Growth factors serum levels in coronary artery disease patients scheduled for bypass surgery: perioperative dynamics and comparisons with healthy volunteers.

BACKGROUND: Vascular endothelial growth factors are important mediators for neovascularization of chronically ischemic adult heart, but their elevated values have also been connected with acute ischemia. Coronary artery bypass grafting (CABG) is associated with activation of inflammatory processes. We aimed to clarify whether the latter is also accompanied with acute changes in concentrations of vascular growth factors. METHODS: Concentrations of growth factors VEGF and EGF, monocyte chemoattractant protein-1 (MCP-1), and a set of cytokines of 39 patients with stable coronary artery disease (CAD) were evaluated before and after CABG. Preoperative values were compared with data of healthy volunteers. RESULTS: In comparison with CAD patients, healthy controls had significantly higher values of VEGF (15.5 (10.05-35.3) and 119.4 (55.7-136.9) pg/mL, resp.), EGF (1.70 (1.14-3.18) and 37.3 (27.1-51.9) pg/mL, resp.), and MCP-1 (111.6 (81.75-171.9) and 156.9 (134.7-241.3) pg/mL, resp.). MCP-1, but not others, demonstrated a significant rise throughout the postoperative period. Proinflammatory interleukin-6 was significantly higher and anti-inflammatory IL-4 and IL-10 lower in patients with CAD. CONCLUSIONS: Patients with stable CAD have lower serum levels of growth factors than healthy volunteers. MCP-1, but not VEGF and EGF, becomes elevated immediately after CABG. Inflammatory status of CAD patients was drifted towards proinflammatory state.

Effects of 60 minutes of hyperoxia followed by normoxia before coronary artery bypass grafting on the inflammatory response profile and myocardial injury.

BACKGROUND: Ischemic preconditioning induces tolerance against ischemia-reperfusion injury prior a sustained ischemic insult. In experimental studies, exposure to hyperoxia for a limited time before ischemia induces a low-grade systemic oxidative stress and evokes an (ischemic) preconditioning-like effect of the myocardium. We hypothesised that pre-treatment by hyperoxia favours enchanced myocardial protection described by decreased release of cTn T in the 1st postoperative morning and reduces the release of inflammatory cytokines. METHODS: Forty patients with stable coronary artery disease underwent coronary artery bypass grafting with cardiopulmonary bypass. They were ventilated with 40 or >96% oxygen for 60 minutes followed by by 33 (18-59) min normoxia before cardioplegia. RESULTS: In the 1st postoperative morning concentrations of cTnT did not differ between groups ((0.44 (0.26-0.55) ng/mL in control and 0.45 (0.37-0.71) ng/mL in hyperoxia group). Sixty minutes after declamping the aorta, ratios of IL-10/IL-6 (0.73 in controls and 1.47 in hyperoxia, p = 0.03) and IL-10/TNF-α (2.91 and 8.81, resp., p = 0.015) were significantly drifted towards anti-inflammatory, whereas interleukins 6, 8and TNF-α and interferon-γ showed marked postoperative rise, but no intergroup differences were found. CONCLUSIONS: Pre-treatment by 60 minutes of hyperoxia did not reduce postoperative leak of cTn T in patients undergoing coronary artery bypass surgery. In the hyperoxia group higher release of anti-inflammatory IL-10 caused drifting of IL-10/IL-6 and IL-10/TNF-α towards anti-inflammatory.

Inflammatory/oxidative stress during the first week after different types of cardiac surgery.

OBJECTIVES: To compare inflammatory and oxidative stress time course during the first week after different types of cardiac surgery. DESIGN: In patients undergoing coronary artery bypass grafting with cardiopulmonary bypass (CABG) or on the working heart (OPCAB) and aortic valve replacement (VALVE) blood samples for high-sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), myeloperoxidase (MPO), asymmetric dimethylarginine (ADMA) and homocysteine (Hcy) were taken preoperatively and for six consecutive postoperative days. RESULTS: Exploitation of cardiopulmonary bypass (CABG, VALVE groups), but not OPCAB, resulted in significant rise of MPO for two postoperative days. ADMA and Hcy changed in parallel fashion, being significantly decreased in the first postoperative morning and rising to the preoperative levels thereafter. In comparison with coronary artery disease patients, VALVE group had lower preoperative levels of ADMA and different postoperative time course. Postoperative concentrations of IL-6 and hsCRP were increased significantly in all groups and remained elevated during the first postoperative week. CONCLUSIONS: Cardiac surgery results in extensive and complex inflammatory/oxidative stress response regardless of the method or type of surgical procedure used. Myeloperoxidase could be one of the parameters to evaluate the cardiopulmonary bypass-associated inflammatory and oxidative stress response.

Pretreatment by hyperoxia--a tool to reduce ischaemia-reperfusion injury in the myocardium.

Atherosclerosis leads to narrowing and occlusion of coronary arteries, resulting in inadequate oxygen supply for maintenance of normal oxidative metabolism. To avoid profound ischaemia and subsequent necrosis of cardiomyocytes, blood flow has to be restored by means of thrombolysis, percutaneous coronary intervention, or surgical revascularisation. Besides restoring oxygen supply to the cells, introduction of molecular oxygen to the ischaemic tissue results in a spectrum of unfavourable events, termed altogether as reperfusion injury. Exposure to hyperoxia for a limited time before ischaemia induces a low-grade oxidative stress and evokes an (ischaemic) preconditioning-like effect in the myocardium, which protects the heart from subsequent injury. This review addresses the effects of pretreatment by hyperoxia both in experimental and clinical setting.

Off-pump coronary surgery causes immediate release of myocardial damage markers.

Off-pump coronary surgery does not eliminate the risks of ischemia-reperfusion injury. The main objective of this study was to describe the extent and time course of changes in myocardial metabolism and development of myocardial injury associated with revascularization. Coronary sinus and arterial blood samples for measurement of troponin I, creatine kinase MB, lactate, glutathione, and interleukin-6 were taken from 23 patients prior to grafting, after completion of each anastomosis, and up to the 1st postoperative morning. The results were evaluated together with parameters of cardiac function. Release of lactate, creatinine kinase MB, and troponin I into the coronary sinus was evident after completion of the 1st graft, and increased over time. During the procedure, only trace amounts of oxidized and reduced glutathione were detected in coronary sinus and arterial blood. Significant increases in interleukin-6 were found in coronary sinus samples after 5 and 20 min of reperfusion. Surgical trauma during off-pump coronary surgery is sufficient to activate an inflammatory response in the myocardium, together with unfavorable metabolic conditions to cause myocardial necrosis.

Changes of plasma asymmetric dimethylarginine levels after coronary artery bypass grafting.

OBJECTIVES: We investigated whether coronary artery bypass grafting affects plasma asymmetric dimethylarginine (ADMA) concentrations and whether precardioplegic hyperoxia influences ADMA release from the heart. DESIGN: Twenty two patients were randomized into control (n = 11) and hyperoxia (n = 11, ventilated with >96% oxygen before cardiopulmonary bypass) groups. Arterial and coronary sinus blood was sampled before cardioplegia and during early reperfusion. Arterial samples were drawn 60 min after declamping of the aorta, and on the first postoperative day. RESULTS: Baseline arterial values of ADMA were not different between groups (0.59+/-0.18 micro mol/l control, 0.63+/-0.13 micro mol/l hyperoxia group). Negligible release of ADMA into coronary sinus was detected 20 min after cardioplegia. A significant decrease of arterial ADMA was observed by the first postoperative morning (0.42+/-0.16 micro mol/l in control, and 0.38+/-0.07 in hyperoxia group, p < 0.01 compared to baseline). CONCLUSIONS: CABG with cardioplegia is associated with decrease of ADMA by the first postoperative morning. Reperfusion of cardioplegic heart did not result in significant release of ADMA. Pretreatment with hyperoxia had no influence on myocardial release and arterial levels of ADMA.

Early postoperative function of the heart after coronary artery bypass grafting is not predicted by myocardial necrosis and glutathione-associated oxidative stress.

BACKGROUND: To investigate whether cardioplegia-related myocardial necrosis, lactate and glutathione release are predictive for early postoperative cardiac function after coronary artery bypass grafting (CABG). METHODS: Twelve patients with stabile angina scheduled for elective CABG were included. Myocardial release of troponin I (Tn I), creatine kinase MB isoenzyme mass (CK-MB), oxidized glutathione (GSSG) and lactate in blood were measured before cardioplegia, and up to 20 min thereafter. Cardiac function was assessed for 12 postoperative hours. RESULTS: Release of Tn I and CK-MB peaked at 20 min (-14.5+/-24.1 ng/ml and -23.9+/-30.6 ng/ml, respectively) and lactate at 1 min of reperfusion (-1.5+/-0.6 mmol/l). Significant GSSG release occurred at 5 min, with concomitant increase of glutathione redox ratio. The changes were not correlated to ischemic time. Cardiac index was increased after CPB and remained higher than preoperative value until the first postoperative morning. No correlations between postcardioplegic heart function and markers of tissue injury were found. CONCLUSIONS: The extent of myocardial reversible and irreversible injury does not predict early postoperative contractile function of the heart.