Hemoglobin-associated oxidative stress in the pericardial compartment of postoperative cardiac surgery patients

Abstract

Atherosclerosis and valvular heart disease often require treatment with corrective surgery to prevent future myocardial infarction, ischemic heart disease, and heart failure. Mechanisms underlying the development of the associated complications of surgery are multifactorial and have been linked to inflammation and oxidative stress, classically as measured in the blood or plasma of patients. Post-operative pericardial fluid (PO-PCF) has not been investigated in depth with respect to the potential to induce oxidative stress. This is important since cardiac surgery disrupts the integrity of the pericardial membrane surrounding the heart, and causes significant alterations in the composition of the pericardial fluid (PCF). This includes contamination with hemolyzed blood and high concentrations of oxidized hemoglobin, which suggests that cardiac surgery results in oxidative stress within the pericardial space. Accordingly, we tested the hypothesis that PO-PCF is highly pro-oxidant and that the potential interaction between inflammatory cell-derived hydrogen peroxide with hemoglobin is associated with oxidative stress. Blood and PCF were collected from 31 patients at the time of surgery and postoperatively from 4 to 48 hours after coronary artery bypass grafting, valve replacement, or valve repair (mitral or aortic). PO-PCF contained high concentrations of neutrophils and monocytes which are capable of generating elevated amounts of superoxide and hydrogen peroxide through the oxidative burst. In addition, PO-PCF primed naïve neutrophils resulting in an enhanced oxidative burst upon stimulation. The PO-PCF also contained increased concentrations of cell-free oxidized hemoglobin which was associated with elevated levels of F2α-isoprostanes and prostaglandins, consistent with both oxidative stress and activation of cyclooxygenase. Lastly, protein analysis of the PO-PCF revealed evidence of protein thiol oxidation and protein carbonylation. We conclude that PO-PCF is highly pro-oxidant and speculate that it may contribute to the risk of post-operative complications.

Decreased Bioenergetic Health Index in monocytes isolated from the pericardial fluid and blood of post-operative cardiac surgery patients

“…ment. We have recently shown that this compartment is a highly pro-oxidant environment with evidence of protein and lipid oxidation [5]. In addition, 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.…”

“…The changes in the composition and volume of the pericardial fluid that occur post-surgery, include the accumulation of inflammatory cells, pro-oxidants including hydrogen peroxide and oxidized lipids which could alter cardiac mitochondrial function [5,10]. An important concept in cellular bioenergetics is that leucocytes and platelets can act as biomarkers for mitochondrial dysfunction where tissue collection is not feasible [23].…”

“…Oxidized haemoglobin (Hb) and lipid peroxidation products are found at high levels of in the PO-PCF but to a much lower extent in the blood [5]. Both oxidized lipids and hydrogen peroxide are known to damage mitochondria [14,22].…”

“…Some inflammatory markers in the serum of post-operative cardiac surgery patients have appeared elevated and correlated with increased occurrences of cardiac dysfunction and atrial fibrillation [6][7][8]. We have recently proposed that the focus for the initiation of the pro-inflammatory response after surgery is the post-operative pericardial fluid (PO-PCF) and that the oxidative stress in this compartment is more severe than in the blood [5].…”

Increased Inflammation in Pericardial Fluid Persists 48 Hours After Cardiac Surgery

“…Enzyme-linked immunosorbent assay (ELISA) analysis 2 revealed that neutrophil products (myeloperoxidase [MPO] and neutrophil-gelatinase associated lipocalin [NGAL]), neutrophil chemotactic factors (CXCL6 and interleukin[IL]-8) and cardiac inflammatory factors (tumor necrosis factor[TNF]-α and oncostatin M [OSM]) were many-fold higher in PCF compared with blood over the 4- to 48-hour time course after cardiac surgery (Figure 1A). Matrix metallopeptidase-9 (MMP-9), a major product of neutrophils, was significantly higher in blood as compared with PCF at time 0, but quickly rose in PCF to 2.6-, 2.3-, and 2.7-fold higher than blood at 4, 12, and 24 hours, respectively.…”