In situ arterial and brain tissue PCO2 responses to acetazolamide in cats

We have studied how in situ arterial (PaCO2) and brain tissue PCO2 (PbCO2) responses to acetazolamide (AZ) are affected by respiratory patterns. Sixteen cats were anesthetized with ketamine. Group 1 cats (n = 7) breathed air spontaneously. Group 2 cats (n = 6) were paralyzed and ventilated mechanically to maintain PaCO2 at 37 +/- 1 Torr before AZ administration; the respiratory rate and depth did not change during the course of measurements. Two CO2 sensors to measure in situ PaCO2 and PbCO2 continuously were used. One was placed through a burr hole into the cerebral white matter 15 mm in depth, and another was inserted into the femoral artery. After intravenous administration of AZ (20 mg/kg), PaCO2 decreased, after a significant transient rise, and then returned gradually to the baseline in group 1, but it increased gradually and reached a new steady state in group 2. PbCO2 and the PbCO2-PaCO2 gradient increased remarkably in the two groups immediately after administration. We conclude that AZ resulted in a large increase in both PbCO2 and the PbCO2-PaCO2 gradient and that there are two distinct in situ PaCO2 responses to AZ in spontaneously breathing vs. mechanically ventilated animals. The mechanisms for these observations are discussed.

Tissue Pco2 in Brain Ischemia Related to Lactate Content in Normo- and Hypercapnic Rats

The amount of lactate formed during ischemia determines the rise in tissue Pco2 (Ptco2). Conflicting results exist on the relationship between lactate and Ptco2. The objective of this study was to settle this issue. We varied the preischemic plasma glucose concentration of normo- and hypercapnic rats, assessed tissue lactate and total CO2 contents, and determined the Pco2/lactate relationship over the lactate range 2–40 mmol kg−1. The results showed that whatever the equilibration time, the Pco2/lactate relationship was linear. The results obtained could be reproduced by a theoretical buffer system that mimics the buffering behavior of intracellular fluid. Our results bear on the question of whether compartmentation of H+ occurs during ischemia, with glial cells becoming more acid than neurons. A discontinuous Pco2/lactate relationship, with a constant Pco2 above a certain lactate content, would support this contention. Since our results demonstrate a linear relationship between lactate and Pco2 over the lactate range 2–40 mmol kg−1, they considerably weaken any argument for gross compartmentation of H+.

Validation of tonometric measurement of gut intramural pH during endotoxemia and mesenteric occlusion in pigs

Tonometry is a minimally invasive method for estimating gastrointestinal intramural pH (pHi). Tissue pH is calculated by using the Henderson-Hasselbalch equation and measurements of arterial [HCO-3] and CO2 tension (PCO3) of saline contained in a Silastic balloon within the lumen of the gut. The validity of the method rests on two key assumptions: 1) PCO2 in saline in the tonometer balloon is similar to tissue PCO2 and 2) tissue and arterial [HCO-3] are similar. To validate this method, ileal pHi measured directly with a microelectrode was compared with pHi estimated tonometrically in four groups of anesthetized pigs. Group I (n = 4) were controls. In group II (n = 4), intestinal tissue acidosis was induced by total occlusion of the superior mesenteric artery (SMA). In group III (n = 5), acidosis was induced by partial occlusion of the SMA. In group IV (n = 4), tissue acidosis was induced by endotoxemia. Agreement was excellent between direct and tonometric measurements in groups I and IV and less good in groups II and III. Weighted mean correlation coefficients (rw) for the two measurement methods were 0.743 and 0.9447 in groups II and IV, respectively. Correlation coefficients for the individual animals in group III were more variable than the other groups and ranged from 0.547 to 0.990. The tonometric method for measuring GI pHi is invalid under conditions of zero flow and leads to error under conditions of low flow. However, the method is reliable in the setting of tissue acidosis induced by endotoxemia.

Effect of aortic balloon inflation on ventilation and brain stem blood flow in piglets

Increases in brain stem blood flow (BBF) during hypoxia may decrease tissue PCO2/[H+], causing minute ventilation (VE) to decrease. To determine whether an increase in BBF, isolated from changes in arterial PO2 and PCO2, can affect respiration, we obstructed the thoracic aorta with a balloon in 31 intact and 24 peripherally chemobarodenervated, anesthetized, spontaneously breathing newborn piglets. Continuous measurements of cardiorespiratory variables were made before and during 2 min of aortic obstruction. Radiolabeled microspheres were used to measure BBF before and approximately 30 s after balloon inflation in eight intact and five denervated animals. After balloon inflation, there was a rapid increase in mean blood pressure in both the intact and denervated animals, followed within 10 s by a decrease in tidal volume and VE. In the intact animals, the decrease in VE after acute hypertension can be ascribed to a baroreceptor-mediated reflex. After peripheral chemobarodenervation, however, acute hypertension continued to produce a decrease in VE, which cannot be explained by baroreceptor stimulation. In these denervated animals, aortic balloon inflation was associated with an increase in BBF (13.1 +/- 2.7%; P less than 0.05). We speculate that the increase in BBF during hypoxia may contribute to the decrease in ventilation observed after carotid body denervation.

No effect of brain blood flow on ventilatory depression during sustained hypoxia

Minute ventilation (VE) during sustained hypoxia is not constant but begins to decline within 10–25 min in adult humans. The decrease in brain tissue PCO2 may be related to this decline in VE, because hypoxia causes an increase in brain blood flow, thus resulting in enhanced clearance of CO2 from the brain tissue. To examine the validity of this hypothesis, we measured VE and arterial and internal jugular venous blood gases simultaneously and repeatedly in 15 healthy male volunteers during progressive and subsequent sustained isocapnic hypoxia (arterial PO2 = 45 Torr) for 20 min. It was assumed that jugular venous PCO2 was an index of brain tissue PCO2. Mean VE declined significantly from the initial (16.5 l/min) to the final phase (14.1 l/min) of sustained hypoxia (P less than 0.05). Compared with the control (50.9 Torr), jugular venous PCO2 significantly decreased to 47.4 Torr at the initial phase of hypoxia but did not differ among the phases of hypoxia (47.2 Torr for the intermediate phase and 47.7 Torr for the final phase). We classified the subjects into two groups by hypoxic ventilatory response during progressive hypoxia at the mean value. The decrease in VE during sustained hypoxia was significant in the low responders (n = 9) [13.2 (initial phase) to 9.3 l/min (final phase of hypoxia), P less than 0.01], but not in the high responders (n = 6) (20.9–21.3 l/min, NS). This finding could not be explained by the change of arterial or jugular venous gases, which did not significantly change during sustained hypoxia in either group.(ABSTRACT TRUNCATED AT 250 WORDS)