interleukin-8 and Ventricular-Dysfunction--Left

Inflammation and matrix degradation may play a pathogenic role in chronic heart failure (CHF), and therefore, we examined whether thalidomide, a drug with potential immunomodulating and matrix-stabilizing properties, could improve left ventricular (LV) function in patients with CHF secondary to idiopathic dilated cardiomyopathy (IDCM) or coronary artery disease (CAD).. Fifty-six patients with CHF and an LV ejection fraction (LVEF) <40% who were already on optimal conventional cardiovascular treatment were randomized to thalidomide (25 mg QD increasing to 200 mg QD) or placebo and followed up for 12 weeks. Our main findings were as follows: (1) During thalidomide treatment but not during placebo, there was a marked increase in LVEF (&7 EF units) along with a significant decrease in LV end-diastolic volume and heart rate. (2) This improvement in LVEF was accompanied by a decrease in matrix metalloproteinase-2 without any changes in its endogenous tissue inhibitor, suggesting a matrix-stabilizing net effect. (3) Thalidomide also induced a decrease in total neutrophil count and an increase in plasma levels of tumor necrosis factor-alpha, suggesting both proinflammatory and antiinflammatory effects. (4) The effect of thalidomide on LVEF was more marked in IDCM than in CAD, possibly partly reflecting that the former group was able to tolerate a higher thalidomide dosage.. Although our results must be confirmed in larger studies that also examine the effects on morbidity and mortality, our findings suggest a role for thalidomide in the management of CHF in addition to traditional cardiovascular medications.

Topics: Aged; Cardiomyopathy, Dilated; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Heart Failure; Humans; Immune System; In Vitro Techniques; Interleukin-8; Matrix Metalloproteinase 2; Middle Aged; Placebos; Thalidomide; Tissue Inhibitor of Metalloproteinase-1; Tumor Necrosis Factor-alpha; Ventricular Dysfunction, Left

The aim of the present study was to investigate whether the nitric oxide donor sodium nitroprusside can reduce the cardiac inflammatory response during coronary artery bypass grafting in patients with severely compromised left ventricular function.. Patients (n = 30) were assigned to receive placebo or sodium nitroprusside (0.5 microg. kg(-1). min(-1)) for the first 60 minutes of reperfusion. Interleukin 6, interleukin 8, and tumor necrosis factor alpha levels; platelet adhesion molecule CD41 and CD62 levels; and CD11b on leukocytes were determined in the radial artery and coronary sinus before cardiopulmonary bypass and during reperfusion (1, 5, 10, 35, and 75 minutes).. At 1 minute of reperfusion, coronary venous levels of CD41-positive polymorphonuclear leukocytes were 8% lower than arterial levels in the placebo group and 18% higher in the sodium nitroprusside group (P =.021). At 5 minutes of reperfusion, the respective levels were 29% and 1% for interleukin 6 (P =.015), -5% and 20% for CD41-positive monocytes (P =.032), and -2% and 16% for CD11b-positive monocytes (P =.038). At 10 minutes of reperfusion, these levels were -14% and 21% for CD41-positive monocytes (P =.006). At 35 minutes of reperfusion, these levels were -13% and 7% for CD41-positive monocytes (P =.017), -41% and 23% for CD11b-positive monocytes (P =.001), and 7% and 25% for CD62-positive platelets (P =. 041). At 75 minutes of reperfusion, the levels were 15% and -7% for tumor necrosis factor alpha (P =.025) and -10% and 10% for CD62-positive platelets (P =.041).. Transcardiac production of proinflammatory cytokines is reduced in patients undergoing coronary artery bypass grafting treated with the nitric oxide donor sodium nitroprusside. At the same time, less activated leukocytes and platelets are retained in the coronary circulation.

Topics: Aged; Antigens, CD; Coronary Artery Bypass; Double-Blind Method; Female; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Nitroprusside; Postoperative Complications; Prospective Studies; Tumor Necrosis Factor-alpha; Ventricular Dysfunction, Left

SARS-CoV-2 infection in children can trigger cardiovascular manifestations potentially requiring an intensive treatment and defining a new entity named Multisystem Inflammatory Syndrome in Children (MIS-C), whose features partially overlap with Kawasaki Disease (KD). A cross-sectional study including all diagnoses of MIS-C and KD from April 2020 to May 2021 in our metropolitan area was conducted evaluating clinical, laboratory (including immunological response, cytokines, and markers of myocardial damage), and cardiac (coronary and non-coronary) features at onset of the diseases. Evolution of ventricular dysfunction, valve regurgitations, and coronary lesions was documented. The severity of the disease was also considered based on the need for inotropic support and ICU admission. Twenty-four MIS-C were diagnosed (14 boys, median age 82 months): 13/24 cases (54.17%) presented left ventricular dysfunction, 12/24 (50%) required inotropic support, and 10/24 (41.67%) developed coronary anomalies (CALs). All patients received steroids and IVIG at a median time of 5 days (IQR1:4, IQR3:6.5) from onset of fever and heart function normalized 6 days (IQR1: 5, IQR3: 7) after therapy, while CALs persisted in one. One patient (12.5%) required infliximab because of refractory disease and still presented CALs 18 days after therapy. During the same study period, 15 KD were diagnosed: none had ventricular dysfunction, while 7/15 (46.67%) developed CALs. Three out of 15 patients (20%) still presented CALs 46 days from onset. Compared to KD, MIS-C pts have significantly higher IL8 and similar lymphocytes subpopulations. Despite a more severe presentation and initial cardiac findings compared to KD, the myocardial injury in MIS-C has a rapid response to immunomodulatory treatment (median time 6 days), in terms of ventricular function, valve regurgitations, and troponin. Incidence of CALs is similar at onset, but it tends to regress in most of the cases of MIS-C differently than in KD where CALs persist in up to 40% in the subacute stage after treatment.

Topics: Adolescent; Child; Child, Preschool; COVID-19; Cross-Sectional Studies; Female; Humans; Infant; Infant, Newborn; Interleukin-10; Interleukin-8; Italy; Male; Mucocutaneous Lymph Node Syndrome; Myocardium; Prospective Studies; SARS-CoV-2; Systemic Inflammatory Response Syndrome; Ventricular Dysfunction, Left

Several lines of evidence indicate that increased inflammatory cytokine levels can be used for risk prediction in patients with acute coronary syndrome (ACS). This study therefore aimed to evaluate correlations between levels of soluble interleukin (IL)-2 receptor (sIL-2r), IL-6, and IL-8 and in-hospital incidence of acute heart failure (AHF) and left ventricular (LV) systolic dysfunction in the subacute phase of ACS. In 48 consecutive patients with ACS, circulating levels of sIL-2r, IL-6, and IL-8 were ascertained 72-96 h after onset of symptoms. Clinical data, LV function, and in-hospital incidence of AHF were also evaluated. IL-8 levels were significantly higher in patients with pulmonary edema (1,829 ± 2,496 vs 456 ± 624 pg/ml, p < 0.05); sIL-2r, IL-6, and IL-8 levels were increased proportionally to Killip class (r = 0.35, p < 0.05; r = 0.48, r = 0.47, p < 0.01) and in patients with LV ejection fraction (LVEF) < 30%. Levels of sIL-2r were inversely related to LVEF in subjects with acute myocardial infarction (r = -0.51, p < 0.05). Soluble IL-2r and IL-8 levels were related to mitral regurgitation severity (r = 0.34, p < 0.05; r = 0.37, p < 0.05). Levels of sIL-2 were proportional to LV end-diastolic diameter (r = 0.49, p < 0.001) and LV end-systolic diameter (r = 0.58, p < 0.001). Number of cytokines with circulating values above upper level of normal was significantly correlated with Killip class and LVEF (r = 0.40, r = -0.38, p < 0.05). sIL-2r, IL-6, and IL-8 are increased in patients with ACS and systolic dysfunction or AHF. These data suggest that inflammatory cytokine activity detectable in peripheral blood may be useful in identifying subjects with a worse clinical course.

Topics: Acute Coronary Syndrome; Adult; Aged; Aged, 80 and over; Female; Heart Failure; Humans; Interleukin-2; Interleukin-6; Interleukin-8; Male; Middle Aged; Myocardial Infarction; Pulmonary Edema; Receptors, Interleukin-2; Ventricular Dysfunction, Left

Atrial fibrillation (AF) might be associated with an inflammatory activation and reduced left ventricular (LV) function. Less is known with regard to newly introduced markers of LV dysfunction such as carbohydrate antigen-125 (CA-125) in subjects with AF. The aim of this study was therefore to assess possible associations between AF, inflammatory markers and CA-125.. Forty-eight consecutive patients with AF and 58 control patients in sinus rhythm were enrolled in this study. Patients with acute heart failure, chronic inflammatory or neoplastic disease were excluded from the study. Circulating levels of hs-C-reactive protein (CRP), interleukin-8 (IL-8), IL-6, soluble IL-2 receptor (sIL-2r), TNF-α and CA-125 were assessed; all patients underwent clinical examination with NYHA class assessment and echocardiography. Patients with AF were characterised by higher levels of IL-8 (180 ± 266 vs. 39 ± 43 pg/mL, P < 0·001), sIL-2r (987 ± 1045 vs. 680 ± 336 U/mL, P < 0·05) and TNF-α (26 ± 25 vs. 9 ± 4 pg/mL, P < 0·001). Patients with AF duration < 6 months had higher levels of CRP (54 ± 73 vs. 12 ± 14 mg/dL, P < 0·05) and IL-8 (251 ± 225 vs. 99 ± 123 pg/mL, P < 0·05) when compared with AF duration > 6 months. CA-125 levels were not statistically different if comparing subjects with AF with controls and AF > 6 months with AF < 6 months. Among patients with AF, CA-125 levels were significantly related to NYHA class, (r = 0·33, P < 0·05) as well as IL-6 levels (r = 0·31, P < 0·05). Results remained statistically significant even after multivariable correction for age, gender and LV ejection fraction.. AF is characterised by an inflammatory activation. Impaired functional class in AF subjects might be associated with increased CA-125 levels and higher inflammatory markers.

Topics: Aged; Atrial Fibrillation; Biomarkers; C-Reactive Protein; CA-125 Antigen; Case-Control Studies; Cytokines; Female; Humans; Inflammation; Interleukin-6; Interleukin-8; Male; Multivariate Analysis; Receptors, Interleukin-2; Tumor Necrosis Factor-alpha; Ventricular Dysfunction, Left

Hypertension is one of the main drivers of the heart failure (HF) epidemic. The aims of this study were to profile fibro-inflammatory biomarkers across stages of the hypertensive heart disease (HHD) spectrum and to examine whether particular biochemical profiles in asymptomatic patients identify a higher risk of evolution to HF.. This was a cross-sectional observational study involving a population of 275 stable hypertensive patients divided into two different cohorts: Group 1, asymptomatic hypertension (AH) (n= 94); Group 2, HF with preserved ejection fraction  (n= 181). Asymptomatic hypertension patients were further subdivided according to left atrial volume index ≥34 mL/m(2) (n= 30) and <34 mL/m(2) (n= 64). Study assays involved inflammatory markers [interleukin 6 (IL6), interleukin 8 (IL8), monocyte chemoattractant protein 1 (MCP1), and tumour necrosis factor α], collagen 1 and 3 metabolic markers [carboxy-terminal propeptide of collagen 1, amino-terminal propeptide of collagen 1, amino-terminal propeptide of collagen 3 (PIIINP), and carboxy-terminal telopeptide of collagen 1 (CITP)], extra-cellular matrix turnover markers [matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), and tissue inhibitor of metalloproteinase 1 (TIMP1)], and the brain natriuretic peptide. Data were adjusted for age, sex, systolic blood pressure, and creatinine. Heart failure with preserved ejection fraction  was associated with an increased inflammatory signal (IL6, IL8, and MCP1), an increased fibrotic signal (PIIINP and CITP), and an increased matrix turnover signal (MMP2 and MMP9). Alterations in MMP and TIMP enzymes were found to be significant indicators of greater degrees of asymptomatic left ventricular diastolic dysfunction.. These data define varying fibro-inflammatory profiles throughout different stages of HHD. In particular, the observations on MMP9 and TIMP1 raise the possibility of earlier detection of those at risk of evolution to HF which may help focus effective preventative strategies.

Topics: Aged; Biomarkers; Chemokine CCL2; Cross-Sectional Studies; Diastole; Echocardiography, Doppler; Female; Heart Atria; Heart Failure; Humans; Hypertension; Interleukin-6; Interleukin-8; Male; Matrix Metalloproteinase 9; Tissue Inhibitor of Metalloproteinase-1; Ventricular Dysfunction, Left; Ventricular Remodeling

Patients with depressed left ventricular function are more susceptible to develop postoperative complications after cardiac surgery. The aim of the present study was to examine the effect of severe left ventricular dysfunction on the activation of systemic inflammatory reaction during and after coronary artery bypass grafting (CABG).. Clinical prospective study; 32 selected patients underwent CABG; 16 patients had depressed left ventricular function before the operation (low ejection fraction [EF] <30%)--Low EF group (study group). Sixteen patients had normal left ventricular function (normal EF, >50%)--Normal EF group (control group). The levels of inflammatory mediators TNF-alpha, IL-6, IL-8 and IL-10 were measured preoperatively, during and after cardiopulmonary bypass (CPB) and 24 hours postoperatively.. Higher levels of almost all of inflammatory mediators were detected in patients with depressed left ventricular function compared with patients of normal EF group. IL-6 levels were found statistically significant higher in Low EF group before the induction of anesthesia (P=0.039) and after the administration of protamine (P=0.02). IL-8 levels were found statistically significant higher in Low EF group before the induction of anesthesia (P=0.05), 30 min after the start of CPB (P=0.02), after the administration of protamine (P=0.015) and 24 hours after the end of the operation (P=0.05). No statistically significant differences were demonstrated between the 2 groups of study relative to TNF-alpha and IL-10.. A greater activation of systemic inflammatory reaction occurred in patients with depressed left ventricular function than in patients with normal cardiac function when they underwent CABG with extracorporeal circulation.

Topics: Aged; Coronary Artery Bypass; Female; Humans; Inflammation Mediators; Interleukin-10; Interleukin-6; Interleukin-8; Male; Stroke Volume; Systemic Inflammatory Response Syndrome; Tumor Necrosis Factor-alpha; Ventricular Dysfunction, Left

In the present study, 41 children in Upper Egypt were admitted to Pediatric Intensive Care Unit, Assiut University Hospital, for scorpion envenomation. They were compared with 15 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 cardiac troponin I (cTnI) and interleukin-8 (IL-8) beside the enzymatic activities of creatine phosphokinase (CPK), CPK-isoenzyme-MB (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. Electrocardiography and measurements of echocardiographic (Echo) 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 of 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. 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. In conclusion, cTnI is a specific marker for diagnosis of myoca

Topics: Animals; Antivenins; Child; Creatine Kinase; Creatine Kinase, MB Form; Echocardiography; Electrocardiography; Female; Humans; Interleukin-8; Isoenzymes; L-Lactate Dehydrogenase; Male; Myocarditis; Scorpion Stings; Scorpions; Survival Rate; Troponin I; Ventricular Dysfunction, Left

Cardiopulmonary bypass and cardiac operations are obligatorily connected with systemic inflammatory reaction. Production of proinflammatory cytokines is responsible also for negative effects on the myocardial function.. Follow-up of the dynamic changes of proinflammatory and antiinflammatory cytokine levels in patients with left ventricular dysfunction during the first week after cardiac surgery.. A total of nine patients with a very low left ventricular ejection fraction (22.75 +/- 0.65%) who had undergone cardiac surgery (for coronary artery bypass grafting or aortic valve reconstruction) were investigated during the first after week operation. The preoperative and postoperative plasma levels of tumor necrosis factor (TNF), interleukin-8 (IL-8) and interleukin-10 (IL-10) were estimated by means of ELISA technique.. With respect to the preoperative levels, on the first postoperative day the levels IL-8 (from 9.36 to 16.65 pg/ml) (p < 0.05) and of IL-10 (from 6.93 to 28.09 pg/ml) (p < 0.02) significantly rose with a stepwise decrease down to the seventh day after surgery. From the third to seventh day an insignificant increase in TNF level was also noted.. The results have shown that open heart surgery in patients with a severe left ventricular dysfunction evoked a systemic inflammatory response demonstrated by early increase in proinflammatory cytokine IL-8 and was accompanied by increased level of antiinflammatory cytokine IL-10. Despite stepwise decrease in IL-8 levels, they did not reach the preoperative levels, not even on the seventh postoperative day. (Tab. 1, Fig. 3, Ref. 21.)

Topics: Aged; Cardiac Surgical Procedures; Cytokines; Female; Humans; Interleukin-10; Interleukin-8; Male; Middle Aged; Stroke Volume; Tumor Necrosis Factor-alpha; Ventricular Dysfunction, Left

Proinflammatory cytokines have been implicated in mediating myocardial dysfunction associated with major surgery. We investigated the profile of proinflammatory cytokines and the association of cytokine levels with myocardial function after esophagectomy. We studied 12 patients who underwent subtotal esophagectomy. One patient died of multiple organ failure. This patient had the largest interleukin-6 (IL-6) level of all the subjects. IL-6 levels increased from 14.9 +/- 8.7 pg/mL to 498.4 +/- 294.3 pg/mL (P < 0.05) at 6 h postoperatively. Interleukin-8 (IL-8) levels also significantly increased postoperatively. Right ventricular ejection fraction (RVEF) decreased from 44% +/- 1% to 36% +/- 2% (P < 0.05) and 37% +/- 2% (P < 0.05) at 6 h and 12 h postoperatively. Stroke volume index (SVI) decreased significantly at the end of operation and at 6 h and 12 h postoperatively. The changes of RVEF and SVI showed an independent negative correlation with the IL-6 level (r = -0.70, P < 0.001 and r = -0.62, P < 0.001, respectively). In contrast, the change of RVEF and SVI was not correlated with the IL-8 level. Esophagectomy is associated with transient depression of myocardial function. IL-6 may contribute to this postoperative myocardial dysfunction.. We examined the association between myocardial function and proinflammatory cytokines after esophagectomy. Interleukin-6 may be the cytokine that most sensitively reflects the postoperative myocardial dysfunction.

Topics: Carcinoma, Squamous Cell; Epinephrine; Esophageal Neoplasms; Esophagectomy; Female; Hemodynamics; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Norepinephrine; Stroke Volume; Ventricular Dysfunction, Left

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