Biomedical subjects
Publications and source records attributed to H Darius.
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The diagnostic value of transesophageal echocardiography in monitoring the clinical course has been evaluated in 83 patients with echocardiographic evidence of infective endocarditis. A total of 103 vegetations attached to the aortic or mitral valves were detected by use of the transesophageal approach. The patients were monitored for a mean of 74 weeks and underwent a minimum of two consecutive transesophageal echocardiographic examinations. Group A included patients with increasing or remaining constant size of vegetation (8.2 +/- 1.5 to 11.2 mm, p less than 0.05) during 4 to 8 weeks of antimicrobial therapy, whereas group B was formed by patients with decreasing vegetation size (8.3 +/- 0.8 to 4.9 +/- 0.8 mm, p less than 0.05). The incidences of complications after diagnosis and onset of therapy was higher in group A than in group B: valve replacement (45% versus 2%, p less than 0.05), embolic events (45% versus 17%, p less than 0.05), perivalvular abscess formation (13% versus 2%, p less than 0.05), and mortality (10% versus 0%, respectively, p less than 0.05). Staphylococcus aureus was the most frequent organism isolated in group A (44% versus 11% in B, p less than 0.05) and Streptococcus viridans in group B (33% versus 18% in A, p less than 0.05). Blood cultures were negative in nearly 50% of the patients in each group. There was no difference in the incidences of complications in patients with positive or negative blood cultures. We conclude that an increase in vegetation size during antibiotic therapy predicts a prolonged healing phase of infective endocarditis. This prolonged healing period is associated with a significantly increased risk of complications, independent of blood culture results. Monitoring vegetation size contributes important information concerning prognosis and stage of risk, and it aids in the choice of patient management in infective endocarditis. Because embolic events after diagnosis and onset of treatment are less frequent in rapid-healing endocarditis, surgery cannot be recommended to prevent further events taking into account the high risk of surgery.
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We investigated the in vitro thrombolytic effects of streptokinase, urokinase, alteplase and saruplase, alone or in combination, with the prostacyclin analogues, iloprost and taprostene. Human platelet-rich plasma was stimulated with collagen (1 microgram/ml) to generate thrombi containing platelets and fibrin. Following treatment with fibrinolytic agents, lysis was allowed to proceed for 30 min and was then terminated with aprotinin (2,000 CIU/ml). To evaluate the combinatory effects of fibrinolytic agents and prostacyclin analogues, we used concentrations of fibrinolytic agents which reduced thrombi weight by less than 50%. Neither iloprost nor taprostene alone demonstrated any thrombolytic effects. Furthermore, the thrombolytic efficacies of streptokinase, alteplase and saruplase were not enhanced by prostacyclin analogues. The thrombolytic activities of alteplase and urokinase, however, were additive. Similarly, the combination of urokinase with saruplase had an additive thrombolytic effect in our in vitro model. The effects of alteplase and saruplase were synergistic at a molar ratio of 1:4.7.
BACKGROUND: We studied the effects of recombinant growth hormone (rhGH) on exercise capacity and cardiac function in patients with ischemic cardiomyopathy. METHODS AND RESULTS: Seven patients (aged 55+/-9 years) with mild to moderate congestive heart failure (ejection fraction 31+/-4%) who were on standard therapy were included. The patients were studied at baseline, after 3 months of rhGH treatment, and 3 months after rhGH discontinuation. Cardiac function was assessed by exercise capacity, right heart catheterization at rest and after submaximal exercise, MRI, echocardiography, and Holter monitoring. When administered at a dose of 2 IU/d, rhGH doubled the serum concentration of insulin-like growth factor-I. rhGH improved clinical symptoms and exercise capacity significantly (New York Heart Association class 2.4+/-0.5 initially versus 1.4+/-0.5 at 3 months [mean+/-SD], P<0.05; VO2max 13.6+/-3.8 versus 17.4+/-5.4 mL. kg-1. min-1, P<0.05). Additionally, pulmonary capillary wedge pressures at rest and after submaximal exercise were reduced significantly. Cardiac output increased, particularly at rest (5.0+/-1.1 versus 5.8+/-1.3 L/min; P<0.05). Posterior wall thickness was increased (1.08+/-0.1 versus 1. 24+/-0.3 cm; P<0.05), and the end-diastolic and end-systolic volume indexes decreased significantly after rhGH treatment. There was no significant increase in left ventricular ejection fraction. The improvements were partially reversed 3 months after rhGH discontinuation. CONCLUSIONS: The administration of rhGH for 3 months in patients with ischemic cardiomyopathy results in significant improvement in hemodynamics and clinical function. The attenuation of left ventricular remodeling persisted 3 months after discontinuation of treatment.
We studied the potential therapeutic value of the chemically stable carbacyclin analogue ZK 36 375 during acute myocardial ischemia and compared the cardiovascular and anti- and disaggregatory effects of the compound in vitro and ex vivo. In anesthetized cats the left anterior descending coronary artery was ligated, and 30 min later an intravenous infusion of ZK 36 375 (3.6 micrograms/kg X min) or vehicle was initiated and continued for 4.5 h. ZK 36 375 reduced the ST-segment elevation at 2-5 h (p less than 0.01) when compared to vehicle-treated cats. ZK 36 375 significantly inhibited both the loss of creatine phosphokinase--specific activity and the decrease in the percentage of bound cathepsin D in the infarcted area of the myocardium (p less than 0.05). ZK 36 375 did not reverse ischemia-induced formation of platelet aggregates in vivo and was found ex vivo to be two to three orders of magnitude less active in preventing platelet aggregation, redispersing platelet aggregates, and relaxing bovine coronary arteries than prostacyclin (PGI2) or its (5E) stereoisomer ZK 36 374. It is concluded that ZK 36 375 has a significant cardioprotective activity in acute myocardial ischemia of the cat that can be dissociated from antiplatelet effects in vivo.
We studied the action of the biologically active metabolite of molsidomine, N-morpholino-N-nitrosoamino-acetonitrile (SIN), on eicosanoid formation and functional behavior of bovine coronary arteries and human platelets in vitro. Glyceryltrinitrate (GTN) and prostaglandin (PG) I2 were used as reference compounds. SIN dose-dependently inhibited the thrombin-, collagen-, and primary ADP-induced platelet aggregation. The IC50 was in the range of 0.1-0.8 mumol/L. At these concentrations SIN also inhibited thromboxane formation, but did not influence the PGI2 biosynthesis of coronary vessels. Molsidomine itself was inactive. GTN stimulated vascular PGI2 formation, but did not modify the platelet aggregation at comparable concentrations. A particularly interesting finding was the dose-dependent and apparently complete inhibition of formation of the hydroperoxide of 12L-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HPETE) in human platelets by SIN. The IC50 amounted to 1.7 +/- 0.4 mumol/L and was in the same range as with 5,8,11,14-eicosatetraynoic acid (2.0 +/- 0.3 mumol/L). Although the results may not suggest a common mechanism of the antiaggregatory action of GTN and SIN, they provide no evidence of a similar or dissimilar mechanism of action in vascular smooth muscle.