts were lower in the blood hibernation group (P < 0.05 versus other four groups after CPB). Plasma prothrombin fragment (PTF)1+2, and platelet activation factors were lower, while platelet counts were higher in the blood hibernation group (P < 0.05 versus other four groups at 6 and 12 hours after CPB). Electron microscopy showed endothelial pseudopods protrusion, with cell adherence in all four groups except the blood hibernation group where endothelial cells remained intact.


CONCLUSIONS
Blood hibernation, effected by the addition of nitric oxide, PGE1 and aprotinin to the circulating blood during extra-corporeal circulation, was observed to attenuate the inflammation and coagulation induced by cardiopulmonary bypass, most likely by inhibiting the important common intermediates between the two cross-linked processes.
Zhou
Jing
J
Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Wu
Xiao-Dong
XD
Lin
Ke
K
Lui
Raphael C
RC
An
Qi
Q
Tao
Kai-Yu
KY
Du
Lei
L
Liu
Jin
J
D000527:Alprostadil / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D007611:Aprotinin / Q000494:pharmacology / Q000627:therapeutic use; D001777:Blood Coagulation / Q000187:drug effects; D039481:CD11b Antigen / Q000235:genetics; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D004285:Dogs; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction
D039481:CD11b Antigen; D009569:Nitric Oxide; D007611:Aprotinin; D000527:Alprostadil