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Clinical aspects of dopexamine
J Mol
Cell
Cardiol
24 (Supplement
II) (1992)
v-4
CURRENT TREATMENT FOR CHRONIC HEART FAILURE - VESNARINONE(OPC-8212) Shigetake Sasayama, Toyama Medical and Pharmaceutical University, Toyama, Japan OPC-8212 is d newly synthesized, orally effective inotropic agent. Preliminary studies have shown short-term hemodynamic and symptomatic improvement in patients with congestive heart failure. Then the long-term efficacy of this agent was assessed in 83 patients with chronic heart failure who were randomly assigned to treatment with either OPC-8212 (1~45) or matching placebo (n=38). Of the placebo-treated patients, 2 patients died and another 6 patients were withdrawn from the study because of a deterioration of heart failure while only one out of 45 OPC-8212 treated patients were withdrawn because of increased the congestive symptoms. After 12 weeks of treatment, the OPC-8212 group showed a significant improvement of numerical scores on sense of well-being (p
V-5
CLINICAL ASPECTS OF DOPEXAMINE G. R. Park. Director of Intensive Care, Addenbrooke’s Hospital, Cambridge CBZ ZPP. England, UK. Dopexamine is a catecholamine with its principal activity at the beta-2 and dopaminergic (Dl) adrenergic receptors. In addition, there is minimal activity at beta-l receptors, caused by inhibition of neuronal catecholamine re-uptake (uptake-l). There is no activity at the alpha receptors (1). When given to patients dopexamine reduces systemic. pulmonary. splanchnic and renal vascular resistance. There is an increase in cardiac output because of the afterload reduction and its inotropic action. Systemic blood pressure dose not change. Blood flow to snne organs, especially the kidneys, gut and liver markedly increases. There effects can be of great value in some patients with acute cardiac failure. Besides the low cardiac output these patients are often vasoconstricted. The oliguria and cardiac failure contribute to fluid retention leading to pulmonary oedema. When dopexamine is given the vasodilation and positive inotropy increase the low cardiac output. This combined with renal vasodilation improves urine output (‘2). These useful properties of dopexamine can also be used in patients with other diseases in which heart failure may be secondary to other conditions. It can be used for its specific renal effects during surgery (3) and for renal protection during hepatic transplantation (4). The effects on the vasoculature of the hepatic and splanchnic circulation are also useful (5) (6). 1. Smith GW. UConner SE. Am J Cardiol 1988;62:9C-l?C. 2. Tan LB et al. Brit Heart 1 I987;57:81. 3. F&enham AR, Park GR. lntens Care Med 1986:14:663-665. 4. Gray P. Bodenham A. Park CR. Anaesthesia 1991:46:638641. 5. Munglani R. Gray P. Park GR. Clin lntens Care 1990:1:134-135. 6. Haji-Michael P. Park GR. Clin Intents Care 1992 (in press).
V-6
ACUTE EFFECTS OF PIMOBENDAN ON HEMODPNAMICS AND EXERCISE TOLERANCE IN PATIENTS WITH HEART FAILURE The Cardiovascular Institute, Tokyo. *Kasumigaura Haruki Itoh, Koichi Taniguchi*. Branch Hospital, Tokyo Medical and Dental University, Ibaragi, JAPAN. The acute effects of pimobendan (PMB), a new calcium sensitizer with phosphoinvestidiesterase inhibiting activity, on hemodynamics and exercise tolerance were Twenty-five patients (3 in NYHA class II, 10 in class gated in heart failure patients. III, and 12 in class IV) received l-5mg of PMB intravenously. Hemodynamics was The preload reduction (12.7 th./+mmHg redunction monitored using a Swan-Ganz catheter. in PCWP by f+-5mg) and increase in cardiac index (1.14 +0.721/min/m* increase by 4-5mg) were observed in a dose dependent manner which lasting more than 6 hours. To evaluate the effects of single oral dose of PMB on exercise tolerance, a placebo controlled double-blind study was performed. Five mg of PMB or placebo(PL) were allocated randomly to 33 patients (18 in NYHA class II, 15 in class III), who then underwent exercise tests before and 3 hours after dosing, using a cycle cardiopulmonary Systolic blood pressure decreased from 134i7 mmHg to 115+7 only in .ths ergometer. PMB group. Anaerobic threshold increased significantly from 12.3tO.5 ml/min/kg (V02) but there was no change in the PL group. PMB showed to 13.2 i 0.6 in the PMB group, metabolic response during inotropic action, and it also improved vasodilating and exercise. These results suggest that PMB is beneficial to heart failure patients. S.36
Cell
Cardiol
24 (Supplement
II) (1992)
v-4
CURRENT TREATMENT FOR CHRONIC HEART FAILURE - VESNARINONE(OPC-8212) Shigetake Sasayama, Toyama Medical and Pharmaceutical University, Toyama, Japan OPC-8212 is d newly synthesized, orally effective inotropic agent. Preliminary studies have shown short-term hemodynamic and symptomatic improvement in patients with congestive heart failure. Then the long-term efficacy of this agent was assessed in 83 patients with chronic heart failure who were randomly assigned to treatment with either OPC-8212 (1~45) or matching placebo (n=38). Of the placebo-treated patients, 2 patients died and another 6 patients were withdrawn from the study because of a deterioration of heart failure while only one out of 45 OPC-8212 treated patients were withdrawn because of increased the congestive symptoms. After 12 weeks of treatment, the OPC-8212 group showed a significant improvement of numerical scores on sense of well-being (p
V-5
CLINICAL ASPECTS OF DOPEXAMINE G. R. Park. Director of Intensive Care, Addenbrooke’s Hospital, Cambridge CBZ ZPP. England, UK. Dopexamine is a catecholamine with its principal activity at the beta-2 and dopaminergic (Dl) adrenergic receptors. In addition, there is minimal activity at beta-l receptors, caused by inhibition of neuronal catecholamine re-uptake (uptake-l). There is no activity at the alpha receptors (1). When given to patients dopexamine reduces systemic. pulmonary. splanchnic and renal vascular resistance. There is an increase in cardiac output because of the afterload reduction and its inotropic action. Systemic blood pressure dose not change. Blood flow to snne organs, especially the kidneys, gut and liver markedly increases. There effects can be of great value in some patients with acute cardiac failure. Besides the low cardiac output these patients are often vasoconstricted. The oliguria and cardiac failure contribute to fluid retention leading to pulmonary oedema. When dopexamine is given the vasodilation and positive inotropy increase the low cardiac output. This combined with renal vasodilation improves urine output (‘2). These useful properties of dopexamine can also be used in patients with other diseases in which heart failure may be secondary to other conditions. It can be used for its specific renal effects during surgery (3) and for renal protection during hepatic transplantation (4). The effects on the vasoculature of the hepatic and splanchnic circulation are also useful (5) (6). 1. Smith GW. UConner SE. Am J Cardiol 1988;62:9C-l?C. 2. Tan LB et al. Brit Heart 1 I987;57:81. 3. F&enham AR, Park GR. lntens Care Med 1986:14:663-665. 4. Gray P. Bodenham A. Park CR. Anaesthesia 1991:46:638641. 5. Munglani R. Gray P. Park GR. Clin lntens Care 1990:1:134-135. 6. Haji-Michael P. Park GR. Clin Intents Care 1992 (in press).
V-6
ACUTE EFFECTS OF PIMOBENDAN ON HEMODPNAMICS AND EXERCISE TOLERANCE IN PATIENTS WITH HEART FAILURE The Cardiovascular Institute, Tokyo. *Kasumigaura Haruki Itoh, Koichi Taniguchi*. Branch Hospital, Tokyo Medical and Dental University, Ibaragi, JAPAN. The acute effects of pimobendan (PMB), a new calcium sensitizer with phosphoinvestidiesterase inhibiting activity, on hemodynamics and exercise tolerance were Twenty-five patients (3 in NYHA class II, 10 in class gated in heart failure patients. III, and 12 in class IV) received l-5mg of PMB intravenously. Hemodynamics was The preload reduction (12.7 th./+mmHg redunction monitored using a Swan-Ganz catheter. in PCWP by f+-5mg) and increase in cardiac index (1.14 +0.721/min/m* increase by 4-5mg) were observed in a dose dependent manner which lasting more than 6 hours. To evaluate the effects of single oral dose of PMB on exercise tolerance, a placebo controlled double-blind study was performed. Five mg of PMB or placebo(PL) were allocated randomly to 33 patients (18 in NYHA class II, 15 in class III), who then underwent exercise tests before and 3 hours after dosing, using a cycle cardiopulmonary Systolic blood pressure decreased from 134i7 mmHg to 115+7 only in .ths ergometer. PMB group. Anaerobic threshold increased significantly from 12.3tO.5 ml/min/kg (V02) but there was no change in the PL group. PMB showed to 13.2 i 0.6 in the PMB group, metabolic response during inotropic action, and it also improved vasodilating and exercise. These results suggest that PMB is beneficial to heart failure patients. S.36