Altered purinergic signaling in women undergoing cardiac surgery under cardiopulmonary bypass

Abstract

Abstract Despite recent advances in cardiac surgery, adverse outcomes remain more prevalent in females as compared to males. Our study aimed to further understand whether purinergic signaling plays a role in the discrepancy in outcomes of females presenting for cardiac surgery. Right atrial tissue was harvested from 80 patients undergoing cardiac surgery before and after and cardiopulmonary bypass (CPB). Human tissue experimentation was complemented by experiments in 40 mice subject to a high fat diet and ovariectomy. Females had clinically significant increased incidence of diastolic dysfunction, length of stay, and fibrosis as well as significantly increased markers of inflammation (IL-6, leptin), apoptosis, and oxidative stress. Western blotting demonstrated that CD39, responsible for the enzymatic lysis of inflammatory extracellular ATP, was significantly decreased in women post-bypass when compared to men (P < 0.05). CD73 expression was significantly higher pre-bypass with decreased expression of adenosine deaminase post-bypass in women, suggestive of perturbed adenosine homeostasis (p < 0.05). Our experimental mice model demonstrated cardiac dysfunction and changes in purine-adenosine signaling pathways correlating to significantly decreased adenosine levels in high-fat diet and ovariectomy groups compared to control (p < 0.05). Our findings suggest that the imbalance of pro-inflammatory ATP and adenosine may play a role in sex-specific outcomes in cardiac surgery.