Myocardial lactate deprivation is associated with decreased cardiovascular performance, decreased myocardial energetics, and early death in endotoxic shock.
OBJECTIVE
We examined whether lactate availability is a limiting factor for heart function during endotoxic shock, and whether lactate deprivation thus induces heart energy depletion, thereby altering cardiovascular performance. The study goals were to determine whether muscle lactate production is linked to beta(2)-stimulation and to ascertain the effects of systemic lactate deprivation on hemodynamics, lactate metabolism, heart energetics, and outcome in a lethal model of rat's endotoxic shock.


METHODS
We modulated the adrenergic pathway in skeletal muscle using microdialysis with ICI-118551, a selective beta(2)-blocker. Muscle lactate formation in endotoxic shock was further inhibited by intravenous infusion of ICI-118551 or dichloroacetate (DCA), an activator of pyruvate dehydrogenase (DCA) and their combination.


RESULTS
Muscle lactate formation was decreased by ICI-118551. During endotoxic shock both ICI-118151 and DCA decreased circulating and heart lactate concentrations in parallel with a decrease in tissue ATP content. The combination ICI-118551-DCA resulted in early cardiovascular collapse and death. The addition of molar lactate to ICI-1185111 plus DCA blunted the effects of ICI-118551+DCA on hemodynamics. Survival was markedly less with ICI-118551 than with endotoxin alone.


CONCLUSIONS
Systemic lactate deprivation is detrimental to myocardial energetics, cardiovascular performance, and outcome.
Levy
Bruno
B
Coordination Circulation UHP-INSERM, Groupe CHOC, Faculté de Médecine, Université Henri Poincaré Nancy 1, Nancy, France. b.levy@chu-nancy.fr
Mansart
Arnauld
A
Montemont
Chantal
C
Gibot
Sebastien
S
Mallie
Jean-Pierre
JP
Regnault
Veronique
V
Lecompte
Thomas
T
Lacolley
Patrick
P
D000704:Analysis of Variance; D000818:Animals; D003326:Coronary Circulation; D004734:Energy Metabolism; D004837:Epinephrine / Q000378:metabolism; D006019:Glycolysis; D000860:Hypoxia / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D012772:Shock, Septic / Q000378:metabolism / Q000503:physiopathology*; D016019:Survival Analysis
D018343:Receptors, Adrenergic, beta-2; D019344:Lactic Acid; D004837:Epinephrine