Atsuko Masuda

Individual differences in ventilatory and HR responses to progressive hypoxia following 100% O2 exposure in humans.

Ventilatory response to sustained hypoxia is known to exhibit a biphasic profile: an initial rapid augmentation followed by a gradual decline. The former is induced by an excitation of the peripheral chemoreceptor. Interestingly, regarding the latter secondary depression (defined as hypoxic ventilatory depression, HVD), it has been suggested by several investigators that its magnitude is in some way also determined by a centrally mediated discharge from the peripheral chemoreceptor (4).

Heart rate response to breath-holding during supramaximal exercise

SummaryThe cardiovascular responses to breath-holding (BH) during short-lasting supramaximal exercise (415 W) on a cycle ergometer were investigated in 15 healthy male subjects. The arterial oxygen saturation, heart rate (HR), endtidal PO2 and PCO2 were continuously monitored. Firstly, 15 subjects performed exercise during BH, preceded by air breathing (air-BH test), and secondly, exercise without BH. Then 9 of the subjects performed the same procedure as in the air-BH test, except that all subjects breathed 100% O2 for 1 min before apnoea (O2-BH test). In 2 of these subjects, the systemic arterial blood pressure was continuously measured via a catheter in the radial artery and plasma catecholamine concentration [CA] was also measured both during the air-BH and the O2-BH tests. In the later period of the air-BH test, the high HR level became progressively depressed. This response, however, was absent in the O2-BH test. There was a late increase in the arterial blood pressure in both tests, and both tests produced hypercapnia. Only the air-BH test resulted in hypoxia, substantial hypertension and HR-depression. The increase in plasma CA was similar in both tests. The marked HR-depression demonstrated here is ascribed mainly to activation of the peripheral arterial chemoreceptors by asphyxia, and partially to baroreceptor activity due to elevated blood pressure.

Relationship Between Ventilatory and Circulatory Responses to Sustained Mild Hypoxia in Humans

The ventilatory response to isocapnic moderate hypoxia in humans is biphasic, consisting of an initial brisk increase followed by a gradual decrease in ventilation, namely hypoxic ventilatory depression (HVD)1. A similar biphasic response in the heart rate (HR) during sustained hypoxia was also observed in our previous study2. Although some mechanisms of the HVD have been proposed (the increase in inhibitory neuromodulators in the central nervous systems3, adaptation of the peripheral chemoreceptors4, increase in brain blood flow5 etc.), little has been known about the circulatory parameters, especially about stroke volume (SV) and cardiac output (CO) behaviors during sustained hypoxia in humans. Accurate measurement of SV (and CO) is difficult noninvasively, during sustained hypoxic exposure. In order to compare the effect of sustained mild hypoxia (SpO2 = 80%) on ventilatory vs. circulatory responses, healthy young humans were exposed to sustained hypoxia (end-tidal Po2 = 55∼60 mmHg) for 20 min, applying a newly developed apparatus for measuring CO (pulse dye densitometry).

Effect of Unilateral Pulmonary Vagotomy on Respiratory Control in Man

We studied the breathing pattern and pulmonary function at rest, and ventilatory responses to progressive hypoxia and hypercapnia in 7 awake patients who had undergone esophageal-carcinoma resection with sectioning of the right pulmonary vagal branch by lymphadenectomy. Twelve control patients, who had received the same surgery without vagotomy, were also studied by the same protocol. Two months after the operation, both patient groups demonstrated substantial depressions in FVC and FEV1.0, and slight augmentations in breathing frequency, minute ventilation, and occlusion pressure at 0.2s (P0.2) at rest. In the vagotomized group, the occlusion pressure responses to hypercapnia (delta P0.2/delta PaCO2) and hypoxia (delta P0.2/delta SaO2) in terms of response curve slope increased from 1.3 +/- 1.2 to 1.9 +/- 1.1 cm H2O/Torr and from 0.29 +/- 0.19 to 0.88 +/- 0.53 cm H2O/% (p less than 0.05), respectively. Contrary to the vagotomized patients, the nonvagotomized control group exhibited no significant changes in ventilatory chemosensitivities. Furthermore, when comparing the control and vagotomized groups, postoperative ventilatory chemosensitivity responses in terms of both hypercapnic and hypoxic occlusion pressure responses were significantly higher in the latter. We suggest that (1) due to the development of the substantial mechanical limitation in pulmonary functions, the Hering-Breuer inflation reflex became activated after surgery, and (2) a diminished Hering-Breuer reflex effect to inhibit the respiratory centers by unilateral vagotomy may have resulted in augmented ventilatory chemosensitivities.

Augmented ventilatory response to sustained normocapnic hypoxia following 100% O2 breathing in humans.

The presence of hyperoxic hyperventilation seems to have been well confirmed in humans by Becker et al (1995) when the PETco2 is maintained at a normocapnic level. They also observed that augmented ventilation at higher than the control level still continued even 15 min after termination of hyperoxia, suggesting that a humoral agent might be involved to stimulate ventilation.

Effect of Progressive Hypoxia with Moderate Hypercapnia on Ventilatory vs. Respiratory Sensation Responses in Humans

Ventilatory response to CO2 combined with hypoxic stimulation has been well documented as exhibiting a positive interaction between the two stimuli in humans1, and in cats2,3. Furthermore, Mohan and Duffin4 examined the effect of hypoxia on ventilatory response to CO2 using a modified Read’s rebreathing method, covering wide range of CO2 including hypocapnic region following prior hyperventilation.

Different profile in ventilatory vs. respiratory sensation responses to CO2 with varying Po2.

Recently, we1 reported that the slope of the respiratory sensation response curve to CO2 assessed by visual analog scale (VAS), exhibited a parallel leftward shift when combined with hypoxic stimulation. However, further analysis additionally elucidated the presence of significant upward shift of this VAS response curve in the same experimental condition. On the other hand, the CO2-ventilation response curve increased its slope with increasing hypoxic stimulation, and the extrapolated response lines converged at the horizontal axis known as the so-called Oxford fan2. These contrasting change between ventilatory vs. VAS response curves led us to certain speculations and assumptions about the different control mechanisms and anatomical regions possibly responsible for our experimental findings.

Possible presence of hypoxic ventilatory depression while breathing ambient air at sea level in humans

Abstract The ventilatory response to progressive isocapnic hypoxia (HVR) was examined in 14 healthy subjects, following 10 min hyperoxic or control normoxic exposure (defined +O 2 and −O 2 runs, respectively). During HVR test, it was tried to keep end-tidal P CO 2 constant at the level of room air breathing in both +O 2 (39.1±4.2 mmHg) and −O 2 (39.2±4.8 mmHg) runs. Six of the 14 subjects had a consistent and definitely higher slope of HVR (VE/Sa O 2 ) in +O 2 runs than −O 2 runs (−0.45±0.07 vs. −0.19±0.04 l/min per %Sa O 2 , P 2 exposure and were defined the negative responders. It was also noted that the slope of HVR in the positive responders while breathing ambient air (0.19±0.04 l/min per %Sa O 2 ) was significantly lower than the negative responders (0.36±0.07 l/min per %Sa O 2 ) ( P

Effect of Prior O2 Breathing on Hypoxic Hypercapnic Ventilatory Responses in Humans

In the previous communication(11), we reported that prior O2 breathing lasted for 10 min effectively augmented the subsequent ventilatory level in isocapnic sustained hypoxia. In addition, we found that involvement of a humoral agent, excitatory amino acid glutamate, may be responsible for inducing this phenomenon.

Altitude Acclimatization and Hypoxic Ventilatory Depression: Lowlanders and Highlanders

It has been well established that altitude acclimatization not only induces augmented ventilatory response to hypoxia3 but also deteriorative effect on ventilation1. The latter is well known as hypoxic ventilatory depression (HVD) for patients with chronic mountain sickness2, 4. As is presented in our other report in this proceedings8, in early acclimatizing period we should take such HVD into account for comprehending serial change of ventilatory response. HVD in humans has been observed and studied by many scientists. In addition to biphasic ventilatory response to sustained mild hypoxia5, paradoxical hyperpnea in response to oxygen administration in patients with chronic mountain sickness is also another important topics in current studies7, 10. If a subject developed hyperpnea by oxygen breathing, it can be considered to be relieved from hypoxic ventilatory depression.