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Eur J Cardiothorac Surg 2004;25:985-992
© 2004 Elsevier Science NL

On-pump versus off-pump coronary artery bypass grafting: more heat-shock protein 70 is released after on-pump surgery

^a Faculty of Medicine, Institute of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, N-7489 Trondheim, Norway
^b Department of Clinical Chemistry, Ulleval University Hospital, N-0407 Oslo, Norway
^c St Elisabeth Heart Center, Trondheim University Hospital, N-7018 Trondheim, Norway

Received 23 October 2003; received in revised form 23 February 2004; accepted 2 March 2004.

^* Corresponding author. Department of Clinical Chemistry, FUS, 1-K, Ulleval University Hospital, N-0407 Oslo, Norway. Tel.: +47-2301-5034; fax: +47-2211-8479
e-mail: brit.dybdahl{at}ulleval.no

Objectives: The use of cardiopulmonary bypass in coronary artery bypass grafting (CABG) may contribute to the postoperative inflammatory response. The molecular chaperone heat-shock protein (HSP) 70 may be induced by ischemia, and has been detected both in the myocardium and in the circulation after CABG. In vitro, extracellular HSP70 may activate both innate and adaptive immunity. Hypothesizing that use of cardiopulmonary bypass (CPB) leads to more circulating HSP70, we explored the release of it in 10 patients undergoing CABG with the use of CPB, and in 10 patients undergoing off-pump surgery CABG (OPCAB). Methods: Blood samples were taken preoperatively, twice peroperatively, 2 and 6 h postoperatively and the next day. Serum analyses were performed by means of immunoassays. Results: We detected a significant difference in postoperative circulating HSP70 between on-pump and off-pump patients (median peaks of 2849 and 756 pg/ml, respectively, P<0.01, 2 h postoperatively). Interleukin-6 and -8 increased in all patients, without significant differences between the groups. Serum interleukin-10 increased at the end of the operation in 7 of 10 patients operated with cardiopulmonary bypass (median 51.7 pg/ml), but in none of the off-pump patients. Furthermore, in the first group, interleukin-10 correlated with the HSP70 concentration at the end of the operation, r=0.75, P<0.05. Serum markers of myocardial damage were higher in conventional than off-pump patients on day 1 postoperatively: median cardiac Troponin T was 0.358 and 0.126 µg/l, respectively, P<0.01. Correspondingly, median creatine kinase-MB was 23.6 and 7.8 µg/l in on-pump and off-pump patients, respectively, P<0.01. Peak HSP70 correlated with both Troponin T and creatine kinase-MB measured on day 1. Conclusions: Significantly more HSP70 was released into the circulation following conventional than following off-pump CABG. Circulating HSP70 may indicate cellular stress or damage. Furthermore, HSPs are suggested as immunoregulatory agents, and may be important in the host defence postoperatively.

Key Words: Cell-signaling proteins • Coronary artery bypass surgery • Heat-shock proteins • Immunology • Ischemia/reperfusion • Off-pump

Abbreviations: ACC, aortic cross-clamp • CABG, coronary artery bypass grafting • CD, cluster of differentiation molecule • CK-MB, creatine kinase-MB • CPB, cardiopulmonary bypass • CRP, C-reactive protein • cTnT, cardiac Troponin T • ECG, electrocardiogram • ELISA, enzyme-linked immunosorbent assay • HSP, heat-shock protein • ICU, intensive care unit • IL, interleukin • IRAK, IL-1R-associated kinase • LVEF, left ventricular ejection fraction • MyD88, myeloid differentiation factor 88 • NF-B, nuclear factor-kappa B • NO, nitric oxide • NSAID, non-steroidal anti-inflammatory drug • OPCAB, off-pump coronary artery bypass grafting • PRBC, packed red blood cells • Th, T helper cell • TLR, toll-like receptor • TNF, tumor necrosis factor-alpha

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