Effects of dichloroacetate and bicarbonate on haemodynamic parameters in healthy volunteers

Abstract

1. It has been shown that sodium bicarbonate has no effect or could even be detrimental in various forms of metabolic acidosis. Dichloroacetate, a stimulator of the pyruvate dehydrogenase complex, might offer an alternative treatment. The present study therefore examines the metabolic and haemodynamic effects of dichloroacetate and sodium bicarbonate in healthy volunteers. 2. On 2 different days, sodium dichloroacetate (50 mg/kg body weight) or sodium bicarbonate (1.5 mmol/kg body weight) was given intravenously as a single bolus in 10 healthy volunteers. Haemodynamic parameters were measured using a microprocessor-controlled system. Measurements were performed before and 30 and 60 min after infusion. 3. After administration of dichloroacetate, cardiac index increased from 2.3 +/- 0.03 to 2.7 +/- 0.1 1 min-1 m-2 (P less than 0.05), peripheral vascular resistance decreased from 266 +/- 9.7 to 240 +/- 1.7 kPa s l-1 (2662 +/- 97 to 2398 +/- 169 dyn s cm-5, P less than 0.05), oxygen availability increased from 442 +/- 16 to 535 +/- 30 ml min-1 m-2 (P less than 0.05) and serum lactate concentration fell from 1.4 +/- 0.14 to 0.6 +/- 0.1 mmol/l (P less than 0.05). With infusion of sodium bicarbonate there were no significant effects on any of these variables. 4. Our results show that dichloroacetate administered intravenously reduces the serum lactate concentration. The main effects of dichloroacetate itself are on the haemodynamic variables. Dichloroacetate increases cardiac index and oxygen availability and decreases peripheral vascular resistance, whereas sodium bicarbonate has no effect on haemodynamic or metabolic parameters. These data give some further insights in the actions of dichloroacetate and support the use of dichloroacetate as alternative therapy in various forms of metabolic acidosis.

Effects of dichloroacetate on V̇o2and intramuscular31P metabolite kinetics during high-intensity exercise in humans

“…Intramuscular pH (pH i) was estimated from the chemical shift of the Pi peak relative to the PCr peak in the 31 P spectrum, by using the relationship determined by Moon and Richards 29pH i ϭ 6.75 ϩ log ͫ ␦ Ϫ 3. 27 5.69 Ϫ ␦ ͬ…”

Substrate availability limits human skeletal muscle oxidative ATP regeneration at the onset of ischemic exercise.

“…The metabolic effects of dichloroacetate (DCA) 1 administration have been examined in humans at rest (1,2) and during submaximal and maximal exercise (3,4). These studies have consistently demonstrated that DCA can reduce blood lactate concentration at rest and during exercise.…”

The Biological Activity of Sodium Dichloroacetate and Its Effectiveness During the Experimental Clinical Studies

“…В исследовании на здоровых добровольцах из-учалось влияние НДХА на некоторые гемодинами-ческие параметры [28]. …”