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 possible chronotropic and arrhythmogenic effects of newly-developed oral inotropic agents were studied in 60 patients with idiopathic dilated cardiomyopathy (NYHA class II-IV). Changes in heart rates and the incidence of arrhythmias were evaluated using ambulatory electrocardiography. Denopamine 30 and 60 mg (beta 1 agonist), xamoterol 200 and 400 mg (beta 1 partial agonist) and OPC-8212 60, 90 and 120 mg (non-catecholamine) were sequentially administered for 10 +/- 2 months. Denopamine slightly increased heart rate throughout the day. Denopamine 60 mg caused excessive tachycardia in patients with atrial fibrillation, and could be used without digoxin. With xamoterol, maximum heart rate decreased during the daytime, while heart rate increased at night. Xamoterol was highly effective in patients with atrial fibrillation who not only had excessive tachycardia during exercise but marked bradycardia at night. Xamoterol increased the severity of heart failure in two patients who belonged to NYHA class IV, whose heart rates at rest had exceeded 100 beats/min. OPC-8212 did not affect heart rate, and was considered an ideal inotropic agent. None of these agents aggravated arrhythmias or caused sustained ventricular tachycardia. It was concluded that not only the severity of heart failure but the chronotropic and arrhythmogenic effects should be considered when choosing inotropic agents.
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PMID:[How to select newly-developed oral inotropic agents: an evaluation based on their effects on heart rate and arrhythmias]. 215 66

Denopamine (DP) is a new, orally active, selectively positive inotropic agent and used for the treatment of chronic cardiac insufficiency. The therapeutic effects of DP is highly related to its serum concentrations. A simple analytical method has been developed to determine the serum concentration of DP by use of high performance liquid chromatography (HPLC) with electrochemical detection (ECD). In order to extract the DP from the serum, a disposable solid extraction column (Sep-Pak cartridge, C-18) was used. The average recovery was 84.6 +/- 2.7%. The working electrode potential was fixed at 400 mV with a T1 cell, 600 mV with a T2 cell and 650 mV with a Guard cell in ECD. The analysis was performed on a Nova-Pak cartridge C-18 reverse-phase column (100 mm X 8 mm i.d., 4 microns). The mobile phase consisted of 0.1 M potassium phosphate buffer (pH 6.0) and acetonitrile (83: 17, v/v), and the flow rate was 1.0 ml/min. DP and internal standard phenolphthalein (PP) were eluted at 16.5 and 36.0 min, respectively. The peak-height ratio of DP to PP was linearly correlated (r = 0.9998) over a concentrations range between 1.25 and 15.0 ng/ml in the serum. The lowest detectable concentration was 1.0 ng/ml in the serum. The coefficient of variation of reproducibility in the assay was 6.0% By using the present method, serum concentration of DP was measured for four healthy volunteers after a single oral administration of 10 mg DP tablet after a overnight fast. From these DP concentration profiles, pharmacokinetic parameters were calculated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Development of a simple analytical method to determine the serum concentration of denopamine by high performance liquid chromatography with electrochemical detection and its clinical application]. 261 68

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.
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PMID:Long-term denopamine therapy for hemodialysis patients with chronic heart failure. 755 46

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.
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PMID:Diminished responsiveness to cardiac beta 1-adrenoceptor agonists in rats with chronic heart failure following myocardial infarction. 859 37

Influence of cardiotonic agents on the prognosis of heart failure depends on the individual therapeutic agents, and favorable and unfavorable effects of these agents have been reported in clinical trials. We studied the effect of the cardiotonic agent denopamine on the life span of cardiomyopathic hamsters (BIO 14.6 strain) in the heart failure period. Non-treated hamsters started to die at 40 weeks of age, and their survival rate decreased to 23.8% at the age of 65 weeks. Hamsters treated with denopamine (400 ppm in diet) from 36 weeks of age did not die until the age of 52 weeks, except in cases of accidental death. The survival rate of this group at 65 weeks of age was about 40%. Survival rates of these 2 groups were significantly different (P < 0.05) when animals with accidental death were excluded. To elucidate the mechanism of the effect of denopamine, we performed several experiments after dietary treatment with denopamine for 4 to 6 weeks from 37 weeks of age. Denopamine treatment lowered plasma levels of noradrenaline and dopamine (P < 0.05), but affected neither the cardiac contractility nor the beta-adrenoceptor density. In summary, denopamine significantly decreases the mortality of cardiomyopathic hamsters. Its effect to lower the plasma catecholamine levels may be responsible for the beneficial effect of denopamine.
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PMID:Prolongation of the life span of cardiomyopathic hamster by the adrenergic beta 1-selective partial agonist denopamine. 901 41

Denopamine is a new, orally active, positive inotropic agent. We evaluated its clinical effects in 13 patients who had undergone cardiac operations, 8 were in early postoperative periods and 5 were in late postoperative periods. In the former, denopamine therapy (30 mg/day) were started on the 6-14 th postoperative day in 5 patients so that they might free from catecholamine drip infusion (2-14 micrograms/kg/min), and on the 14-24th postoperative day in 3 patients in order that pleural effusion might reduce. All 5 patients were weaned from catecholamine, and pleural effusion in 3 patients disappeared completely. In the latter, denopamine therapy were indicated so that they might get relief from the symptoms of chronic heart failure. Although they had undergone combined valvular operations, they still remained in NYHA class II or III postoperatively, associated with cardiomegaly, hepatomegaly and atrial fibrillation. Denopamine therapy (15-30 mg/day) were quite effective in improving subjective symptoms but not in reducing cardiomegaly or hepatomegaly. No clinically significant side effects were noticed during 9-14 months of denopamine therapy. We conclude that denopamine is a quite useful cardiotonic agent in the postoperative management of patients with cardiac surgery.
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PMID:[Clinical effects of denopamine in patients with cardiac operations]. 930 66