Association Between Cardiac High-Energy Phosphate Metabolism and Whole Body Metabolism in Healthy Female Adults

Decline in cardiac high-energy phosphate metabolism [phosphocreatine-to-ATP (PCr/ATP) ratio] and whole body metabolism increase the risk of heart failure and metabolic diseases. The aim of the present study was to assess the relationship between PCr/ATP ratio and measures of body metabolic function. A total of 35 healthy women (56±14.0 years of age) underwent cardiac 31P magnetic resonance spectroscopy to assess PCr/ATP ratio – an index of cardiac high-energy phosphate metabolism. Fasting and 2-hour glucose levels were assessed using oral glucose tolerance test. Indirect calorimetry was performed to determine oxygen consumption and resting metabolic rate. There were no significant relationships between PCr/ATP ratio and resting metabolic rate (r=-0.09, p=0.62), oxygen consumption (r=-0.11, p=0.54), fasting glucose levels (r=-0.31, p=0.07), and 2-hour plasma glucose (r=-0.10, p=0.58). Adjusted analysis for covariates including age, body mass index, fat mass, and physical activity, had no significant influence on the relationship between PCr/ATP ratio and body metabolism. In conclusion, the lack of relationship between cardiac PCr/ATP ratio, glucose control and metabolic rate may suggest that overall metabolic function does not influence cardiac high-energy phosphate metabolism.

Fingolimod (FTY720) Preserves High Energy Phosphates and Improves Cardiac Function in Heterotopic Heart Transplantation Model

During heart transplantation, donor heart leads to reduced oxygen supply resulting in low level of high energy phosphate (HEP) reserves in cardiomyocyte. Lower HEP is one of the underlying reasons of cell death due to ischemia. In this study we investigated the role of Fingolimod (FTY720) in heart transplantation ischemia. Eight groups of Sprague-Dawley rats (n = 5 for each subgroup) were made, A1 and C1 were given FTY720 1 mg/kg while B1 and D1 were given normal saline. The hearts were implanted into another set of similar rats after preservation period of 1 h at 4–8 °C. Significantly higher Left ventricular systolic pressure (LVSP), dP/dT maximum (p < 0.05), dP/dT minimum (p < 0.05) were recorded in the FTY720 treated group after 24 h of reperfusion while after 1 h of reperfusion, there were no significant differences in LVSP, maximum and negative dP/dT, and Left ventricular end diastolic pressure (LVEDP) between the control and the FTY720-treated transplant groups. Coronary blood flow (CBF) was enhanced (p < 0.05) in the FTY720 treated group after 1 and 24 h. ATP p < 0.001, p < 0.05 at 1 and 24 h, ADP p < 0.001, p > 0.05 at 1 and 24 h, and phosphocreatine p < 0.05, p > 0.05 at 1 and 24 h were better preserved by FTY720 treatment as compared to control group. The study concluded that pretreatment of grafted hearts with FTY720 improved hemodynamics, CBF, high energy phosphate reserves, reduces the peroxynitrite level and poly (ADP ribose) polymerase (PARP) inhibition that prevents ischemia-reperfusion injury.

Mathematical absurdities in the California net energy system

Net energy systems, such as the California Net Energy System (CNES), are useful for prediction of input:output relationships not because of fidelity to the laws of thermodynamics, but because they were designed to predict well. Unless model descriptions of input:output relationships are consistent with the laws of thermodynamics, conclusions regarding those relationships may be incorrect. Heat energy (HE) + recovered energy (RE) = ME intake (MEI) is basic to descriptions of energy utilization found in the CNES and is consistent with the laws of thermodynamics; it may be the only relationship described in the CNES consistent with the first law of thermodynamics. In the CNES, efficiencies of ME utilization for maintenance (km) and gain (kg) were estimated using ordinary least squares (OLS) equations. Efficiencies thus estimated using static linear models are often inconsistent with the biochemistry of processes underlying maintenance and gain. Reactions in support of oxidative mitochondrial metabolism are thermodynamically favorable and irreversible; these reactions yield ATP, or other high-energy phosphate bonds, used for what is generally termed maintenance. Synthesis of biomass (gain) is less thermodynamically favorable; reactions do not proceed unless coupled with hydrolysis of high-energy phosphate bonds and lie closer to equilibrium than those in support of oxidative mitochondrial metabolism. The opposite is described in the CNES (km &gt; kg) due to failure of partitioning of HE; insufficient HE is accounted for in maintenance. Efficiencies of ME utilization (km and kg) as described in the CNES are variable. Further neither km nor kg are uniformly monotonic f (ME, Mcal/kg); for ME (Mcal/kg) &lt;0.512 or &gt;4.26, km are inconsistent with thermodynamically allowed values for efficiencies (&gt;1.0); kg are a monotonically positive f (ME) concentration (Mcal/kg) for ME &lt;3.27 Mcal/kg. For ME &lt;1.42 Mcal/kg, kg are not in the range of thermodynamically allowed values for efficiencies (0 to 1.0). Variable efficiencies of ME utilization require that the first law may not be observed in all cases. The CNES is an excellent empirical tool for prediction of input:output relationship, but many CNES parameter estimates evaluated in this study lack consistency with biology and the laws of thermodynamics.