Objective: To investigate the long term effects of trimetazidine in patients with dilated ischaemic cardiomyopathy. The effects of trimetazidine on left ventricular function as well as its tolerability profile and potential anti-inflammatory effects were studied. Design: 61 patients were randomly assigned either to receive trimetazidine (20 mg thrice daily) in addition to their conventional treatment or to continue their usual drug treatment for 18 months. Patients were evaluated at baseline and at 6, 12, and 18 months with a clinical examination, echocardiography, and biochemical analysis (C reactive protein). Results: Trimetazidine added to the usual treatment significantly improved the patients' functional status (assessed by New York Heart Association functional class). The functional improvement of trimetazidine treated patients was associated with a significant increase in left ventricular ejection fraction (30 (6)%, 32 (8)%, 38 (7)%, and 37 (6)% v 31 (8)%, 30 (7)%, 28 (6)%, and 26 (9)% in control patients at baseline and at 6, 12, and 18 months, respectively) and with a significant effect on ventricular remodelling. C reactive protein plasma concentrations remained stable throughout the study in patients receiving trimetazidine (2.5 (1.0), 2.7 (2.0), 2.7 (3.0), and 3.0 (2.0) mg/l at baseline and at 6, 12, and 18 months, respectively) but increased significantly in the control group (2.4 (1.0), 3.4 (1.2), 6.0 (4.0), and 7.0 (5.0) mg/l, respectively). No significant adverse event or changes in clinical or biochemical parameters were detected. Conclusion: Treatment with trimetazidine added to the usual treatment for up to 18 months was well tolerated and induced a functional improvement in patients with dilated cardiomyopathy. Trimetazidine treatment was associated with a significant improvement of left ventricular function and the remodelling process. Results also suggest that the inflammatory response was limited in patients treated with trimetazidine.

In this model, in the absence of perfusing granulocytes, the acute administration of a pharmacologically relevant simvastatin concentration reduces ischemia-reperfusion injury and prevents coronary endothelial cell and cardiomyocyte damage by cholesterol-independent, NO-dependent mechanisms.

Chronic treatment with rosuvastatin before ischemia reduces ischemia-reperfusion injury and prevents coronary endothelial cell and cardiomyocyte damage by NO-dependent mechanisms.

Cardiac stem cells or myoblasts are vulnerable to inflammatory stimulation in hearts with infarction or ischemic injury. Widely used for the prevention and treatment of atherosclerotic heart disease, the cholesterol-lowering drugs statins may exert anti-inflammatory effects. In this study, we examined the impact of inhibition of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase with simvastatin on the expression of inducible nitric-oxide synthase (iNOS) in embryonic cardiac myoblasts stimulated with the proinflammatory cytokines, interleukin-1 or tumor necrosis factor. Treatment with simvastatin significantly reduced the levels of iNOS mRNA and protein in cytokine-treated rat H9c2 cardiac embryonic myoblasts. Addition of the HMG-CoA reductase product, Lmevalonate, and the by-product of cholesterol synthesis, geranylgeranyl pyrophosphate, could reverse the statin inhibitory effect on iNOS expression. Simvastatin treatment lowered the Rho GTPase activities, whereas the Rho-associated kinase inhibitor Y27632 partially blocked the statin inhibitory effect on nitrite production in the cytokine-treated H9c2 cells. Treatment with simvastatin led to inactivation of NF-B by elevation of the NF-B inhibitor IB and reduction of the NF-B nuclear contents in the cytokine-stimulated H9c2 cells. Hence, treatment with simvastatin can attenuate iNOS expression and NO synthesis in cytokine-stimulated embryonic cardiac myoblasts. The statin inhibitory effect may occur through isoprenoid-mediated intracellular signal transduction, which involves several key signal proteins, such as Rho kinase and IB/NF-B. These data suggest that statin therapy may protect the cardiac myocyte progenitors against the cytotoxicity of cytokine-induced high output of NO production in infarcted or ischemic hearts with inflammation.

No abstract