S.M. Tenney

Control of breathing in experimental anemia

Abstract Pulmonary ventilation was measured by a plethysmographic technique in unanesthetized, unrestrained rats and cats before and several days after they were made anemic or underwent a sham procedure. Animals were tested while breathing air, pure O 2 , 10% O 2 in N 2 , 7% CO 2 in air, and a mixture of 11% O 2 and 6% CO 2 in N 2 . Baseline observations showed that ventilation on pure O 2 was no different from that on air, whereas hypoxia, hypercapnia and asphyxia evoked brisk ventilatory responses in all animals. Anemia did not influence ventilation during exposure to air or any of the other gas mixtures. Resting O 2 consumption was also found to be unaltered by anemia, as was the pH of arterial blood, evaluated by an in vitro equilibration method. Although the anemic state is associated with several processes that might be expected to affect the chemical control of breathing, the results of these experiments in resting, unanesthetized animals were all negative.

Oxygen transport during progressive hypoxia in high-altitude and sea-level waterfowl☆

Under conditions of progressive hypoxia, oxygen transport was compared in bar-headed geese (Anser indicus), a species which breeds on the Tibetan Plateau and migrates at altitudes up to 9200 m, and Pekin ducks (Anas platyrhynchos, forma domestica), a similarly sized, sea-level water fowl that does not fly. Pekin ducks showed no altitude-induced behavioral effects (e.g., restlessness) up to 7620 m, while bar-headed geese tolerated 10,668 m with no observable behavioral changes. Ventilatory and cardiac responses to hypoxia as functions of PaO2 followed a typical hyperbolic contour, but the response began at almost 20 Torr lower in the bar-headed goose. Both ventilation and cardiac output appeared to follow a common response curve for the two species, when the independent variable was expressed as arterial oxygen content. The goose had a high oxygen affinity hemoglobin, compared with the duck; the oxyhemoglobin curves of both shifted slightly to the right as a result of acclimation to 5640 m; but only the duck developed erythrocytosis as a consequence of acclimation. Under sea level conditions the duck maintained a higher mixed venous PO2, but with acute hypoxic exposures PVO2 was higher in the goose. Following acclimation, cardiac output in the duck was lower than in pre-acclimatized state, but in the goose it was higher up to the altitude at which it migrates. The selective pressures leading to the evolution of favorable oxygen transport in the bar-headed goose are discussed.

A theoretical analysis of the relationship between venous blood and mean tissue oxygen pressures

Abstract Starting with the Krogh-Erlang equation, and the assumptions necessary for that simple model, an equation for mean tissue oxygen pressure is derived and solved for a number of plausible conditions in order to examine the degree to which venous blood P O 2 approximates the calculated mean tissue value. For normal resting conditions there is a remarkably close agreement between the two values, but there are significant deviations when capillary density, metabolic rate, hemoglobin concentration and cardiac output are altered. The purpose of the analysis is not to defend quantitatively the Krogh tissue model, which is admittedly crude, nor to propose that the mean tissue P O 2 has any unique physiological significance, but to make a first approximation of tissue oxygenation, and to define the usefulness of venous blood as an index of mean tissue P O 2 applicable to the Krogh model. Insights are provided concerning optimal modes of response to hypoxic stress and the. problems of tissue oxygenation in physiological and patho-physiological states.

Ventilatory response of decorticate and decerebrate cats to hypoxia and CO2.

The steady state ventilatory response of normal, fully awake cats was studied under graded hypoxia (at PAO2 = 110, 55, 45 torr) with PACO2 controlled throughout at the resting, normoxic level and at +5 torr. Subsequently, either a mid-collicular decerebration or a decortication was performed, and the ventilatory studies were repeated. Respiratory frequency, tidal volume, and ventilation in the decerebrate state responded to hypoxia and hypercapnia in a manner indistinguishable from the control. The decorticate cats, however, exhibited an exaggerated response to hypoxia, principally the result of increased frequency. The negative hypoxic, hypercapnic interaction, characteristic of awake cats, was demonstrable in both the decerebrate and decorticate animals. The findings are interpreted as revealing coupled descending influences on the medullary respiratory centers in hypoxia--one that is facilitatory and originates in the diencephalon, and the other, inhibitory, from the cerebrum. The significance of this suprapontine system in normal hypoxic ventilatory control is discussed.

Quantitative morphology of cold-blooded lungs: Amphibia and reptilia

Abstract A morphometric study of the lungs of seven species of Amphibia and fifteen species of Reptilia, selected to provide a wide range of body size and a variety of habitats and habits, was undertaken to discover general rules of pulmonary design. The allometric law, X = aBWb for several quantified characteristics of the lung, X, led to the following values for the allometric exponent, b. Amphibia: lung weight, b = 1; lung volume, b = 1.05; total respiratory surface area, b = 0.98; “alveolar” diameter, b = 0.2. Reptilia: lung weight, b = 1.0; lung volume, b = 0.75; pulmonary surface area, b = 0.75; “alveolar” diameter, for weights up to 1 kg, b = 0.2, for weights greater than 1 kg, b = 0. The morphometric characteristics have been compared with mammals, and the principal distinction is the prominent influence of environmental factors on the cold-blooded animals.

Hypoxia-induced tachypnea in carotid-deafferented cats

Ventilation while breathing air and in response to hypoxia was studied in unanesthetized cats after carotid body chemo-defferentation. Hypoxic exposure (FIO2 equal to 0.07-0.12) of chemo-deafferented animals rapidly produced a high frequency, low tidal volume tachypnea. Tachypneic breathing, although usually associated with an increased expired ventilation, was accompanied by an increase in PACO2. In contrast to intact cats, behavioral arousal during hypoxic exposure was not observed after chemo-deafferentation. The response to milder hypoxia (FIO2 equal to 0.14-0.16) occurred with an increased latency, and there resulted a less marked depression of tidal volume and stimulation of respiratory frequency. Elevation of PACO2 to 5 mm Hg above the resting value, by addition of CO2 to the inspired gas, prevented the appearance of tachypnea upon subsequent reduction of FIO2 from 0.21 to 0.07. Depletion of central catecholamine stores, by administration of reserpine, did not prevent the tachypneic response to hypoxia. Following administration of anesthesia (pentobarbital, 30 mg/kg, IP), hypoxic exposure (FIO2 equal to 0.10) led to depression of both respiratory frequency and tidal volume, resulting in apnea within 1.5 minutes. It is concluded that hypoxia (FLO2 equal to 0.07-0.16) acts, in a concentration-related manner, as a powerful stimulant to central respiratory frequency generation and as a depressant of the tidal volume in the unanesthetized cat.

Hyperoxic hyperventilation in carotid-deafferented cats.

Ventilation when breathing air and during exposure to hyperoxia (PAO2 equal to 400-450 mm Hg) was studied in unanesthetized cats before and after carotid sinus nerve section (chemo-deafferentation). Chemo-deafferentation resulted in lowered values of measured ventilation, tidal volume, and respiratory frequency, during air breathing PACO2 increased by an average of 7.9 mm Hg. In intact animals, ventilation after 10 minutes of exposure to hyperoxia was similar in magnitude and pattern to that measured during air breathing. Exposure of chemo-deafferented animals to hyperoxia resulted in an increased ventilation, due entirely to augmented tidal volume. Increased ventilation was accompanied by a decrease in PACO2. This response to hyperoxia developed gradually duringa 3-4-minute period, the rise in ventilation and fall in PACO2 invariably stabilizing by 5 minutes. It is concluded that carotid body chemoreceptor activity is essential for the maintenance of normal values of ventilation and PACO2 in unanesthetized cats. In addition, central mechanisms responsible for tidal volume production may, in the absence of carotid body afferent input, be depressed by the PO2 characteristic of normal arterial blood. The significance of these findings to the chemical control of breathing is discussed.

Properties of mitochondria from hearts of cattle acclimatized to high altitude.

Abstract Hearts of domestic cattle from two groups, one born and raised at sea level and the other born and raised at an altitude of 4250 m, were studied to determine whether any mitochondrial adaptations to high altitude could be demonstrated. Direct counts of mitochondrial number revealed a 40 % increase in the high altitude hearts, but mitochondrial size was the same as at sea level. Measurements of enzyme content indicated an individual mitochondrial increase in electron transport system; and oxygen uptake and cytochrome a oxidase, per mitochondrion, were increased in the same proportion. These changes are discussed as an intracellular mechanism which would serve to preserve oxidative metabolism in hypoxia, particularly under exercising conditions. The effective conservation of oxygen pressure head by this means is probably less than one mm Hg.

Comparative mechanics of mammalian respiratory system

Compliances (C) of lung, thorax and respiratory system as well as resistances (R) of the respiratory system (lower airways + lung + chest wall) and of upper airway (primarily laryngeal and nasal) were measured in 5 species of mammals, spanning a 1000-fold range of body weights (mouse to dog), immediately following sacrifice with an overdose of sodium pentobarbital. The results indicate that compliance is proportional to BW1.0, while respiratory resistance and upper airway resistance have exponents of -0.819 and -0.702, respectively. The reciprocal of the time constant, tau -1 = (RC)-1 is proportional to BW-0.298 for respiratory resistance alone and BW-0.326 when upper airway resistance is included. Since breathing frequency varies as BW-0.28, these results indicate a proportional relationship between breathing frequency and passive emptying time. This suggests that passive respiratory mechanics play a major role in determining TE and therefore TTOT for animals during quiet breathing. Changes in volume history were found not to affect the slope of the relationships between compliance and body weight.

The perception of some sensations associated with breathing

The ability to estimate several sensations associated with breathing was studied in man by comparing physical stimulus intensity with the subjects judgment of magnitude. The data were expressed by the psychophysical power law, Ψ = Kφn, in which Ψ is apparent, or psychological magnitude, and φ is physical or real stimulus intensity. K and n are constants. The group mean value of n for pressure stimuli was about 1.5; for volume, about 1.3; and for ventilation, about 1.9. Refinements in experimental design to separate “active” (i.e., subject generated stimulus by his own motor function) as compared with “passive” (observer generated stimulus) did not reveal significant differences in manner of assessment of pressure or volume (criterion was value of n), nor were pressure assessments of either kind affected by lung volume. The origin of the sensations probably resides in the chest wall.