Anti-inflammatory effects of atorvastatin improve left ventricular function in experimental diabetic cardiomyopathy.

AIMS/HYPOTHESIS: Emerging evidence suggests that statins exert beneficial effects beyond those predicted by their cholesterol-lowering actions. We investigated whether atorvastatin influences the development of left ventricular (LV) dysfunction, independently of cholesterol-lowering, in an experimental model of type 1 diabetes mellitus cardiomyopathy. METHODS: Streptozotocin-induced diabetic rats were treated with atorvastatin (50 mg/kg daily, orally) or with vehicle for 6 weeks. LV function was analysed using tip-catheter measurements. Cardiac stainings of TNF-alpha, IL-1beta, intercellular adhesion molecule-1, vascular cellular adhesion molecule-1, CD11a/lymphocyte-associated antigen-1, CD11b/macrophage antigen alpha, CD18/beta2-integrin, ED1/CD68, collagen I and III, and Sirius Red were assessed by digital image analysis. Ras-related C3 botulinum toxin substrate (RAC1) and ras homologue gene family, member A (RHOA) activities were determined by RAC1 glutathione-S-transferase-p21-activated kinase and rhotekin pull-down assays, respectively. Cardiac lipid peroxides were measured by a colorimetric assay. The phosphorylation state of p38 mitogen-activated protein kinase (MAPK) and endothelial nitric oxide synthase (eNOS) protein production were analysed by western blot. RESULTS: Diabetes was associated with induced cardiac stainings of TNF-alpha, IL-1beta, cellular adhesion molecules, increased leucocyte infiltration, macrophage residence and cardiac collagen content. In contrast, atorvastatin reduced both intramyocardial inflammation and myocardial fibrosis, resulting in improved LV function. This effect was paralleled with a normalisation of diabetes-induced RAC1 and RHOA activity, in the absence of LDL-cholesterol lowering. In addition, atorvastatin decreased diabetes-induced cardiac lipid peroxide levels and p38 MAPK phosphorylation by 1.3-fold (p < 0.05) and 3.2-fold (p < 0.0005), respectively, and normalised the reduced eNOS production caused by diabetes. CONCLUSIONS/INTERPRETATION: These data indicate that atorvastatin, independently of its LDL-cholesterol-lowering capacity, reduces intramyocardial inflammation and myocardial fibrosis, resulting in improved LV function in an experimental model of diabetic cardiomyopathy.

[On the 150th birthday of César Roux (1857-1918). Memories of the life and work of an important pupil of Kocher]. / Zum 150. Geburtstag von César Roux (1857-1918). Erinnerung an Leben und Schaffen eines bedeutenden Kocher-Schülers.

César Roux was one of the few universal surgeons at the end of the 19th century who dominated all fields of surgery and influenced current surgery with his innovative spirit. Pioneering spirit and the story of the success of modern surgery are linked with his name. On the occasion of his 150th birthday, we recall the memory of this great surgeon. The personality and the history of Professor César Roux form a part of our medical and surgical heritage.