On the merit of making comparisons.
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Animals↗
Biomedical subjects
S M Tenney
Publications and source records attributed to S M Tenney.
One hundred volumes and going strong.
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Animals↗
Water balance and lung fluids in rats at high altitude.
A disturbed water and electrolyte homeostasis is not generally held to be a primary mechanism in the pathogenesis of acute mountain sickness (AMS) and high altitude pulmonary edema (HAPE), but the association of oliguria and weight gain with AMS and HAPE has led to the hypothesis that water retention may be a facilitative mechanism, possibly caused by an effect of hypoxia to release antidiuretic hormone (ADH). To examine the problem, normal Long-Evans rats (N) and the strain with congenital diabetes insipidus (DI) were exposed to hypobaric hypoxia (0.5 atm) for 4 days, and fluid balance in the whole animals and in their lungs was studied. Both strains reduced water intake and were oliguric on acute exposure, but the N rats gained body weight and increased lung water, while the DI rats increased neither body weight nor lung water. Neither strain increased lung blood at high altitude. The oliguria in the DI rats could not have been due to a release of antidiuretic hormone, and was attributed to the diminished water intake in both strains. The protection against HAPE in the DI rats was probably due to their more severe dehydration that exists already in normoxia, and its further increase in hypoxia, compared with N rats.
Altitude Sickness↗
Relationship between blood-oxygen affinity and blood volume.
The hypothesis was tested that total blood volume (TBV) is correlated with hemoglobin oxygen affinity. Intraspecifically Hb-O2 affinity was manipulated in rats using NaOCN. Interspecifically the hypothesis was evaluated using data gathered from the literature. Both intra- and interspecifically TBV increased with increasing hemoglobin oxygen affinity (delta TBV/delta P50 = -1.18). Intraspecifically decreases in P50 were associated with an increase in red blood cell mass and hematocrit. Interspecifically plasma volume had an inverse relationship with Hb-O2 affinity (delta TBV/delta P50 = -1.10) and hematocrit showed no changes. These data suggest that an increased blood volume may be part of the mechanism explaining the inverse correlation between P50 and hypoxic tolerance.
Animals↗
Hyperoxic ventilatory responses of high altitude acclimatized cats.
We have examined the effect of steady-state hyperoxia on the ventilation of sea level (SL) cats and cats acclimatized to simulated high altitude (HA) at 5500 m for three weeks. Three groups of cats were studied. In group I, the ventilatory responses to 10%, 21% and 100% O2 were studied at SL, and after acclimatization to HA, the ventilatory responses to 10% and 100% O2 were measured. In group II the ventilatory responses and femoral artery and superior sagittal sinus blood gases were measured in two sets of cats, one at SL and one at HA, during exposure to the gases outlined in group I. In group III, we examined the effect of chronic vagotomy on the ventilatory responses to the gas mixtures outlined in group I. Breathing 100% O2 at SL had no significant effect on ventilation, tidal volume, respiratory frequency, or cerebral blood flow (inferred from the cerebral veno-arterial CO2 difference). Ventilation was constant in the HA acclimatized cats while breathing 10% and 100% O2, but the ventilatory pattern changed dramatically during hyperoxia: respiratory frequency increased and tidal volume fell. Breathing 100% O2 was associated with changes in CBF, and venous PCO2 that might be expected to stimulate ventilation, but the change in ventilatory pattern suggests to us that hyperoxic disinhibition of central respiratory processes (which were modified by HA acclimatization) is the mechanism whereby ventilation is sustained during hyperoxia at HA. After vagotomy at HA, ventilation remained constant while breathing 100% O2, but the changes in respiratory pattern were no longer apparent. Therefore, vagal afferents seems to have a role in determining the pattern, but not necessarily the absolute level, of ventilation during hyperoxia. Cats vagotomized at SL prior to HA exposure did not show any evidence of HA ventilatory acclimatization; thus, the vagi may also play a heretofore unrecognized role in the process of acclimatization.
Acclimatization↗
Acute and chronic pulmonary pressor responses to hypoxia: the role of blunting in acclimatization.
We studied two strains of Sprague-Dawley rats: the Madison (M) that acclimatizes successfully to high altitude; and the Hilltop (H), that manifests signs of chronic mountain sickness at high altitude and has a high mortality rate. Awake, chronically instrumented animals were tested at sea level, at intervals during 30 days at a simulated altitude of 5500 m, and during 10 to 15 days of recovery at sea level. Mean pulmonary artery pressure (PAP) rose at high altitude to reach 60 mm Hg in H and 40 mm Hg in M, but the acute pressor response to hypoxia at sea level was much more pronounced in M than H. Depression of PAP by normoxic exposures in H rats at high altitude was slightly early in the period of stay but was enhanced with further prolongation of high altitude residence. The M rats, in contrast, had a blunted response (normoxia had very little depressant effect on PAP) after the first 24 h at high altitude, and it remained so for the duration of the stay. On return to sea level the response of H rats remained unchanged for 7 days, but the blunted response of the M rats at high altitude reversed at sea level to become exaggerated. We conclude: that responses of PAP to acute hypoxia do not forecast what the chronic response will be; that the appearance of an unidentified mechanism during chronic hypoxia in the M strain attenuates the vasoreactivity of the pulmonary vessels to hypoxia; and that the absence of such a blunting mechanism in H leads to the higher PAP in this strain and its morbid consequences. The hypothesis is put forward that the existence of such a blunting mechanism is an important factor in the adaptability of species to high altitude.
Adaptation, Physiological↗
The hypoxic ventilatory response of rats with increased blood oxygen affinity.
Experimental work has established an interspecific relationship between the threshold for the hypoxic ventilatory response and the 'knee' of the Hb-O2 dissociation curve. However, whether this relationship exists intraspecifically remains unclear. To examine the problem further rats were treated with sodium cyanate (NaOCN) to lower P50 and their hypoxic ventilatory response was measured. NaOCN treated rats had a lower PaO2 and higher Hct than control rats. There was no difference between the control and lowered P50 condition in the ventilatory response to hypoxia when % delta VI was plotted against PaO2. The results are consistent with PaO2 sensing chemoreceptors.
Animals↗
Effects of hyperoxia on ventilatory and metabolic rates of newborn mice.
Newborn mammals of medium or large sized species have ventilatory rates, expressed per kg body weight, larger than adults of corresponding size, while newborns of the smallest species do not. We hypothesized that the oxygen consumption of the smallest newborns is limited by the supply of oxygen and reasoned that if this were the case, an increase in Po2 of the inspired air should decrease their ventilation/oxygen consumption (VE/Vo2) ratio. We exposed 1-2 days old newborn mice for 5 min to 21% O2 in N2 or 100% O2, then measured their breathing pattern, by flow plethysmography, and Vo2 with an isovolume closed system. During hyperoxia the VE/Vo2 ratio dropped in average 36%, since VE decreased in 14 out of 18 animals and Vo2 increased in all the animals tested. The drop in VE was due to a prolongation of the expiratory time, with no changes in inspiratory time or tidal volume. During expiration, interruptions of the expiratory flow and tendency to maintain the lung inflated, a characteristic of neonatal respiration, were more pronounced with 100% O2 than 21% O2 breathing. We conclude that the resting metabolic rate of newborn mice is limited by the supply of oxygen; when Po2 is raised, metabolism increases and ventilatory rate decreases in favor of a breathing pattern aimed to preserve lung volume elevated.
Airway Resistance↗
A comparative analysis of contractile characteristics of the diaphragm and of respiratory system mechanics.
The mean inspiratory flow rate (VT/TI) is used as an index of central respiratory 'drive', and, at rest, it varies interspecifically in proportion to body weight (BW) raised to the 0.74 power (Boggs and Tenney, 1984). VT/TI is determined by the level of central neural respiratory output, the velocity of contraction of respiratory muscles, and the mechanical characteristics of the respiratory system. We have examined the last two factors in 13 species ranging in weight from 0.025 to 515 kg. We determined the 'effective' inspiratory mechanical characteristics of the respiratory system (time constant, resistance, and compliance) and the time course of diaphragmatic contraction during bilateral supramaximal phrenic nerve stimulation in anesthetized animals. We also measured passive expiratory mechanical variables and made morphometric measurements of the diaphragm. We found that VT/TI during phrenic nerve stimulation was proportional to BW0.82. The 'effective' respiratory time constant (tau'rs) and passive expiratory time constant (tau rs) scaled in proportion to body weight with nearly similar exponents: tau'rs alpha BW0.26 and tau rs alpha BW0.21. In addition, the time constant of diaphragmatic contraction (tau mc) was proportional to BW0.20. Inspiratory time is proportional to tau'rs and tau mc, and tidal volume during stimulation was almost directly proportional to body weight. Thus, interspecific changes in VT/TI during stimulation were related to interspecific changes in the mechanical characteristics of the respiratory system and the velocity of muscular contraction. We conclude that interspecific changes in VT/TI need not reflect interspecific variation in central respiratory drive under resting conditions. We found that diaphragm weight and volume and diaphragm muscle thickness were geometrically similar in all species studied. Inspiratory pressure is an interspecific constant; therefore, by the Law of Laplace, smaller animals must develop greater tension per unit of muscle mass.
Airway Resistance↗
A cautionary note on the interpretation of the power law for respiratory effort.
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Humans↗
Oxygen supply and limiting oxygen pressures in an insect larva.
Larvae of the moth, Carpocapsa saltitans, demonstrate a diurnal activity pattern of rhythmic twitching which, under conditions of controlled light and temperature, is characterized by a predictable frequency and regularity. The twitching activity is shown to be sensitive to the partial pressure of environmental oxygen, and it ceases altogether at a particular PO2 called 'critical'. Use is made of the 'critical' PO2 in normobaric and hypobaric conditions to deduce the roles of diffusion and convection in the larval oxygen transport mechanisms; and also as a value for the total decrement of PO2 from ambient air to mitochondria, in order to evaluate predicted values based on calculations of resistance to oxygen flow. For this latter study 'porosity' of the larva and the seed pod in which it is normally housed was inferred from measured rates of water vapor loss, and oxygen uptake rates of the larvae were measured by the manometric technique of Warburg. Applying these data to a model system the conclusion was reached that almost the total resistance to oxygen flow is at the spiracle.
Animals↗
Responses of blood volume and red cell mass in two strains of rats acclimatized to high altitude.
Two strains of rats, one that adapts successfully to high altitude (HA) (Madison = M) and the other that adapts poorly and suffers a high mortality rate at high altitude (Hilltop = H) were studied during 40 days of exposure to a simulated altitude of 18 000 ft (5450 m; PB = 175). The time rate of change of blood volume (TBV), red cell volume (RBCV), plasma volume (PV) and hematocrit (Hct), and the interrelationships of these variables, particularly emphasizing TBV, PV and Hct as functions of RBCV, were compared in the M and H strains. Sea level control values in the two strains were not different, but by the 5th day at HA RBCV and TBV had expanded to a greater extent in H than M - a difference that was maintained throughout the 40 days - but PV decreased similarly in the two strains. By 30 days the inter-strain differences of RBCV, TBV, and Hct became more pronounced but still no difference of PV was noted. The most significant feature was the greater polycythemic response of H, which at the extreme range was not associated with any further decrease of PV and therefore resulted in rapid expansion of TBV. The probable effects of these responses on cardiovascular function and oxygen transport are discussed, comparing the differences of H and M strains, which became maladaptive in H. The similarity of the responses in H to those of man with chronic mountain sickness is noted.
Adaptation, Physiological↗
Characterization by stimulation of medullary mechanisms underlying gasping neurogenesis.
Our purpose was to evaluate the hypothesis that neurons in the lateral tegmental field of the medulla comprise a pattern generator for neurogenesis of gasping. Stimulations in this area produced changes characteristic of pattern generators in other systems. These included shifts in gasping rhythm and refractory periods for eliciting gasps; the latter varied inversely with spontaneous gasping frequency. These responses were recorded from activities of phrenic and hypoglossal nerves of decerebrate, cerebellectomized, vagotomized, paralyzed, and ventilated cats. Gasping followed freezing the brain stem between pons and medulla. In addition to lateral tegmental loci, gasps were elicited by stimulating areas extending lateral to the nucleus ambiguus and medial to the contralateral medulla. These areas are envisaged to contain axons to or from the pattern generator of lateral tegmental field. Finally, stimulations in sites approximating nucleus tractus solitarius and nucleus ambiguus delayed spontaneous gasps and terminated ongoing gasps. Current required to terminate gasps fell during neural inspiration. Our data are consistent with the lateral tegmental field of medulla comprising a central pattern generator for gasping and pacemaker elements being a component of this pattern generator.
Animals↗
Scaling respiratory pattern and respiratory 'drive'.
We tested three predictions regarding the relationship between body size and respiratory 'drive' and timing in mammals. Mechanical considerations had led to the prediction that TE/TTOT and probably TI/TTOT would be interspecific constants. In eleven species of mammals, ranging in size from 0.033 kg to 520 kg, TE/TTOT during awake quiet breathing was an interspecific constant with a value of 0.65 (+/- 0.004); TI/TTOT was 0.345 (+/- 0.004). Given that VT is directly proportional to BW1.0 (Stahl, 1967), if TE and TI are directly proportional to BW0.28 (Bennett and Tenney, 1982), and if VT/TI is an index of respiratory 'drive', then 'drive' should be directly proportional to BW0.72, following the same proportionality with body size as does basal metabolic rate (VO2). Data for the same eleven species gave the relationship VT/TI BW0.74. Testing further the notion that 'drive', on a weight specific basis, is proportional to BW-0.26, we studied the response, % delta VI, in eleven species to approximately 12% inspired O2. This 'output' of the system in response to a hypoxic stimulus was found to scale with BW-0.27. The question whether this reflects a higher set 'gain' of the respiratory controller of smaller animals and/or some feature of the innervation, or intrinsic properties of the respiratory muscles that varies with body size is discussed.
Animals↗
Effect of perinatal hypercapnia on the adult ventilatory response to carbon dioxide.
Burrowing mammals show a reduced ventilatory response to CO2 and CO2 retention. We examined whether this reduced responsiveness could be due to modification of chemoreceptors by persistent hypercapnia during development. Mice and rats were exposed to 6.0% CO2 throughout gestation and/or weaning and then removed to normocapnic air for a minimum of 6 weeks. Mouse gas pocket O2 and CO2 tensions and hematocrits were analyzed and compared with normocapnically raised controls. The ventilatory and blood gas and pH response to CO2 were compared in chronically cannulated test and control rats. Hematocrits and gas pocket CO2 and O2 tensions of mice and rat ventilatory and arterial blood CO2 and O2 tensions and pH responses were not different in test and control groups. There appears to be little or no developmental affect of CO2 suggesting that the reduced CO2 response seen in burrowers is genetically determined.
Animals↗
Ventilatory responses and blood gases in susceptible and resistant rats to high altitude.
On exposure to a stimulated altitude of 5500 m (18 000 ft), the Hilltop (H) strain of Sprague-Dawley rats develops signs of chronic mountain sickness (CMS) (severe polycythemia, severe pulmonary hypertension and right ventricular hypertrophy) associated with a high mortality rate. In contrast, the Madison (M) strain of Sprague-Dawley rats remains healthy with less severe cardiopulmonary and hematological responses. We tested the hypothesis that hypoventilation in the H rats relative to the M rats, leading to greater alveolar hypoxia or hypoxemia, could account for the different hematological and cardiopulmonary responses between the two strains. Ventilatory responses and blood gases were compared under normoxia and acute and chronic hypoxia in fully awake and unrestrained animals of the two strains. There were no differences in VE, Pao2, PaCO2, pHa, P-vO2, PvCO2 and pH-v under either acute or chronic hypoxia between the two strains of rats. It is concluded that relative hypoventilation does not contribute to altitude susceptibility in H rats.
Acid-Base Equilibrium↗
Role of the carotid bodies in ventilatory acclimation to chronic hypoxia by the awake cat.
Steady-state breathing patterns during air and hypoxia (PIO2 = 84 Torr) were measured in awake cats in the following conditions: (1) during 7 months of exposure to air following carotid body resection (CBR; N = 6); (2) during 7 months of hypobaric hypoxia (PIO2 = 84 Torr; N = 5) following CBR; (3) during 5 months of exposure to hypobaric hypoxia (N = 4) while intact and then following CBR. Also, in groups (1) and (2) the aortic nerves were sectioned (ANX) at the end of the acclimation periods. The results show that the awake cat hypoventilates if the carotid bodies have been removed, and hypoxic sensitivity is reduced during long-term exposures to either hypoxia or normoxia. ANX caused a slight increase in respiratory frequency, indicating a minor role for the aortic bodies. CBR after acclimation to hypoxia resulted in decreased tidal volume but no change in respiratory frequency. The slight ventilatory acclimation to hypoxia in CBR cats was solely due to increased respiratory frequency. The phenomenon of 'hypoxic tachypnea' was modulated by acclimation, indicating that the effect of hypoxic acclimation upon respiratory frequency is due to central mechanisms.
Adaptation, Physiological↗
The contribution of central mechanisms rostral to the pons in high altitude ventilatory acclimatization.
In order to explore the role of suprapontine mechanisms in the ventilatory features of acclimatization to high altitude (HAVA) a study was made of: (a) normal cats after 48 h of exposure to a simulated altitude of 5500 m; (b) those same acclimatized cats 6 h following mid-collicular decerebration; (c) decerebrate cats after 48 h of exposure to a simulated altitude of 5500 m; (d) decerebrate cats after 48 h of exposure to room air at sea level. In a pilot study in which high altitude exposure was maintained for 30 days it was determined that normal cats show all of the manifestations of HAVA after 48 h. These were: increase of VI over acute hypoxic value and a maintained hyperventilation with normoxic inhaled gas; increase of both VT and f, the latter predominantly due to shortened TE; increase of VT/TI. Following decerebration the ventilatory pattern of these cats reverted to the preoperative, acute hypoxic exposure characteristics. Decerebrate cats maintained under normoxic conditions for 48 h showed no changes that were statistically significant, but brief (20 min) hypoxic tests indicated an increase of ventilatory response at the end of the second day. Decerebrate cats maintained for 48 h in the hypoxic environment showed all of the main features of HAVA. We conclude that suprapontine mechanisms in the intact cat exert a facilitatory influence which supports the development of HAVA, but if the structures in which those mechanisms normally reside are chronically removed, a comparable mechanism in the ponto-medullary region is capable of assuming the same function.
Acclimatization↗