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Excessive levels of catecholamines are believed to contribute to cardiac dysfunction in a variety of disease states, including myocardial infarction and heart failure, and are particularly implicated in stress-induced cardiomyopathy, an increasingly recognized cardiomyopathy associated with significant morbidity and mortality. We have previously shown that a high dose of isoprenaline induces reversible regional dysfunction of the left ventricle in mice. We now hypothesize that adenosine can prevent cardiac dysfunction in this mouse model of stress-induced cardiomyopathy. Hundred male C57BL/6 mice were injected with 400mg/kg isoprenaline and then randomized to either 400mg/kg adenosine or saline. Cardiac function was evaluated by echocardiography at baseline and 2, 24, 48, 72, 96 and 120 min post isoprenaline. Myocardial fibrosis was quantified after 10 days. Intracellular lipid accumulation was quantified after 2 and 24h. Electrophysiological parameters and degree of lipid accumulation were evaluated in cultured HL1 cardiomyocytes. Two hours post isoprenaline treatment, echocardiographic parameters of global and posterior wall regional function were significantly better in adenosine-treated mice (P<0.05). This difference persisted at 24h, but saline-treated mice gradually recovered over the next 96 h. Intracellular lipid accumulation was also significantly lower in adenosine mice. We found no sign of fibrosis in the adenosine mice, whereas the extent of fibrosis in isoprenaline mice was 1.3% (P<0.05). Furthermore, adenosine-treated HL1 cells showed preserved electrophysiological function and displayed less severe intracellular lipid accumulation in response to isoprenaline. In conclusion, adenosine attenuates isoprenaline-induced cardiac dysfunction in mice and cells., (© 2013 Elsevier B.V. All rights reserved.)

Objectives: The objective of this study was to assess the relationship between inflammation, endothelial activation and incipient atherosclerosis in type 2 diabetes., Design: Cross-sectional study. Setting and subjects. We studied 239 type 2 diabetic patients [71 with clinical cardiovascular disease (CVD)] and 78 healthy control subjects, aged 50-75 in a single research centre., Methods: Carotid intima-media thickness (IMT) was determined by ultrasound. Circulating intracellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, ultra-sensitive C-reactive protein, human serum amyloid A, interleukin-6, monocyte colony-stimulating factor, secretory nonpancreatic phospholipase A(2) type IIA, glucose, HbA1c, and lipid/lipoprotein variables were measured., Results: Carotid IMT was significantly thicker in diabetic patients than healthy controls across the whole age range. IMT was also thicker in diabetic patients with, than without, CVD, but this difference disappeared after controlling for confounding factors. Concentrations of the inflammatory and endothelial markers except IL-6 were significantly higher in the diabetic patients than in healthy controls, but comparable in diabetic patients with and without CVD. The main determinants of IMT in the diabetic patients were blood pressure, age and diabetes duration., Conclusions: Low-grade inflammation and endothelial activation are increased in diabetic patients but do not associate with IMT or clinical CVD. The inflammatory reaction seems to be rather a feature of the metabolic syndrome than a direct determinant of atherosclerosis.

Background: Previously we have demonstrated anabolic effects and improved functional status after growth hormone (GH)-therapy in elderly patients in chronic hemodialysis. The aim of this study is to elucidate the effects of GH-therapy on lipid profiles, blood pressure and bone metabolism., Methods: Twenty patients, mean age 73 years, were randomized into two groups i), growth hormone (rHuGH) therapy at a dose of 0.2 IU/kg/BW, or ii) placebo subcutaneously after each dialysis session in a scheme of 3 dialysis per week during 6 months. Two patients in the GH group died (92 and 79 years old) and 1 patient was transplanted. Ten placebo treated patients and 7 GH treated patients were evaluable., Results: The uremic lipid profile with increased triglycerides (TG), low high density lipoproteins, normal lipo-protein Apo-B and relatively low Apo-E values was changed after GH therapy. An unexpected decrease of TG and an indication of decrease of Apo-E values was noted. This differs from GH-treatment to non-uremic adults. Ambulatory 24-hr blood pressures showed a normal circadian rhythm in all patients (GH:n=7, placebo:n=7) at the start and the end of the study. Bone metabolism was increased in the GH group reflected in significant increases of the osteocalcin and telopeptide of type I collagen values. An indication of increased values of propeptide of type I procollagen did not reach statistical significance., Conclusions: Our study of GH-therapy to elderly patients on hemodialysis demonstrated decreased triglyceride levels, no effect on 24-hr blood pressure and increased bone metabolism.