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A novel inotropic vasodilator, OPC-18790, reduces myocardial oxygen consumption and improves mechanical efficiency
H Kanda1, M Yokota, H Ishihara
1First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Abstract:
We analyzed the left ventricular (LV) pressure-volume relation and obtained direct measurements of myocardial oxygen consumption (MVO2) before and after drug administration in 21 patients with New York Heart Association functional class II to III congestive heart failure to compare the mechanoenergetic effects of OPC-18790, a novel inotropic agent, and dobutamine. Pressure-volume data were obtained by the conductance method, and MVO2 measurements were obtained with a double-thermistor coronary sinus catheter before and after administration of OPC-18790 and dobutamine. The LV end-diastolic volume index decreased significantly without an increase in the heart rate after administration of OPC-18790, unlike that after administration of dobutamine. Both drugs significantly increased the LV contractility index (Emax) and caused similar improvements in ventricular-arterial coupling. OPC-18790 significantly reduced MVo2, whereas dobutamine increased MVo2. The ratio of the pressure-volume area to myocardial oxygen consumption (PVA/MVo2) remained unchanged after administration of OPC-18790 and decreased after administration of dobutamine. The ratio of external work to the pressure-volume area (EW/PVA) was similarly increased by both drugs, resulting in an improvement in mechanical efficiency (EW/MVo2) with OPC-18790 (p < 0.05) and in a deterioration with dobutamine (p < 0.05). OPC-18790 had an energetic advantage over dobutamine in spite of its positive inotropic effect. Our findings suggest that OPC-18790 may be useful for the treatment of patients with congestive heart failure.
Insights
OPC-18790, a novel inotropic agent, improved mechanical efficiency and reduced myocardial oxygen consumption in heart failure patients, unlike dobutamine. This suggests OPC-18790 offers an energetic advantage for treating congestive heart failure.
Area of Science:
- Cardiology
- Pharmacology
- Physiology
Background:
- Congestive heart failure (CHF) is characterized by impaired cardiac function.
- Evaluating novel inotropic agents for CHF treatment is crucial.
- Mechanoenergetic effects of inotropic drugs require detailed analysis.
Purpose of the Study:
- To compare the mechanoenergetic effects of OPC-18790 and dobutamine in patients with CHF.
- To assess the impact of these drugs on myocardial oxygen consumption (MVO2) and mechanical efficiency.
Main Methods:
- Left ventricular (LV) pressure-volume relations and MVO2 were measured in 21 CHF patients.
- Drug administration involved OPC-18790 and dobutamine.
- Conductance method and coronary sinus catheterization were utilized.
Main Results:
- OPC-18790 decreased LV end-diastolic volume without increasing heart rate, unlike dobutamine.
- Both drugs increased LV contractility (Emax) and improved ventricular-arterial coupling.
- OPC-18790 reduced MVO2, enhancing mechanical efficiency (EW/MVO2), while dobutamine increased MVO2 and worsened efficiency.
Conclusions:
- OPC-18790 demonstrates an energetic advantage over dobutamine in CHF patients.
- OPC-18790's ability to reduce MVO2 while improving mechanical efficiency is significant.
- OPC-18790 shows potential as a therapeutic agent for congestive heart failure.