Differential effects of OPC‐18790, amrinone and dobutamine on cardiac function and energy metabolism in the guinea‐pig isolated ischaemic heart

Itoh, Shigeo; Mori, Toyoki; Tominaga, Michiaki; Ishikawa, Makoto; Koga, Keiko; Yabuuchi, Youichi

doi:10.1111/j.1476-5381.1995.tb13318.x

Cited by 10 publications

(6 citation statements)

References 15 publications

(22 reference statements)

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“…In isolated Langendorff perfused ischemic guinea pig heart, inorganic phosphates were increased (Pi) and creatine phosphate (PCr), ATP, and pH decreased by ischemia. These parameters were not changed by an inotropic dose of OPC-18790, while equipotent positive inotropic doses of amrinone or dobutamine further increased Pi and decreased PCr, ATP and pH (9). This result reflects the well-balanced cardiovascular profile of OPC-18790, i.e., positive inotropic, slight chronotropic, and moderate coronary vasodilator effects.…”

Section: Effects On Cardiac Performance and Metabolismsupporting

confidence: 48%

“…In the isolated ischemic Langendorff guinea pig hearts, OPC-18790 did not alter the heart rate, while amrinone and dobutamine increased the heart rate, at doses that produced a 60% increase in the LVdP/dt (9). In the failing canine heart, an 0.1 to 3 mg/kg i.v.…”

Section: Chronotropic and Dromotropic Actionsmentioning

confidence: 89%

“…caused no significant blood pressure decrease in conscious instrumented dogs (7). In the isolated ischemic Langendorff perfused guinea pig heart, OPC-18790, amrinone, or dobutamine at equiinotropic doses increased coronary perfusion flow to the same extent (9). In conscious dogs with tricuspidal insufficiency and pulmonary stenosis, OPC-18790 administered i.v.…”

Section: Vasodilator Actionmentioning

confidence: 99%

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OPC‐18790, A New Positive Inotropic Agent

Hashimoto

Mori

Yabuuchi

1995

Cardiovascular Drug Reviews

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Section: Effects On Cardiac Performance and Metabolismsupporting

confidence: 48%

Section: Chronotropic and Dromotropic Actionsmentioning

confidence: 89%

Section: Vasodilator Actionmentioning

confidence: 99%

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OPC‐18790, A New Positive Inotropic Agent

Hashimoto

Mori

Yabuuchi

1995

Cardiovascular Drug Reviews

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“…is a novel positive inotropic agent (1) that lacks direct chronotropic action and has moderate coronary vasodilatory action (2,3). In whole-animal preparations, OPC-18790 increased cardiac output and contractility with little change in heart rate and blood pressure (2,4).…”

Section: Opc-18790 (±)-6-[3-(34-dimethoxybenzylamino)-2-hydroxypropmentioning

confidence: 99%

Cardiovascular Effects of the Combination of OPC-18790 and Dopamine in Halothane-Anesthetized Dogs

Itoh

Mori

Yoshida

et al. 1995

Japanese Journal of Pharmacology

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ABSTRACT-OPC-18790, (±)-6-[3-(3,4-dimethoxybenzylamino)-2-hydroxypropoxy]-2(1H)-quinolinone, is a novel positive inotropic agent, and its mechanism of positive inotropic action involves not only phosphodiesterase inhibition, but also a prolongation of action potential duration in ventricular muscle. Prolongation of action potential duration is also a property of class III antiarrhythmic agents; therefore, we examined the cardiohemodynamic effects and arrhythmogenicity of a combination of OPC-18790 and dopamine in halothane-anesthetized dogs. Dopamine (5 pg/kg/min) alone increased the peak of the first derivative of left ventricular pressure (LVdP/dtm ) and cardiac output (CO) by 43-48% and 16-20%, respectively, while OPC-18790 (10 pg/kg/min) increased these parameters by 56% and 22%, respectively. The combination of OPC-18790 (10 pg/kg/min) and dopamine (5 pg/kg/min) and dopamine alone at an increased dose of 10 ,pg/kg/min further increased LVdP/dtm , and CO by 104-113% and 29-30%, respectively. Thus, positive inotropic effects were equally observed in both groups, and the effects of OPC-18790 and dopamine seemed to be additive. The other hemodynamic effects were similar among all groups. Arrhythmias such as premature ventricular contraction developed in 5 out of 7 dogs (71.4%) in the 10-pg/kg/min dopamine group, while only one premature ventricular contraction was observed in 1 of 7 dogs (14.3%) in the OPC-18790 (10 pg/kg/min) and dopamine (5 pg/kg/min) combination group. These results suggest that the combination of OPC-18790 and dopamine may provide new therapeutic options for the treatment of heart failure.

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“…In addition, it has no significant effect on myocardial oxygen consumption and improves cardiac energetics in ischemic hearts. [7][8][9] Although toborinone is known to be a vasodilator, [3][4][5] previous studies have focused on arterial dilatation, with little being known about its venous effects. Our current understanding of its effects on veins is based on indirect hemodynamic measurements.…”

mentioning

confidence: 99%

Acute Effects of Toborinone on Vascular Capacitance and Conductance in Experimental Heart Failure

1998

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Background-Toborinone (OPC-18790), a phosphodiesterase III inhibitor, enhances cardiac contractility and is an arterial dilator. However, its effects on the venous system have not yet been clearly defined. Because toborinone administration reduces left ventricular (LV) end-diastolic pressure, it is probably also a venodilator. Because of the known arterial effects and the hypothesized venous effects, we compared changes in systemic vascular conductance (the inverse of resistance) with changes in venous capacitance. Methods and Results-In 15 anesthetized, splenectomized dogs (10 treatment, 5 control), pressures were measured in the right atrium, aorta, portal vein, and LV. A cuff constrictor was placed around the portal vein. Cardiac output was measured by thermodilution, and splanchnic vascular capacitance was measured by blood-pool scintigraphic methods. Data were collected at baseline, after induction of heart failure (microsphere embolization into the left coronary artery), and then after toborinone boluses of 0.1, 0.2, 0.4, and 0.8 mg/kg. Heart failure was associated with decreased capacitance and conductance (to 87Ϯ3% and 64Ϯ4% of baseline values, respectively, PϽ0.05). After administration of the lower doses of toborinone, capacitance increased more than conductance; however, the effects were more balanced at the higher doses. Compared with nitroglycerin, hydralazine, and enalaprilat (results of an earlier study) in the same model, toborinone increased capacitance to a degree similar to that with nitroglycerin, at higher doses increased conductance similarly to hydralazine, and increased both capacitance and conductance considerably more than did enalaprilat. Conclusions-Toborinone is a potent balanced venous and arterial dilator in experimental acute heart failure. These marked effects suggest that it may prove to be a clinically important alternative to other vasodilators. (Circulation. 1998;98:58-63.)

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Differential effects of OPC‐18790, amrinone and dobutamine on cardiac function and energy metabolism in the guinea‐pig isolated ischaemic heart

Cited by 10 publications

References 15 publications

OPC‐18790, A New Positive Inotropic Agent

OPC‐18790, A New Positive Inotropic Agent

Cardiovascular Effects of the Combination of OPC-18790 and Dopamine in Halothane-Anesthetized Dogs

Acute Effects of Toborinone on Vascular Capacitance and Conductance in Experimental Heart Failure

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