interleukin-8 and Myocardial-Ischemia

Topics: Animals; Cell Adhesion Molecules; Cell Movement; Chemokines; Chemotactic Factors; Complement Activation; Humans; Inflammation; Inflammation Mediators; Interleukin-8; Lipids; Models, Cardiovascular; Myocardial Ischemia; Myocardial Reperfusion Injury; Neutrophils; Selectins

Granulocyte apoptosis is a key control process in the clearance of neutrophils from inflammatory sites, and its rate is modulated by a number of inflammatory mediators. In this study, we investigated whether the use of left ventricular-assisted technique (LVA) in beating heart myocardial revascularization would exert less impact on neutrophil apoptosis compared with conventional cardiopulmonary bypass (CPB).. Forty consecutive patients who underwent myocardial revascularization were randomly assigned to LVA (group A, 21 patients) or CPB (group B, 19 patients). Blood samples for detection of interleukin-6, interleukin-8, and tumor necrosis factor-alpha were measured at baseline and at various time points postoperatively. Neutrophil apoptosis was detected by light microscopy as well as by the annexin-V assays together with the activity of caspase 3 on postoperative samples.. Preoperative clinical and demographic data did not differ between the two groups. The two groups also were similar with respect to mortality, number of grafts performed, duration of extracorporeal circulation, and need for inotropes. However postoperatively, spontaneous apoptosis was significantly delayed in neutrophils from CPB patients compared with LVA patients. Neutrophils were activated, as indicated by increased surface expression of CD11b. Caspase 3 activity was found to be significantly reduced in neutrophils from CPB patients after 18 and 24 hours of culture.. Patients who underwent beating heart myocardial revascularization with LVA show a better preserved neutrophil apoptosis than patients treated with the CPB.

Topics: Aged; Analysis of Variance; Annexin A5; Apoptosis; Cardiopulmonary Bypass; Caspase 3; Chi-Square Distribution; Female; Heart-Assist Devices; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Myocardial Ischemia; Myocardial Revascularization; Neutrophils; Prospective Studies; Statistics, Nonparametric; Treatment Outcome; Tumor Necrosis Factor-alpha

We studied effects of beta-adrenoblocker carvedilol vs placebo in 60 patients with chronic cardiac failure (CCF) of functional classes III-IV in a 6-month open randomized trial. We examined clinical course, exercise tolerance (a 6 min walk test), endothelial state markers (endothelium-dependent vasodilation, number of circulating endotheliocytes) and activity of systems affecting endothelium (triglycerides, malonic dialdehyde, IL-8, uric acid). The drug was added to conventional therapy (ACE inhibitors, diuretics, cardiac glycosides) in a stable CCF course. Carvedilol group of patients demonstrated a marked trend to reduction of the number of hospitalizations, attenuation of CCF, better tolerance to exercise, lower levels of uric acid (p < 0.05), malonic dialdehyde (p < 0.05) and IL-8 (p = 0.09). There was also wider basal diameter of the brachial artery, and in the diameter at the peak of reactive hyperemia (p = 0.07). The effect was dose-dependent: in patients given 25-50 mg/day of carvedilol there was a trend to a lower circulation of endotheliocytes, triglyceridemia, lipid peroxidation and chronic inflammation. Thus, long-term treatment of CCF with inclusion of standard doses of carvedilol not only improves clinical status of the patients but produces a noticeable endothelioprotective effect.

Topics: Adrenergic beta-Antagonists; Carbazoles; Carvedilol; Dose-Response Relationship, Drug; Drug Therapy, Combination; Endothelium, Vascular; Heart Failure; Humans; Interleukin-8; Lipid Peroxidation; Male; Malondialdehyde; Middle Aged; Myocardial Ischemia; Propanolamines; Time Factors; Treatment Outcome; Triglycerides; Uric Acid

The release of proinflammatory cytokines has been shown to be associated with the development of complications after coronary artery bypass grafting with cardiopulmonary bypass. The purpose of the present study was to establish whether ischemic preconditioning (IP) could limit inflammatory cytokines release in patients undergoing elective coronary artery bypass surgery.. Twenty-two patients with multiple-vessel coronary artery disease and stable angina admitted for first-time elective coronary artery bypass surgery were randomized into control or ischemic preconditioning groups. Patients in the IP group were exposed to two cycles of two-minute myocardial ischemia, followed by three minutes of reperfusion, at the beginning of the revascularization operation, before the cross-clamping and ischemic period used for coronary artery bypass graft anastomosis. Peripheral plasma levels of TNF-alpha, IL-6, IL-8 and IL-10 were measured perioperatively.. Significant elevation of IL-6, IL-8 and IL-10 were observed in both groups after reperfusion. Ischemic preconditioning has no effect on cytokine release in the early stage after reperfusion. Arterial blood IL-6 levels in the preconditioning group were significantly lower than in controls at 20 h after declamping (52.93 +/- 9.79 vs 96.04 +/- 17.56 pg/ml, p < 0.05).. The results indicate that ischemic preconditioning results in no effect on systemic inflammatory cytokine release in the early stage but a delayed reduction in IL-6 levels at 20 h after reperfusion.

Topics: Aged; Coronary Artery Bypass; Cytokines; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Ischemic Preconditioning, Myocardial; Male; Middle Aged; Myocardial Ischemia; Postoperative Period; Tumor Necrosis Factor-alpha

Many cardiac surgeries are performed with blood cardioplegia. However, some studies suggest that activated neutrophils form blood cardioplegia can cause reperfusion injury. In this study we assessed myocardial protection using a leukocyte-depleted cardioplegic solution. Patients undergoing elective coronary artery bypass grafting (CABG) with continuous blood cardioplegia were divided into two groups: the LD group, which received leukocyte-depleted blood cardioplegia (n = 11); and the control group, which received nonfiltered blood cardioplegia (n = 11). IL-6, IL-8, CK-MB, and troponin T were measured in the coronary sinus blood immediately after the release of the aortic cross-clamp. Cytokine concentrations were also measured upon the patient's return to the ICU. The total dopamine and dobutamine doses, hemodynamic measurements after surgery, and the leukocyte filtration rate were also measured. During antegrade cardioplegia infusion, leukocytes were almost completely removed (filtration rate: 85.8+/-4.0%). However, during terminal warm cardioplegia, leukocyte removal decreased (filtration rate: 39.9+/-7.8%). Immediately after the release of the aortic cross-clamp, plasma CK-MB and troponin T concentrations were significantly lower in the LD group (17.7+/-1.9 U/l and 0.017+/-0.002 ng/ml, respectively) than in the control group (30.3+/-3.6 U/l and 0.072+/-0.029 ng/ml, respectively). The IL-6 and IL-8 concentrations were similar in the LD group and the control group. After the return to the ICU, the CK-MB and troponin T concentrations were similar in the two groups. No significant differences were found in the total doses of dopamine or dobutamine after surgery in the two groups (99+/-77 vs 101+/-128 microg/kg/min). No significant differences were found in the hemodynamic parameters after surgery in the two groups. In patients undergoing CABG with continuous blood cardioplegia, leukocyte-depleted blood cardioplegic solution may attenuate reperfusion injury.

Topics: Cardioplegic Solutions; Casein Kinase II; Coronary Artery Bypass; Heart Arrest, Induced; Humans; Interleukin-6; Interleukin-8; Leukapheresis; Middle Aged; Myocardial Ischemia; Myocardial Reperfusion Injury; Protein Serine-Threonine Kinases

Interleukin-8 (IL-8) secreted from endothelial cells is a powerful neutrophil chemoattractant and activator. We hypothesized that human endothelial cells deprived of oxygen would secrete IL-8, which might translate into elevated IL-8 production after cardiac ischemia. Furthermore, we hypothesized that coronary sinus (CS) IL-8 levels would be particularly high after cardiac preservation for transplantation, due to extended ischemic times.. Human saphenous vein endothelial cells exposed to a hypoxic environment (PO2 < 20 mm Hg) demonstrated a time-dependent release of IL-8 (measured by ELISA) into the culture supernatant as early as 4 hours after exposure. To determine whether cardiac preservation in humans was associated with IL-8 production, we obtained CS blood samples 5 minutes after reperfusion in a consecutive series of patients after they underwent cardiac transplantation (CTX, n = 20) or elective cardiac surgery (non-CTX, n = 21). CTX patients demonstrated significantly higher CS IL-8 levels than non-CTX patients (325 +/- 123 versus 50 +/- 17 ng/mL, respectively, P < .05). Further analysis of the CS samples revealed that a biochemical marker of myocyte injury (myoglobin) was similarly elevated in the CTX patients compared with the non-CTX patients (3340 +/- 625 versus 1151 +/- 525 ng/mL, respectively, P < .05).. These differences may reflect the longer ischemic times of CTX compared with non-CTX hearts (161 +/- 10 versus 80 +/- 6 minutes, P < .0001) and suggest that the neutrophil chemoattractant/activator IL-8 may contribute to myocyte injury after prolonged hypothermic cardiac ischemia, as occurs during human cardiac transplantation.

Topics: Aged; Cells, Cultured; Endothelium, Vascular; Female; Heart Transplantation; Humans; Interleukin-8; Male; Middle Aged; Myocardial Ischemia; Postoperative Period; Reference Values; Saphenous Vein

Imbalances of proatherogenic inflammatory and antiatherogenic inflammatory mediators were involved in the pathogenesis of atherosclerosis. This study sought to investigate the effects of proatherogenic inflammatory and antiatherogenic inflammatory mediators on the proximal, middle, and distal coronary artery reocclusions in elderly patients after coronary stent implantations. We measured the expression levels of proatherogenic inflammatory/antiatherogenic inflammatory cytokines. This included interleukin-1

Topics: Aged; Aged, 80 and over; Angina Pectoris; C-Reactive Protein; Coronary Artery Disease; Cytokines; Female; Humans; Interleukin-1; Interleukin-10; Interleukin-13; Interleukin-6; Interleukin-8; Male; Multivariate Analysis; Myocardial Ischemia; Tumor Necrosis Factor-alpha

Ischemic heart disease remains the largest cause of death worldwide. Accordingly, many researchers have sought curative options, often using laboratory animal models such as rodents. However, the physiology of the human heart differs significantly from that of the rodent heart. In this study, we developed a model of ischemic heart disease using cardiomyocytes differentiated from human induced pluripotent stem cells (hiPS-CMs). After optimizing the conditions of ischemia, including the concentration of oxygen and duration of application, we evaluated the consequent damage to hiPS-CMs. Notably, exposure to 2% oxygen, 0 mg/ml glucose, and 0% fetal bovine serum increased the percentage of nuclei stained with propidium iodide, an indicator of membrane damage, and decreased cellular viability. These conditions also decreased the contractility of hiPS-CMs. Furthermore, ischemic conditioning increased the mRNA expression of IL-8, consistent with observed conditions in the in vivo heart. Taken together, these findings suggest that our hiPS-CM-based model can provide a useful platform for human ischemic heart disease research.

Topics: Animals; Cell Differentiation; Cell Line; Cell Survival; Cells, Cultured; Gene Expression; Humans; Induced Pluripotent Stem Cells; Interleukin-8; Models, Cardiovascular; Myocardial Contraction; Myocardial Ischemia; Myocytes, Cardiac; Rats; RNA, Messenger

Interleukin 8 (IL-8) is an important pro-inflammatory cytokine that recruits neutrophil to the areas of inflammation and has been implicated in myocardial ischemia reperfusion injury (MIRI). This study aimed to apply IL-8 targeted myocardial contrast echocardiography (MCE) to evaluate MIRI in rabbits. MCE imaging with IL-8 targeted microbubbles (MB

Topics: Animals; Contrast Media; Echocardiography; Interleukin-8; Male; Microbubbles; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion; Myocardial Reperfusion Injury; Myocardium; Rabbits

To observe the effects of electroacupuncture (EA) on inflammatory reaction of acute myocardial ischemia (MI) in mice, and to explore its action mechanism.. Forty adult male C57BL/6 mice were randomly divided into a control group, a sham operation group, a model group and an EA group, 10 mice in each one. The model was established in the model group and EA group by ligating the left anterior descending branch of coronary artery. The mice in the EA group were treated with EA at "Neiguan" (PC 6) with 2 mA of intensity and 2 Hz /100 Hz of frequency; EA was given 30 min per treatment, once a day for totally 5 days. The mice in the control group and model group were treated with immobilization and no EA was given. The mice in the sham operation group were not treated with ligating at the left anterior descending branch of coronary artery, but the remaining procedure was identical to the model group. The electrocardiogram was recorded and △ST was calculated to evaluate the model. TTC and HE staining methods were applied to evaluate the infarct size and pathologic change of myocardial tissue, respectively. Western blot method was applied to test the protein expression levels of tumor necrosis factor-α (TNF-α), nuclear factor-κB p65 (NF-κB p65), interleukin-1β (IL-1β) and interleukin-8 (IL-8).. Compared with the sham operation group, the S-T segments in the model group and EA group were increased obviously after modeling (both. EA might reduce the protein expression levels of TNF-α, NF-κB p65, IL-1β and IL-8 in cardiac muscle tissue to inhibit inflammatory reaction and achieve myocardial protective effect in mice with acute myocardial ischemia.

Topics: Animals; Electroacupuncture; Inflammation; Interleukin-1beta; Interleukin-8; Male; Mice; Mice, Inbred C57BL; Myocardial Ischemia; Myocardium; Random Allocation; Transcription Factor RelA; Tumor Necrosis Factor-alpha

The increase in Rheumatoid arthritis (RA) associated mortality is predominantly due to accelerated coronary artery and cerebrovascular atherosclerosis with increased risk of ischemic heart disease about 50% in RA patients compared to controls.. To study the pathogenesis of ischemic heart disease in RA, role of inflammatory cytokine interplay, disease activity and rheumatoid factor positivity.. Eighty RA patients and 44 healthy controls were included. All subjects were younger than 45years for females and 55years for males with exclusion of all traditional risk factors for atherosclerosis. Interleukin (IL) 1, 6 and 18 were assessed in all subjects. RA patients fulfilled ACR/EULAR 2010 criteria and were subjected to Dobutaminestress-echocardiography, diseases activity assessed by DAS-28, X-ray hands for Larsen score and function assessment by HAQ.. RA patients had significantly higher serum IL 1, 6 and 18 than controls (p=0.00 in all). Thirty four (42.5%) patients had hypertensive reaction on Dobutamine-stress-echocardiography, four of them had ischemic change, and 46 (57.5%) had normal reaction. All patients with hypertensive reaction had positive RF (p=0.00), 10 had DAS-28>5.1, 20 had DAS-28 from 3.2 to5.1 and 4 were in remission (p=0.001). CRP was higher in patients with hypertensive reaction (p=0.003) while serum levels of IL1, 6 and 18 showed no significant difference. In all patients, serum levels of IL1, 6 and 18 showed significant positive correlation with VAS, HAQ and DAS-28 (p<0.001 in all). Only IL18 showed significant positive correlation with X-ray score in all patients.. Disease activity and RF positivity play an important risk factor for ischemic heart disease in RA. Serum levels of IL1, 6 and 18 did not help much in detecting patients at risk of ischemic heart disease. Better control of RA disease activity with early remission helps in preventing cardiac complications. More studies on larger number of patients are needed for better understanding of mechanism of ischemic heart disease in RA.

Topics: Adult; Arthritis, Rheumatoid; Atherosclerosis; Coronary Artery Disease; Cross-Sectional Studies; Cytokines; Female; Humans; Inflammation; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Middle Aged; Myocardial Ischemia; Risk Factors; Severity of Illness Index

The role of endothelium in the progression of atheromasic disease has already been demonstrated. Endothelin-1 (ET-1) is released from endothelial cells during acute and chronic vascular damage and it appears to be the strongest vasoconstrictor agent known.The aim of this study is to investigate the amount of endothelial damage in patients with unstable angina (UA), as defined by serum levels of ET-1, to verify a possible correlation with increased ischaemic damage by evaluation of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and interleukin 8 (IL-8) levels.Serum levels of ET-1, IL-8 and NT-proBNP obtained from 10 patients affected by low-risk UA were compared to those belonging to eight healthy subjects. In order to compare the laboratory data pertaining to the two populations, a Student's t-test and a Mann-Whitney U test were performed.Levels of ET-1, IL-8 and NT-proBNP in samples of peripheral blood of patients affected by UA were significantly elevated, compared with those of the control group. The linear correlation analysis demonstrated a positive and significant correlation between levels of ET-1 and IL-8, between levels of ET-1 and NT-proBNP, and between levels of IL-8 and NT-proBNP in subjects affected by UA.Early elevated levels of ET-1, IL-8 and NT-proBNP in patients with UA show a coexistence between ischaemic insults and endothelial damages. A positive and significant linear correlation between levels of ET-1 and IL-8, between levels of ET-1 and NT-proBNP, and between levels of IL-8 and NT-proBNP confirms that an increased ischaemic insult is correlated to inflammation signs and endothelium damage signs.In patients with UA, ischaemia is always associated with a systemic immuno-mediated activity induced by acute endothelial damage. We suggest early administration of ET-1-selective receptor blockers and anti-inflammatory drugs.

Topics: Acute Disease; Adult; Angina, Unstable; Endothelial Cells; Endothelin-1; Endothelium; Female; Humans; Immunologic Factors; Inflammation; Interleukin-8; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments

This study was designed to investigate whether epigallocatechin-3-gallate (EGCG) postconditioning protects the heart against ischemic-reperfusion injury (IRI), and to explore its potential mechanisms in a rat model.. Male Wistar rats were subjected to myocardial ischemia (30 min) and reperfusion (up to 2 h) and the rats were divided into sham group (SO) group, ischemia-reperfusion (I/R) model group and EGCG group. EGCG group were treated with EGCG (10 mg/kg) via intravenous infusion 5 min before reperfusion. Electrocardiogram were applied to record ventricular arrhythmia frequency. The severity of myocardial injury [serum level of lactate dehydrogenase (LDH) and creatine kinase (CK), hematoxylineosin (HE) staining] and ventricular arrhythmia, and the serum levels of inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukins-6 (IL-6) and IL-8] were assessed with ELISA, electrocardiogram and Western blot respectively.. EGCG given before reperfusion could effectively reduce the serum level of LDH and CK and the incidence of ventricular arrhythmia (P < 0.05, respectively), improved the pathological damage. Meanwhile, EGCG could down-regulate the expression levels of TNF-α, IL-6, IL-8 in the myocardial tissue after IRI (P < 0.05, repectively). The expression levels of p-p85 and p-Akt in the EGCG group were significantly up-regulated compared to those in I/R group (P < 0.05, repectively).. EGCG-related anti-inflammatory action could attenuate rat myocardial IRI and this cardioprotective effect might be activated through the PI3K/Akt pathway.

Topics: Animals; Catechin; Creatine Kinase; Interleukin-6; Interleukin-8; Male; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats; Rats, Wistar; Signal Transduction; Tumor Necrosis Factor-alpha; Up-Regulation

Cardiovascular disease is the leading cause of death globally, and stem cell therapy remains one of the most promising strategies for regeneration or repair of the damaged heart. We report that human placenta-derived multipotent cells (hPDMCs) can modulate cardiac injury in small and large animal models of myocardial ischemia (MI) and elucidate the mechanisms involved. We found that hPDMCs can undergo in vitro cardiomyogenic differentiation when cocultured with mouse neonatal cardiomyocytes. Moreover, hPDMCs exert strong proangiogenic responses in vitro toward human endothelial cells mediated by secretion of hepatocyte growth factor, growth-regulated oncogene-α, and interleukin-8. To test the in vivo relevance of these results, small and large animal models of acute MI were induced in mice and minipigs, respectively, by permanent left anterior descending (LAD) artery ligation, followed by hPDMC or culture medium-only implantation with follow-up for up to 8 weeks. Transplantation of hPDMCs into mouse heart post-acute MI induction improved left ventricular function, with significantly enhanced vascularity in the cell-treated group. Furthermore, in minipigs post-acute MI induction, hPDMC transplantation significantly improved myocardial contractility compared to the control group (p = 0.016) at 8 weeks postinjury. In addition, tissue analysis confirmed that hPDMC transplantation induced increased vascularity, cardiomyogenic differentiation, and antiapoptotic effects. Our findings offer evidence that hPDMCs can modulate cardiac injury in both small and large animal models, possibly through proangiogenesis, cardiomyogenesis, and suppression of cardiomyocyte apoptosis. Our study offers mechanistic insights and preclinical evidence on using hPDMCs as a therapeutic strategy to treat severe cardiovascular diseases.

Topics: Animals; Apoptosis; Cell Differentiation; Cell- and Tissue-Based Therapy; Cells, Cultured; Chemokine CXCL1; Coculture Techniques; Disease Models, Animal; Endothelial Cells; Female; Hepatocyte Growth Factor; Humans; Interleukin-8; Male; Mice; Mice, Inbred C57BL; Mice, SCID; Multipotent Stem Cells; Muscle Development; Myocardial Contraction; Myocardial Infarction; Myocardial Ischemia; Myocytes, Cardiac; Neovascularization, Physiologic; Placenta; Pregnancy; Swine; Swine, Miniature; Ventricular Function, Left

Since the introduction of angiogenic cell therapy using early endothelial progenitor cells (EPCs), myeloid angiogenic cells (MACs) have been expected to be useful in treating ischemic diseases. In order to elucidate the angiogenic properties of MACs/EPCs, we clarified the characteristics of MACs as compared to M2 macrophages (Mϕs). Comparison of the gene expression profiles of MACs and late EPCs revealed that MACs expressed greater amounts of metalloproteinase (MMP)-9. It should be noted that the profile of MMP-2/9 expression on the cell surface of MACs was similar to that of M2 Mϕs, and that cell surface MMP-2/9 might be an active form based on molecular size. In addition, the invasion of MACs was prohibited not only by MMP-2/9 inhibitor, but also by the hyaluronidase treatment that caused the down-regulation of MMP-9 on the cell surface of MACs and inhibited their invasion activity. These results indicate that cell surface MMP-2/9 plays an important role in the high invasion ability of MACs. The conditioned medium of both MACs and M2 Mϕs stimulated tube formation of endothelial cells in vitro. MACs caused an increase in vessel formation in in vivo models through the production of IL-8. We propose that the role of MACs with cell surfaces expressing MMP-2/9 is rapidly invading ischemic tissue.

Topics: Culture Media, Conditioned; Endothelial Progenitor Cells; Humans; Interleukin-8; Macrophages; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Myeloid Cells; Myocardial Ischemia; Neovascularization, Pathologic; Neovascularization, Physiologic; Vascular Endothelial Growth Factor A

To investigate the effects of Yindanxinnaotong capsule (YDXNTC) and main components compatibility and ratios on myocardium against ischemia/reperfusion injury and the effect's underlying mechanism.. Myocardial ischemia/reperfusion injury (MIRI) was induced by ischemia for 30 min and reperfusion for 30 min. Electrocardiogram data and coronary flow were recorded, and superoxide dismutase (SOD), malondialdehyde (MDA), lactate dehydrogenase, creatine kinase-MB, cardiac troponin T and I (cTnT, cTnI) and interleukin-1β, interleukin-8, interleukin-18 (IL-1β, IL-8, IL-18) in myocardium were measured. Hypoxia/reoxygenation and hydrogen peroxide (H2O2) injury were induced by hypoxia for 3 h/reoxygenation for 2 h, and 100 μM H2O2 for 1 h, respectively, in vitro rat myocardial cells (H9c2). Cell viability, SOD, MDA, cTnT and inflammatory factors (IL-1β, IL-8 and IL-18) were determined, and Toll-like receptor 4 (TLR-4) expression was measured by western blotting.. In the isolated heart experiment, elevated heart function, coronary flow and SOD levels, and decreased MDA levels and inflammatory factors were noted in the YDXNTC, main components and main components compatibility groups. Ventricular tachycardia/ventricular fibrillation occurrence decreased in the ginkgo biloba extract (GBE), and GBE and salvia miltiorrhiza ethanol extract compatibility (SM-E, GSEC) groups. Lactic dehydrogenase levels decreased in the YDXNTC and aqueous extract of salvia miltiorrhiza (SM-H) groups. Creatine kinase-MB decreased with GBE, SM-E, SM-H and GSEC treatment, and cTnI and cTnT levels decreased with GSEC. In the in vitro cell study, YDXNTC and main components ratios improved cell viability and SOD levels, and suppressed MDA, cTnT and inflammatory factors. TLR-4 expression was down-regulated.. YDXNTC and main components compatibility showed protective effects on MIRI in this rat model and in vitro study. Regulating the Toll-like receptor signaling pathway may affect the mechanism.

Topics: Animals; Capsules; Disease Models, Animal; Drugs, Chinese Herbal; Humans; Interleukin-1beta; Interleukin-8; Male; Malondialdehyde; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Protective Agents; Rats; Rats, Sprague-Dawley; Superoxide Dismutase

Patients with chronic obstructive pulmonary disease (COPD) have elevated cardiovascular risk, and myocardial injury is common during severe exacerbations. Little is known about the prevalence, magnitude, and underlying mechanisms of cardiovascular risk in community-treated exacerbations.. To investigate how COPD exacerbations and exacerbation frequency impact cardiovascular risk and myocardial injury, and whether this is related to airway infection and inflammation.. We prospectively measured arterial stiffness (aortic pulse wave velocity [aPWV]) and cardiac biomarkers in 98 patients with stable COPD. Fifty-five patients had paired stable and exacerbation assessments, repeated at Days 3, 7, 14, and 35 during recovery. Airway infection was identified using polymerase chain reaction.. COPD exacerbation frequency was related to stable-state arterial stiffness (rho = 0.209; P = 0.040). Frequent exacerbators had greater aPWV than infrequent exacerbators (mean ± SD aPWV, 11.4 ± 2.1 vs. 10.3 ± 2.0 ms(-1); P = 0.025). Arterial stiffness rose by an average of 1.2 ms(-1) (11.1%) from stable state to exacerbation (n = 55) and fell slowly during recovery. In those with airway infection at exacerbation (n = 24) this rise was greater (1.4 ± 1.6 vs. 0.7 ± 1.3 ms(-1); P = 0.048); prolonged; and related to sputum IL-6 (rho = 0.753; P < 0.001). Increases in cardiac biomarkers at exacerbation were higher in those with ischemic heart disease (n = 12) than those without (n = 43) (mean ± SD increase in troponin T, 0.011 ± 0.009 vs. 0.003 ± 0.006 μg/L, P = 0.003; N-terminal pro-brain natriuretic peptide, 38.1 ± 37.7 vs. 5.9 ± 12.3 pg/ml, P < 0.001).. Frequent COPD exacerbators have greater arterial stiffness than infrequent exacerbators. Arterial stiffness rises acutely during COPD exacerbations, particularly with airway infection. Increases in arterial stiffness are related to inflammation, and are slow to recover. Myocardial injury is common and clinically significant during COPD exacerbations, particularly in those with underlying ischemic heart disease.

Topics: Aged; Aged, 80 and over; Aorta; Blood Pressure; C-Reactive Protein; Cardiomyopathies; Cardiovascular Diseases; Cohort Studies; Disease Progression; Female; Fibrinogen; Heart Rate; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Pulse Wave Analysis; Risk Factors; Spirometry; Sputum; Troponin T; Vascular Stiffness

TLR (Toll-like receptor) activation-induced inflammatory responses are important in the progression of atherosclerosis. We previously showed that TLR-dependent leucocyte responsiveness is acutely attenuated following percutaneous coronary intervention or vascular surgery. Furthermore, cytokine release following whole-blood TLR-2 and TLR-4 stimulation is negatively correlated with fractional flow reserve, suggesting that chronic ischaemia can elicit an enhanced inflammatory response. In the present study, we assessed the association between leucocyte TLR-2 and TLR-4 responsiveness and pre-existent and inducible ischaemia in patients undergoing SPECT (single-photon emission computed tomography)-MPI (myocardial perfusion imaging). TLR-2, TLR-4 and CD11b expression on monocytes were measured in blood samples that were obtained from 100 patients with suspected coronary artery disease before and after myocardial stress testing for SPECT-MPI. IL-8 (interleukin-8) levels were determined after whole-blood stimulation with Pam3Cys (TLR-2) and LPS (lipopolysaccharide; TLR-4). On the basis of SPECT-MPI, patients were categorized into three groups: reversible defect, irreversible defect and no defect. Myocardial stress induced a reduction in TLR-4 expression (2.46±0.21 compared with 2.17±0.16 arbitrary units, P=0.001) and CD11b expression (83.2±1.73 compared with 76.0±1.89 arbitrary units, P<0.001). TLR-induced IL-8 production before myocardial stress induction was not associated with the results of SPECT-MPI. However, a significant decrease in IL-8 production following TLR stimulation was observed after stress, which was more pronounced in patients with a reversible defect. In conclusion, inducible ischaemia is associated with a decrease in whole-blood TLR-2 and TLR-4 response. These results point to a regulating role of TLRs in order to prevent excessive inflammatory events known to occur during acute ischaemia.

Topics: Adult; Echocardiography, Stress; Female; Humans; Interleukin-8; Leukocyte Count; Male; Middle Aged; Myocardial Ischemia; Toll-Like Receptor 2; Toll-Like Receptor 4; Tomography, Emission-Computed, Single-Photon

Chronic parodontit inflammation in elderly patients was found to be accompanied by inbalance of complement system; IgA (sIgA), IgA, IgG, IgM hyperproduction; the increase of IL-8, IL-1α concentration and decrease of IL-4 level; increase Hsp-70 antibodies.

Topics: Aged; Chronic Disease; Complement System Proteins; Female; HSP70 Heat-Shock Proteins; Humans; Immunoglobulin A, Secretory; Immunoglobulin G; Immunoglobulin M; Interleukin-1alpha; Interleukin-8; Male; Middle Aged; Myocardial Ischemia; Periodontal Diseases

Off-pump coronary artery bypass surgery reduces the myocardial injury associated with on pump surgery with cardiopulmonary bypass (CPB) and ischemic-cardioplegic arrest (CA). We sought to find a mechanistic explanation for this by comparing the transcriptomic changes in the myocardium of patients undergoing on- and off-pump surgery. Transcriptomic analyses were performed on left ventricular biopsies obtained from patients prior to (pre-op) and after completion of all coronary anastomoses (post-op). Microarray results were validated with real-time polymerase chain reaction. In on-pump group, 68 genes were upregulated in post-op vs. pre-op biopsies (P < 0.01, >or=2-fold). They included inflammatory genes CCL3 and CCL4, apoptotic gene GADD45B and prostaglandin synthesis gene PTGS2 (COX-2). In the off-pump group, 17 genes were upregulated in post-op vs. pre-op biopsies (P < 0.01, >or=2-fold), all shared with on-pump patients. To uncover the genes implicated in CPB and ischemic-CA response, we compared the postoperative gene profiles of the two groups. Thirty-eight genes were upregulated in the on-pump vs. off-pump patients (P < 0.01, >or=2-fold). On-pump surgery induces injury-related response, as demonstrated by the upregulation of apoptosis and remodeling markers, whereas off-pump surgery ameliorates that by mainly upregulating a cytoprotective genetic program. Blood levels of the identified cytokines and chemokines followed the same pattern obtained by transcriptomics, suggesting that the myocardium is a likely source for these proteomic changes. In conclusion, off-pump surgery is associated with fewer alterations in gene expression connected with inflammation, apoptosis, and remodeling seen after on-pump surgery with CPB and ischemic-CA.

Topics: Adaptor Proteins, Signal Transducing; Aged; Chemokine CCL2; Coronary Artery Bypass; Coronary Artery Bypass, Off-Pump; Female; Gene Expression Profiling; Gene Regulatory Networks; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Myocardial Ischemia; Myocardium; Oligonucleotide Array Sequence Analysis; Reverse Transcriptase Polymerase Chain Reaction; Time Factors

Ischemia-reperfusion (I/R) injury may influence graft function after transplantation. Erythropoietin (EPO) attenuates I/R injury in various animal organs such as intestine, brain, and kidney.. To evaluate the effects of pretreatment with recombinant human EPO (rhEPO) on I/R-induced heart injury.. A rat model of I/R injury was established by ligating the left descending coronary artery for 30 minutes, followed by reperfusion for 4 hours. Fifty Sprague-Dawley rats were divided into 5 groups: sham operation; I/R; I/R+rhEPO, 100 U/kg; I/R+rhEPO, 1000 U/kg; and I/R+rhEPO, 5000 U/kg. Electrocardiograms were assessed continuously to note arrhythmia caused by reperfusion. Serum concentrations of interleukin (IL)-6 and IL-8, and tumor necrosis factor-alpha were measured at 2 and 4 hours after reperfusion.. The rhEPO-treated animals exhibited dosage-dependent significant reduction in the incidence of ventricular arrhythmia caused by reperfusion, and markedly decreased serum concentrations of IL-6, IL-8, and tumor necrosis factor-alpha (P < .05) compared with the I/R group (P < .05).. The rhEPO attenuates myocardial I/R injury in rats, at least in part related to inhibition of the system inflammatory response.

Topics: Animals; Erythropoietin; Humans; Inflammation; Interleukin-6; Interleukin-8; Myocardial Ischemia; Myocardial Reperfusion Injury; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Reperfusion Injury; Tumor Necrosis Factor-alpha

To investigate the effect of nicotine on inflammatory cytokines in myocardial ischemia/reperfusion (I/R) injury in rat.. Fifty male Sprague-Dawley (SD) rats were divided into five groups by random numbers table (each n=10): sham operation group (S group), I/R group, nicotine 400 μg/kg group (H group), nicotine 40 μg/kg group (L group) and α-bungarotoxin (α-BGT,1 μg/kg) group. The anterior descending branch of left coronary artery was occluded for 30 minutes followed by 90 minutes reperfusion to reproduce myocardial I/R injury rat model, while in S group the anterior descending branch of left coronary artery was only exposed without occlusion procedure. Thirty minutes before myocardial ischemia, drugs in corresponding doses were given intravenously via jugular vein. At the end of 90 minutes of reperfusion, blood samples were collected from carotid artery to determine the levels of tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), IL-10, MB isoenzyme of creatine kinase (CK-MB), and cardiac troponin I (cTnI), then the animals were sacrificed and the hearts were harvested for pathological study and determination of myeloperoxidase (MPO) activity. Immunohistochemistry and reverse transcription- polymerase chain reaction (RT-PCR) were used to assess intercellular adhesion molecule-1 (ICAM-1) protein and mRNA expression in heart tissue.. Compared with the S group, the concentrations of TNF-α, IL-8, IL-10, CK-MB, cTnI, MPO activity, ICAM-1 protein and mRNA expression were significantly increased in I/R group [TNF-α (ng/L): 158.7±32.7 vs. 31.5±5.8, IL-8 (ng/L): 0.71±0.06 vs. 0.30±0.04, IL-10 (ng/L): 69.0±7.8 vs. 41.4±4.3, CK-MB (U/L): 2 540±169 vs. 1 120±120, cTnI (μg/L): 26.2±4.6 vs. 0.9±0.2, MPO (U/g): 4.2±0.6 vs. 1.6±0.4, ICAM-1 protein: 0.210±0.025 vs. 0.100±0.018, ICAM-1 mRNA: 1.82±0.23 vs. 1.18±0.20, P<0.05 or P<0.01]. Injury to myocardial ultrastructure was worse in I/R group. Compared with the I/R group, the plasma levels of TNF-α and IL-8 were lower [TNF-α (67.3±9.8) ng/L, IL-8 (0.47±0.04) ng/L], IL-10 was higher [(147.5±12.5) ng/L], CK-MB, cTnI, MPO, ICAM-1 protein and mRNA were lower obviously in H group [CK-MB (1 282±145) U/L, cTnI (4.7±1.4) μg/L, MPO (2.5±0.4) U/g, ICAM-1 protein 0.140±0.026, ICAM-1 mRNA 1.31±0.25, P<0.05 or P<0.01]. Injury to the myocardial ultrastructure was less marked in H group. The indexes of those in L group and α-BGT group compared with I/R group were not statistically significantly different.. Nicotine can block endothelial expression of adhesion molecules and neutrophil adhesion and infiltration to promote a balance of anti-inflammatory and pro-inflammatory response, thus prevents excessive inflammatory response to myocardial I/R injury in rat.

Topics: Animals; Cell Adhesion Molecules; Intercellular Adhesion Molecule-1; Interleukin-10; Interleukin-8; Male; Myocardial Ischemia; Myocardial Reperfusion Injury; Nicotine; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

Cardiac surgery using cardiopulmonary bypass (CPB) is performed widely, given the progress in cardioprotective methods. However, endotoxemia caused by CPB leads to systemic inflammatory response syndrome and deterioration of organ function. We evaluated the effectiveness of endotoxin removal with a polymyxin B-immobilized hemoperfusion cartridge (PMX) in CPB.. Pigs weighing about 25 kg were divided into control (n = 5) and PMX (n = 5) groups. Normothermic CPB was performed in the control group, while endotoxin was removed with PMX under normothermic CPB in the PMX group. Endotoxin removal was performed from the start to end of CPB. The end-systolic pressure-volume ratio (E(max)), left ventricular pressure (LVP), maximum and minimum rates of increase in LVP (+/-LVdp/dt), and cardiac output (CO) were measured 2 h after CPB, and the recovery rates of the parameters were compared between the two groups. A histopathological study was also conducted.. The recovery rates of E(max), CO, and LVP were significantly better (P < 0.05) in the PMX group than in the control group. The PaO(2) 2 h after CPB was significantly higher (P < 0.05) in the PMX group than in the control group. The interleukin (IL)-8 level 2 h after CPB was significantly lower (P < 0.05) in the PMX group. Histopathologically, the heart and pulmonary tissues were better preserved in the PMX group.. The PMX treatment reduced the inflammatory reaction caused by CPB, and cardiac and pulmonary functions after normothermic CPB were well preserved.

Topics: Animals; Cardiac Output; Cardiopulmonary Bypass; Endotoxemia; Endotoxins; Heart; Hemoperfusion; Interleukin-6; Interleukin-8; Liver; Lung; Male; Models, Animal; Myocardial Ischemia; Myocardium; Polymyxin B; Swine; Ventricular Function, Left; Warm Ischemia

Elimination of cardiotomy suction increases reliance on cell-saver blood-conservation techniques. Reinfusion of processed cell-saver blood (PCSB) even without using cardiotomy field suction may contribute to thrombin, cytokines, platelet activators, and hemolytic factors measured systemically.. This study was designed as a prospective, unblinded observational study of patients undergoing first-time, nonemergent on-pump coronary artery bypass graft surgery.. A university medical center.. Fourteen patients were enrolled after informed consent.. Arterial blood was sampled (1) before cardiopulmonary bypass, (2) immediately after bypass, and (3) 4 hours after bypass. PCSB, using the AutoLog (Medtronic, Inc, Minneapolis, MN), was sampled after bypass.. Blood and PCSB levels of prothrombin fragments 1.2, beta-thromboglobulin, interleukin-6, interleukin-8, polymorphonuclear leukocyte-elastase, neuron-specific enolase, and S-100beta were assayed by using enzyme-linked immunosorbent assay. Paired comparisons were performed by using paired t tests. Compared with postbypass blood, processed cell-saver blood (prepatient infusion) had higher levels of polymorphonuclear leukocyte-elastase, interleukin-8, neuron-specific enolase, and S-100beta (p

Topics: beta-Thromboglobulin; Biomarkers; Coronary Artery Bypass; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Hemolysis; Humans; Inflammation; Interleukin-6; Interleukin-8; Leukocyte Elastase; Male; Middle Aged; Myocardial Ischemia; Peptide Fragments; Phosphopyruvate Hydratase; Platelet Activation; Prospective Studies; Prothrombin; Thrombin; Treatment Outcome

In the adult, new blood vessel formation can occur either through angiogenesis from pre-existing mature endothelium or vasculogenesis mediated by bone marrow-derived endothelial precursors. We recently isolated endothelial progenitor cells, or angioblasts, in human adult bone marrow which have selective migratory properties for ischemic tissues, including myocardium, to where they home and induce vasculogenesis. Here we show that myocardial production of the IL-8/Gro-alpha CXC chemokine family is significantly increased after acute ischemia, and that this provides a chemoattractant gradient for bone marrow-derived endothelial progenitors, or angioblasts. This chemokine-mediated homing of bone marrow angioblasts to the ischemic heart regulates their ability to induce myocardial neovascularization, protection against cardiomyocyte apoptosis, and functional cardiac recovery. Together, our results indicate that CXC chemokines play a central role in regulating vasculogenesis in the adult, and suggest that manipulation of interactions between chemokines and their receptors on autologous human bone marrow-derived angioblasts could augment neovascularization of ischemic myocardial tissue.

Topics: Animals; Apoptosis; Bone Marrow Cells; Cell Movement; Chemokine CXCL1; Chemokines, CXC; Endothelial Cells; Humans; Interleukin-8; Myocardial Ischemia; Myocardium; Neovascularization, Pathologic; Rats; Rats, Nude; Recovery of Function; Stem Cell Transplantation; Stem Cells

Topics: Animals; Apoptosis; Bone Marrow Cells; Cell Movement; Chemokines, CXC; Endothelial Cells; Humans; Interleukin-8; Myocardial Ischemia; Myocardium; Neovascularization, Pathologic; Rats; Rats, Nude; Recovery of Function; Stem Cell Transplantation; Stem Cells

To test the hypothesis that heat shock protein (Hsp) 70 may be released into the circulation after acute myocardial infarction (AMI) by exploring the kinetics of Hsp70 release and the relations between Hsp70 and markers of inflammation and myocardial damage in AMI.. Blood samples from 24 patients were prospectively collected through to the first day after AMI. Hsp70, interleukin (IL) 6, IL-8, and IL-10 in serum were measured by enzyme linked immunosorbent assay (ELISA).. Median Hsp70 concentrations in AMI patients measured at arrival, six hours thereafter, and the following morning were 686, 868, and 607 pg/ml, respectively. These concentrations were all significantly different from those of the control patients with angina with a median serum Hsp70 concentration of 306 pg/ml. Peak Hsp70 correlated with creatine kinase (CK) MB (r = 0.62, p < 0.01) and cardiac troponin T (r = 0.58, p < 0.01). Furthermore, serum Hsp70 correlated with IL-6 and IL-8 at six hours (r = 0.60, p < 0.01 and r = 0.59, p < 0.01, respectively).. In this study, Hsp70 was rapidly released into the circulation after AMI. Circulating Hsp70 is suggested as a marker of myocardial damage. In addition, Hsp70 may have a role in the inflammatory response after AMI.

Topics: Biomarkers; Creatine Kinase; Female; HSP70 Heat-Shock Proteins; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Myocardium; Necrosis; Prospective Studies; Troponin

The aim of the present study was to investigate the prognostic value of plasma interleukin-8 (IL-8) for early complications after percutaneous coronary intervention (PCI). The pre- and postprocedural plasma levels of IL-8 and serum C-reactive protein (CRP) were examined by immunoassay, and the expression of CD11b/CD18 on neutrophils was assessed by flow cytometry. Early complications (abrupt occlusion, threatened abrupt occlusion, early recurrence of ischemia, myocardial infarction, cardiac sudden death, and target vessel revascularization) occurred intra-procedure and 30 days after PCI and were observed in 121 consecutive patients with coronary heart disease. Sixteen patients with early complications had high preprocedural levels and high postprocedural differentials of IL-8, CRP, and CD11b/CD18 compared to those without complications (all P < 0.05). The occurrence of complications showed a significant increase in the patients according to the tertiles of IL-8, CRP, and CD11b/CD18. Preprocedural levels of IL-8 (RR = 5.864, CI = 1.658-20.734, P = 0.006) and diabetes (RR = 1.587, CI = 1.246-2.132, P = 0.038) were independent predictors of early complications. There were significant correlations in the postprocedural differential between IL-8 and CD11b/CD18 (r = 0.776, P = 0.002) in patients with complications. The results reveal that the early complications after PCI contribute to preprocedural inflammatory responses. Normal levels of IL-8 may be powerful negative predictors of early complications in patients with CHD following PCI.

Topics: Aged; Angioplasty, Balloon, Coronary; C-Reactive Protein; CD11b Antigen; CD18 Antigens; Coronary Disease; Coronary Restenosis; Female; Forecasting; Humans; Interleukin-8; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia

The aim of this study was to assess the early prognostic value of the inflammatory cytokines interleukin 6, interleukin 8, and tumor necrosis factor alpha in a cohort of emergency department (ED) patients with chest pain who have suspected myocardial ischemia.. One hundred eighteen patients with chest pain presenting to 2 urban EDs were studied. Interleukin 6, interleukin 8, and tumor necrosis factor alpha levels were assayed at presentation. The end point was the occurrence of a serious cardiac event (death, nonfatal acute myocardial infarction, myocardial revascularization, or readmission with an acute coronary syndrome) during the index admission or subsequent 3 months.. Mean levels of all 3 cytokines were higher among patients experiencing a serious cardiac event, with the greatest differences observed in levels of interleukin 6 (mean 2.5 pg/mL [95% confidence interval (CI) 1.2 to 3.7 pg/mL] versus mean 9.8 pg/mL [95% CI 2.4 to 17.2 pg/mL]). Interleukin 6 had a sensitivity of 35% (95% CI 20% to 54%), a specificity of 86% (95% CI 76% to 92%), and an overall prognostic accuracy of 71% (95% CI 63% to 79%) for predicting serious cardiac events. However, logistic regression analysis revealed that the only independent predictor of an adverse outcome was an ECG suggestive of ischemia at presentation.. Among patients presenting to the ED with suspected myocardial ischemia, higher levels of inflammatory cytokines are associated with an increased risk of a serious cardiac event during the subsequent 3 months. There is, however, considerable overlap in levels among patients who do and do not have a serious cardiac event, limiting their utility as predictors of outcome in individual patients.

Topics: Chest Pain; Emergency Service, Hospital; Female; Hospitals, Urban; Humans; Interleukin-6; Interleukin-8; Logistic Models; Male; Middle Aged; Myocardial Ischemia; Predictive Value of Tests; Prognosis; Prospective Studies; ROC Curve; Sensitivity and Specificity; Tumor Necrosis Factor-alpha

The aim of present study was to observe the protective effects of electroacupuncture (EA) and Salviae Miltiorrhizae (SM) on myocardial ischemia/reperfusion in rabbits. Acute ischemia/reperfusion of myocardium was set up by ligating left anterior descending branch of coronary artery in 24 rabbits which were divided randomly into control, EA, SM, and EA+SM group. Changes of plasma myocardial zymogram were found after ischemia in these groups. EA and SM were observed to decrease plasma IL-8 and epinephrine concentration and to increase 99mTc-MIBI intake ratio of myocardial mitochondrial, but enhancing or antagonistic effect between EA and SM was negligible. There was positive correlation between concentrations of plasma epinephrine and IL-8. The results indicated that EA and SM could reduce myocardial ischemia/reperfusion injury and protect myocardial mitochondrial by reducing concentrations of plasma epinephrine and IL-8. EA and SM could reduce the release of endogenic epinephrine, which was one of the mechanisms of lowering plasma IL-8.

Topics: Animals; Combined Modality Therapy; Drugs, Chinese Herbal; Electroacupuncture; Epinephrine; Interleukin-8; Myocardial Ischemia; Myocardial Reperfusion Injury; Phytotherapy; Rabbits; Radionuclide Imaging; Salvia miltiorrhiza; Treatment Outcome

Neonates undergoing cardiac surgery have a systemic inflammatory reaction with release of proinflammatory cytokines, which could be responsible for myocardial dysfunction as a result of myocardial cell damage. The purpose of this study was to test the hypothesis that the production of proinflammatory cytokines during cardiac surgery would be associated with myocardial dysfunction after the arterial switch operation in neonates.. A total of 63 neonates with transposition of the great arteries were operated on with combined deep hypothermic circulatory arrest and low-flow cardiopulmonary bypass at a median age of 7 days. Perioperative plasma concentrations of interleukins 6 and 8 were correlated with myocardial dysfunction, as assessed clinically and by echocardiography within 24 hours after the operation, and with perioperative cardiac troponin T blood levels as a marker of myocardial cell damage.. Myocardial dysfunction was observed in 11 patients (17.5%), and 2 of them died. Durations of cardiopulmonary bypass and aortic crossclamping, but not of circulatory arrest, were correlated with myocardial dysfunction. Patients with myocardial dysfunction had significantly higher cardiac troponin T blood levels at the end of cardiopulmonary bypass and 4 and 24 hours after the operation than did patients without myocardial dysfunction. Patients with myocardial dysfunction also had higher interleukin 6 plasma concentrations after cardiopulmonary bypass and 4 hours after the operation, as well as higher interleukin 8 plasma concentrations 4 and 24 hours after the operation, than did those without myocardial dysfunction. Postoperative interleukin 6 and 8 plasma concentrations were significantly correlated with postoperative cardiac troponin T blood levels. Multivariable analysis of independent risk factors for myocardial dysfunction comprising cytokine and troponin levels and bypass duration revealed interleukin 6 levels 4 hours after the operation as significant (P =.047).. Cardiac operations in neonates stimulate the production of proinflammatory cytokines, which may contribute to myocardial cell damage and myocardial dysfunction.

Topics: Cardiopulmonary Bypass; Hospital Mortality; Humans; Infant, Newborn; Interleukin-6; Interleukin-8; Myocardial Ischemia; Postoperative Period; Risk Factors; Transposition of Great Vessels; Troponin T

The aim of this study was to determine the effect of FR183998 (5-(2,5-dichlorothiophen-3-yl)-3-[(2-dimethylaminoethyl)carbamoyl]benzoylguanidine dihydrochloride), an Na+/H+ exchange inhibitor, on myocardial interleukin-8 (IL-8) content and myocardial infarct size in a rat ischaemia and reperfusion model. Rats underwent 30 min of ischaemia followed by 1 to 24 h of reperfusion. IL-8 content rapidly increased in reperfused rat hearts. The maximum increase in IL-8 was obtained after 3 h of reperfusion. Intravenous administration of FR183998 at 1 and 3.2 mg kg(-1), 5 min before ischaemia, significantly reduced the IL-8 level after 3 h of reperfusion (122 +/- 16 and 149 +/- 23 pg mg(-1) protein, respectively), compared with that of the saline-treated group (258 +/- 27 pg mg(-1) protein). Myeloperoxidase activity after 3 h of reperfusion was also reduced by FR183998 (from 0.83+0.19 unit g(-1) weight of tissue in the saline-treated group to 0.36 +/- 0.09 and 0.33 +/- 0.06 unit g(-1) weight of tissue in FR183998-treated groups at 1.0 and 3.2 mg kg(-1), respectively). Myocardial infarction induced by 30 min of ischaemia and 24 h of reperfusion was significantly suppressed by the same doses of FR183998 (14.0 +/- 1.5,13.5 +/- 1.9% at 1.0 and 3.2 mg kg(-1)), compared with 22.2+2.7% in the saline-treated group. These results suggestthat IL-8 may contribute to the generation of myocardial infarction in an ischaemia and reperfusion model in rats.

Topics: Animals; Depression, Chemical; Disease Models, Animal; Guanidines; Interleukin-8; Male; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion Injury; Peroxidase; Rats; Rats, Sprague-Dawley; Sodium-Hydrogen Exchangers; Thiophenes

Increasing evidence has indicated the important roles of inflammation and immune response in the development of atherosclerosis and ischemic heart disease (IHD). We measured the serum interleukin (IL)-8 and IL-12 levels of patients with unstable angina pectoris (UAP) and patients with acute myocardial infarction (AMI), and compared findings with those of normal subjects. The results showed that the serum level of IL-8 was significantly higher in patients with UAP and patients with AMI than in healthy control subjects. To our knowledge, this is the first report that serum IL-12 level was elevated in patients with AMI but not in patients with UAP. These findings suggest that IL-8 and IL-12 are involved in the process of IHD, and serum IL-12 may be a marker for differentiating AMI from UAP.

Topics: Aged; Angina Pectoris; China; Female; Humans; Interleukin-12; Interleukin-8; Male; Middle Aged; Myocardial Ischemia; Reference Values

Recently, several types of centrifugal pumps have been widely used as the main pumps for cardiopulmonary bypass (CPB). However, according to the results of our experimental studies, after cardiogenic shock, pulsatile flow was effective in maintaining the functions and microcirculations of end organs, especially those of the liver and kidney. To estimate the effectiveness of pulsatility during CPB, cytokine and endothelin and other metabolic parameters were measured in clinical pulsatile and nonpulsatile CPB cases. From March to May 1997, CPB was performed in 18 elective cases (14 ischemic and 4 valvular disease). In 9 cases, pulsatile perfusion was achieved by the Jostra HL20, which is a newly developed CPB pump (Group P). A nonpulsatile centrifugal pump was used in 9 patients (Group NP). In both groups, as chemical and metabolic mediators, interleukin-8 (IL-8), endothelin-1 (ET-1), and plasma free hemoglobin were measured before and during CPB, and 0.5, 3, 6, 9, 18 h after weaning from CPB. This pulsatile CPB pump could be very simply and easily controlled and could easily produce pulsatile flow. There were no significant differences in CPB time (CPBT), aortic cross clamp time (ACCT), mean aortic pressure, or pump flow during CPB between the both groups. The ET-1 level of Group P was significantly (p < 0.05) lower than that of Group NP 9 h after CPB weaning. The IL-8 level of Group P also showed a lower value than that of Group NP. As for plasma free hemoglobin, there were no significant differences between the groups. These results suggested that even in conventional CPB, pulsatility was effective to reduce endothelial damage and suppress cytokine activation. It may play a important role in maintaining the functions and microcirculations of end organs during CPB.

Topics: Aged; Aorta; Blood Pressure; Cardiopulmonary Bypass; Coronary Artery Bypass; Elective Surgical Procedures; Endothelin-1; Endothelium, Vascular; Female; Follow-Up Studies; Heart Valve Prosthesis Implantation; Hemoglobins; Humans; Interleukin-8; Kidney; Liver; Male; Microcirculation; Middle Aged; Myocardial Ischemia; Pulsatile Flow; Shock, Cardiogenic; Time Factors

Neutrophil accumulation and activation of the complement system with subsequent deposition of the cytolytic membrane attack complex (MAC) have been implicated in the pathogenesis of myocardial ischemia/reperfusion injury. The MAC, when present in high concentrations, promotes target cell lysis. However, relatively little is known about the potential modulatory role of sublytic concentrations of the MAC on nucleated cell function in vivo. In vitro studies demonstrated that the MAC regulates cell function by promoting the expression of pro-inflammatory mediators, including adhesion molecules and pro-inflammatory cytokines. We examined, using C6-deficient and C6-sufficient rabbits, the regulatory role of the MAC in mediating IL-8 expression and subsequent neutrophil recruitment in the setting of myocardial ischemia/reperfusion injury. C6-deficient and C6-sufficient rabbits were subjected to 30 min of regional myocardial ischemia followed by a period of reperfusion. In addition to a significant reduction in myocardial infarct size in C6-deficient animals, analysis of myocardial tissue demonstrated a decrease in neutrophil influx into the infarcted region. The reduction in neutrophil influx correlated with the decreased expression of the neutrophil chemotactic cytokine IL-8, as determined by ELISA and immunohistochemical analysis. The results derived from this study provide evidence that the MAC has an important function in mediating the recruitment of neutrophils to the reperfused myocardium through the local induction of IL-8.

Topics: Animals; Cell Movement; Complement C6; Complement Membrane Attack Complex; Interleukin-8; Leukocyte Count; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Neutrophils; Peroxidase; Rabbits

Topics: Adult; Biomarkers; Bronchoalveolar Lavage Fluid; Cardiovascular Surgical Procedures; Female; Humans; Interleukin-8; Male; Myocardial Ischemia; Respiratory Distress Syndrome; Sensitivity and Specificity; Tumor Necrosis Factor-alpha

Both the hemostatic and inflammatory system are thought to play a role in the pathogenesis of acute coronary syndromes. However, their respective contribution and interrelationship remain unclear, therefore, we studied the relationship between activation of the coagulation system and proinflammatory activity in ischemic coronary syndromes.. Thrombin-antithrombin III (TAT), prothrombin fragments F1 + 2, fibrinopeptide A (FPA), interleukin-6 (IL-6) and interleukin-8 (IL-8) were measured in 50 patients with unstable angina (UA), 60 patients with acute myocardial infarction (AMI) and in 50 patients with stable angina (SA).. FPA levels were significantly higher in patients with UA and AMI than in patients with SA (p = 0.0015 and p < 0.0001), and were higher in patients with AMI than UA (p = 0.0013). Plasma IL-6 concentrations were significantly higher in patients with UA and AMI than in patients with SA (p = 0.0020 and p < 0.001), and again were higher in AMI than UA (p = 0.001). Interestingly, FPA or IL-6 elevations on admission were found in different patients. In contrast, TAT, F1 + 2 and IL-8 levels were not different between the three groups.. IL-6 and FPA were shown to be independent predictive markers with equal discriminative power to distinguish stable (SA) from unstable (UA + AMI) patients. Moreover, hemostatic and inflammatory markers can be elevated independently in the acute phase of ischemic coronary syndromes.

Topics: Angina, Unstable; Antithrombin III; Biomarkers; Female; Fibrinopeptide A; Humans; Interleukin-6; Interleukin-8; Interleukins; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Peptide Fragments; Prothrombin; Statistics, Nonparametric; Thrombin

The neutrophil chemoattractants generated in a model of myocardial infarction in the anesthetized rabbit were investigated. Coronary artery occlusion was followed by reperfusion for periods from 5 min to 4.5 h. Extracts of myocardial tissue in normal and post-ischemic zones were tested for C5a and interleukin-8 (IL-8) using specific radioimmunoassays. In the post-ischemic zone, immunoreactive C5a was detected within 5 min and rose progressively to reach a plateau at 3-4.5 h. In contrast, immunoreactive IL-8 concentrations rose after a delay and were highest at the last time point tested, 4.5 h. Myeloperoxidase activity levels, an index of neutrophil accumulation, rose progressively as the concentrations of chemoattractants increased. Using cation exchange and reversed phase HPLC, immunoreactive C5a and IL-8 co-eluted with authentic standards. Fractions taken at the C5a and IL-8 peaks from reversed phase HPLC exhibited neutrophil aggregating activity which was neutralized by the respective antibody used in the radioimmunoassays. Depletion of circulating neutrophils virtually abolished immunoreactive IL-8 in the post-ischemic myocardial tissue. These observations suggest a sequential release of chemoattractants: the first, C5a is generated in interstitial fluid, followed by IL-8 generated by infiltrating neutrophils. Thus, over the time period studied, IL-8 generation would be expected to be indirectly dependent on C5a production.

Topics: Animals; Blood Pressure; Cell Aggregation; Chemotactic Factors; Chemotaxis, Leukocyte; Complement C5a; Female; Heart; Heart Rate; Interleukin-8; Male; Myocardial Ischemia; Myocardium; Neutrophils; Peroxidase; Rabbits; Reperfusion Injury

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

Interventions that inhibit neutrophil infiltration into myocardial tissue after ischaemia and reperfusion are reported to reduce the size of the infarct. We examined whether administration of trimetazidine, which is reported to reduce myocardial infarct size, affects this process. [111In]Neutrophils and [125I]albumin were administered intravenously (i.v.) to anaesthetized rabbits to allow measurement of cell accumulation and changes in microvascular plasma protein leakage. A 30-min period of coronary artery occlusion followed by 3-h reperfusion was used, and the area at risk (AR) myocardium was defined by dye exclusion. Twelve rabbits received 2.5 mg/kg trimetazidine i.v., 10 min before coronary artery occlusion; the 13 controls received saline. In the control group, the number of [111In]neutrophils/g tissue in the AR (30,591 +/- 6,725) was significantly greater than in the normal zone (NZ, 11,519 +/- 1,605, p < 0.01). In the trimetazidine-treated group, the number of [111In]neutrophils in the AR was significantly lower than in the control group (12,717 +/- 1,958 [111In]neutrophils/g, p < 0.01). There was no significant difference in neutrophil content of the NZ (7,832 +/- 1,117 [111In]neutrophils/g) in treated animals as compared with that in control. Accumulation of [111In]neutrophils in response to intradermal administration of leukotriene B4, interleukin-8 (IL-8), or zymosan-activated plasma was not affected by the drug. The effect of trimetazidine on neutrophil accumulation into post-ischaemic reperfused myocardium therefore does not appear to result from a direct action on the neutrophil.

Topics: Animals; Blood Pressure; Capillary Permeability; Disease Models, Animal; Heart Rate; Interleukin-8; Leukotriene B4; Male; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion Injury; Neutrophils; Rabbits; Trimetazidine; Zymosan

Myocardial ischaemia is one of the major causes of low output syndrome during open heart surgery. Injury associated with ischaemia and reperfusion has been considered to result, in part, from the action of neutrophils, the interaction of neutrophils with vascular endothelial cells, and the effects of cytokines which are mediators that induce and modify reactions between these substances. We investigated cell injury in relation to the concentrations of interleukins 6 and 8 (IL-6 and IL-8), which have recently received attention as neutrophil activators. Neutrophil counts, granulocyte elastase (GEL), IL-6, IL-8, tumour necrosis factor-alpha (TNF-alpha), CK, and CK-MB concentrations were determined serially in 11 patients undergoing open heart surgery with cardiopulmonary bypass (CPB). Neutrophil counts (mean +/- SD 2717 +/- 2421 microliters-1 preoperatively) peaked 60 min after declamping the aorta at 7432 +/- 4357 microliters-1 (P < 0.01) and remained elevated 7136 +/- 5194 microliters-1 at 180 min (P < 0.01). Plasma GEL level (168 +/- 71 micrograms.L-1 preoperatively) peaked at 1134 +/- 453 micrograms.L-1 120 min after declamping of the aorta (P < 0.01) and remained elevated, 1062 +/- 467 micrograms.L-1, after 180 min (P < 0.01). Serum IL-6 level (118 +/- 59 pg.ml-1 preoperatively) peaked at 436 +/- 143 pg.ml-1 60 min after declamping of the aorta (P < 0.01) and remained elevated, 332 +/- 109 pg.ml-1, after 180 min. Serum IL-8 level (37 +/- 44 pg.ml-1 preoperatively) peaked at 169 +/- 86 pg.ml-1 at 60 min after declamping of the aorta (P < 0.001) and remained elevated at 113 +/- 78 pg.ml-1 180 min after declamping of the aorta.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Creatine Kinase; Cytokines; Humans; Interleukin-6; Interleukin-8; Isoenzymes; Leukocyte Count; Leukocyte Elastase; Middle Aged; Myocardial Ischemia; Myocardial Reperfusion Injury; Neutrophils; Pancreatic Elastase; Tumor Necrosis Factor-alpha