Changes in Autophagic Flux in Patients Undergoing Cardiac Surgery

Autophagy is an endogenous survival mechanism and adaptive response to cellular stress. We hypothesized that autophagy plays an important cardioprotective role in humans and would be accelerated during the ischemic stress of conventional heart surgery. In a prospective study to test this hypothesis, we measured key autophagy proteins (Beclin-1, Atg5-12, p62) in cardiac tissue from 5 patients undergoing cardiac surgery. Right atrial biopsies were obtained before and after cessation of cardiopulmonary bypass (CPB). In 4 of these patients, CPB was associated with a marked decrease in cardiac Beclin-1, Atg5-12, and p62. We believe that depletion of these factors, particularly p62, reflects a brisk increase in autophagic flux (Fig. 1). In one patient (#02), autophagic flux appeared to be impaired. This occurred in an aged patient with characteristics of metabolic syndrome (MetS) who had the highest predicted operative morbidity/mortality. While the number of patients studied is small and insufficient to reach any definitive conclusions, these preliminary data confirm the feasibility of studying autophagy in the human heart and suggest that ischemic stress during heart surgery is associated with a marked upregulation of autophagic flux. A better understanding of the role of autophagy could lead to the development of new cardioprotective strategies. [Figure 1: Changes in cardiac autophagy proteins in patients undergoing heart surgery before and after cross-clamping the aorta (after restoration of myocardial blood flow).]