Effects of dichloroacetate and bicarbonate on haemodynamic parameters in healthy volunteers.
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.
Ludvik
B
B
2nd Department of Medicine, University of Vienna, Austria.
Peer
G
G
Berzlanovich
A
A
Stifter
S
S
Graf
H
H
D000328:Adult; D001639:Bicarbonates / Q000097:blood / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D002302:Cardiac Output / Q000187:drug effects; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007773:Lactates / Q000097:blood; D008297:Male; D010100:Oxygen / Q000097:blood; D012964:Sodium / Q000494:pharmacology*; D017693:Sodium Bicarbonate; D014655:Vascular Resistance / Q000187:drug effects
D001639:Bicarbonates; D007773:Lactates; D002245:Carbon Dioxide; D017693:Sodium Bicarbonate; D003999:Dichloroacetic Acid; D012964:Sodium; D010100:Oxygen