Giles F. Filley

Hypoxic ventilatory drive in normal man

A technique is described which permits the inscription of the ventilatory response to isocapnic hypoxia in man as a continuous curve relating alveolar oxygen tension and minute ventilation. The adjustment of ventilation to changes in alveolar oxygen tension is complete in 18-23 sec and this is sufficiently rapid to justify the use of a non-steady-state method. Changes in alveolar carbon dioxide tension are prevented by addition of carbon dioxide to the inspired gas. The resulting [unk]V(E)-P(Ao2) curves are hyperbolic such that falling P(Ao2) produces only slight rises in [unk]V(E) until a critical P(Ao2) range of 50-60 mm Hg is reached. With further fall in P(Ao2), [unk]V(E) increases steeply and the slope of the curve approaches infinity at a tension of 30-40 mm Hg. For purposes of quantitation these curves are approximated by a simple hyperbolic function, the parameters of which are evaluated by a least squares fit of the data. The parameter A denotes curve shape such that the higher the value of A. the greater the increase in ventilation for a given decrease in P(Ao2) and hence the greater the hypoxic drive. Curves are highly reproducible for each subject and curves from different subjects are similar. In 10 normal subjects at resting P(ACo2), A = 180.2 +/-14.5 (SEM). When P(ACo2) is adjusted to levels 5 mm Hg above and below control in six subjects A = 453.4 +/-103 and 30.2 +/-6.8 respectively. These latter values differed significantly from control (P < 0.05). These changes in curve shape provide a clear graphic description of interaction between hypercapnic and hypoxic ventilatory stimuli. At normal P(ACo2) the [unk]V(E)-P(Ao2) curve has an inflection zone located over the same P(o2) range as the inflection in the oxygen-hemoglobin dissociation curve. This indicated that ventilation might be a linear function of arterial oxygen saturation or content. Studies in four subjects have demonstrated that ventilation is indeed related to arterial oxygen content in a linear fashion. These data suggest, but do not prove, that oxygen tension in chemoreceptor tissue as in part determined by circulatory oxygen delivery may be an important factor in controlling the ventilatory response to hypoxia.

Chronic obstructive bronchopulmonary disease: II. Oxygen transport in two clinical types

Abstract Two contrasting types of patients with chronic airway obstruction were distinguished by purely clinical criteria: the emphysematous type (herein referred to as PP patients) and the bronchial type (BB patients). In the autopsy cases there was somewhat more extensive emphysematous destruction of the lungs and much less evidence of active bronchial mucous gland hyperplasia in the former type than in the latter. These two types of patients were studied physiologically and were found to have equivalent degrees of ventilatory impairment. However, PP patients had larger lungs, more uniform distribution of inert gas (helium) and hyperventilated both at rest and during exercise. BB patients had higher carbon dioxide tensions and much lower arterial oxygen saturations than did PP patients. The severe hypoxemia in BB patients was not caused by alveolar hypoventilation per se nor could it be satisfactorily explained by calculations of gas and blood flow distribution in the lungs. The most consistent measured difference relevant to pulmonary oxygen transport in the two types was in pulmonary blood flow: PP patients had subnormal and BB patients normal cardiac outputs both at rest and during exercise. The higher ratio of total ventilation to total blood flow in PP patients probably accounted for the nearly normal arterial oxygenation. The hypoxemia in BB patients is considered to be a form of diffusion impairment resulting from too rapid flow of red blood cells through hypoventilated alveoli. The most consistent measured difference relevant to tissue oxygenation in the two types was in the systemic oxygen transport (product of total blood flow and arterial blood oxygen content). Because of their low cardiac outputs, PP patients, although their arterial blood had a higher oxygen pressure, delivered less oxygen to their tissues than BB patients, who maintained a normal cardiac output despite a greater degree of pulmonary hypertension. These findings may account for the cachexia of the former and the cor pulmonale of the latter patients.

Acquired attenuation of chemoreceptor function in chronically hypoxic man at high altitude

To determine whether chronic exposure to hypoxia during adulthood produces alterations in the control of ventilation, measurements of the resting ventilatory response to hypoxia and hypercapnia, as well as ventilatory response to hypoxia during exercise, were carried out in a group of 10 long-term (3-39 yr) non-native residents of Leadville, Colo. (elevation 3100 m). A group of 8 subjects native to Leadville was also studied and 10 low altitude subjects of Denver, Colo. (elevation 1600 m) served as controls. Hypoxic ventilatory drive was measured as the shape parameter A of isocapnic VE-PA(o2) curves. In the non-native high altitude resident this parameter averaged 43% of the value for low altitude controls (P<0.05) denoting a diminished ventilatory response to hypoxia. The degree of attenuation was related to the length of time spent at high altitude. In the high altitude natives the parameter A averaged 9.6% of control (P<0.01). Similarly hypercapnic ventilatory drive as measured by the slope of the isoxic VE-PA(co2) lines was reduced in the non-native residents to 65% of control (P<0.05) and in the natives averaged 54% of control (P<0.01). In contrast with these findings at rest induction of hypoxia during exercise produced an increase in ventilation comparable to that in the controls in both groups of highlanders. Hence chronic exposure to hypoxia during adulthood in man results in marked attenuation of the ventilatory response to hypoxia at rest and this is a function of the length of exposure to hypoxia. This attenuation of the ventilatory response to hypoxia was associated with a decrease in hypercapnic ventilatory drive. The fact that hypoxic ventilatory drive was almost completely absent while hypercapnic drive was only partially reduced parallels closely the more important role of the peripheral chemoreceptors in mediating ventilatory responses to hypoxia than to hypercapnia. This suggests that the alterations in ventilatory control at altitude are due to failure of peripheral chemoreceptor function.

Pulmonary fibrosis and respiratory function

Abstract From a priori considerations we have made an attempt to predict the manner in which pulmonary fibrosis might alter respiratory function. Confirmation of these predictions has been sought in a study of the alterations of respiratory function that are discoverable in diseased individuals who exemplify the various patterns of fibrosis. Although most of the predictions were confirmed, no specific pattern of fibrosis was found to be invariably associated with a specific alteration of respiratory function.