Efficacy and Safety of Denopamine in Patients with Chronic Heart Failure / 薬剤疫学

Objective : To investigate the safety and effects of long-term administration of denopamine, β-1 stimulant, on the activities of daily living in heart failure patients.<BR>Design : Case-series.<BR>Methods : One hundred forty patients with mild to moderate chronic heart failure were administered denopamine at dose of 5 to 10 mg three times daily for 24 weeks. Concomitant circulatory system drugs such as digitalis, diuretics, vasodilator drugs, etc., were used without changing the administration method and dose. However, the use of a concomitant β-blocker was prohibited.<BR>Results : Following administration of denopamine, the NYHA cardiac function classification improved by one degree or more in 50 patients (35.7%). The body weight decreased significantly from 54.9± 10.2kg (mean±SD) before administration to 54.0±10.2kg after administration (P<0.05), and the cardiothoracic ratio also decreased from 58.0±7.3% to 56.6±7.2% (P<0.001). No significant changes were observed in the heart rate, systolic blood pressure, or diastolic blood pressure. The activities of daily living improved by one level or more for 49 patients (51.6%). There were 36 withdrawal or dropout cases (patients' own convenience : 12 cases ; complications/accidental symptoms : 7 cases) during the investigation period. Four patients (2.9%) exhibited adverse reactions.<BR>Conclusion : Denopamine seemed to improve the quality of life, which is one of the therapeutic purposes for patients with chronic cardiac failure. A large-scale study including investigation of the long-term prognosis for such patients needs to be performed.

Clinical and Echocardiographic Changes after Short-Term Denopamine (Cardopamin(R)) Therapy in Patients with Chronic Congestive Heart Failure

BACKGROUND: Inotropic agents have been shown to improve cardiac function in patients with congestive heart failure. The purpose of the present study is to evaluate the short-term efficacy and safety of denopamine(Cardopamin(R)), and orally available beta-stimulant, in patients with chronic congestive heart failure. SUBJECTS AND METHODS: Twenty-four patients(54.1+/-10.9 years, male:female=1.4:1) with chronic congestive heart failure whose functional classes were equal or greater than New York Heart Association(NYHA) Class II were enrolled in this study after informed consents were obtained. Upon completion of baseline evaluation, denopamine(Cardopamin(R)) was administered orally, startion with 15 mg per day and increased to 30 mg per day according to the clinical response of each patient. Blood pressure, heart rate, electrocardiographic(EKG) findings, AST, BUN, and creatinine were also followed up at 4 weeks' interval. The clinical effects and side effects at 4 weeks' interbal and echocardiographic examination at baseline and 8 weeks after trentment were evaluated. RESULTS: Mean dosage of denopamine(Cardopamin(R)) was 22.9+/-5.3mg per day. The clinical symptoms of 18(75%) of 24 patients were improved. The echocardiographic follow-up revealed a significant decrease in left vetricular(LV) end-Systolic dimemsion(fron 4.8+/-0.2mm to 4.5+/-0.1mm. p<0.005) and LV end-systolic volume(from 92.0+/-8.5ml to 80.3+/-4.5ml, p<0.005). However, there was no significant interval change in LV end-diastolic dimension, LV end-diastolic volume, ejection fraction, and fractional shortening. Blood pressure, heart rate, EKG findings, AST, BUN, and creatinine were not changed significantly during treatment. CONCLUSION: Above results suggest that short-term therapy of denopamine(Cardopamin(R)) may improve clinical symptom with no side effect in patients with chronic congestive heart failure, but the long-term efficacy remains to be determined with a randomized long-term follow up study.

Effect of denopamine on alveolar fluid clearance in hypoxic rat lungs / 中国病理生理杂志

AIM:To study the effect of ?1-adrenergic agonist on alveolar fluid clearance in hypoxic rat lungs. METHODS: Rats were exposed to 10% oxygen. Alveolar fluid clearance (AFC) and lung water content (TLW) were calculated in rats exposed to hypoxia for 24 h and 48 h. Isotonic 5% albumin in solutions with different pharmacological agents were instilled into the distal airways in the hypoxia exposed and room air-exposed rat lungs, and the AFC was examined. RESULTS: As compared with the room air-exposed rats (17.50%?2.66%), AFC in the rats exposed to 10% oxygen was not decreased (18.70%?3.19%), AFC in the rats exposed to 10% oxygen for 48 h was decreased (8.59%?2.60%). Denopamine, a ?1-adrenergic agonist, increased AFC significantly in the rats exposed to room air and hypoxia. The potency of 10-5 mol/L denopamine was similar to that of 10-5mol/L terbutaline. The denopamine effect was partly blocked by inhibitors of sodium transport amiloride and ouabain (AFC were 11.80%?2.79% and 8.53%?2.17%). CONCLUSION: Denopamine, a selective ?1-adrenergic agonist, stimulates alveolar fluid clearance in rats exposed to hypoxia through the active sodium transport, and may have therapeutical effect on pulmonary edema after acute lung injury.