RT Journal Article
SR Electronic
T1 P22 Cardiac energy metabolism increases with ketone oxidation
JF Heart
JO Heart
FD BMJ Publishing Group Ltd and British Cardiovascular Society
SP A9
OP A9
DO 10.1136/heartjnl-2018-BSCR.27
VO 104
IS Suppl 3
A1 Cher-Rin Chong
A1 Mark Cole
A1 Carolyn Carr
A1 Henry Lee
A1 Brianna Stubbs
A1 Azrul bin Abdul Kadir
A1 Rhys Evans
A1 Pete Cox
A1 Kieran Clarke
YR 2018
UL http://heart.bmj.com/content/104/Suppl_3/A9.3.abstract
AB Rationale The oxidation of ketone bodies plus glucose improves the efficiency of the working rat heart by ~30% compared to glucose alone.1 However, perfusions of hearts with ketones alone led to gradual functional decline with reduced flux through α-ketoglutarate dehydrogenase.2 We have shown that that the rate of d-β-hydroxybutyrate (βHB) oxidation in isolated perfused rat heart increases with the glycogen content via replenishing anaplerotic substrates. Therefore, we aimed to determine whether the availability of glycogen increases the oxidation of ketones and improves myocardial energetics.Methods Hearts from male Wistar rats (320–360 g) were isolated and perfused with buffer to alter the glycogen content, before perfusion with either 11 mM glucose or 11 mM glucose plus 4 mM βHB. Fully relaxed 31P-MR spectra were acquired at each stage of the protocol to measure pH, PCr, Pi and ATP concentrations ([PCr], [Pi], [ATP]). Results were analysed using 2-way ANOVA with Bonferroni’s correction.Results [ATP] remained constant under all perfusion conditions, irrespective of the cardiac glycogen content. In hearts with high glycogen, addition of βHB increased [PCr] by 41%, from 15.4±0.5 to 21.7±0.5 mM, and ▵GATP by −6.3 kJ/mol (both p<0.001). In low glycogen hearts, addition of βHB did not alter [PCr] or ▵GATP.Conclusion High glycogen concentrations increased the oxidation of βHB, thereby improving cardiac energetics.References. Sato, et al. FASEB1995;9(8):651–8.. Russell RR, Taegtmeyer H. JCI1991;87(2):384–390.