lactoferrin and Myocardial-Ischemia

The pathogenesis of diabetes and atherosclerosis is linked through inflammation. Neutrophils contribute to atherosclerotic plaque development, and are dysfunctional in diabetes. The aim of this study was to compare the predictive values of two neutrophil degranulation products, myeloperoxidase and lactoferrin, on long-term risk for fatal ischemic heart disease in persons with newly diagnosed diabetes and controls.. Prospective population-based cohort study.. In 1984-1986, a large population study, HUNT 1, was conducted in Norway. Previously unknown diabetes was diagnosed in 205 persons. A matched control group without diabetes was selected from the HUNT 1.. Fatal ischemic heart disease was registered until 2004. Baseline serum was analysed for myeloperoxidase and lactoferrin. Cox regression analysis with adjustments for age, gender, hypertension, body mass index, established cardiovascular disease and total cholesterol was used to estimate hazard ratios for fatal ischemic heart disease.. In the diabetes group (200 subjects), the two highest tertiles of lactoferrin predicted fatal ischemic heart disease, hazard ratio 2.54 (95% CI, 1.00-6.45) and 4.06 (1.72-9.60). Myeloperoxidase did not predict death from ischemic heart disease in subjects with diabetes. In the controls (198 subjects), none of the biomarkers predicted fatal ischemic heart disease.. Increased baseline concentration of lactoferrin strongly predicted the long-term risk for fatal ischemic heart disease in patients with newly diagnosed diabetes. Based on the literature, we hypothesize that the increased concentrations may reflect neutrophil priming caused by hyperglycemia.

Topics: Aged; Cohort Studies; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Inflammation; Lactoferrin; Male; Myocardial Ischemia; Neutrophils; Peroxidase; Proportional Hazards Models; Risk Factors; Time Factors

Isoproterenol hydrochloride (ISO), a beta adrenergic agonist, is known to cause ischemic necrosis in rats. Cardiotoxicity of three different doses of ISO were studied using physiological, biochemical and histopathological parameters. The effects of single and double dose of ISO were analysed, which illustrated that single ISO dose was more cardiotoxic than double ISO dose due to ischemic preconditioning. The tetrapeptide derivatives L-lysine-L-arginine-L-aspartic acid-L-serine (tetrapeptide A) and di-tert.butyloxycarbonyl-L-lysine-L-arginine-L-aspartic acid-tert.butyl O-tert.butyl-L-serinate (tetrapeptide B) along with acetylsalicylic acid as positive control were analysed at different time points for their cardioprotective effect. The results demonstrated that optimal protective effects were observed by pretreatment with 5 mg/kg of tetrapeptide B and this was found to be slightly better than that of acetylsalicylic acid. A lesser degree of cardioprotection was noticed when low doses of tetrapeptide B were administered. This study clearly showed that single dose of ISO (50 mg/kg, s.c.) induced myocardial necrosis could be used as a model to assess cardiovascular drugs and in this model, it was demonstrated that the tetrapeptide B could exhibit optimal cardioprotective effect.

Topics: Adrenergic beta-Agonists; Animals; Aspirin; Body Weight; Creatine Kinase; Disease Models, Animal; Female; Hemodynamics; Hemorrhage; Isoproterenol; L-Lactate Dehydrogenase; Lactoferrin; Myocardial Ischemia; Myocardium; Necrosis; Oligopeptides; Organ Size; Peptide Fragments; Platelet Aggregation Inhibitors; Rats; Rats, Wistar

The aim was to determine if neutrophils are activated and sequestered as they pass through postischaemic human myocardium.. The occurrence of neutrophil activation during the reperfusion of the ischaemic myocardium was investigated in 16 selected patients undergoing coronary artery bypass surgery. Neutrophils were counted and elastase and lactoferrin released into the plasma were measured simultaneously in myocardial venous blood and in peripheral venous blood, before aortic cross clamping (T0), and two (T1), 10 (T2), and 20 (T3) min after unclamping.. At T0, no statistically significant difference was noted between peripheral and myocardial blood with respect to the three variables studied. Reperfusion was associated with a significantly lower neutrophil count in myocardial blood compared to peripheral blood (p < 0.001), suggesting that neutrophils were trapped within the myocardium during reperfusion. In addition, levels of elastase (T1, T2, and T3), and lactoferrin (T1) were significantly higher in myocardial blood as compared to peripheral blood (p < 0.001), suggesting that activated neutrophils released their granular content into the plasma milieu.. We provide evidence consistent with local neutrophil activation during myocardial reperfusion in patients undergoing coronary artery bypass surgery, in addition to the well described systemic activation related to cardiopulmonary bypass.

Topics: Adult; Aged; Coronary Artery Bypass; Coronary Circulation; Female; Humans; Lactoferrin; Leukocyte Count; Male; Middle Aged; Myocardial Ischemia; Myocardial Reperfusion; Myocardium; Neutrophils; Pancreatic Elastase; Prospective Studies