Abu Romeh S, Tannen R L
Am J Physiol. 1986 Apr;250(4 Pt 2):F702-9. doi: 10.1152/ajprenal.1986.250.4.F702.
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).
最近的研究表明，酮酸生成对全身pH值的变化极为敏感，pH值降低会抑制生成速率，而pH值升高则会刺激生成速率。为了确定抑制内源性酸净生成是否是一种广泛适用的酸碱平衡防御机制，我们研究了叠加酸中毒对缺氧大鼠乳酸生成的影响。在正常碳酸血症状态下，麻醉、瘫痪并机械通气的大鼠，吸入8%的氧气分数（FIO2，动脉血氧分压35 - 38 mmHg）时，血乳酸水平会逐渐升高，3小时时达到7.0±1.2 mM。缺氧1小时后，叠加轻度呼吸性酸中毒（二氧化碳分压59 mmHg）或外源性无机代谢性酸中毒（动脉内注入盐酸，足以使pH值从7.33降至7.23），会显著减少血乳酸的升高。在第三小时末，叠加呼吸性酸中毒时血乳酸水平平均为1.7±0.6 mM，叠加代谢性酸中毒时为2.7±0.4 mM，这两个值均显著低于缺氧对照组。终止叠加的呼吸性酸中毒会导致血乳酸水平迅速升高，这表明乳酸生成的pH调节具有可逆性。因此，全身酸中毒似乎以一种保护性方式反馈，抑制缺氧诱导的乳酸酸中毒大鼠的乳酸净生成。这些发现表明，在增强内源性酸生成的两种主要情况下（即酮症酸中毒和乳酸酸中毒），存在将全身pH值维持在狭窄范围内的精细反馈控制机制。
