October 1, 1990AJP Heart and Circulatory Physiology184 citations
View Full PaperDichloroacetate stimulation of glucose oxidation improves recovery of ischemic rat hearts
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.
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
Dichloroacetate improves mechanical recovery of ischemic rat hearts when administered at reperfusion by stimulating glucose oxidation.
Main Result
Absolute Event Rate: 73% vs 37%
Abstract
We have previously shown that high concentrations of fatty acids depress reperfusion recovery of ischemic rat hearts as a result of a fatty acid inhibition of glucose oxidation. In this study, we determined whether dichloroacetate, an activator of pyruvate dehydrogenase, could overcome fatty acid inhibition of glucose oxidation and thereby improve mechanical recovery of hearts reperfused after a period of transient global ischemia. Isolated working rat hearts, perfused with 11 mM glucose, 1.2 mM palmitate, and 500 microU/ml insulin, were subjected to a 30-min period of no flow ischemia, followed by a 30-min period of reperfusion. Under these conditions, control hearts recovered 37% of preischemic function. The addition of 1 mM dichloroacetate to the perfusate at reperfusion resulted in a significant improvement in recovery of mechanical function (to 73% of preischemic function). When dichloroacetate was added before the onset of ischemia, however, this protective effect was lost, and a significant increase in myocardial lactate accumulation during ischemia was observed. The effects of dichloroacetate on glucose oxidation rates in both nonischemic and reperfused ischemic hearts was determined by perfusing hearts with 11 mM U-14Cglucose and 1.2 mM palmitate and quantitatively collecting 14CO2 produced by the heart. In nonischemic hearts, 1 mM dichloroacetate increased steady-state glucose oxidation rates from 298 +/- 69 to 1,223 +/- 135 nmol.g dry wt-1.min-1. The addition of dichloroacetate to hearts reperfused after a 25-min period of ischemia also increased glucose oxidation rates from (112 +/- 25 to 561 +/- 83 nmol.g dry wt-1.min-1).(ABSTRACT TRUNCATED AT 250 WORDS)