Acute effects of a novel inotropic agent, OPC-18790 (toborinone), on hemodynamics and myocardial energetics in patients with chronic heart failure

H. Kanda, M. Yokota, T. Sobue, H. Ishihara, K. Nagata, H. Izawa

Research output: Contribution to journalArticle

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Abstract

We examined the acute effects and safety of OPC-18790 (toborinone), a novel water-soluble quinolinone derivative, on mechanoenergetics in 12 patients with chronic congestive heart failure. OPC-18790 was intravenously administered at a rate of 5 μg/kg/min or 10 μg/kg/min. Left ventricular (LV) pressure-volume data were obtained by conductance methods and myocardial oxygen consumption (MVO2) was measured using a Webster catheter. Heart rate was slightly increased in all patients after receiving OPC-18790. Ventricular preload as assessed by LV end-diastolic volume index significantly declined, and mean and systolic pulmonary artery pressure also fell after OPC-18790 infusion. In addition to venodilation, systemic vasodilation was observed after OPC-18790 infusion. Systolic and mean arterial pressure, and systemic vascular resistance significantly declined after OPC-18790 infusion. Effective arterial elastance (Ea), which represents both the mean vascular resistance and the pulsatile components, fell significantly. LV contractility as assessed by end-systolic elastance (Ees) significantly rose after OPC- 18790 infusion. Cardiac index and ejection fraction improved significantly. External work (EW) was unchanged. The isovolumic relaxation time constant was prolonged before OPC-18790 infusion and OPC-18790 shortened this time constant rate. MVO2 was reduced after OPC-18790 infusion probably due to a reduction of wall tension. Ventricular-arterial coupling (Ea/Ees) was far less than optimal before OPC-18790 infusion and was near optimal after OPC 18790 infusion. Mechanical efficiency (EW/MVO2) was improved along with the Ea/Ees ratio. Systolic arterial pressure fell by 40 or 50 mmHg after OPC- 18790 infusion in 2 patients probably due to vasodilation. In conclusion, OPC-18790 had favorable mechanoenergetic effects in patients with congestive heart failure. Despite enhancing contractility, OPC-18790 reduced MVO2 and improved mechanical efficiency probably due to its favorable effects on loading conditions. These findings suggest that OPC-18790 may be useful for short-term treatment of patients with congestive heart failure.

Original languageEnglish
Pages (from-to)699-712
Number of pages14
JournalJapanese Journal of Clinical Pharmacology and Therapeutics
Volume27
Issue number4
DOIs
Publication statusPublished - 01-01-1996

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Heart Failure
Hemodynamics
toborinone
Vasodilation
Vascular Resistance
Arterial Pressure
Quinolones
Ventricular Pressure
Oxygen Consumption
Stroke Volume
Pulmonary Artery
Catheters
Heart Rate
Blood Pressure

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Cite this

@article{0a372352df284c968c04d349efa936ac,
title = "Acute effects of a novel inotropic agent, OPC-18790 (toborinone), on hemodynamics and myocardial energetics in patients with chronic heart failure",
abstract = "We examined the acute effects and safety of OPC-18790 (toborinone), a novel water-soluble quinolinone derivative, on mechanoenergetics in 12 patients with chronic congestive heart failure. OPC-18790 was intravenously administered at a rate of 5 μg/kg/min or 10 μg/kg/min. Left ventricular (LV) pressure-volume data were obtained by conductance methods and myocardial oxygen consumption (MVO2) was measured using a Webster catheter. Heart rate was slightly increased in all patients after receiving OPC-18790. Ventricular preload as assessed by LV end-diastolic volume index significantly declined, and mean and systolic pulmonary artery pressure also fell after OPC-18790 infusion. In addition to venodilation, systemic vasodilation was observed after OPC-18790 infusion. Systolic and mean arterial pressure, and systemic vascular resistance significantly declined after OPC-18790 infusion. Effective arterial elastance (Ea), which represents both the mean vascular resistance and the pulsatile components, fell significantly. LV contractility as assessed by end-systolic elastance (Ees) significantly rose after OPC- 18790 infusion. Cardiac index and ejection fraction improved significantly. External work (EW) was unchanged. The isovolumic relaxation time constant was prolonged before OPC-18790 infusion and OPC-18790 shortened this time constant rate. MVO2 was reduced after OPC-18790 infusion probably due to a reduction of wall tension. Ventricular-arterial coupling (Ea/Ees) was far less than optimal before OPC-18790 infusion and was near optimal after OPC 18790 infusion. Mechanical efficiency (EW/MVO2) was improved along with the Ea/Ees ratio. Systolic arterial pressure fell by 40 or 50 mmHg after OPC- 18790 infusion in 2 patients probably due to vasodilation. In conclusion, OPC-18790 had favorable mechanoenergetic effects in patients with congestive heart failure. Despite enhancing contractility, OPC-18790 reduced MVO2 and improved mechanical efficiency probably due to its favorable effects on loading conditions. These findings suggest that OPC-18790 may be useful for short-term treatment of patients with congestive heart failure.",
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Acute effects of a novel inotropic agent, OPC-18790 (toborinone), on hemodynamics and myocardial energetics in patients with chronic heart failure. / Kanda, H.; Yokota, M.; Sobue, T.; Ishihara, H.; Nagata, K.; Izawa, H.

In: Japanese Journal of Clinical Pharmacology and Therapeutics, Vol. 27, No. 4, 01.01.1996, p. 699-712.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Acute effects of a novel inotropic agent, OPC-18790 (toborinone), on hemodynamics and myocardial energetics in patients with chronic heart failure

AU - Kanda, H.

AU - Yokota, M.

AU - Sobue, T.

AU - Ishihara, H.

AU - Nagata, K.

AU - Izawa, H.

PY - 1996/1/1

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N2 - We examined the acute effects and safety of OPC-18790 (toborinone), a novel water-soluble quinolinone derivative, on mechanoenergetics in 12 patients with chronic congestive heart failure. OPC-18790 was intravenously administered at a rate of 5 μg/kg/min or 10 μg/kg/min. Left ventricular (LV) pressure-volume data were obtained by conductance methods and myocardial oxygen consumption (MVO2) was measured using a Webster catheter. Heart rate was slightly increased in all patients after receiving OPC-18790. Ventricular preload as assessed by LV end-diastolic volume index significantly declined, and mean and systolic pulmonary artery pressure also fell after OPC-18790 infusion. In addition to venodilation, systemic vasodilation was observed after OPC-18790 infusion. Systolic and mean arterial pressure, and systemic vascular resistance significantly declined after OPC-18790 infusion. Effective arterial elastance (Ea), which represents both the mean vascular resistance and the pulsatile components, fell significantly. LV contractility as assessed by end-systolic elastance (Ees) significantly rose after OPC- 18790 infusion. Cardiac index and ejection fraction improved significantly. External work (EW) was unchanged. The isovolumic relaxation time constant was prolonged before OPC-18790 infusion and OPC-18790 shortened this time constant rate. MVO2 was reduced after OPC-18790 infusion probably due to a reduction of wall tension. Ventricular-arterial coupling (Ea/Ees) was far less than optimal before OPC-18790 infusion and was near optimal after OPC 18790 infusion. Mechanical efficiency (EW/MVO2) was improved along with the Ea/Ees ratio. Systolic arterial pressure fell by 40 or 50 mmHg after OPC- 18790 infusion in 2 patients probably due to vasodilation. In conclusion, OPC-18790 had favorable mechanoenergetic effects in patients with congestive heart failure. Despite enhancing contractility, OPC-18790 reduced MVO2 and improved mechanical efficiency probably due to its favorable effects on loading conditions. These findings suggest that OPC-18790 may be useful for short-term treatment of patients with congestive heart failure.

AB - We examined the acute effects and safety of OPC-18790 (toborinone), a novel water-soluble quinolinone derivative, on mechanoenergetics in 12 patients with chronic congestive heart failure. OPC-18790 was intravenously administered at a rate of 5 μg/kg/min or 10 μg/kg/min. Left ventricular (LV) pressure-volume data were obtained by conductance methods and myocardial oxygen consumption (MVO2) was measured using a Webster catheter. Heart rate was slightly increased in all patients after receiving OPC-18790. Ventricular preload as assessed by LV end-diastolic volume index significantly declined, and mean and systolic pulmonary artery pressure also fell after OPC-18790 infusion. In addition to venodilation, systemic vasodilation was observed after OPC-18790 infusion. Systolic and mean arterial pressure, and systemic vascular resistance significantly declined after OPC-18790 infusion. Effective arterial elastance (Ea), which represents both the mean vascular resistance and the pulsatile components, fell significantly. LV contractility as assessed by end-systolic elastance (Ees) significantly rose after OPC- 18790 infusion. Cardiac index and ejection fraction improved significantly. External work (EW) was unchanged. The isovolumic relaxation time constant was prolonged before OPC-18790 infusion and OPC-18790 shortened this time constant rate. MVO2 was reduced after OPC-18790 infusion probably due to a reduction of wall tension. Ventricular-arterial coupling (Ea/Ees) was far less than optimal before OPC-18790 infusion and was near optimal after OPC 18790 infusion. Mechanical efficiency (EW/MVO2) was improved along with the Ea/Ees ratio. Systolic arterial pressure fell by 40 or 50 mmHg after OPC- 18790 infusion in 2 patients probably due to vasodilation. In conclusion, OPC-18790 had favorable mechanoenergetic effects in patients with congestive heart failure. Despite enhancing contractility, OPC-18790 reduced MVO2 and improved mechanical efficiency probably due to its favorable effects on loading conditions. These findings suggest that OPC-18790 may be useful for short-term treatment of patients with congestive heart failure.

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