Telmisartan and metabolic syndrome after heart transplantation.

INTRODUCTION: Metabolic syndrome (MS) is a cardiovascular risk predictor. Prevalence of MS after heart transplantation (HTx) is high. Recent data suggest a positive metabolic effect of telmisartan. AIM: To describe the influence of telmisartan on lipid and glycide metabolism in MS after HTx. METHODS: Fifteen patients aged 55+/-12 yr, 88+/-25 months after HTx with MS receiving statins were followed. The reason for telmisartan administration was arterial hypertension with either drug intolerance or poor control. Body mass index (BMI), waist circumference, total cholesterol, low density lipoprotein LDL-cholesterol, high density lipoprotein-cholesterol, triglycerides, C-reactive protein (CRP), fasting glucose, immunoreactive insulin (IRI), C-peptide and the homeostasis model assessment (HOMA) index were determined. Ambulatory blood pressure monitoring was performed. After initial evaluation, telmisartan 80 mg was started. After 20 +/- 5 wk follow-up, identical parameters were measured. Statistical significance was evaluated using Student's t-test. RESULTS: BMI, waist circumference, systolic and diastolic blood pressures, serum lipids and CRP remained unchanged after telmisartan. Significant reduction in fasting glucose (6.7 vs. 5.6 mmol/L, p < 0.02), IRI (8.8 vs. 8.5 U/mL p = 0.05), HOMA (7.3 vs. 5.8 mmol/L x muU/mL, p < 0.05) and C-peptide (4.0 vs. 3.3 ng/mL, p < 0.02) was found. CONCLUSIONS: Telmisartan had a positive impact on insulin sensitivity parameters (fasting glucose, IRI, C-peptide and HOMA) in this population. No effect on obesity, serum lipids and systemic inflammation was observed.

Changes in gene expression of phenylethanolamine N-methyltransferase in the transplanted human heart.

Heart transplantation (HTx) is an accepted treatment for precisely defined patients with chronic congestive heart failure; however, as a result of the procedure, the graft is completely denervated. Our study focused on the catecholamine biosynthetic pathway, that is, the production of epinephrine, which is known to have positive chronotropic and inotropic effects on the heart. mRNA levels of the phenylethanolamine N-methyltransferase (PNMT), the enzyme catalyzing epinephrine synthesis in myocardial tissue, were determined in 18 patients (0 to 10 yr after HTx). Samples of myocardium were obtained from the right ventricle at the time of a routine endomyocardial biopsy performed for the diagnosis of graft rejection. Results were correlated with the following clinical parameters: heart rate, heart rate variability, blood pressure, graft systolic function, and the presence of the rejection. We observed that heart PNMT mRNA levels were significantly higher during the first 3 yr as compared to longer periods after HTx. Also, a decrease in the average heart rate and an increase in the heart rate variability were documented. Levels of the PNMT mRNA do not correlate with blood pressure, left ventricular systolic function at rest, and rejection. Thus, a gradual decrease of the heart rate and an increase in the heart rate variability after HTx is considered to be a sign of cardiac graft reinervation. We speculate that the increased PNMT transcription in human myocardium in early intervals after HTx reflects "autonomous sympathicotrophy." A decrease in the PNMT gene expression with the number of years after HTx could be a consequence of the reinnervation process.

Oxidative stress and antioxidant defense systems in patients after heart transplantation.

Heart transplantation ranks among those surgical interventions associated with ischemia-reperfusion injury to the donor heart as well as to the recipient. These events are connected with increased production of reactive oxygen species which evoke metabolic, structural and functional disturbances. Twenty-four transplant patients were investigated for oxidative stress (plasma levels of thiobarbituric acid reactive substances, TBARS) and antioxidant capacity (plasma total antioxidant status, TAS), and for activities of erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GPx) during the first year after heart transplantation. The post-transplant period was characterized by progressive decrease of plasma TAS, indicating a significant long-term drop of antioxidant reserves in patients after successful heart transplantation. The decrease in plasma TAS is accompanied by long-lasting increase of TBARS levels, which may represent oxidative stress of the organism. We conclude that additional therapy with antioxidant substances should be an important component of the complex therapeutic programme of patients after heart transplantation.