Does the Rewarmed Heart Restore the Myocardial Proteome to That of the Pre-Cooled State?　– A Proteomic Analysis of Surgical Samples

Background:Hypothermia is utilized in cardiac and aortic surgery to protect organs from ischemic reperfusion injury. Although the cooled body is invariably rewarmed after the procedure, it is still unknown whether the rewarmed body regains its former biological state. This study determined the modulatory effects of hypothermia on the human myocardial proteome and whether subsequent rewarming restores the proteome to the state prior to cooling.Methods and Results:A quantitative proteomic analysis was performed using isobaric tags for relative and absolute quantification labeling tandem mass spectrometry. Right atrial samples were taken 3 times (pre, during and post cooling) during deep hypothermic cardiopulmonary bypass (CPB) from 8 patients with aortic arch aneurysms and 3 corresponding time points during normothermic CPB from 8 patients with ascending aortic or valsalva aneurysms. In total, 697 proteins were identified, with 222 proteins having high protein confidence. Bioinformatic analyses revealed significant downregulation of 19 proteins associated with energy production at hypothermic cardioplegic arrest. On rewarmed beating, 10 proteins remained downregulated, including those regulating cardiac contraction and adaptor proteins, although levels of the aforementioned 19 downregulated proteins returned to their initial values. Additional echocardiographic evaluation demonstrated that hypothermia preserved the variables of diastolic function to a greater extent than normothermic surgery.Conclusions:Rewarming restores the human myocardial proteome to the pre-cooled state, except for proteins regulating cardiac contraction and adaptor proteins. (Circ J 2015; 79: 2648–2658)