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Oxygen-saving effect of a new cardiotonic agent, MCI-154, in diseased human hearts
M Mori1, M Takeuchi, H Takaoka
1First Department of Internal Medicine, Kobe University School of Medicine, Japan.
Objectives:
The aim of this study was to examine the left ventricular mechanoenergetic effects of a novel Ca2+ sensitizing agent, MCI-154, on diseased human hearts compared with dobutamine.
Background:
Unlike conventional cardiotonic agents, a Ca2+ sensitizer that could produce a positive inotropic action by altering the responsiveness of myofilament to Ca2+ could generate force with smaller amounts of Ca2+; thus, it may potentially save energy expenditure.
Methods:
The left ventricular pressure-volume relation and myocardial oxygen consumption per beat (Vo2) were measured by a conductance (volume) catheter and a Webster catheter. Left ventricular contractility (Emax), systolic pressure-volume area (PVA [index of left ventricular total mechanical energy]) and Vo2 were assessed before and after infusion of MCI-154 or dobut-amine. The PVA-independent Vo2 (Vo2 mainly for excitation-contraction coupling) was assessed as the Vo2 at zero PVA.
Results:
Both agents increased Emax comparably (dobutamine: from 3.55 +/- 1.10 [mean +/- SD] to 5.04 +/- 1.16 mm Hg/ml per m2, p < 0.0001; MCI-154: from 3.36 +/- 1.26 to 5.37 +/- 2.14 mm Hg/ml per m2, p < 0.0001); dobutamine increased total Vo2 (from 0.22 +/- 0.08 to 0.27 +/- 0.09 ml O2, p < 0.05) and PVA-independent Vo2 (from 0.019 +/- 0.019 to 0.091 +/- 0.051 ml O2, p < 0.005); but MCI-154 did not change these variables significantly. Consequently, the oxygen cost of contractility (delta PVA-independent Vo2/delta Emax) was less with MCI-154 than with dobutamine (0.14 +/- 0.18 vs. 1.10 +/- 0.80 J/mm Hg per ml per m2, p < 0.05).
Conclusions:
These results suggest that the cardiotonic action mediated by MCI-154 could provide an energetic advantage over the conventional cardiotonic action with currently used inotropic agents.
Insights
The novel calcium sensitizer MCI-154 offers an energetic advantage for treating heart failure compared to dobutamine. This agent improves contractility with less oxygen consumption, potentially saving energy in diseased hearts.
Area of Science:
- Cardiology
- Pharmacology
- Physiology
Background:
- Conventional cardiotonic agents increase calcium levels, potentially leading to energy inefficiency.
- Calcium sensitizers like MCI-154 enhance myofilament responsiveness to calcium, potentially reducing energy expenditure.
- This study investigates the mechanoenergetic effects of MCI-154, a novel calcium sensitizer, in diseased human hearts.
Purpose of the Study:
- To compare the left ventricular mechanoenergetic effects of MCI-154 with dobutamine in diseased human hearts.
- To evaluate the impact of MCI-154 on myocardial oxygen consumption and contractility.
- To determine the energetic advantage of MCI-154 over conventional inotropic agents.
Main Methods:
- Left ventricular pressure-volume loops and myocardial oxygen consumption (Vo2) were measured using conductance and Webster catheters.
- Left ventricular contractility (Emax) and total mechanical energy (PVA) were assessed before and after drug infusion.
- PVA-independent Vo2, representing excitation-contraction coupling energy, was calculated at zero PVA.
Main Results:
- Both MCI-154 and dobutamine significantly increased Emax.
- Dobutamine increased total Vo2 and PVA-independent Vo2, indicating higher energy consumption.
- MCI-154 did not significantly alter Vo2, suggesting improved energy efficiency, with a lower oxygen cost of contractility.
Conclusions:
- MCI-154 demonstrates a potential energetic advantage over dobutamine in improving cardiac function.
- The cardiotonic action of MCI-154 may be more energy-efficient for treating heart failure.
- These findings suggest MCI-154 as a promising agent for improving cardiac energetics.