Pulsatile pulmonary perfusion during cardiopulmonary bypass reduces the pulmonary inflammatory response.
BACKGROUND
Pulmonary dysfunction presumably linked to an inflammatory response is frequent after cardiac operations using cardiopulmonary bypass (CPB) and pulmonary hypoperfusion. We previously demonstrated that active perfusion of the lungs during CPB reduces ischemic lung injury. We now hypothesized that avoiding ischemia of the lungs during CPB by active pulmonary perfusion would decrease pulmonary inflammatory response.


METHODS
Pigs were randomized to a control group with CPB for 120 minutes, followed by 120 minutes of postbypass reperfusion, or to the study groups where animals underwent active pulmonary perfusion with pulsatile or nonpulsatile perfusion during CPB (n = 7 in each group). Activation of transcription factor activity (nuclear factor [NF]-kappaB and activating protein [AP]-1) was determined by electrophoretic mobility shift assay. Levels of proinflammatory protein expression (interleukin [IL]-1, IL-6, and tumor necrosis factor [TNF]-alpha) were quantified by enzyme-linked immunoabsorbent assay. Caspase-3 activity was measured using a fluorogenic assay.


RESULTS
The activation of transcription factor AP-1 and NF-kappaB was reduced in the pulsatile pulmonary perfusion group. The caspase-3 activity and the expression of IL-1, IL-6, and TNF-alpha revealed a significant decrease in the pulsatile and nonpulsatile pulmonary perfusion groups. Animals of the pulsatile pulmonary perfusion group showed significantly reduced IL-6 expression and caspase-3 activity compared with the nonpulsatile pulmonary perfusion group.


CONCLUSIONS
Active pulmonary perfusion reduces the inflammatory response and apoptosis in the lungs observed during conventional CPB. This effect is greatest when pulmonary perfusion is performed with pulsatility. The reduction in cytokine expression by pulsatile pulmonary perfusion might be mediated by AP-1 and NF-kappaB.
Siepe
Matthias
M
Department of Cardiovascular Surgery, University Medical Center, Freiburg, Germany.
Goebel
Ulrich
U
Mecklenburg
Anne
A
Doenst
Torsten
T
Benk
Christoph
C
Stein
Philipp
P
Beyersdorf
Friedhelm
F
Loop
Torsten
T
Schlensak
Christian
C
D000818:Animals; D002315:Cardiopulmonary Bypass / Q000009:adverse effects / Q000379:methods*; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006439:Hemodynamics / Q000502:physiology; D007249:Inflammation / Q000517:prevention & control; D018836:Inflammation Mediators / Q000032:analysis*; D007378:Interleukins / Q000032:analysis; D007430:Intraoperative Care / Q000379:methods; D008168:Lung / Q000098:blood supply*; D055370:Lung Injury; D015999:Multivariate Analysis; D011183:Postoperative Complications / Q000517:prevention & control; D011336:Probability; D011659:Pulmonary Gas Exchange; D011673:Pulsatile Flow; D011897:Random Allocation; D012016:Reference Values; D015427:Reperfusion Injury / Q000517:prevention & control*; D012307:Risk Factors; D012680:Sensitivity and Specificity; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D016207:Cytokines; D018836:Inflammation Mediators; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha