Endothelial Ca2+ signal transduction is altered by postoperative serum from patients undergoing coronary surgery with cardiopulmonary bypass.

Abstract

Endothelial dysfunction after surgery may be caused by alterations in the intracellular signaling properties of endothelial cells. Functional alterations are believed to be systemic and dependent on the amount of invasiveness. This led us to assume that there would be a mediator in the blood. Therefore, we investigated the influence of perioperative serum obtained from patients undergoing highly invasive surgical interventions (cardiac surgery [CS] with cardiopulmonary bypass) and less invasiveness (total joint arthroplasty [TJA]) on endothelial single cell Ca2+ responses. Aortic endothelial cells were incubated with preoperative and postoperative serum samples from 26 patients undergoing CS and from 15 patients undergoing TJA. Adenosine triphosphate (100 microM)-induced alterations in FURA-2 fluorescence was used to measure intracellular Ca2+ in single cells. In CS samples the induced [Ca2+]i signals were enhanced by postoperative serum (peak levels: 96 +/- 41 FU versus 116 +/- 45 FU; P < 0.05). These postoperative enhancements were absent in TJA patients serum. Preincubation of CS samples with nifedipine to block voltage gated Ca2+ channels did not alter this effect, but the absence of extracellular Ca2+ abolished the increased response from postoperative CS serum exposure. Ca2+ entry probed with Mn2+ quenching was increased in endothelial cells exposed with postoperative CS serum and Ca2+ entry correlated with postoperative circulating interleukin-6 levels (P < 0.007). Endothelial functional alterations after CS with cardiopulmonary bypass are attributable, in part, to systemic factors present in serum that lead to specific endothelial enhanced Ca2+-signaling. This enhancement can be separated in vitro as an increased Ca2+ entry not present in serum from patients recovering from TJA.