Dynamic response of the peripheral chemoreflex loop to changes in end-tidal O2.

We studied the peripheral ventilatory response dynamics to changes in end-tidal O2 tension (PETO2) in 13 cats anesthetized with alpha-chloralose-urethan. The arterial O2 tension in the medulla oblongata was kept constant using the technique of artificial perfusion of the brain stem. At constant end-tidal CO2 tension, 72 ventilatory on-responses due to stepwise changes in PETO2 from hyperoxia (45-55 kPa) to hypoxia (4.7-9.0 kPa) and 62 ventilatory off-responses due to changes from hypoxia to hyperoxia were assessed. We fitted two exponential functions with the same time delay to the breath-by-breath ventilation and found a fast and a slow component in 85% of the ventilatory on-responses and in 76% of the off-responses. The time constant of the fast component of the ventilatory on-response was 1.6 +/- 1.5 (SD) s, and that of the off-response was 2.4 +/- 1.3 s; the gain of the on-response was smaller than that of the off-response (P = 0.020). For the slow component, the time constant of the on-response (72.6 +/- 36.4 s) was larger (P = 0.028) than that of the off-response (43.7 +/- 28.3 s), whereas the gain of the on-response exceeded that of the off-response (P = 0.031). We conclude that the ventilatory response of the peripheral chemoreflex loop to stepwise changes in PETO2 contains a fast and a slow component.     

Step changes in end-tidal CO2: methods and implications.

A dynamic end-tidal forcing technique for producing step changes in end-tidal CO2 with end-tidal O2 held constant independent of the ventilation response or the mixed venous return is introduced for characterizing the human ventilation response to end-tidal CO2 step changes for both normoxic (PAO2 = 125 Torr) and hypoxic (PAO2 = 60 Torr) conditions. The ventilation response approaches a steady state within 5 min. In normoxia, the on-transient is faster than the off-transient, presumably reflecting the action of cerebral blood flow. The hypoxic step response is faster than the normoxic response presumably reflecting the increased contribution from the carotid body. The delay in the ventilation response after the change in end-tidal CO2 is less in hypoxia than in normoxia and reflects the action of a transport delay and that of a virtual delay. These delays are interpreted with respect to the high-frequency phase shift data for the same subject, generated using sinusoidal end-tidal forcing. The methods of others for experiments utilizing step changes in inspired CO2 are considered with respect to our methods.     

Cerebrovascular responsiveness to steady-state changes in end-tidal CO2 during passive heat stress.

This study tested the hypothesis that passive heat stress alters cerebrovascular responsiveness to steady-state changes in end-tidal CO(2) (Pet(CO(2))). Nine healthy subjects (4 men and 5 women), each dressed in a water-perfused suit, underwent normoxic hypocapnic hyperventilation (decrease Pet(CO(2)) approximately 20 Torr) and normoxic hypercapnic (increase in Pet(CO(2)) approximately 9 Torr) challenges under normothermic and passive heat stress conditions. The slope of the relationship between calculated cerebrovascular conductance (CBVC; middle cerebral artery blood velocity/mean arterial blood pressure) and Pet(CO(2)) was used to evaluate cerebrovascular CO(2) responsiveness. Passive heat stress increased core temperature (1.1 +/- 0.2 degrees C, P < 0.001) and reduced middle cerebral artery blood velocity by 8 +/- 8 cm/s (P = 0.01), reduced CBVC by 0.09 +/- 0.09 CBVC units (P = 0.02), and decreased Pet(CO(2)) by 3 +/- 4 Torr (P = 0.07), while mean arterial blood pressure was well maintained (P = 0.36). The slope of the CBVC-Pet(CO(2)) relationship to the hypocapnic challenge was not different between normothermia and heat stress conditions (0.009 +/- 0.006 vs. 0.009 +/- 0.004 CBVC units/Torr, P = 0.63). Similarly, in response to the hypercapnic challenge, the slope of the CBVC-Pet(CO(2)) relationship was not different between normothermia and heat stress conditions (0.028 +/- 0.020 vs. 0.023 +/- 0.008 CBVC units/Torr, P = 0.31). These results indicate that cerebrovascular CO(2) responsiveness, to the prescribed steady-state changes in Pet(CO(2)), is unchanged during passive heat stress.     

Single breath of CO2 as a clinical test of the peripheral chemoreflex

Peripheral chemoreceptor responsiveness is usually examined clinically by hypoxic testing, but the usefulness of this approach is limited by safety considerations, and the interpretation of results may be confounded by the direct central nervous system effects of hypoxia. Therefore we examined the single-breath (SB) CO2 test to determine its reproducibility and applicability as a clinical test of peripheral chemoreceptor function. The technique involved the inhalation of a SB of 13% CO2 in air. The ventilatory response was determined from the increase in ventilation (VE) during the first 20 s after the test breath and from the difference in end-tidal PCO2 between the test breath and preceding control breaths. The peak increase in VE occurred during the second or third breath after the test breath, corresponding to a delay of approximately 10 s. The mean of 10 SB tests administered at 2- to 3-min intervals was taken as the subject's response. Five healthy subjects were tested in this manner on each of 6 consecutive days with the response having an interday coefficient of variation of 25 +/- 6% (SD). The response in 26 healthy females (aged 22-61 yr) was 0.32 +/- 0.11 l.min-1.Torr-1, and in 26 healthy males (aged 24-69 yr) the response was 0.38 +/- 0.14 (P NS). No significant correlation was found between the age of the subjects and their ventilatory response. Thirty-six of the subjects also underwent hyperoxic CO2 rebreathing tests, the response to which is dependent on central chemoreceptor function. No correlation was found between rebreathing and SB tests.(ABSTRACT TRUNCATED AT 250 WORDS)     

Almitrine bismesylate and the central and peripheral ventilatory response to CO2

Effects of almitrine bismesylate on the peripheral and central chemoreflex to a CO2 challenge during normoxia were studied in nine alpha-chloralose-urethan anesthetized cats. With the dynamic end-tidal CO2 forcing technique the ventilatory response after a square-wave change in end-tidal PCO2 (PETCO2) was partitioned into a central and a peripheral part using a two-compartment model. With almitrine administered intravenously (0.6 mg/kg followed by a maintenance dose of 0.4 mg.kg-1 X h-1) the CO2 sensitivity of the peripheral chemoreflex increased on the average from 0.315 to 0.564 l.min-1 X kPa-1 (P less than 0.001, 6 cats, 73 runs), whereas the CO2 sensitivity of the central chemoreflex remained the same (P = 0.87). The extrapolated PETCO2 at zero ventilation (apneic threshold) of the (total) steady-state response curve decreased on the average from 3.50 to 2.36 kPa (P less than 0.001). With the artificial brain stem perfusion technique it was confirmed that almitrine did not affect ventilation by administering it to the blood perfusing the brain stem. We conclude that almitrine bismesylate during normoxia enhances the CO2 sensitivity of the peripheral chemoreflex loop and decreases the apneic threshold due to an action located outside the brain stem.     

Change in the peripheral CO2 chemoreflex from rest to exercise

A single-breath CO₂ test of peripheral chemosensitivity has recently been described, and elaborated based on model simulations. This study was designed to measure the peripheral CO₂ chemoreflex at rest and during heavy exercise to see if carotid chemosensitivity to CO₂ increased. Ten healthy, adult males performed an incremental exercise test to determine their ventilatory anaerobic threshold (VAT), and 20 minutes of steady-state exercise at a pre-determined power output above VAT. Arterialized venous blood was obtained during each minute of incremental exercise to verify development of metabolic acidosis. Carotid chemosensitivity was tested repeatedly at rest and in steady-state exercise by the ventilatory response to a single breath of 13% CO₂ in air. The peripheral chemoreflex for CO₂ for the group of subjects doubled from rest to exercise (mean 0.0961 · s^–1 · kPa^–1) with all subjects showing an increase. We conclude that the gain of the carotid CO₂ chemoreflex increases from rest to exercise at work above the VAT.     

Lipid accumulation and CO2 utilization of Nannochloropsis oculata in response to CO2 aeration

In order to produce microalgal lipids that can be transformed to biodiesel fuel, effects of concentration of CO(2) aeration on the biomass production and lipid accumulation of Nannochloropsis oculata in a semicontinuous culture were investigated in this study. Lipid content of N. oculata cells at different growth phases was also explored. The results showed that the lipid accumulation from logarithmic phase to stationary phase of N. oculata NCTU-3 was significantly increased from 30.8% to 50.4%. In the microalgal cultures aerated with 2%, 5%, 10% and 15% CO(2), the maximal biomass and lipid productivity in the semicontinuous system were 0.480 and 0.142 g L(-1)d(-1) with 2% CO(2) aeration, respectively. Even the N. oculata NCTU-3 cultured in the semicontinuous system aerated with 15% CO(2), the biomass and lipid productivity could reach to 0.372 and 0.084 g L(-1)d(-1), respectively. In the comparison of productive efficiencies, the semicontinuous system was operated with two culture approaches over 12d. The biomass and lipid productivity of N. oculata NCTU-3 were 0.497 and 0.151 g L(-1)d(-1) in one-day replacement (half broth was replaced each day), and were 0.296 and 0.121 g L(-1)d(-1) in three-day replacement (three fifth broth was replaced every 3d), respectively. To optimize the condition for long-term biomass and lipid yield from N. oculata NCTU-3, this microalga was suggested to grow in the semicontinuous system aerated with 2% CO(2) and operated by one-day replacement.