Power 2014 Abstract MiP2014

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The hot heart: cardiac mitochondrial energetics during hyperthermia.
Link:
Power A
Mitochondr Physiol Network 19.13 - MiP2014

Power A, Pearson N, Pham T, Cheung C, Phillips AR, Hickey AJ (2014)

Event: MiP2014

Heart failure is a common cause of death with hyperthermia [1], while the exact cause of hyperthermic heart failure appears elusive. It has been shown that there is an increase in inner-mitochondrial membrane permeability with hyperthermia starting at 42 °C [3]. We hypothesized that this would result in an impaired ATP supply by oxidative phosphorylation (OXPHOS) and hence compromise normal working heart function.

Sprague Dawley rat ex vivo working heart function was assessed with a graded increase in perfusion temperature up to 43.5 °C. Mitochondrial high-resolution respirometry coupled to fluorometry was employed to determine the effects of moderate (40 °C) and severe (43 °C) hyperthermia on both ATP production (using magnesium green) and mitochondrial membrane potential (ΔΨmt; using safranine) in vitro, using a comprehensive metabolic substrate complement with isolated mitochondria [2].

Ex vivo working rat hearts showed breakpoints in all functional parameters (heart rate, cardiac output and ventricular contractility) at ~40.5 °C. Relative to 37 °C and 40 °C, 43 °C elevated LEAK O2 flux and depressed OXPHOS O2 flux and ∆Ψmt. Measurement of steady-state ATP flow from mitochondria revealed decreased ATP synthesis capacity and a negative steady-state ~P/O ratio at 43 °C. This approach offers a more powerful analysis of the effects of temperature on OXPHOS that cannot be measured using simple measures, such as the traditional RCR or ~P/O ratio, which respectively can only approach 1 or 0 with inner-membrane failure.

At 40 °C there was only a slight enhancement of the LEAK O2 flux and this did not significantly affect ATP production rate. Therefore, during mild hyperthermia (40 °C) there is no enhancement of ATP supply by mitochondria, to accompany increasing cardiac energy demands, while between this and critical hyperthermia (43 °C), mitochondria become net consumers of ATP. This consumption would contribute to cardiac failure or permanent tissue damage during severe hyperthermia.


O2k-Network Lab: NZ Auckland Hickey AJ


Labels: MiParea: Respiration 

Stress:Permeability transition, Temperature  Organism: Rat  Tissue;cell: Heart  Preparation: Isolated mitochondria 

Regulation: ATP production, mt-Membrane potential  Coupling state: LEAK, OXPHOS 

HRR: Oxygraph-2k, O2k-Fluorometer  Event: C4, Oral  MiP2014 

Affiliation

1-School Biol Sc, Fac Sc; 2-Dep Physiol, Fac Medical Health Sc; 3-Dep Surgery, Fac Medical Health Sc; Univ Auckland, New Zealand. - amelia.s.power@gmail.com

References

  1. Bouchama A, Dehbi M, Chaves-Carballo E (2007) Cooling and hemodynamic management in heatstroke: practical recommendations. Crit Care 11: R54.
  2. Goo S, Pham T, Han JC, Nielsen P, Taberner A, Hickey A, Loiselle D (2013) Multiscale measurement of cardiac energetics. Clin Exp Pharmacol Physiol 8: 1440-1681.
  3. Nauciene Z, Zukiene R, Degutyte-Fomins L, Mildaziene V 2012 Mitochondrial membrane barrier function as a target of hyperthermia. Medicina 48: 249-55.