Issn Print: 0265-0215

Publication Date: 2010/06/12


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Carbon monoxide inhalation prevents acute kidney injury after cardiopulmonary bypass in pigs: 4AP4–8

U. Goebel; M. Siepe; C. Schlensak; T. Loop

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Background and Goal of Study: Cardiopulmonary bypass (CPB) may be associated with acute kidney injury (AKI).[1] Carbon monoxide (CO) exerts organprotective effects via an induction of the heat shock protein (HSP) expression.[2,3] We hypothesized that preoperatively inhaled CO induces renal HSP expression during CPB and prevents AKI in pigs.
Materials and Methods: Pigs were randomised either into SHAM group [n=3], CPB [n=7], CPB with preoperative inhalation of 250 ppm CO [CO+CPB; n=7], Q+CO+CPB (Q=Quercetin, an inhibitor of the heat shock response [n=7]) or SnPP-IX+CO+CPB (SnPP-IX=tinprotoporphrine, an inhibitor of the the hemeoxygenase type 1 [n=7]). CPB was established for 2 hours, followed by 2 hours observation time post CPB. Kidney tissue was harvested at the end of the experiment. The parameters of kidney injury and protein expression of TNF-α, Il-6, HSP-70, and HSP-32 in kidney tissue were analysed, as well as serum parameters of AKI. Apoptosis was determined using the caspase-3-activity assay. Statistial significance was assumed at a p-value <0.05.
Results and Discussion: Haemodynamic parameters were largely unaffected by CPB or carbon monoxide inhalation in all groups. Compared to CPB, parameters of AKI revealed lower levels of cystatin C (CPB vs. CO+CPB: 64±14 vs. 28±9 ng/ml, P <0.001) and neutrophil gelatinase-associated lipocalin (CPB vs CO+CPB: 391±65 vs. 183±56 ng/ml, P < 0.001) in CO treated animals. Renal expression of TNF-α (450±73 vs. 179±110 pg/ml, P < 0.001) and IL-6 (483±102 vs. 125±67 pg/ml, P < 0.001) were lower after CO inhalation. HSP-70 and HSP-32 expression (196±64 vs. 554±149 ng/ml, P < 0.001) were induced after CO inhalation, while caspase-3 activity (550±66 vs. 259±52 RFU, P < 0.001) was inhibited. Q and SnPP-IX partially inhibited the CO mediated effects.
Conclusion(s): As Q and SnPP-IX reversed carbon monoxide-mediated effects, we conclude that protective effects of preconditioning by inhaled CO during CPB are mediated by an activation of the heat shock response.
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