Abstract

Monitoring the bioenergetics of leucocytes is now emerging as an important approach in translational research to detect mitochondrial dysfunction in blood or other patient samples. Using the mitochondrial stress test, which involves the sequential addition of mitochondrial inhibitors to adherent leucocytes, we have calculated a single value, the Bioenergetic Health Index (BHI), which represents the mitochondrial function in cells isolated from patients. In the present report, we assess the BHI of monocytes isolated from the post-operative blood and post-operative pericardial fluid (PO-PCF) from patients undergoing cardiac surgery. Analysis of the bioenergetics of monocytes isolated from patients' PO-PCF revealed a profound decrease in mitochondrial function compared with monocytes isolated from their blood or from healthy controls. Further, patient blood monocytes showed no significant difference in the individual energetic parameters from the mitochondrial stress test but, when integrated into the BHI evaluation, there was a significant decrease in BHI compared with healthy control monocytes. These data support the utility of BHI measurements in integrating the individual parameters from the mitochondrial stress test into a single value. Supporting our previous finding that the PO-PCF is pro-oxidant, we found that exposure of rat cardiomyocytes to PO-PCF caused a significant loss of mitochondrial membrane potential and increased reactive oxygen species (ROS). These findings support the hypothesis that integrated measures of bioenergetic health could have prognostic and diagnostic value in translational bioenergetics.

Highlights

  • Cardiac surgery is a common procedure with a significant incidence of post-operative complications associated with increased morbidity and several complications which have few effective therapies [1,2,3,4]

  • These findings suggested to us the hypothesis that the monocytes isolated from the post-operative pericardial fluid (PO-PCF), which is more pro-oxidant than the plasma, would exhibit increased mitochondrial dysfunction compared with cells isolated from the patients’ blood

  • Basal, ATP-linked, proton leak, reserve capacity and maximal mitochondrial oxygen consumption rate (OCR) were significantly decreased in PO-PCF monocytes relative to their matched blood and healthy donor blood monocytes

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Summary

Introduction

Cardiac surgery is a common procedure with a significant incidence of post-operative complications associated with increased morbidity and several complications which have few effective therapies [1,2,3,4]. Cardiac surgery inevitably results in varying degrees of cardiac ischaemia, trauma and introduction of blood and other foreign material into the pericardial compartment. Within a few hours following surgery, the pericardial compartment is populated by monocytes and neutrophils, which we have demonstrated are capable of generating high levels of hydrogen peroxide. Some inflammatory markers in the serum of post-operative cardiac surgery patients have appeared c 2015 Authors.

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