Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Cardiac and hemodynamic effects of the sinus node inhibitor tedisamil dihydrochloride in patients with congestive heart failure due to dilated cardiomyopathy. 986 3

Decreasing heart rate is potentially useful in ischaemic heart disease. Tedisamil is a bradycardic agent resulting from its ability to inhibit transient outward current (I(to)) in atria. Tedisamil inhibits I(to), potassium current (IK), K(ATP) and the protein kinase A-activated chloride channel in ventricles as well as vascular IK and Ca(2+)-activated IK (IK((Ca))). Tedisamil prolongs cardiac action potentials and the corrected QT (QTc) of the ECG and also increases cardiac refractoriness. Tedisamil is anti-arrhythmic in animal models of ventricular arrhythmias and atrial flutter. The bradycardic effect of tedisamil is associated with a reduction in myocardial oxygen demand. On isolated rat ventricle, tedisamil is a positive inotrope and on isolated rabbit atria, tedisamil reverses the negative inotropic effect of pinacidil. Tedisamil contracts the isolated rat portal vein and aorta, reduces cromakalim-induced relaxations of contracted rat aorta and increases blood pressure in animals and humans. Tedisamil is 96% bound to plasma proteins, has a plasma half-life of about 10 h and is cleared from the kidney unchanged. Clinical trials have shown that the electrophysiology of tedisamil is that of a class III anti-arrhythmic. In coronary artery disease, tedisamil has no effect on inotropism and increases the threshold for angina. Potassium channel blockade with tedisamil may have advantages over calcium channel blockers or K(ATP) channel openers as an anti-ischaemic mechanism in coronary artery disease. In exercise-induced myocardial ischaemia, beta-blockers are probably favourable to tedisamil, as they will limit the increase in heart rate, contractility and blood pressure caused by sympathetic stimulation, whereas tedisamil will not. In heart failure patients, tedisamil reduces heart rate, but increases blood pressure. The usefulness of tedisamil as a bradycardic agent is limited by the increase in blood pressure. A drug that is bradycardic without increasing blood pressure would be an improvement on tedisamil as the master switch of nature for ischaemic heart disease.
 ...
PMID:Tedisamil: master switch of nature? 1111 86

Atrial fibrillation has recently come into clinical and research focus. In particular, ventricular rate control has been carefully compared with atrial rhythm control. Additionally, the recent discovery of atrial stunning has initiated clinical and research interest in atrial remodeling. Atrial fibrillation is more likely to occur when the atria are damaged by increased fibrosis. The ideal way to prevent atrial fibrillation and the risk of repetition is by tackling the root causes, such as ischemic heart disease, heart failure, and left ventricular hypertrophy. Tedisamil is an unusual antifibrillatory compound that has a novel mechanism of action by inhibiting the transient outward current (Ito) and the repolarizing potassium currents in the sinoatrial node. Tedisamil works acutely against atrial fibrillation. Importantly, atrial fibrillation is often caused by or related to cardiac ischemia, and conversely, ischemia is caused by the increased oxygen demand of atrial fibrillation. Hence, the double properties of tedisamil as a drug that both inhibits atrial fibrillation and acts in an anti-ischemic mode are an attractive basis for future clinical research.
 ...
PMID:Tedisamil in coronary disease: additional benefits in the therapy of atrial fibrillation? 1274 50