V. Fencl

Stewart's quantitative acid-base chemistry : applications in biology and medicine

We review P.A. Stewarts quantitative approach to acid-base chemistry, starting with its historical context. We outline its implications for cellular and membrane processes in acid-base physiology; discuss its contributions to the understanding and analysis of acid-base phenomena; show how it can be applied in clinical problems; and propose a classification of clinical acid-base disturbances based on this general approach.

Respiration of Chemodenervated Goats in Acute Metabolic Acidosis

In awake goats before and after ablation of carotid bodies (CBx) we studied the effect of acute metabolic acidosis (AMA) produced by intravenous infusion of HCl on composition of arterial blood and CSF, and on ventilatory responsiveness to hyperoxic CO2 rebreathing AMA caused decrease in PaCO2 (breathing air at rest) indicating that alveolar ventilation was increased relative to CO2 production; position of CO2 response curves was shifted toward lower values of PCO2. These changes were similar before and after CBx, though the levels of PCO2 in arterial blood during air breathing at rest, and in expired gas at a given level of ventilation during CO2 rebreathing, were higher after CBx. We conclude that a respiratory adaptation to AMA does occur in goats deprived of peripheral chemoreceptors, and is probably mediated by the central chemoreceptors.

Endogenous Opioids and Ventilatory Adaptation to Prolonged Hypoxia in Goats

To investigate whether endogenous opioid peptides mediate time-dependent changes in ventilatory control during prolonged hypoxia, we studied four adult goats at rest during 14 days at simulated high altitude in a hypobaric chamber (PB approximately 450 Torr). Arterial PCO2 fell during the first several hours of hypoxia, remained stable over the next 7 days, and then rose slightly (but without statistical significance) by day 14. Ventilatory responsiveness to CO2 increased during the first week of hypoxia. By day 14, while still greater than control, the ventilatory response to CO2 was less than that observed on day 7. Immunoactive beta-endorphin levels in plasma and CSF did not change during the 14-day period. Administration of naloxone on day 14 did not restore the ventilatory response to CO2 to the level observed during the first week of acclimatization. We conclude that in adult goats, time-dependent changes in ventilatory response to CO2 during acclimatization to prolonged hypoxia are not primarily attributable to alterations in endogenous opioid peptide activity.

Adrenergic Blockade Does Not Change Ventilatory Response to CO2 in Awake Resting Goats

Although adrenergic agonists increase resting ventilation and responsiveness to CO2, there are conflicting data about the effect of adrenergic blockade on ventilatory responses. In this study, we investigated the effect of alpha- or beta-adrenergic blockade on the response to hyperoxic CO2 rebreathing in awake goats. In 5 goats, studied before and after intravenous administration of phentolamine or propranolol, there was no difference (compared to control studies) in the mean slope, x-intercept, or ventilation at end-tidal PCO2 (PETCO2) = 70 torr for the CO2 response curves after either drug. When mean inspiratory flow rate (VT/Ti) was plotted against PETCO2, there was also no change in these measurements after propranolol. After phentolamine, there was a slight decrease in the slope and x-intercept, but no change in VT/Ti at PETCO2 = 70 torr. We conclude that acute administration of alpha- or beta-adrenergic blockers does not affect ventilatory response to CO2 inhalation in goats, and suggest that adrenergic activity is not an important modulating influence for CO2 responsiveness in this species.