Microvascular oxygen distribution in awake hamster window chamber model during hyperoxia

The microvascular effects and hemodynamic events following exposure to normobaric hyperoxia (because of inspiration of 100% O2) were studied in the awake hamster window chamber model and compared with normoxia. Hyperoxia increased arterial blood Po2 to 477.9 ± 19.9 from 60.0 ± 1.2 mmHg ( P < 0.05). Heart rate and blood pressure were unaltered, whereas cardiac index was reduced from 196 ± 13 to 144 ± 31 ml · min–1 · kg–1 ( P < 0.05) in hyperoxia. Direct measurements in the microcirculation showed there was arteriolar vasoconstriction, reduction of microvascular flow (83% of control, P < 0.05), and functional capillary density (FCD, 74 ± 16% of control), the latter change being significant ( P < 0.05). Calculations of oxygen delivery and oxygen consumption based on the measured changes in microvascular blood flow velocity and diameter and estimates of oxygen saturation corrected for the Bohr effect due to the lowered pH and increased Pco2 showed that oxygen transport in the microvascular network did not change between normal and hyperoxic condition. The congruence of systemic and microvascular hemodynamics events found with hyperoxia suggests that the microvascular findings are common to most tissues in the organism, and that hyperoxia, due to vasoconstriction and the decrease of FCD, causes a maldistribution of perfusion in the microcirculation.

Interaction of chemical and state effects on ventilation during sleep onset

Dunai, Judith, Mal Wilkinson, and John Trinder.Interaction of chemical and state effects on ventilation during sleep onset. J. Appl. Physiol. 81(5): 2235–2243, 1996.—Ventilation varies as a function of state, being higher during wakefulness (as indicated by alpha electroencephalogram activity) than during sleep (theta activity). A recent experiment observed a progressive increase in the magnitude of these state-related fluctuations in ventilation over the sleep-onset period (28). The aim of the present experiment was to test the hypothesis that this effect resulted from chemical (feedback-related) amplification of state effects on ventilation. A hyperoxic condition was used to eliminate peripheral chemoreceptor activity. It was hypothesized that hyperoxia would reduce the amplification of changes in ventilation associated with electroencephalogram state transitions. Ventilation was measured over the sleep-onset period under both hyperoxic and normoxic conditions in 10 young healthy male subjects. Sleep onsets were divided into three phases. Phase 1 corresponded to presleep wakefulness; and phases 2 and 3 corresponded to early and late sleep onset, respectively. The magnitudes of state-related changes in ventilation during phases 2 and 3, and under hyperoxic and normoxic conditions were compared using a phase by condition analysis of variance. Results revealed a significant phase by condition interaction, confirming that hyperoxia reduced the amplification of state-related changes in ventilation by selectively decreasing the magnitude of phase 3 state changes in ventilation. However, some degree of amplification was evident during hyperoxia, thus the results demonstrated that peripheral chemoreceptor activity contributed to the amplification of state-related changes in ventilation but that additional factors may also be involved.

Effect of hypoxia on reflex responses of tracheal submucosal glands

The effects of moderate sustained normocapnic hypoxia on tracheal submucosal gland reflex responses were studied. Experiments were performed in anesthetized, paralyzed, and mechanically ventilated dogs. The changes in the number of secreting glands and volume of secreted fluid in the subsequent period of time were recorded after 15–30 min of controlled ventilation with room air [arterial PO2 (PaO2) 86 +/- 3 Torr], hypoxic gas mixture (PaO2 49 +/- 4 Torr), or 100% O2 (PaO2 339 +/- 39 Torr), under isocapnic and isohydric conditions. The hillocks method was used to quantify the changes in submucosal gland secretion. The changes in secretion 30 s after stimulation of pulmonary C-fiber receptors by right atrial injection of capsaicin (10 micrograms/kg; n = 10) were markedly lower during moderate hypoxia than in normoxia or hyperoxia. Differences in the number of liquid droplets and the volume of secreted fluid were statistically significant (P < 0.05 and P < 0.001, respectively). Stimulation of airway rapidly adapting receptors by lung deflation increased airway secretion; the number of “hillocks” and the volume of secreted fluid were lower in hypoxic than in hyperoxic state. Differences between response curves for the number of glands activated and secreted volume were statistically significant (P < 0.05 and P < 0.001). The number of glands activated by substance P given locally by arterial infusion was not affected by the state of oxygenation, but the calculated volume of secreted fluid was lower during the hypoxic state than under hyperoxic condition (P = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Ventilatory variability induced by spontaneous variations of PaCO2 in humans

We tested the hypothesis that breath-to-breath variations in arterial CO2 partial pressure (PaCO2) during spontaneous breathing of awake humans cause a significant portion of spontaneous ventilatory variability (including periodic oscillations). This hypothesis was tested in two ways. First, using a recently developed adaptive PaCO2 buffering technique we reduced the spontaneous variability in PaCO2 of six awake normal young human subjects during hyperoxia and observed a corresponding decrease in their breath-to-breath ventilatory variations. Second, we predicted the ventilatory responses to CO2 disturbances by using a model of chemical control of ventilation, both examining the hyperoxic condition (similar to experimental studies) and predicting the responses to CO2 variations of a normal subject breathing room air. In all experimental and theoretical studies, we found that small random disturbances to PaCO2 have significant effects on ventilation, including the potential for such PaCO2 disturbances to elicit oscillatory fluctuations in ventilation even though the ventilatory chemical control system was stable (i.e., a brief disturbance to PaCO2 did not elicit sustained ventilatory oscillations). On the basis of these results we propose that the stability of chemoreflex ventilatory control loops depends on both “loop gain” factors and the characteristics of random disturbances to PaCO2.

Effect of hyperoxia on oxygen consumption in exercising ponies

Published reports of oxygen consumption (VO2) during exercise in hyperoxia are equivocal. By and large, when measured at the lung using respiratory gas equations, VO2 is elevated in hyperoxia and, when measured at the blood-tissue level using the cardiovascular Fick (CVF) equation, it is unchanged. We sought to provide some insight into this problem by making through the use of both equations simultaneous determinations of VO2 during hyperoxia in exercising ponies. In normoxia, during treadmill exercise (115 m/min, 10% grade) of seven ponies, there was no difference in exercise VO2, whether it was measured by the Haldane transformation (HT) or CVF equations (P greater than 0.05). In hyperoxia, the exercise VO2 was significantly increased from the normoxia condition (P less than 0.05) when measured by the HT equation but not when measured by the CVF equation (P greater than 0.05). By use of the CVF equation as the method of choice for VO2 determinations in hyperoxia, the present data show no change in exercise VO2 in the hyperoxic condition.