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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirty-two patients with angiographically proven coronary artery disease and reproducible ST-segment depression in the exercise ECG took part in this open dose-finding study on the hemodynamic and anti-ischemic effects of tedisamil, using right heart catheterization and bicycle exercise testing. Tedisamil--a bispidine derivative--is a new potassium channel blocking agent with negative chronotropic (i.e., direct effects on sinus node automaticity) and class III antiarrhythmic properties. Four groups of 8 patients each received rising doses of 0.1, 0.2, 0.3, and 0.4 mg/kg BW tedisamil intravenously. Being well tolerated, tedisamil was found to be dose-linear with the dose of 0.3 mg/kg BW having the most favorable anti-ischemic effects accompanied by a significant decrease in heart rate at rest (-13%, p < 0.001) and maximum exercise (-9%, p < 0.05). There was a consecutive fall of CO (by 10%, p < 0.05), while stroke volume remained unaltered. Despite singular significant changes, PCWPm and RV-EF, as indirect parameters of ventricular function, showed different responses without a clear tendency. PAPm increased slightly in accordance with peripheral and pulmonary vascular resistance, being significant at 3.3 mm Hg (p < 0.05) only at the dose of 0.4 mg/kg BW. Mean arterial pressure demonstrated a slight increase at rest (9% at 0.4 mg/kg BW; p < 0.05). Plasma catecholamine levels fell in a dose-dependent way by a maximum of 115-150 pg/ml (p < 0.01) on treatment with 0.4 mg/kg BW. QTc was found significantly prolonged by 16% (p < 0.001) on 0.4 mg/kg BW. During treatment with 0.3 mg/kg BW, tedisamil produced a dose-dependent reduction of ST segment depression at a maximum of 42% (p < 0.001) as well as a decrease in myocardial oxygen consumption, pressure rate product, and plasma lactate concentrations. In conclusion, tedisamil lowered heart rate and showed favorable hemodynamic, anti-ischemic, and neurohumoral effects in patients with coronary artery disease.
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PMID:[The new potassium channel blocker tedisamil and its hemodynamic, anti-ischemic and neurohumoral effect in patients with coronary heart disease]. 908 75

Clinical and experimental investigations have demonstrated an inverse relation between heart rate and myocardial performance in patients with congestive heart failure. Accordingly, this study was designed to investigate the hemodynamic effect of the novel bradycardic compound tedisamil in patients with heart failure. We hypothesized that tedisamil would reduce heart rate and thereby improve hemodynamic parameters of failing hearts with an inverse force-frequency relation. Tedisamil was administered intravenously in nine patients with dilated cardiomyopathy (NYHA II-III). Hemodynamic measurements by right heart catheterization were carried out at time points -30, 10, 20 min, 1, 2, 4, and 6 h. Tedisamil decreased heart rate significantly from 84 +/- 6 beats/min to 73 +/- 4 beats/min (at 10 min; p < 0.05). Stroke volume index remained unchanged, and cardiac index tended to decrease transiently. Mean blood pressure increased from 98 +/- 5 to 104 +/- 6 mm Hg (p < 0.05) because of an increase in systemic vascular resistance from 1,619 +/- 145 to 2,079 +/- 198 dyn x s x cm(-5) (at 20 min; p < 0.05). Diastolic pulmonary pressure and pulmonary vascular resistance showed similar changes. Pulmonary capillary wedge pressure increased from 12 +/- 3 to 16 +/- 4 mm Hg (at 20 min; p < 0.05). Although tedisamil resulted in a significant heart-rate reduction, this was not associated with an improvement of hemodynamics. This may be due to increased afterload of the left and right ventricle. In these patients, tedisamil increased vascular resistance, which is unwanted in the treatment of congestive heart failure.
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PMID:Cardiac and hemodynamic effects of the sinus node inhibitor tedisamil dihydrochloride in patients with congestive heart failure due to dilated cardiomyopathy. 986 3

Clinical drawbacks of beta-blocker treatment in stable angina have motivated researchers to provide alternative heart-rate-lowering agents, such as tedisamil, which additionally exerts antiischemic and antiarrhythmic effects by blockade of cellular repolarizing K+ currents. Forty-eight patients with stable angina pectoris were investigated (doubleblind, randomized, parallel grouped) comparing the hemodynamic, antiischemic, metabolic and neurohumoral effects of tedisamil 100 mg b.i.d. and atenolol 50 mg b.i.d. after a single dose and over 6 days of treatment. Tedisamil and atenolol produced a decrease in heart rate both at rest [day 1:-13.6 versus - 15.4 bpm; day 6: - 14.8 versus - 22.2 bpm, resp.; p > 0.05] and exercise [day 1: - 9.1 versus - 18.3 bpm; p = 0.001; day 6: - 12.0 versus - 24.8 bpm, resp.; p = 0.001], while anginal threshold increased. Cardiac output decreased with tedisamil and atenolol at rest [day 1: -1.01 versus -1.19 l/min; p > 0.05; day 6: - 0.86 versus - 1.10 l/min, resp.; p > 0.05] and exercise [day 1: - 0.82 versus - 1.28 l/min; p > 0.05; day 6: - 0.65 versus - 2.68 l/min, resp.; p = 0.03], while stroke volume remained unchanged. Right atrial pressure changed during exercise only: it decreased with tedisamil (-1.7 mmHg) and increased with atenolol (+ 3.7 mmHg) (p < .001). Mean pulmonary capillary wedge pressures decreased both at rest (- 0.5 mmHg) and exercise (- 6.9 mmHg) in the tedisamil group but tended to increase with atenolol on day 6 of treatment [rest: + 1.7; exercise: + 3.7 mmHg) (p = 0.03). Arterial pressure decreased under atenolol treatment only. Exercise-induced plasma norepinephrine levels were reduced by tedisamil (- 93 pg/ml) but elevated by atenolol (+ 172 pg/ml) (p = 0.001). As compared to atenolol, tedisamil produced a prolongation of QTc interval [+ 31 versus 8 ms] at initial values of 0.408 +/- 0.018 s with PQ and QRS remaining unaltered. In patients with stable angina, tedisamil (100 mg b.i.d.) as compared to atenolol (50 mg b.i.d.) generated similar hemodynamic, neurohumoral and antiischemic effects. The antiischemic efficacy of tedisamil, as measured by ST segment depression and angina threshold, was comparable to that of atenolol.
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PMID:Hemodynamic, antiischemic, and neurohumoral effects of tedisamil and atenolol in patients with coronary artery disease. 1110 Nov 99