Previous studies have found that administration of dichloroacetate (DCA), a
n agent that reduces lactic acid generation, increases limb muscle enduranc
e. The purpose of the present study was to determine if this agent also imp
roves respiratory muscle performance. To examine this issue, we determined
the effect of DCA administration on the response to application of a large
inspiratory resistive load (32,000 cm H2O/L/s) in unanesthetized decerebrat
e rats. Studies were carried out in four groups of animals: saline unloaded
, DCA unloaded, saline loaded, and DCA loaded. DCA was administered as 100
mg/kg, given intravenously over 30 min, prior to respiratory loading. We fo
und that diaphragm lactate levels were higher in saline-treated loaded anim
als than in unloaded controls and that DCA administration prevented loading
-induced increases in diaphragm lactate (p < 0.001). DCA-treated animals to
lerated loading poorly, however, with a more rapid reduction in diaphragm p
ressure generation and a shorter time to respiratory arrest (42 +/- 3 min)
than for saline-treated animals (57 +/- 3 min, p < 0.01). These data indica
te that DCA administration decreases the tolerance to loaded breathing desp
ite reductions in diaphragm lactate concentrations. We speculate that suppr
ession of lactate formation by DCA may impair metabolic regulation within t
he diaphragm during resistive loaded breathing.