Author + information
- Giovanni Davogustto, MD and
- Heinrich Taegtmeyer, MD, DPhil∗ ()
- ↵∗Division of Cardiology, Department of Internal Medicine, The University of Texas Health Science Center at Houston, 6431 Fannin Street, MSB 1.220, Houston, Texas 77030
“The sum of the actual and potential energies in the universe is unchangeable.”
—William J.M. Rankine, 1853 (1)We read with interest the recent study by Beadle et al. (2), describing the improvement in cardiac energetics of patients with heart failure treated with perhexiline. One of the investigators’ main conclusions is that perhexiline improves cardiac energetics without evidence of altered cardiac substrate utilization. On the basis of the First Law of Thermodynamics and on our experimental observations (3,4), we offer a different interpretation.
The heart is a self-renewing biological pump that converts chemical energy into mechanical energy, with some energy loss as heat and kinetic energy. As in any other system, energy transfer in the cardiovascular system obeys the First Law of Thermodynamics, which states that within a closed system, energy can only be converted from one form into another (4). This principle was first proposed by Helmholtz in his treatise “On the Conservation of Force” (1847) and summarized by William Rankin in 1853 as follows: “…The sum of the actual and potential energies in the universe is unchangeable” (1).
Based on this law, and assuming no change in cardiac power after treatment in either group (data not provided), the improvement in phosphocreatine (PCr)/ATP ratio observed in the hearts of patients treated with perhexiline (2) may be explained by either the switch from the predominant oxidation of one energy providing substrate to another; increased efficiency in energy provision from the oxidation of the same substrates by decreased energy loss as heat or kinetic energy; or a sum of these mechanisms.
The authors’ conclusion is based on the fact that there were no differences between the 2 groups in cross-heart respiratory exchange ratio or cardiac metabolite extraction. However, these measurements were only performed after the intervention, at a point where there were already no differences in PCr/ATP between the groups. The authors comment that, despite this, one would have expected a difference in the transmyocardial substrate differences and/or the respiratory quotient if perhexiline worked through substrate switches. Without any pre-treatment data, this cannot be determined.
In addition, the authors comment that the lack of difference in blood substrate levels between the groups further supported their hypothesis. The reader appreciates the data on glucose, glycerol, lactate, NEFA, triglycerides, pyruvate, and insulin. However, neither amino acids nor ketone bodies have been taken into consideration, both of which can be used by the heart as fuel given its omnivorous nature (3,4). In addition, the heart’s endogenous fuels, glycogen and triglycerides have been overlooked (4).
An interesting aspect would be to measure energy loss as heat production and, perhaps even more interesting, to measure differences in turbulent kinetic energy before and after drug treatment, because increased energy loss as turbulent flow occurs in patients with dilated cardiomyopathy (5).
In summary, the work by Beadle et al. (2) points to a promising metabolic approach to improve contractile efficiency in heart failure. However, when considering the results, the flow of energy and First Law of Thermodynamics are still valid.
Please note: Work in the authors’ laboratory is supported by a grant from the U.S. Public Health Service (R01 HL 061483). Dr. Davogustto receives fellowship support from the University of Texas System Medical Foundation. Dr. Taegtmeyer has reported that he has no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation
- Rankine W.J.M.
- Beadle R.M.,
- Williams L.K.,
- Kuehl M.,
- et al.
- Taegtmeyer H.,
- Hems R.,
- Krebs H.A.