AJP - Renal Physiology, Vol 250, Issue 4 702-F709, Copyright © 1986 by American Physiological Society
Amelioration of hypoxia-induced lactic acidosis by superimposed hypercapnea or hydrochloric acid infusion
S. Abu Romeh and R. L. Tannen
Recent studies have shown that ketoacid production is exquisitely sensitive
to changes in systemic pH, with a decrease inhibiting and an increase
stimulating the production rate. To determine whether inhibition of net
endogenous acid production is a widely applicable mechanism for the defense
of acid-base homeostasis, we examined the effect of superimposed acidosis
on lactic acid production by hypoxic rats. Anesthetized paralyzed
mechanically ventilated rats with normocapnia increased blood lactate
progressively in response to a fractional inspired O2 (FIO2) of 8% (PaO2,
35-38 mmHg) and achieved a level of 7.0 +/- 1.2 mM at 3 h. Superimposition
of either mild respiratory acidosis (PCO2, 59 mmHg) or exogenous inorganic
metabolic acidosis (intra-arterial HCl sufficient to decrease pH from 7.33
to 7.23) after 1 h of hypoxia dramatically diminished the rise in blood
lactate. At the end of the third hour, blood lactate levels averaged 1.7
+/- 0.6 mM with superimposed respiratory acidosis and 2.7 +/- 0.4 mM with
superimposed metabolic acidosis, both values being significantly less than
the hypoxic controls. Termination of the superimposed respiratory acidosis
resulted in a rapid increase in blood lactate levels, demonstrating the
reversibility of the pH modulation of lactic acid production. Thus systemic
acidosis appears to feed back in a protective fashion to inhibit net lactic
acid production in rats with hypoxia-induced lactic acidosis. These
findings suggest that finely tuned feedback control mechanisms that keep
systemic pH within a narrow range operate under both major conditions of
enhanced endogenous acid production (i.e., keto- and lactic acidosis).
