Reduced pulmonary inflammatory response during cardiopulmonary bypass: effects of combined pulmonary perfusion and carbon monoxide inhalation.
OBJECTIVE
Pulmonary inflammation induced by cardiopulmonary bypass (CPB) is one of the main causes for lung injury after cardiac surgery. Pulmonary perfusions as well as carbon monoxide (CO) inhalation are known to reduce the inflammatory reaction of the lung. We hypothesized that a combination of pulmonary perfusion and carbon monoxide inhalation leads to an even stronger reduction of the lung inflammation.


METHODS
Pigs (n=7 per experimental group) were randomized to sham operation (SHAM), conventional CPB (CPB), inhalation of CO (CPB+CO, 250 ppm), pulmonary perfusion (CPB+PP) or pulmonary perfusion plus inhalation of CO (CPB+PP+CO). Various cytokine levels (TNF-alpha, IL-1, IL-6, and IL-10) and caspase-3 activity were measured using enzyme-linked immunosorbent assay (ELISA). Transcription factor activity was analyzed via electrophoretic mobility shift assay (EMSA). Blood gases and hemodynamics were measured continuously. A p value <0.05 assessed by Holm-Sidak method was considered statistically significant.


RESULTS
Hemodynamic parameters and blood gas analysis showed no significant differences between the groups. While IL-1 protein expression was comparable between the groups, TNF-alpha (478+/-58 vs 869+/-95 pg/ml; p<0.001) and IL-6 protein levels in the lung (256+/-82 vs 936+/-76 pg/ml; p<0.001) showed a significant inhibition in the CPB+PP+CO group at 120 min post-bypass time compared to the CPB group. The cytokine levels were comparable to the CPB+PP and CPB+CO group. IL-10 protein expression (325+/-47 vs 65+/-27 pg/ml; p<0.05) was significantly higher in the CO-treated compared to CPB+PP and CPB-treated animals at 120 min post-bypass. Activation of the transcription factors NF-kappaB and AP-1 showed a CO-mediated induction compared to the CPB or CPB+PP group. Caspase-3 activity revealed a CO-dependent, significant inhibition in CO and CPB+PP+CO-treated animals compared to CPB animals (p<0.05).


CONCLUSIONS
The combination of pulmonary perfusion and inhalative carbon monoxide inhibits CPB-mediated pulmonary inflammation as well as pulmonary apoptosis stronger than pulmonary perfusion or carbon monoxide alone.
Goebel
Ulrich
U
Department of Anesthesiology and Critical Care Medicine, University Medical Center Freiburg, Freiburg, Germany.
Siepe
Matthias
M
Mecklenburg
Anne
A
Doenst
Torsten
T
Beyersdorf
Friedhelm
F
Loop
Torsten
T
Schlensak
Christian
C
D000280:Administration, Inhalation; D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000032:analysis; D002248:Carbon Monoxide / Q000008:administration & dosage*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D053148:Caspase 3 / Q000032:analysis; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D016753:Interleukin-10 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008168:Lung / Q000276:immunology / Q000473:pathology; D023421:Models, Animal; D016328:NF-kappa B / Q000032:analysis; D010477:Perfusion; D011014:Pneumonia / Q000209:etiology* / Q000473:pathology / Q000628:therapy*; D011485:Protein Binding; D011897:Random Allocation; D013552:Swine; D018808:Transcription Factor AP-1 / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D015415:Biomarkers; D015850:Interleukin-6; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D002248:Carbon Monoxide; D053148:Caspase 3