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

The haemodynamic dose-response effects of intravenous indoramin were evaluated in 12 patients with acute heart failure (pulmonary artery occluded pressure of greater than 20 mm Hg) complicating a recent myocardial infarction. Following a 1-h control period with confirmed stable haemodynamics, the effects of three intravenous bolus doses of indoramin (0.125, 0.125, and 0.25 mg/kg at 15-min intervals) were determined in the 10- to 15-min period following each intravenous injection. Plasma drug concentrations rose with the administered dose and were in the previously established therapeutic range. Ten patients tolerated all three doses of the drug; two patients were withdrawn following the second dose owing to clinically evident hypotension (systolic blood pressure of less than 100 mm Hg). Indoramin resulted in progressive falls in systolic, diastolic, and mean systemic arterial pressures (p less than 0.01) without change in cardiac index. There was a dose-related reduction in the heart rate (0.5 mg/kg; -7 beats/min; p less than 0.01). The left ventricular filling pressure showed a significant and quadratic reduction over the dose range (0.5 mg/kg, -5 mm Hg; p less than 0.01). The systemic vascular resistance index was reduced (-333 dynes X s X cm-5 X m2; p less than 0.001) and the stroke volume index increased (+3 ml/m2; p less than 0.05) following the maximum cumulative dosage. These data established the therapeutic safety of indoramin (0.125-0.5 mg/kg) in acute heart failure following myocardial infarction. An improvement in cardiac performance in these patients was compatible with circulatory actions on both cardiac preload and afterload.
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PMID:Haemodynamic dose-response effects of intravenous indoramin in acute heart failure complicating myocardial infarction. 242 81

Indoramin, an alpha 1 antagonist, and guanabenz, an alpha 2 agonist, were given to 10 patients with severe congestive heart failure to compare the hemodynamic and hormonal effects of a reduction in sympathetic tone obtained through inhibition of postsynaptic alpha 1 receptors versus the decrease in sympathetic activity achieved by stimulating central or presynaptic peripheral alpha 2 adrenoceptors. Both drugs produced similar reduction in systemic arterial pressure. However, only indoramin significantly decreased systemic and pulmonary vascular resistances from 1529 +/- 526 to 1071 +/- 356 and from 721 +/- 422 to 412 +/- 257 dynes X s X cm-5, respectively, and increased stroke index from 26.6 +/- 9.5 to 33.3 +/- 9.5 ml/m2 (all p less than 0.01). Heart rate fell significantly only after guanabenz. Plasma norepinephrine, unchanged after indoramin, fell in each patient after guanabenz; the mean value decreased from 746 +/- 332 to 461 +/- 255 pg/ml (p less than 0.01). Plasma renin activity increased only after indoramin. The data demonstrate: (a) a decrease in sympathetic activity due to blockade of alpha 1 adrenoreceptors produces marked peripheral and pulmonary vasodilation; (b) noradrenergic transmitter release in heart failure is regulated by alpha 2 receptors; (c) an alpha 2-mediated decrease in sympathetic activity and in plasma norepinephrine has a bradycardic effect but does not produce a vasodilator effect. Although the acute hemodynamic effects of indoramin were more prominent than those of guanabenz, the more favorable neurohumoral effects of guanabenz suggest the possibility of long-term benefit in the treatment of heart failure.
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PMID:Acute hemodynamic and hormonal effects of central versus peripheral sympathetic inhibition in patients with congestive heart failure. 242 99

Indoramin is an alpha 1-adrenergic antagonist vasodilator of potential value in heart failure. We measured hemodynamics and exercise capacity in 12 patients with heart failure, before and after 1 week of indoramin dosing, 75 mg b.i.d. Maximal hemodynamic effects 2 hours after the first dose of indoramin consisted of reduced mean systemic arterial pressure from 96.0 +/- 15.3 to 87.9 +/- 15.3 mm Hg (P less than 0.05) and pulmonary wedge pressure from 23.6 +/- 7.8 to 16.9 +/- 6.6 mm Hg (P less than 0.001). Heart rate, cardiac index, and total systemic resistance did not change acutely after indoramin, but after 1 week mean systemic arterial pressure was still reduced whereas cardiac index fell from 2.69 +/- 0.38 to 2.32 +/- 0.44 L/min/m2 (P less than 0.05) and total systemic resistance rose from 20.4 +/- 2.8 to 21.9 +/- 4.0 U (P less than 0.1). After 1 week maximal exercise oxygen uptake fell from 16.8 +/- 5.6 to 12.5 +/- 3.5 ml/min/kg (P less than 0.02). This limited observation suggests that indoramin is a predominant venodilator acutely in patients with heart failure but that despite this effect it may worsen functional capacity and hemodynamics during continuous dosing in these patients.
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PMID:Indoramin in heart failure: possible adverse effects on hemodynamics and exercise capacity. 376 87