The extracellular stress response to pediatric cardiopulmonary bypass

The heat shock response, also frequently referred to as the stress response, is an ancient, highly conserved, endogenous cellular defense mechanism characterized by the rapid upregulation of a specific class of proteins known collectively as heat shock proteins, or stress proteins. The 70 kDa family of heat shock proteins are highly inducible and have been shown to possess important immunomodulatory effects in both the intracellular and extracellular compartments. In the current prospective translational study, we measured extracellular (i.e. plasma) levels of heat shock protein 72 (Hsp72) in 49 children undergoing cardiopulmonary bypass (CPB) for either palliation or repair of congenital heart disease. There was a significant and transient increase (less than 24 h) in extracellular Hsp72 levels following CPB. Extracellular Hsp72 levels significantly correlated with levels of the pro-inflammatory cytokines interleukin (IL)-6 and IL-8, as well as the anti-inflammatory cytokine, IL-10. In addition, plasma Hsp72 levels correlated with troponin-I levels, a marker of myocardial injury. Increased extracellular Hsp72 levels at 6 h following CPB were independently associated with increased length of stay in the cardiac intensive care unit. Importantly, the source of extracellular Hsp72 does not appear to be cardiomyocytes. However, the mechanism of release and clinical relevance of the increase in extracellular Hsp72 need to be further delineated.