denopamine and Chronic-Disease

In 1993, we reported the pathophysiology of postprandial hypotension (PPH) in patients with sympathetic dysfunction: a fall of BP resulted from both excess systemic vasodilation and lack of compensatory increase of cardiac output and vascular resistance in the leg arteries. In that article, we showed the beneficial results of combined oral administration of denopamine (a selective beta 1-agonist) and midodrine HCI (a selective alpha 1-agonist) on this condition. The present study was undertaken to further evaluate the efficacy and safety of this agonist combination in autonomic failure (AF) patients with PPH. This was a one-month trial. A total of 13 chronic AF patients received orally 30 mg of denopamine and 12 mg of midodrine three times a day, 30 minutes before each meal. We measured brachial BP every 10 min in the daytime and every 15 min in the nighttime, using a 24-h indirect BP recorder. The combined use of these agonists produced a significant improvement in PPH and maintained a near-normal BP level. In conclusion, the combined administration of denopamine and midodrine three times a day is a well-tolerated and efficacious treatment for PPH.

Topics: Adrenergic alpha-Agonists; Adrenergic beta-Agonists; Aged; Autonomic Nervous System Diseases; Chronic Disease; Drug Therapy, Combination; Ethanolamines; Female; Humans; Hypotension; Male; Middle Aged; Midodrine; Postprandial Period; Treatment Outcome

The short-term effects of denopamine, an orally available beta-stimulant, on exercise capacity were studied in patients with chronic heart failure.. Nineteen patients entered the study. Three patients had ischemic heart disease, 13 had dilated cardiomyopathy, and three had valvular disease; 16 patients were in New York Heart Association class II, and three patients were in New York Heart Association class III. Symptom-limited exercise testing (ramp protocol) on a bicycle ergometer with gas exchange analysis was conducted 1 hour after oral administration of either 20 mg denopamine or placebo. Drug administration sequence was randomly assigned in a double-blind crossover method, with 1 week between drugs. Peak VO2 was 20.4 +/- 3.2 and 21.2 +/- 3.1 ml/min/kg, respectively, for those administered the placebo and the drug, and anaerobic threshold was 13.1 +/- 2.1 and 14.0 +/- 2.0 ml/min/kg. There was a significant increase in peak VO2 (p < 0.05) and anaerobic threshold (p < 0.01) with denopamine, whereas no significant change was observed in peak work rate or exercise time. Denopamine increased heart rate in patients with atrial fibrillation but had little effect on heart rate in patients with sinus rhythm.. Data obtained from gas exchange analysis are more sensitive and potentially more useful in the detection of short-term changes in exercise capacity than data obtained from either exercise time or peak work rate, indexes that are commonly used to assess drug therapy. Patients with mild-to-moderate heart failure with sinus rhythm, but not those with atrial fibrillation because of its frequent induction of tachycardia, may be good candidates for denopamine therapy.

Topics: Adrenergic beta-Agonists; Adult; Aged; Anaerobic Threshold; Blood Pressure; Cardiotonic Agents; Chronic Disease; Double-Blind Method; Ethanolamines; Female; Heart Diseases; Heart Rate; Humans; Male; Middle Aged

The hemodynamic effect of oral TA-064 (20 mg), a newly synthesized inotropic agent, was compared with that of intravenous dobutamine (5 micrograms/kg/min) in eight patients with congestive heart failure who had been treated with intravenous dobutamine, digitalis, diuretics, and prazosin. Hemodynamics was measured using a Swan-Ganz catheter during the pre-dobutamine control period, during dobutamine infusion period, during the pre-TA-064 control period and at 90 minutes after oral administration of TA-064. Stroke work index was increased and mean pulmonary capillary wedge pressure was decreased with TA-064 or dobutamine. Cardiac index and stroke index was increased by each drug, and pulmonary and systemic vascular resistances were decreased. Mean systemic arterial pressure, heart rate and pressure-rate product did not significantly change in comparison with the control level. In conclusion, TA-064 has a hemodynamic effect similar to that of dobutamine and may be useful as an oral substitute for dobutamine in patients with congestive heart failure after temporary management with dobutamine.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Cardiac Output, Low; Cardiotonic Agents; Chronic Disease; Clinical Trials as Topic; Dobutamine; Ethanolamines; Female; Heart Failure; Hemodynamics; Humans; Infusions, Intravenous; Male; Middle Aged; Time Factors

Denopamine was orally administered for more than 12 months to patients with chronic heart failure on maintenance hemodialysis. The plasma level in subjects treated with denopamine at 30 mg/day tended to be higher than that in subjects on 15 mg/day. There was no gradual increase in plasma level as the duration of therapy prolonged. Left ventricular end-diastolic and end-systolic diameters as well as ejection fraction on echocardiography showed a tendency to be improved by denopamine. Similarly, the cardiothoracic ratio was improved temporarily. No adverse effects were detected by electrocardiography and laboratory tests. These observations suggest that denopamine is safe and effective for hemodialysis patients with chronic heart failure.

Topics: Administration, Oral; Adult; Aged; Cardiotonic Agents; Chronic Disease; Echocardiography; Electrocardiography; Ethanolamines; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Renal Dialysis

The present study was undertaken to determine whether cardiac response to beta 1-adrenergic agonists is altered in rats with chronic heart failure (CHF), and whether this alteration is related to beta-adrenergic receptor down-regulation in the viable tissue of the left ventricle of these rats. For this purpose, the cardiac response to denopamine, a selective beta 1-adrenergic agonist, and the change in cardiac beta-adrenoceptor density were examined in rats with CHF. A non-selective beta-adrenergic agonist, isoprenaline, was also examined as a comparison. Cardiac output and stroke volume indices were reduced 12 weeks after left coronary artery ligation, suggesting that CHF had developed at this time. Denopamine (2, 4 and 8 micrograms/kg i.v.), and isoprenaline (0.01 microgram/kg i.v.) increased the cardiac output and stroke volume indices in sham-operated rats, whereas such increases were attenuated in the CHF rat. The cardiac beta-adrenergic receptor density, measured by [3H]CGP-12177 binding assay, was reduced in homogenates and microsomal membranes in the viable tissue of the left ventricle of the CHF rat (homogenates: 29% reduction, microsomal membrane: 23% reduction). These results suggest that the cardiac responsiveness to denopamine is diminished in the CHF rat and this alteration is accounted for, in part, by a decrease in cardiac beta-adrenoceptor density.

Topics: Adrenergic beta-1 Receptor Agonists; Adrenergic beta-Agonists; Animals; Cardiac Output; Chronic Disease; DNA; Down-Regulation; Ethanolamines; Heart; Heart Failure; Hemodynamics; In Vitro Techniques; Isoproterenol; Male; Myocardial Infarction; Myocardium; Organ Size; Radioligand Assay; Rats; Rats, Wistar; Receptors, Adrenergic, beta-1; Stroke Volume