The human heart releases cardiotrophin-1 after coronary artery bypass grafting with cardiopulmonary bypass.

OBJECTIVES: Cardiotrophin-1 (CT-1) is closely linked to many cardiovascular diseases, such as myocardial infarction and heart failure, and exhibits cardioprotective effect in ischemia-reperfusion injury. The present study was designed to investigate the course of CT-1 in patients undergoing on-pump coronary artery bypass grafting (CABG), and to evaluate the relationship between plasma CT-1 levels and postoperative cardiac function. METHODS: Twenty-four patients undergoing elective CABG were studied. Radial artery blood samples were collected before cardiopulmonary bypass (CPB), 5 min and 20 min after reperfusion, and 1 h, 6 h, 12 h and 24 h after CPB. Coronary sinus blood samples were collected before CPB, 5 min and 20 min after reperfusion. Plasma CT-1 levels were measured using the ELISA method. Hemodynamic data were collected. RESULTS: Peripheral CT-1 levels did not change significantly postoperatively. Trans-myocardial CT-1 levels increased significantly 5 min and 20 minutes after reperfusion as compared to baseline. A weak positive correlation (r = 0.408, p = 0.048) was found between trans-myocardial CT-1 levels at 20 min after reperfusion and CI at 12 h after CPB. CONCLUSIONS: The heart secretes CT-1 after ischemic injury. The precise effect of CT-1 in CABG needs further investigation.

Cytokines in bronchoalveolar lavage fluid and serum of lung cancer patients during radiotherapy - Association of interleukin-8 and VEGF with survival.

Radiotherapy (RT) produces oxidative stress and local inflammation. This study aimed at clarifying the role of different cytokines (VEGF, TNFalpha, IL-1beta, IL-6, IL-8, IL-12 and IL-18) in bronchoalveolar lavage (BAL) fluid and in the serum of lung cancer patients at baseline and during RT. Bronchoscopy and BAL were performed on 36 lung cancer patients and 36 controls for diagnosis; patients receiving RT had a second bronchoscopy during RT. Serum samples were obtained during RT and three months after RT. In this study lung cancer patients had higher levels of serum and BAL fluid IL-6 and serum IL-8 compared to controls (p<0.001, p=0.039 and p=0.030, respectively). RT caused a significant increase of BAL fluid IL-6 (p=0.037). There were no significant associations between baseline cytokine levels and adverse events or response to treatment. Higher baseline serum and BAL fluid IL-8 and serum VEGF levels (p=0.036, p=0.027 and p=0.014, respectively) were associated with shorter survival. This study shows that lung cancer is associated with upregulation of IL-6 and IL-8. The increase of BAL fluid IL-6 during RT might be attributed to enhanced RT-related oxidative stress or increased cell death. Serum and BAL fluid IL-8 and serum VEGF might have a prognostic role in survival of lung cancer.

Association of the IL6-174(G/C) polymorphism with C-reactive protein concentration after weight loss in obese men.

Elevated plasma concentration of C-reactive protein has emerged as an important predictor of future cardiovascular diseases and metabolic abnormalities in apparently healthy individuals. Obese individuals tend to have elevated C-reactive protein concentrations. Weight loss induces a change in this protein, and single nucleotide polymorphisms in regulating genes might affect this change, since C-reactive protein concentration is known to be approximately 40-50% heritable. Our aim was to study the association between the IL6 -174(G/C), IL1B +3,954(C/T) and CRP +1,059(G/C) single nucleotide polymorphisms, and CRP concentrations in obese men during a weight reduction program. We genotyped 72 obese men who had participated in a weight reduction program. Their C-reactive protein concentrations, interleukin-6 levels and fat mass were determined at two time points: at baseline and after weight reduction (after 2 months). After weight reduction, the mean weight loss was 14.3 kg. Median C-reactive protein concentrations decreased, after weight reduction, from 1.72 to 1.22 mg/l (p < 0.02). The baseline C-reactive protein concentration did not differ between the IL6-174(G/C) genotypes, but after weight loss, concentrations differed (p = 0.03 Kruskal-Wallis test); the highest concentration was found in the CC genotype (CC 1.01 versus GG 1.93 mg/l, p = 0.007 ANOVA post-hoc test). This change in concentration was associated with the IL6-174(G/C) genotype (p = 0.01, Kruskal-Wallis test), being least in the CC genotype. The other single nucleotide polymorphisms studied were not associated with CRP concentrations. Our results show that, at baseline, there is no difference in C-reactive protein concentrations among the different IL6-174(G/C) genotypes, but after weight loss the CC genotype is associated with highest C-reactive protein concentrations, resulting from the fact that C-reactive protein seems not to decrease with weight loss in this genotype.

Soluble adhesion molecules and myocardial injury during coronary artery bypass grafting.

Cardiopulmonary bypass is acknowledged to be one of the major causes of a complex systemic inflammatory response after cardiac surgery. Leukocyte-endothelial binding followed by neutrophil migration appears to play a central role. These interactions are mediated by adhesion molecules on the surface of activated cells. The present study compared the perioperative levels of soluble adhesion molecules after coronary artery bypass grafting (CABG) in patients with or without cardiopulmonary bypass (CPB). Altogether, 9 patients underwent off-pump revascularization and 11 did so with CPB. Plasma levels of soluble adhesion molecules sE-selectin and sP-selectin and soluble intercellular adhesion molecule-1 (sICAM-1) were measured before anesthesia induction and 1, 4, and 20 hours after reperfusion to the myocardium. The baseline plasma levels of the adhesion molecules were similar in the two groups. Perioperative levels of sE-selectin remained the same and did not differ between groups. Plasma sP-selectin increased in both groups, the change being significantly greater in the CPB group than that in the off-pump group (p = 0.001). Plasma sICAM-1 decreased during an early stage after CABG with CPB, recovering at 4 hours after reperfusion; and a significant increase in ICAM-1 was observed 20 hours later. In the off-pump group, sICAM-1 levels did not change at 1 and 4 hours after reperfusion but increased 20 hours later. Postoperative creatine kinase-muscle bound (CK-MB) levels were significantly higher in the CPB group than in the off-pump group (p = 0.001). The change in sP-selectin levels also showed a correlation with CK-MB values (r = 0.676, p = 0.001). The results indicated that off-pump revascularization is associated with reduced endothelial activation and myocardial injury.

Imbalance of pro- and anti-inflammatory cytokine responses in elderly patients after coronary artery bypass grafting.

BACKGROUND AND AIMS: Increased inflammatory activity has been observed in elderly people. The aim of this study was to determine whether cytokine responses after coronary artery bypass grafting (CABG) in elderly patients are different from those in younger patients. METHODS: Fifty-five male patients admitted for first-time elective coronary artery bypass surgery were divided into two age groups: group I, patients younger than 70 years (N=40); and group II, patients aged 70 years or older (N=15). Perioperative levels of cytokines and CK-MB were measured. Hemodynamic data were recorded. RESULTS: Marginally higher IL-6 (p=0.048) and IL-8 (p=0.041) levels were observed during the intensive care unit (ICU) stay in the elderly as compared with younger patients. Lower IL-10 levels were detected in the elderly 5 minutes after reperfusion to the myocardium (p<0.05). Although the postoperative hemodynamic change was similar in both groups, the elderly needed vasopressor treatment more often during the ICU stay. This was associated with lower IL-10 levels 5 minutes after reperfusion. CONCLUSIONS: The present results show the age-related imbalance of pro- and anti-inflammatory responses after CABG, associated with hemodynamic instability in the elderly.

Association of mannan-binding lectin deficiency with venous bypass graft occlusions in patients with coronary heart disease.

We investigated the effect of mannan-binding lectin (MBL) deficiency on the susceptibility to bypass graft occlusion in 62 patients with coronary heart disease. MBL deficiency appeared to be associated with occlusion (p = 0.0099). A high level of anti-cardiolipin IgG as well as the number of venous bypass grafts were also involved (p = 0.0018 and p = 0.0104, respectively). Since early occlusion (<5 years after surgery) of a venous bypass graft is considered to be caused by thrombosis or fibro-intimal hyperplasia superimposed by thrombosis, our finding also implies an association of MBL deficiency with thrombotic events. It remains unclear whether the previously confirmed effect of MBL deficiency in coronary disease is mediated through this possible thrombotic mechanism, or whether plaque formation is also involved in the process. Further studies are clearly warranted.

Soluble adhesion molecules in coronary surgery and cardiopulmonary bypass with pump prime aprotinin.

OBJECTIVE: The purpose of the present study was to establish whether pump prime aprotinin could influence soluble adhesion molecules in patients undergoing elective coronary artery bypass surgery. DESIGN: Thirty patients admitted for first-time elective coronary artery bypass surgery were randomized into control or aprotinin groups. Patients in the aprotinin group received 280 mg of aprotinin in the pump prime. Plasma levels of soluble adhesion molecules were analyzed perioperatively. RESULTS: There were no significant changes in plasma sE-selectin after the operation in either group. Plasma sP-selectin increased significantly up to 20 h after reperfusion to the myocardium. Plasma sICAM-1 decreased in the early stage after cardiopulmonary bypass (CPB), then recovered at 4 h after reperfusion and a significant increase in sICAM-1 was observed 20 h later. There were no significant differences between the groups in postoperative changes in sP-selectin (p = 0.21) and sICAM-1 (p = 0.91). CONCLUSION: Pump prime aprotinin did not influence plasma levels of E-selectin, P-selectin and ICAM-1 in the present patients. The present results do not support the concept of an anti-inflammatory effect of pump prime aprotinin.

Cytokine Responses in Low-Risk Coronary Artery Bypass Surgery.

Inflammatory cytokines have been implicated in myocardial function, severe congestive heart failure and sepsis. The present study tested the hypothesis that cytokine levels are elevated after low-risk coronary artery bypass surgery (CABG), and that they may be associated with postoperative cardiac dysfunction. Twenty male patients undergoing elective CABG in cardiopulmonary bypass (CPB) were studied. Plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-8, and IL-10 were measured before anesthesia induction, 5 minutes after, and 1, 4, and 20 hours after reperfusion to the myocardium. Levels of the MB isoenzyme of creatine kinase (CK-MB) were measured postoperatively. Hemodynamic data were also recorded. Myocardial ischemia was followed by an increase in the plasma levels of IL-6, IL-8, and IL-10. The duration of IL-6 response lasted throughout the postoperative period studied. Plasma cytokine levels at 1 hour after reperfusion correlated with the maximum CK-MB value (IL-6, r = 0.587, p < 0.01; IL-8, r = 0.460, p < 0.05; IL-10, r = 0.570, p < 0.05). Higher plasma IL-6 and IL-8 levels after reperfusion tended to be linked with lower cardiac index. The present results confirm that the levels of inflammatory cytokines IL-6, IL-8, and IL-10 are elevated after CABG. Increased systemic pro-inflammatory cytokine levels were partially associated with postoperative myocardial dysfunction.