interleukin-8 and Heart-Diseases

This study aimed to investigate the effect of sevoflurane on serum levels of interleukin (IL)-6 and IL-8 in patients who underwent cardiopulmonary bypass (CPB). The strength of the association between sevoflurane treatment and serum level of IL-6 and IL-8 was determined in patients who underwent CPB by summary standard mean differences (SMDs); 95% confidence interval (CI) was used. In total, seven case-control studies showed decreased IL-6 and IL-8 levels in sevoflurane-treated patients than in controls (IL-6: SMD = 1.56, 95%CI: 0.95-2.17, P < 0.001; IL-8: SMD = 1.63, 95%CI: 0.30-2.96, P < 0.001, respectively). Further, IL-6 and IL-8 levels were significantly higher in sevoflurane-treated patients than in sevoflurane-pretreated patients (IL-6 post vs pre: SMD = 2.17, 95%CI: 1.40-2.95, P < 0.001; IL-8 post vs pre: SMD = 4.01, 95%CI: 2.80-5.21, P < 0.001, respectively). CPB-stratified analysis showed significant decrease in IL-6 and IL-8 levels in sevoflurane-treated patients than in controls, irrespective of the time after CPB surgery (P < 0.05). Moreover, sevoflurane-pretreated patients under the <12-h subgroup showed decreased IL-6 levels (P = 0.698), while all other subgroups showed decreased IL-8 levels (P < 0.05). Further, subgroup analysis by different dose of sevoflurane showed decreased IL-6 and IL-8 levels in subgroups administered with a dose of <2 and ≥ 2% sevoflurane under the case vs control and pre- vs post-treatment of sevoflurane models. Serum IL-6 and IL-8 levels were significantly lower in sevoflurane-treated patients who underwent CPB, suggesting sevoflurane pretreatment to be more beneficial than post-treatment.

Topics: Anti-Inflammatory Agents; Cardiopulmonary Bypass; Case-Control Studies; Down-Regulation; Heart Diseases; Humans; Interleukin-6; Interleukin-8; Methyl Ethers; Premedication; Sevoflurane

Myocardial dysfunction is common in sepsis but optimal treatment strategies are unclear. The inodilator, levosimendan was suggested as a possible therapy; however, the levosimendan to prevent acute organ dysfunction in Sepsis (LeoPARDS) trial found it to have no benefit in reducing organ dysfunction in septic shock. In this study we evaluated the effects of levosimendan in patients with and without biochemical cardiac dysfunction and examined its non-inotropic effects.. Two cardiac biomarkers, troponin I (cTnI) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and five inflammatory mediators were measured in plasma from patients recruited to the LeoPARDS trial at baseline and over the first 6 days. Mean total Sequential Organ Failure Assessment (SOFA) score and 28-day mortality were compared between patients with normal and raised cTnI and NT-proBNP values, and between patients above and below median values.. Levosimendan produced no benefit in SOFA score or 28-day mortality in patients with cardiac dysfunction. There was a statistically significant treatment by subgroup interaction (p = 0.04) in patients with NT-proBNP above or below the median value. Those with NT-proBNP values above the median receiving levosimendan had higher SOFA scores than those receiving placebo (mean daily total SOFA score 7.64 (4.41) vs 6.09 (3.88), mean difference 1.55, 95% CI 0.43-2.68). Levosimendan had no effect on the rate of decline of inflammatory biomarkers.. Adding levosimendan to standard care in septic shock was not associated with less severe organ dysfunction nor lower mortality in patients with biochemical evidence of cardiac dysfunction.

Topics: Aged; Biomarkers; Chemokine CCL2; Double-Blind Method; Female; Heart Diseases; HSP90 Heat-Shock Proteins; Humans; Intensive Care Units; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Natriuretic Peptide, Brain; Organ Dysfunction Scores; Peptide Fragments; Prognosis; Shock, Septic; Simendan; Troponin I; United Kingdom

Postprandial state is characterized by metabolic changes which may elevate circulating inflammatory biomarkers, used to assess cardiometabolic risk. It is unclear if biological benefits of certain food components could be obtained by a short-term change in a single meal of Brazilian's habitual diet. We investigated the postprandial effects of 2 fat tolerance tests (FTT) with different isocaloric meals (a typical Brazilian and a modified meal) differing by type of fatty acids and fiber contents, prior to and after breakfast interventions.. This crossover clinical trial included 80 overweight individuals with at least one cardiometabolic risk factor, (35-69 years) who received two isocaloric breakfast interventions for 4 weeks, with a 2-week washout. The Brazilian breakfast was saturated fat-enriched while the modified one was rich in unsaturated fatty acids and fibers. Before and after intervention periods, individuals underwent two FTT with meals with similar composition to the interventions breakfasts but higher energy content. Variables were compared by repeated-measures ANOVA. Correlations were assessed by Pearson's coefficient.. At the end of both interventions, participants did not change plasma glucose or triglycerides. The higher IL-6 and IL-8 responses to the FTT with the Brazilian meal compared to that with the modified meal was accentuated after the interventions (p-diet <0.01; p-time <0.01). Acutely, E-selectin, TNF-α, IFN-γ, IL-10 and IL-17 concentrations did not increase in response to the FTTs, but showed higher values only after the Brazilian intervention. In contrast, intervention with the modified breakfast induced reductions in fasting and postprandial cytokines (p-diet <0.01). Changes in MUFA and PUFA intakes were inversely correlated to changes in inflammatory markers, while changes in saturated fat intake were directly correlated to IFN-γ and IL-6.. Isocaloric meals with distinct nutrient composition elicit different postprandial inflammatory responses after a relatively short intervention in a single meal. Each saturated fat-enriched meal consumed, as well as each unsaturated fat and fiber-enriched meal may induce pro- or anti-inflammatory responses that could impact on the cardiometabolic risk profile.

Topics: Adult; Aged; Blood Glucose; Body Mass Index; Brazil; Breakfast; Cross-Over Studies; Cytokines; Dietary Fats; Dietary Fiber; Energy Intake; Fasting; Fatty Acids; Heart Diseases; Humans; Inflammation; Interleukin-6; Interleukin-8; Metabolic Diseases; Middle Aged; Overweight; Postprandial Period; Risk Factors; Triglycerides

To evaluate the effects of leukocyte-depleting filtration on myocardial and pulmonary protection and the inflammatory response in patients undergoing valve surgery.. Fifty-two patients who underwent mitral valve or mitral and aortic valve replacement were randomized into two groups with or without a leukocyte-depleting filter during surgery. The filter was used from 10 minutes before the release of the aortic cross-clamp to the end of cardiopulmonary bypass.. Total leukocyte and neutrophil counts showed a short-term reduction in patients undergoing leukocyte filtration, but there was no significant difference between the two groups during the study. Serum levels of cardiac troponin I were lower than that of the control group (p=0.030). Leukocyte depletion resulted in a significantly higher oxygenation index (p=0.002) and a lower respiratory index (p=0.003) compared with the control group. Serum levels of interleukin-8 were significantly elevated in patients undergoing leukocyte filtration compared with patients without leukocyte filtration (p=0.001). There were no statistically significant differences between the two groups with regards to the concentration of interleukin-6 and TNFα, or the duration of intensive care and hospital stay.. Leukocyte depletion is associated with improved myocardial and lung protection but does not appear to attenuate the inflammatory response in valve surgery.

Topics: Adult; Analysis of Variance; Aortic Valve; Biomarkers; Cardiopulmonary Bypass; China; Female; Heart Diseases; Heart Valve Prosthesis Implantation; Humans; Inflammation; Inflammation Mediators; Interleukin-6; Interleukin-8; Leukocyte Reduction Procedures; Lung Diseases; Male; Middle Aged; Mitral Valve; Prospective Studies; Time Factors; Treatment Outcome; Troponin I; Tumor Necrosis Factor-alpha

To study the effect and acting mechanism of puerarin preconditioning (PP) on blood level of cytokines in patients undergoing cardiopulmonary bypass (CPB) in perioperative period.. Forty patients with heart diseases scheduled to take surgical operation were randomized into the control group and the PP group equally. They were treated with the same program, excepting that 0.6 g of puerarin was given to the PP group by adding in 5% glucose solution 250 mL for intravenous dripping every day for one week before operation, but to the control group, normal saline was given instead. The levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 6, 8 and 10 (IL-6, IL-8, IL-10) in arterial blood were measured at 5 time points in the process of CPB, namely, anesthetic induction (T1), 10 min after the clamp of the ascending aorta (T2), 10 min, 2 h and 12 h after the Clamped aorta is unclamped (T3, T4 and T5).. All the above-mentioned indexes (TNF-alpha, IL-6, IL-8 and IL-10) gradually increased after beginning CPB, reached the peak at T4, then lowered gradually but still presented the higher levels at T5 than those at T1 (P < 0.05). Comparison between the two groups showed that levels of TNF-alpha, IL-6 and IL-8 were significantly lower (P < 0.05 or P < 0.01) and level of IL-10 was higher in the PP group than those in the control group respectively at all the time points (P < 0.01).. Injecting puerarin before CPB could effectively suppress the pro-inflammatory cytokines like TNF-alpha, IL-6 and IL-8; and enhance the expression of anti-inflammatory cytokines like IL-10, thus to alleviate the inflammatory reaction induced by CPB.

Topics: Adolescent; Adult; Cardiopulmonary Bypass; Female; Heart Diseases; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Ischemic Preconditioning; Isoflavones; Male; Middle Aged; Perioperative Period; Postoperative Period; Treatment Outcome; Tumor Necrosis Factor-alpha; Young Adult

Cardiopulmonary bypass (CPB) induces an inflammatory response believed to contribute to postoperative morbidity. We hypothesized that the magnitude of the inflammatory response following CPB would be associated with adverse clinical outcomes.. Twenty-nine patients had plasma TNF, IL-6, IL-8, elastase, histamine, complement C5a, and complement C3a measured by ELISA before, during, and after cardiac operations employing CPB. Inflammatory mediator levels were analyzed with respect to outcomes.. Mediator levels peaked at 4 h post-CPB and either returned to baseline or substantially decreased by 24 h. Patients with peak mediator levels above the median for the group as a whole were classified as 'hyper-responders'; those with levels below the median were classified as 'normal responders'. While IL-8, C3a, and IL-6 levels were independently associated with adverse outcomes, TNF, histamine, and C5a levels were not. Elastase levels trended towards adverse outcomes. IL-8 'hyper-responders' experienced significantly greater postoperative weight gain and had higher IL-8 levels at 24 h (p<0.05), with trends towards renal impairment and protracted supplemental oxygen requirements. C3a 'hyper-responders' strongly trended towards increased bleeding, delayed extubation, greater postoperative weight gain, and decreased levels of independent functioning at discharge (p < or = 0.10). IL-6 'hyper-responders' experienced significantly more postoperative bleeding, delayed extubation, and higher IL-6 levels at 24 h compared to 'normal responders' (p < 0.05). They strongly trended towards greater postoperative weight gain and decreased levels of independent functioning at discharge (p < or = 0.10).. Patients who have an exaggerated inflammatory response to CPB tend to bleed more, require more respiratory support, demonstrate greater capillary leak via weight gain, and display a decline in independent functioning relative to normal responders. Thus, it appears that the magnitude of the inflammatory response to CPB adversely influences clinical outcomes.

Topics: Aged; Biomarkers; Cardiopulmonary Bypass; Complement C3a; Enzyme-Linked Immunosorbent Assay; Female; Heart Diseases; Humans; Inflammation; Inflammation Mediators; Interleukin-6; Interleukin-8; Kidney Diseases; Lung Diseases; Male; Middle Aged; Pancreatic Elastase; Postoperative Complications; Treatment Outcome

Inflammation underpinning acute decompensation (AD) of liver disease is an important driver for the development of acute-on-chronic liver failure or death. We aimed to investigate associations between inflammatory biomarkers and impaired cardiac function in patients admitted for AD of cirrhosis.. This is a retrospective analysis of a well-characterized prospective cohort of patients with AD of liver disease admitted to a tertiary referral center. All patients had echocardiographic assessment of cardiac function and serum samples at admission. We reclassified patients according to the CLIF-C AD score, measured inflammatory (IL-6, IL-8, TNF-ɑ, CD206) and cardiac-specific (NT-proBNP, troponin T) biomarkers and tested for associations with echocardiographic parameters of cardiac function. We explored the impact on outcome of these factors in multivariate analysis.. We included 70 patients (58 ± 10 years, 28 women), with a mean CLIF-C AD score of 47 ± 7. Thirty-nine patients (56%) fulfilled the echocardiographic criteria for cardiac dysfunction. We found associations between parameters of diastolic dysfunction and serum concentrations of IL-6 and CD206. Echocardiographic parameters of cardiac function were not associated with markers of liver dysfunction such as the CLIF-C AD score. In multivariate analysis higher MELD, higher NT-proBNP, and IL-8 concentrations as well as the absence of echocardiographic criteria for cardiac dysfunction significantly associated with death during follow-up.. We found evidence in favor of a clinically relevant link between serum biomarkers of inflammation (IL-6, CD206) and echocardiographic signals of cardiac dysfunction in patients with acutely decompensated cirrhosis.

Topics: Acute-On-Chronic Liver Failure; Biomarkers; Female; Heart Diseases; Humans; Inflammation; Interleukin-6; Interleukin-8; Liver Cirrhosis; Prognosis; Prospective Studies; Retrospective Studies

To investigate the suitability of blood granulocyte and monocyte sensitivity, as measured by the quantity of different agonists required to induce CD62L shedding, for assessment of perioperative immune changes in patients undergoing cardiac surgery with cardiopulmonary bypass.. Patients scheduled for aortocoronary bypass grafting or for valve surgery were included in this prospective observational study. Blood samples were drawn before anesthesia induction, directly after surgery and 48 hours after anesthesia induction. We determined the concentration of two different inflammatory stimuli--lipoteichoic acid (LTA) and tumor necrosis factor alpha (TNF)--required to induce shedding of 50% of surface CD62L from blood granulocytes and monocytes. In parallel monocyte surface human leukocyte antigen (HLA)-DR, and plasma interleukin (IL)-8, soluble (s)CD62L, soluble (s)Toll-like receptor (TLR)-2 and ADAM17 quantification were used to illustrate perioperative immunomodulation.. 25 patients were enrolled. Blood granulocytes and monocytes showed decreased sensitivity to the TLR 2/6 agonist Staphylococcus aureus LTA immediately after surgery (p = 0.001 and p = 0.004 respectively). In contrast, granulocytes (p = 0.01), but not monocytes (p = 0.057) displayed a decreased postoperative sensitivity to TNF. We confirmed the presence of a systemic inflammatory response and a decreased immune sensitivity in the post-surgical period by measuring significant increases in the perioperative plasma concentration of IL-8 (p ≤ 0.001) and sTLR (p = 0.004), and decreases in monocyte HLA-DR (p<0.001), plasma sCD62L (p ≤ 0.001). In contrast, ADAM17 plasma levels did not show significant differences over the observation period (p = 0.401).. Monitoring granulocyte and monocyte sensitivity using the "CD62L shedding assay" in the perioperative period in cardiac surgical patients treated with the use of cardiopulmonary bypass reveals common changes in sensitivity to TLR2/6 ligands and to TNF stimulus. Further long-term follow-up studies will address the predictive value of these observations for clinical purposes.

Topics: ADAM Proteins; ADAM17 Protein; Aged; Cardiopulmonary Bypass; Enzyme-Linked Immunosorbent Assay; Female; Heart Diseases; HLA-DR Antigens; Humans; Inflammation; Interleukin-8; L-Selectin; Ligands; Lipopolysaccharides; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Staphylococcus aureus; Teichoic Acids; Tumor Necrosis Factor-alpha

Due to the combination of local trauma, extracorporeal circulation (ECC), and pulmonary and myocardial reperfusion, cardiac surgery leads to substantial changes in the immune system and possibly to post-operative complications. Procedures without ECC, however, have failed to demonstrate clear advantages. We hypothesized that ECC is far less important in this context than the reperfusion/reventilation of the lung parenchyma and the surgical trauma. We therefore conducted a prospective observational study to compare immune reactions after cardiac operations with those after thoracic surgery.. Serum levels of pro-inflammatory interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-alpha as well as C-reactive protein (CRP), lipoprotein-binding protein (LBP) and procalcitonin (PCT) were measured pre-operatively (d0), at the end of the operation (dx), 6h after the operation (dx+), on the 1st (d1), 3rd (d3), and 5th (d5) post-operative days in 108 patients (pts) undergoing elective coronary artery bypass grafting (CAB) with ECC (n=42, CPB CAB), off-pump coronary artery bypass surgery (n=24, OP CAB) without ECC or thoracic surgery (n=42, TS).. After cardiac surgery (CS), IL-6 and IL-8 increased and reached a maximum on dx+. IL-6 returned to baseline values at d3, whereas IL-8 remained elevated until d5. No difference was found between OP CAB and CPB CAB patients. In the TS patients, IL-6 increased later (dx+) and absolute levels were lower than in the CS patients. No increase in IL-8 was noted in the TS patients. Due to the high variation in the results obtained in all three groups, there was no significant change in TNF-alpha. A comparison of TS, OP CAB, and CPB CAB revealed that the CS patients had higher levels on d0, dx, d3, and d5. Serum levels of CRP, LBP, and IL-2R increased from dx+ to d5 in all groups and reached maximum values on d3. Whereas we found no difference in CRP and IL-2R between the groups, LBP levels were significantly higher from dx+ to d3 after OP CAB. PCT was elevated from dx+ to d3 in all pts. Similar levels were noted for the TS and OP CAB patients. The CPB CAB patients showed the highest levels.. Surgical trauma and reperfusion injury appear to represent the predominant factors resulting in immunologic changes after cardiac surgery. Cardiopulmonary bypass (CPB) may be less important for immune response and acute-phase reactions than previously suspected. In addition, our data indicate a relationship between IL-6 synthesis and the degree of surgical trauma. IL-8 appears to be elevated only after cardiac surgery whereas PCT liberation depended on the use of ECC.

Topics: Aged; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cell Division; Coronary Artery Bypass; Coronary Artery Bypass, Off-Pump; Cytokines; Extracorporeal Circulation; Heart Diseases; Humans; Immunity, Innate; Interleukin-6; Interleukin-8; Lymphocyte Activation; Lymphocytes; Middle Aged; Prospective Studies; Protein Precursors; Thoracic Neoplasms; Thoracic Surgical Procedures; Tumor Necrosis Factor-alpha

(1) To investigate the significance of assessment of serum levels of cardiac troponin I (cTnI) and interleukin-8 (IL-8) beside other biomarkers of myocardial injury in scorpion envenomed children. (2) To find the correlation between these biochemical indices with clinical status, prognosis and outcome of these cases.. Forty-one children in Upper Egypt were admitted to Pediatric Intensive Care Unit, Assiut University Hospital, for scorpion envenomation. They were compared with fifteen apparently healthy children of matching age as controls. The victims and controls were subjected to complete clinical examination, full blood count and arterial blood gases analysis. According to severity of scorpion envenomation, 17 children had manifestations of severe envenomation and clinical signs of toxic myocarditis (severe cases), 14 children had moderate manifestations of envenomation without clinical evidence of carditis (moderate cases) and 10 cases showing only mild symptoms of envenomation (mild cases). The serum levels of cTnI and IL-8 beside the enzymatic activities of creatine phosphokinase (CPK), CPK-MB isoenzyme (CPK-MB) and lactate dehydrogenase (LDH) were determined once for mild cases and controls on admission and twice for severe and moderate cases on admission and after 24 hrs. The measurements of electrocardiography (ECG), echocardiographic measurement of % fractional shortening of left ventricule (%SF), left ventricular ejection fraction (LVEF) and cardiac chambers dilatation were done for severe and moderate cases.. All the envenomed victims showed significantly higher mean values of CPK, CPK-MB, LDH, and IL-8 on admission in comparison to control group. cTnI was not detectable in the sera of control group as well as patients with mild envenomation. The mean values of CPK, CPK-MB, LDH, and IL-8 were significantly higher in severe cases while only IL-8 and CPK-MB were significantly higher in moderate cases in comparison with mild cases. The mean values of IL-8, cTnI, CPK, CPK-MB and LDH were significantly higher in severe cases both on admission and on follow-up comparing with moderate cases. The case fatality rate was 12.5% and all were from severe cases with toxic myocarditis (5/41=12.5%). The non-survivors victims showed significant higher mean values of only cTnI on admission and both cTnI and IL-8 on follow up in comparison to the survivors. Significant reduction of % SF and LVEF were noticed among the non-survivors in comparison to survivors. The cTnI showed 100% specificity and sensitivity for diagnosis of myocardial injury in relation to Echo finding in the envenomed victims. In severe cases, cTnI was positively correlated with IL-8 while negatively correlated with %SF and LVEF.. it may be suggested that cTnI is the most specific marker for diagnosis of myocardial injury in scorpion envenomation, which is almost associated with skeletal muscle injury. Other biochemical markers did not show such specificity. Also, IL-8 may be involved in the pathogenesis of myocardial injury of scorpion envenomation. Both cTnI and IL-8 may be useful to forecast the fatal outcome in scorpion envenomation.

Topics: Biomarkers; Bites and Stings; Child; Creatine Kinase; Creatine Kinase, MB Form; Female; Heart Diseases; Humans; Interleukin-8; Isoenzymes; L-Lactate Dehydrogenase; Male; Myocardium; Scorpion Venoms; Troponin I

This study investigated whether cytokines and colony-stimulating factors can predict prognosis in patients with postoperative multiple organ failure (MOF). We evaluated 14 patients with postoperative MOF who underwent operation for cardiovascular disease. Seven patients recovered from MOF (survivors) and seven did not recover and died (nonsurvivors). The white blood cell (WBC) count, granulocyte colony-stimulating factor, monocytic colony-stimulating factor, interleukin-6 (IL-6), and IL-8 were measured on the day the patients were judged to be in MOF and each week thereafter until the patients recovered or died. Survivors and nonsurvivors were equivalent in terms of age, gender, proportion of use of extracorporeal circulation, operation time, volume of blood transfusion, time from operation to the onset of MOF, the MOF score, proportion of bacteremia, duration of MOF, and number of failed organs. The mean duration of MOF was less than 2 weeks in both groups; therefore the measurements were compared on the first day of MOF and 1 week later. No significant differences between the two groups in terms of WBC counts, colony-stimulating factors, and IL-6 levels were noted. However, the serum level of IL-8 was significantly higher in nonsurvivors than in survivors. Patients with a high serum levels of IL-8 at the time of MOF had a poor prognosis.

Topics: Aged; Aged, 80 and over; Bacteremia; Blood Transfusion; Cause of Death; Extracorporeal Circulation; Female; Follow-Up Studies; Forecasting; Granulocyte Colony-Stimulating Factor; Heart Diseases; Humans; Interleukin-6; Interleukin-8; Leukocyte Count; Macrophage Colony-Stimulating Factor; Male; Middle Aged; Multiple Organ Failure; Postoperative Complications; Prognosis; Survival Rate; Time Factors

It is known that lymphocyte function is impaired after cardiopulmonary bypass (CPB). In this study, the lymphocyte stimulation test (LST) with PHA was used before and after CPB in 28 adult patients, and compared with the surgical parameters and serum cytokine (IL-6, IL-8) levels. LST was impaired after CPB in all patients. Although this value usually recovered by the third postoperative day (POD); (normal group, n = 16), some patients showed prolonged duration of the impaired LST (delayed group, n = 12). Therefore, the parameters of surgery, white blood cell (WBC) count, lymphocytes and subsets, and serum cytokine levels were compared between the normal and the delayed groups. There was no significant difference in the number of WBCs or lymphocytes between these two groups. OKT4-positive cells were reduced on the first POD in both groups, and in the normal group, the number of OKT4-positive cells recovered more quickly than in the delayed group. Serum IL-6 and IL-8 levels in the delayed group were elevated after CPB, and were significantly higher in the delayed group than in the normal group. In conclusion, patients who showed prolonged impairment of lymphocyte function may be partly due to prolonged CPB.

Topics: Adult; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Female; Heart Diseases; Heart Valve Prosthesis Implantation; Humans; Interleukin-6; Interleukin-8; Lymphocyte Activation; Lymphocytes; Male; Middle Aged

The proinflammatory cytokines have been implicated in mediating myocardial dysfunction associated with myocardial infarction, severe congestive heart failure, and sepsis. We tested the hypothesis that cytokine levels are elevated after uncomplicated coronary artery bypass grafting and associated with episodes of postoperative myocardial ischemia and dysfunction. Coronary artery bypass grafting was performed under general anesthesia with moderate systemic hypothermia and cold-blood potassium cardioplegic solution. Tumor necrosis factor-alpha and interleukin-6 levels were determined by bioassays, and interleukin-8 levels were measured by a sandwich enzyme-linked immunosorbent assay. Myocardial function and ischemic episodes were assessed by intraoperative transesophageal echocardiography and perioperative 12-channel Holter monitoring. A total of 22 patients were studied, with no deaths or complications. Arterial tumor necrosis factor-alpha rose in a bimodal distribution, peaking at 2 and 18 to 24 hours after the operation (at 20.2 +/- 6.4 pg/ml, [mean +/- standard error of the mean]) and 5.8 +/- 1.6 pg/ml, respectively; before cardiopulmonary bypass: 0.90 +/- 0.20 pg/ml, p < 0.001 for both peaks) then progressively declined to levels before bypass. Arterial interleukin-6 was maximally elevated immediately on termination of cardiopulmonary bypass and peaked again 12 to 18 hours after cardiopulmonary bypass (at 7520 +/- 2439 pg/ml and 6216 +/- 1928 pg/ml, respectively; before bypass: 746 +/- 187 pg/ml, p < 0.0001 for both peaks). Arterial interleukin-8 levels were more variable but followed a similar pattern, peaking in the early period after cardiopulmonary bypass and again at 16 to 18 hours after the operation (at 4110 +/- 1403 pg/ml and 1760 +/- 1145 pg/ml, respectively; before bypass: 461 +/- 158, p < 0.05 for both peaks). By multivariate analysis, the aortic crossclamp time was independently predictive of postoperative cytokine levels. Left ventricular wall motion abnormalities were associated with both interleukin-6 and interleukin-8 levels, worsening scores being associated with increasing levels (for interleukin-6, p = 0.003; for interleukin-8, p = 0.05). Postoperative myocardial ischemic episodes were associated with interleukin-6 levels, six of seven (85%) patients with episodes of myocardial ischemia after a peak in interleukin-6 concentrations (p < 0.01). We conclude that proinflammatory cytokines are elevated after uncomplicated coronary revascul

Topics: Aged; Coronary Artery Bypass; Cytokines; Echocardiography, Transesophageal; Heart Diseases; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Myocardial Ischemia; Postoperative Period; Time Factors; Tumor Necrosis Factor-alpha; Ventricular Dysfunction, Left

To determine the cytokine release during normothermic cardiopulmonary bypass, we have measured plasmatic levels of tumor necrosis factor-alpha and interleukins-1 beta, 6, and 8 in 10 patients during the first 24 hours after the start of bypass. Arterial blood samples were collected at intervals before, during, and after bypass. Interleukin-1 beta was not detectable in the plasma, and traces of tumor necrosis factor-alpha were detected in only three patients at times independent of the cardiopulmonary bypass procedure. Circulating endotoxin remained undetectable. Plasma interleukin-6 and interleukin-8 rose significantly from 2 until 24 hours after the start of bypass (p < 0.05) and peaked respectively at 4 and 2 hours after the beginning of bypass (interleukin-6, 268.1 +/- 131.43 pg/ml; interleukin-8, 370 +/- 420 pg/ml; mean peak +/- standard deviation). Peak values of interleukin-6 and interleukin-8 were correlated neither with the duration of aortic crossclamping or the bypass procedure nor with the hemodynamic parameters recorded at the same times. This study shows that normothermic cardiopulmonary bypass does not induce systemic release of tumor necrosis factor-alpha and interleukin-1 beta. A local production of these cytokines cannot be excluded, because interleukin-6 and interleukin-8 are produced by stimulated macrophages and monocytes in response to tumor necrosis factor-alpha and interleukin-1 beta. Our results, at normothermia, show a similar pattern of interleukin-6 and interleukin-8 release when compared with release during hypothermic cardiopulmonary bypass. Interleukin-8, an important chemotactic neutrophil factor, might play a role in reperfusion injuries observed in lungs and heart after cardiopulmonary bypass.

Topics: Adult; Aged; Aged, 80 and over; Cardiopulmonary Bypass; Cytokines; Endotoxins; Heart Diseases; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Middle Aged; Postoperative Period; Prospective Studies; Temperature; Tumor Necrosis Factor-alpha

To determine whether the serum concentrations of some circulating cytokines (as highly sensitive markers of inflammation) are of value in predicting the outcome of patients with cardiogenic shock and end-stage heart disease, who undergo ventricular assist device implantation until heart transplantation.. Cohort study.. University teaching hospitals.. Twenty patients with cardiogenic shock or end-stage heart disease were consecutively selected for this study, if assist device implantation was performed as a bridge to heart transplantation.. The circulating concentrations of the cytokines interleukin (IL)-1 beta, IL-6, IL-8 and tumor necrosis factor (TNF)-alpha were monitored from the beginning to the end of assist device support two to three times a week, using commercial enzyme-linked immunosorbent assays (ELISA). In all patients, circulating IL-6 and IL-8 values were increased shortly after assist device implantation. In patients with uncomplicated courses, IL-6 and IL-8 concentrations decreased after an initial increase and were low at the time of transplantation, whereas serum cytokine concentrations increased and remained increased in the nonsurvivors (survivors vs. nonsurvivors, p < .001). Circulating IL-1 beta and TNF-alpha concentrations were rarely detectable.. Monitoring of IL-6 and IL-8 values during ventricular assist device support provides a means of early identification of high-risk patients that may allow optimization of antimicrobial therapy and selection of the appropriate time for transplantation.

Topics: Adolescent; Adult; Chi-Square Distribution; Cohort Studies; Female; Heart Diseases; Heart Transplantation; Heart-Assist Devices; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Predictive Value of Tests; Sensitivity and Specificity; Treatment Outcome; Tumor Necrosis Factor-alpha

1 We studied the effects of a form of interleukin-8 (i.e., [Ala-IL8]77) on endothelial dysfunction and myocardial injury in rabbits. Pentobarbitone-anaesthetized rabbits were subjected to 1.5 h occlusion of the marginal coronary artery and 3.5 h reperfusion. [Ala-IL8]77 (50 micrograms or its vehicle) was given i.v. as a bolus 10 min prior to reperfusion. [Ala-IL8]77 was also studied in isolated perfused hearts of rabbits. 2 Myocardial ischaemia plus reperfusion in untreated rabbits produced severe endothelial dysfunction and myocardial injury, including marked myocardial necrosis, elevated cardiac myeloperoxidase (MPO) activity in ischaemic cardiac tissue, and loss of response of marginal coronary rings to the endothelium-dependent vasodilators, acetylcholine (ACh) and A23187. 3 Administration of [Ala-IL8]77 10 min prior to reperfusion resulted in significant protective effects in post-ischaemic reperfusion. Compared with untreated rabbits, [Ala-IL8]77 caused a reduced necrotic zone (P less than 0.01), lower MPO activity in the necrotic zone (P less than 0.05), and significantly preserved vasorelaxant responses of marginal coronary artery rings to endothelium-dependent vasodilators, ACh (P less than 0.001) and A23187 (P less than 0.001). 4 These results indicate that myocardial ischaemia and reperfusion result in a severe endothelial dysfunction and myocardial injury which involved the interaction of neutrophils and endothelial cells. However, [Ala-IL8]77 did not appear to exert a direct endothelial protective effect in the absence of neutrophils in rabbit isolated perfused hearts. 5 Inhibition of neutrophil accumulation in the myocardium, perhaps by prevention of endothelial dysfunction resulting from [Ala-IL8]77, leads to significant protective effects in ischaemia and reperfusion in rabbits.

Topics: Acetylcholine; Animals; Blood Pressure; Calcimycin; Coronary Disease; Endothelium, Vascular; Heart Diseases; Heart Rate; In Vitro Techniques; Interleukin-8; Male; Myocardial Reperfusion Injury; Myocardium; Neutrophils; Nitric Oxide; Peroxidase; Rabbits; Superoxides