Our results add to previous evidence suggesting that the low-molecular-weight heparin dalteparin administered by twice-daily subcutaneous injection may be an alternative to unfractionated heparin in the acute treatment of unstable angina or non-Q-wave myocardial infarction. Prolonged treatment with dalteparin at a lower once-daily dose in our study did not confer any additional benefit over aspirin (75 to 165 mg) alone.

Our data demonstrate that more than one-third of patients clinically diagnosed as having pulmonary embolism presented with elevated serum troponin I concentrations. Troponin I tests helped to identify patients with RV dilatation who had significantly more segmental defects in lung scans. Thus, troponin I assays are useful to detect minor myocardial damage in pulmonary embolism.

Abstract-Coronary heart disease (CHD) is based on the development of atherosclerosis in coronary arteries. Shear stress-induced endothelial nitric oxide (NO) release not only contributes to local blood pressure control but also effectively helps to retard atherosclerosis. Therefore, functionally relevant polymorphisms in the endothelial NO synthase (NOS-3) gene may contribute to the development of CHD. NOS-3 expression was analyzed in endothelial cells isolated from umbilical cords genotyped for the Ϫ786 C/T single nucleotide polymorphism (SNP) of the human nos-3 gene. Moreover, NO-dependent relaxation was examined in segments of saphenous vein isolated from genotyped patients undergoing aortocoronary bypass surgery, and patients subjected to quantitative coronary angiography were genotyped to verify an association between this SNP and CHD. Shear stress-induced NOS-3 mRNA and protein expression was present in TT and CT genotype cells but absent in cells with CC genotype. Pretreatment of these cells with a decoy oligonucleotide comprising position Ϫ800 to Ϫ779 of the C-type nos-3 promoter reconstituted shear stress-induced NOS-3 expression. These results were confirmed by reporter gene analysis with the corresponding nos-3 promoter luciferase constructs. In addition, the NO-mediated relaxant response of vein grafts from CC genotype patients was significantly attenuated as compared with the CT or TT genotype, and in CHD-positive patients, the CC genotype was significantly more frequent (19.0%) than in CHD-negative patients (4.4%). The Ϫ786 C/T SNP of the nos-3 gene thus constitutes a genetic risk factor for CHD, presumably due to binding of an inhibitory transcription factor to the C-type promoter blocking shear stress-dependent maintenance of NOS-3 expression. Key Words: coronary heart disease Ⅲ shear stress Ⅲ atherosclerosis Ⅲ endothelial dysfunction Ⅲ nitric oxide synthase Ⅲ single nucleotide polymorphism Ⅲ decoy oligonucleotide

The defects underlying the impairment of systolic pump function in human dilated cardiomyopathy (DCM) are not known. We isolated mitochondrial particles from 10 hearts of transplant recipients with DCM and from nine normal hearts not used for transplantation. Yield was similar in both groups (2.77 vs 2.81 mg mitochondrial protein per gram heart). Cytochrome content (difference spectrophotometry) was found reduced in DCM mitochondria, e.g. cytochrome c was 0.295 +/- 0.06 in the DCM group and 0.371 +/- 0.04 mumol g-1 in the control group (P less than 0.05). Enzymatic activity of the cytochrome-containing complexes III (3.77 +/- 0.82 vs 4.95 +/- 1.15 mumol min-1.mg-1) and IV (2.63 +/- 0.96 vs 3.65 +/- 0.6 mumol min-1.mg-1) of the respiratory chain was reduced in the DCM group (P less than 0.05). Complex IV, the cytochrome c oxidase, in the DCM group showed impaired activity also in whole heart homogenates (0.173 +/- 0.04 vs 0.258 +/- 0.8 mumol min-1.mg-1). Subunit composition of the cytochrome c oxidase on sodium dodecyl sulphate-gel electrophoresis did not differ between DCM and normal hearts. Activity of complexes II and V of the respiratory chain, not containing cytochromes, was unchanged in DCM mitochondria compared with the control group. The present data show a decrease in cytochrome content and in cytochrome-dependent enzyme activity in human dilated cardiomyopathy. Further studies are necessary to clarify whether these findings are specific for dilated cardiomyopathy or whether they are epiphenomena of failing hearts.