Department of Medicine, Presbyterian Hospital, College of Physicians and Surgeons, Columbia University, New York.
J Clin Invest. 1968 Jan;47(1):188-202. doi: 10.1172/JCI105708.
This study examined the ventilatory adjustment to chronic metabolic alkalosis induced under controlled conditions in normal human volunteers. Metabolic alkalosis induced by buffers (sodium bicarbonate, trishydroxymethylamine methane) or ethacrynic acid was associated with alveolar hypoventilation, as evidenced by a rise in arterial Pco(2), a fall in arterial Po(2), a reduced resting tidal volume, and a diminished ventilatory response to CO(2) inhalation. Alveolar hypoventilation did not occur when metabolic alkalosis was induced in the same subjects by thiazide diuretics or aldosterone despite comparable elevations of the arterial blood pH and bicarbonate concentration.The different ventilatory responses of the two groups could not be ascribed to differences among individuals comprising each group, pharmacological effects of the alkalinizing agents, differences in the composition of the lumber spinal fluid, changes in extracellular fluid volume, or sodium and chloride balance.The differences in ventilatory adjustments were associated with differences in the patterns of hydrogen and potassium ion balance during the induction of alkalosis. Alveolar hypoventilation occurred when hydrogen ions were buffered (sodium bicarbonate, trishydroxymethylamine methane) or when renal hydrogen ion excretion was increased (ethacrynic acid). Alveolar hypoventilation did not occur when induction of similar degrees of extracellular alkalosis was accompanied by marked potassium loss and no demonstrable increase in external hydrogen loss (thiazides and aldosterone).These observations suggest that respiratory depression does not necessarily accompany extracellular alkalosis but depends on the effect of the mode of induction of the alkalosis on the tissues involved in the control of ventilation.
这项研究在正常人类志愿者的受控条件下，检查了慢性代谢性碱中毒引起的通气调节。由缓冲剂（碳酸氢钠、三羟甲基氨基甲烷）或依他尼酸引起的代谢性碱中毒与肺泡通气不足有关，这表现在动脉 Pco2 升高、动脉 Po2 降低、静息潮气量减少以及 CO2 吸入的通气反应减弱。当噻嗪类利尿剂或醛固酮在相同的受试者中引起代谢性碱中毒时，肺泡通气不足并未发生，尽管动脉血 pH 值和碳酸氢盐浓度有类似的升高。
两组不同的通气反应不能归因于每组个体之间的差异、碱化剂的药理学效应、脑脊液成分的差异、细胞外液容量的变化或钠和氯平衡。通气调节的差异与碱中毒诱导过程中氢离子和钾离子平衡模式的差异有关。当氢离子被缓冲（碳酸氢钠、三羟甲基氨基甲烷）或肾脏氢离子排泄增加（依他尼酸）时，肺泡通气不足发生。当诱导类似程度的细胞外碱中毒时伴有明显的钾丢失而无明显的外部氢离子丢失增加（噻嗪类和醛固酮）时，肺泡通气不足不会发生。
这些观察结果表明，呼吸抑制不一定伴随着细胞外碱中毒，但取决于碱中毒诱导方式对参与通气控制的组织的影响。
