ABSTRACT
UNLABELLED: URGENCY: Despite substantial progress in the treatment of coronary heart disease (CHD) and chronic heart failure (CHF) prognosis in these conditions remains extremely serious. This warrants their timely prevention and early detection. Aim. To study influence of inducible NO synthase (iNOS) (CCTTT)n, Glu298Asp and diallel polymorphism in the fourth intron (4a/4b polymorphism) of endothelial NO synthase gene (eNOS gene) on the state of endothelial function and risk of development of CHF in patients with CHD. MATERIALS AND METHODS: 165 patients with CHD were studied (121 male and 44 female, mean age 56.7 + or - 5.3 years). Vasomotor endothelial function was evaluated using ultrasound method in the reactive hyperemia and trinitroglycerol tests. Genotypes were identified using RFLP analysis of PCR products. Control group consisted of 114 persons (54 male and 60 female, mean age 53.2 + or - 4.9 years). RESULTS: It was determined that the number of repeats of polymorphic locus (CCTTT)n of the iNOS gene and Glu allele of the polymorphic locus Glu298Asp of eNOS gene in the homozygous state were associated with the risk of development of CHD and class of severity of CHF clinical manifestation. In addition Glu allele of the polymorphic locus Glu298Asp of eNOS gene in the homozygous state was associated with the severity and unfavorable development of CHF. The endothelial-dependent dysfunction was more severe in homozygotes of Glu allele of the polymorphic locus Glu298Asp of eNOS gene than in carrier of allele 298Asp. Associations between polymorphic variant of VNTR intron 4 gene eNOS and CHF with the risk of development and endothelial dysfunction were not found. CONCLUSION: An association between polymorphism of iNOS gene (CCTTT)n, eNOS gene (Glu298Asp) with development of CHD and severity of CHF was shown. The polymorphism of eNOS gene (Glu298Asp) was associated with endothelial dysfunction.
Subject(s)
DNA/genetics , Heart Failure/genetics , Myocardial Ischemia/complications , Nitric Oxide Synthase Type III/genetics , Nitric Oxide Synthase Type II/genetics , Polymorphism, Genetic , Aged , Alleles , Endothelium, Vascular/physiopathology , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Heart Failure/enzymology , Heart Failure/etiology , Humans , Male , Middle Aged , Myocardial Ischemia/enzymology , Myocardial Ischemia/genetics , Nitric Oxide Synthase Type II/blood , Nitric Oxide Synthase Type III/blood , Vasodilation/physiologyABSTRACT
AIM: Trial of trimetasidine effects on exercise tolerance (ET) and left ventricular diastolic function (LVDF) in patients with coronary heart disease (CHD). MATERIALS AND METHODS: The study group included 40 CHD patients. Of them 10, 18 and 12 had myocardial infarction, unstable angina pectoris and stable angina, respectively. 38 CHD patients of the control group had these disorders, respectively, in 5, 15 and 18 cases. 2-3-month therapy with nitrates, beta-blockers (BB) and inhibitors of angiotensin-converting enzyme (ACE) was given to both groups with adjuvant trimetasidine (60 mg/d) given to patients of the study group. The effects were judged by the results of cycle exercise tests and echo-CG including the loading one. RESULTS: Adjuvant use of trimetasidine improved exercise tolerance, mean threshold capacity, LVDF. When added to BB treatment, trimetasidine reduced damage to LVDF under dipiridamol test. CONCLUSION: Trimetasidine addition to combined treatment of CHD raises exercise tolerance and improves LVDF.
