Amelioration of hypoxia-induced lactic acidosis by superimposed hypercapnea or hydrochloric acid infusion.
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).
Abu Romeh
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Tannen
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D000138:Acidosis / Q000378:metabolism*; D000818:Animals; D002245:Carbon Dioxide / Q000097:blood; D005246:Feedback; D000860:Hypoxia / Q000378:metabolism; D007773:Lactates / Q000378:metabolism*; D008297:Male; D051381:Rats; D013997:Time Factors
D007773:Lactates; D002245:Carbon Dioxide