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October 1, 1990AJP Heart and Circulatory Physiology

Dichloroacetate stimulation of glucose oxidation improves recovery of ischemic rat hearts

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Key result

The addition of 1 mM dichloroacetate at reperfusion significantly improved the recovery of mechanical function in ischemic rat hearts to 73% of preischemic function compared to 37% in controls.

Why the study?

Does dichloroacetate improve mechanical recovery in isolated working rat hearts subjected to ischemia and reperfusion?

Population

Isolated working rat hearts subjected to a 30-min period of no flow ischemia, followed by a 30-min period of…

Comparison

1 mM dichloroacetate added to the perfusate at… vs Control hearts without dichloroacetate

Design

Preclinical

Follow-up

30 minutes of reperfusion

Authors

JMJeffreyJ. McVeighCarolina Veterinary SpecialistsGary D. LopaschukGary D. LopaschukHeart Failure & Transplant

Discussion

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Implication

Does not support clinical use; leaves open whether dichloroacetate improves human ischemia-reperfusion recovery.

Key Points

  • This study aims to investigate whether dichloroacetate can mitigate the inhibitory effects of fatty acids on glucose oxidation and enhance recovery in ischemic rat hearts.
  • Isolated working rat hearts were perfused with glucose, palmitate, and insulin, subjected to 30 minutes of ischemia followed by reperfusion.
  • Dichloroacetate was administered either at reperfusion or before ischemia to evaluate its effects on recovery and glucose oxidation rates.
  • 14C-labeled glucose was used to measure glucose oxidation by collecting 14CO2 produced by the hearts.
  • Control hearts recovered 37% of preischemic function after reperfusion, while addition of 1 mM dichloroacetate improved this to 73%.
  • In nonischemic hearts, dichloroacetate significantly increased glucose oxidation rates from 298 to 1,223 nmol.g dry wt-1.min-1.
  • Dichloroacetate was ineffective when administered before ischemia, leading to increased lactate accumulation during that period.

Structured PICO

Does dichloroacetate improve mechanical recovery in isolated working rat hearts subjected to ischemia and reperfusion?

P
Population
Isolated working rat hearts subjected to transient global ischemia and reperfusion.
I
Intervention
1 mM dichloroacetate added to the perfusate at reperfusion (or before the onset of ischemia)
C
Comparator
Control hearts without dichloroacetate
O
Outcome
Recovery of mechanical functionsurrogate

Main Result

Absolute Event Rate: 73% vs 37%

Dichloroacetate improves mechanical recovery of ischemic rat hearts when administered at reperfusion by stimulating glucose oxidation.

Cite This Study

McVeigh et al. (1990) studied Transient global ischemia. Dichloroacetate vs. Control was evaluated on Recovery of mechanical function (% of preischemic function). The addition of 1 mM dichloroacetate at reperfusion significantly improved the recovery of mechanical function in ischemic rat hearts to 73% of preischemic function compared to 37% in controls.

synapsesocial.com/papers/6a330fef08194afa457c10f0https://doi.org/10.1152/ajpheart.1990.259.4.h1079
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Effects of Dichloroacetate on Mechanical Recovery and Oxidation of Physiologic Substrates After Ischemia and Reperfusion in the Isolated Heart1998 · 16 citations
  2. 2Rate of glycolysis during ischemia determines extent of ischemic injury and functional recovery after reperfusion1994 · 113 citations
  3. 3Pyruvate Dehydrogenase Influences Postischemic Heart Function1995 · 136 citations
  4. 4Feeding the fibrillating heart: Dichloroacetate improves cardiac contractile dysfunction following VF2015 · 17 citations
  5. 5Substrate competition in postischemic myocardium. Effect of substrate availability during reperfusion on metabolic and contractile recovery in isolated rat hearts.1994 · 33 citations