Decreased lung capillary blood volume post-exercise is compensated by increased membrane diffusing capacity.

The diffusing capacity of the lung for carbon monoxide (DLCO) decreases to below the pre-exercise value in the hours following a bout of intense exercise. Two mechanisms have been proposed: (1) development of pulmonary oedema and (2) redistribution of central blood volume to peripheral muscles causing a reduction in pulmonary capillary blood volume ( V(c)). In the present study DLCO, V(c) and the membrane diffusing capacity ( D(m)) were measured in nine healthy females using a rebreathing method, in contrast to the single breath technique employed in previous studies. DLCO, V(c) and D(m) were measured before and at 1, 2, 3, 16 and 24 h following maximal treadmill exercise. Compared with pre-exercise values, DLCO was depressed by up to 8.9 (3.0)% ( P<0.05) for the first 3 h following exercise, but had returned to pre-exercise values by 16 h post-exercise. V(c) fell by 21.2 (4.1)% ( P<0.05) at 3 h post-exercise, but at the same time D(m) increased by 14.7 (9.1)%. It was concluded that: (1) the increase in D(m) made it unlikely that the fall in DLCO was due to interstitial oedema and injury to the blood gas barrier; (2) on the other hand, the reduction in DLCO following exercise was consistent with a redistribution of blood away from the lungs; and (3) the trend for D(m) and V(c) to reciprocate one another indicates a situation in which a fall in V(c) nevertheless promotes gas transfer at the respiratory membrane. It is suggested that this effect is brought about by the reorientation of red blood cells within the pulmonary capillaries following exercise.

Behavioral thermoregulation in obese and lean Zucker rats in a thermal gradient.

Genetically obese Zucker (Z) rats have been reported to display a body core temperature (Tb) that is consistently below that of their lean littermates. We asked the question whether the lower Tb was a result of deficits in thermoregulation or a downward resetting of the set point for Tb. For a period of 45 consecutive hours, lean and obese Z rats were free to move within a thermal gradient with an ambient temperature (T(a)) range of 15-35 degrees C, while subjected to a 12:12-h light-dark cycle. Tb was measured using a miniature radio transmitter implanted within the peritoneal cavity. Oxygen consumption (VO2) was measured using an open flow technique. Movements and most frequently occupied position in the gradient (preferred T(a)) were recorded using a series of infrared phototransmitters. Obese Z rats were compared with lean Z rats matched for either age (A) or body mass (M). Our results show that obese Z rats have a lower Tb [37.1 +/- 0.1 degrees C (SD) vs. 37.3 +/- 0.1 degrees C, P < 0.001] and a lower VO2 (25.3 +/- 1.9 ml x kg(-1) x h(-1)) than lean controls [33.1 +/- 3.7 (A) and 33.9 +/- 3.9 (M) ml x kg(-1) x h(-1), P < 0.001]. Also, the obese Z rats consistently chose to occupy a cooler T(a) [20.9 +/- 0.6 degrees C vs. 22.7 +/- 0.6 degrees C (A) and 22.5 +/- 0.7 degrees C (M), P < 0.001] in the thermal gradient. This suggests a lower set point for Tb in the obese Z rat, as they refused the option to select a warmer T(a) that might allow them to counteract any thermoregulatory deficiency that could lead to a low Tb. Although all rats followed a definite circadian rhythm for both Tb and VO2, there was no discernible circadian pattern for preferred T(a) in either obese or lean rats. Obese Z rats tended to show a far less definite light-dark activity cycle compared with lean rats.

Effect of changing body temperature on the ventilatory and metabolic responses of lean and obese Zucker rats.

We measured body temperature (Tb) and ventilatory and metabolic variables in lean (n = 8) and obese (n = 8) Zucker rats. Measurements were made while rats breathed air, 4% CO2, and 10% O2. Under control conditions, Tb in obese rats was always less than that of their lean counterparts. Obese rats adopted a more rapid, shallow breathing pattern than lean rats in air and had a lower ventilation rate in 4% CO2. Respiration in 10% O2 was similar for the two groups. Metabolic variables did not differ between lean and obese rats whatever the gas breathed. When lean rats were cooled to match Tb in control obese rats with an implanted abdominal heat exchanger, they increased ventilation and metabolism in air; there was no effect of cooling on responses to 4% CO2; and ventilation increased while metabolism decreased in 10% O2. When obese rats were warmed to match Tb in control lean rats, trends in ventilation and metabolism resulted in a tendency toward hyperventilation in air and 4% CO2, but not in 10% O2. Taken overall, matching Tb in lean and obese rats accentuated differences in respiratory and metabolic variables between the two groups. We conclude that differences in respiration between lean and obese Zucker rats are not due to the difference in Tb.

Ventilatory response to asphyxia in conscious rats: effect of ambient and body temperatures.

In many mammals the ventilatory response to hypoxia depends on ambient temperature (Ta), largely because of the hypometabolic effects of hypoxia below thermoneutrality. We questioned whether the ventilatory response to asphyxia also depends upon Ta, and the role played by metabolism and body temperature (Tb). Oxygen consumption (VO2) and pulmonary ventilation (VE) were measured in conscious rats at Ta = 27 degrees C (warm) and 11 degrees C (cold), breathing air or two levels of asphyxic gases, moderate (10% O2-4% CO2), or severe (10% O2-8% CO2), for approximately 30 min each. In the cold, the pattern of the VE response to moderate asphyxia was qualitatively similar to that seen in hypoxia alone, i.e the attained VE/VO2 was similar in warm and cold conditions, with, in the latter, a major drop in VO2 and little or no hyperpnea. During severe asphyxia, however, the VE/VO2 attained in the cold was less than in the warm, and it was accompanied by a large drop in Tb (approximately 6 degrees C). Blood gases confirmed the lower asphyxic hyperventilation in the cold. By maintaining Tb at 38 degrees C with an implanted abdominal heat exchanger, the VE/VO2 levels attained during asphyxia were the same between cold and warm conditions. We conclude that (a) the VE response to asphyxia is Ta-dependent, largely because of the hypometabolic effect of the hypoxic component in the cold, (b) during moderate asphyxia the hypercapnic component is qualitatively unimportant, and (c) with severe asphyxia the hypercapnia becomes an important contributor to the Ta-sensitivity by aggravating the decrease in Tb in the cold and lowering VE sensitivity.

Ventilatory and metabolic responses to cold and hypoxia in conscious rats with discrete hypothalamic lesions.

We tested the hypothesis that hypothalamic nuclei involved in thermoregulatory control could represent a site of integration of the metabolic and ventilatory response to cold and hypoxia. Electrolytic lesions were performed bilaterally under stereotaxic guide, either within the anterior or posterior hypothalamic areas of adult rats. One week later, oxygen consumption (VO2) and ventilation (VE) were measured in the conscious animals during warm (27 degrees C) or cold (12 degrees C) conditions, in normoxia (21% O2) or hypoxia (10% O2), and compared to measurements obtained in control rats, which were either intact or sham-operated. VO2, VE, and body temperature did not differ between lesioned and control rats during warm normoxia. In cold and hypoxia, singly or combined, VE/VO2 was higher in the lesioned rats, because of higher VE. The differences in the cold were mostly confined to rats with anterior lesions, whereas differences in hypoxia were mostly in rats with posterior lesions. We conclude that the integrity of the anterior and posterior hypothalamic areas is important for the proper coupling of metabolism and ventilation during cold or hypoxic stimuli.

Influence of body temperature on responses to hypoxia and hypercapnia: implications for SIDS.

1. This paper reviews current knowledge regarding interactions between body temperature and the respiratory responses to hypoxia and/or hypercapnia, with special emphasis on how these interactions might predispose towards sudden infant death syndrome (SIDS). 2. Use has been made of an adult rat model in which body core temperature is fixed by means of an intra-abdominal heat exchanger. Initial studies indicated that hyperthermia (Tb approximately 41 degrees C) enhanced the ventilatory response to hypercapnia, whereas hypothermia (Tb approximately 35 degrees C) interacted with hypoxia to depress respiration. 3. Studies involving hypothalamic lesions in urethane-anaesthetized rats have implicated the posterior hypothalamic area in the hypoxia/hypothermia interaction. Further studies are directed towards examining the role played by more caudal areas, including the raphe nuclei. 4. It has been shown that not only does the hypoxia/hypothermia interaction depress breathing but it also reduces, or sometimes eliminates, the ventilatory response to hypercapnia, which under normal circumstances provides one of the most powerful excitatory inputs to the respiratory centres. This implies that an expected reversal of the respiratory depression by build up of CO2 levels may not occur, which in turn has important implications for SIDS. 5. The literature dealing with the effects of hyperthermia on hypoxic and hypercapnic responses is also reviewed. It is concluded that environmental heat stress may only become a significant problem when it accompanies a febrile infection, under which circumstances it may seriously compromise thermoregulatory ability and alter breathing responses to chemical stimuli.

Ventilatory and metabolic responses to hypoxia during moderate hypothermia in anesthetized rats.

In resting euthermic mammals, hypoxia elicits a hyperventilation that results from a combination of hyperpnea and hypometabolism. Often accompanying the hypoxia-induced hypometabolism is a drop in body temperature. To separate the synergic effects of hypothermia per se from the direct effects of hypoxia on metabolic rate, ventilation (VE), and O2 consumption (VO2) were measured in anesthetized rats fitted with abdominal heat exchangers and maintained at either normothermic (37.5 degrees C) or hypothermic (35 degrees C) body temperatures while exposed to either normoxia or hypoxia (7% O2). Hypothermia induced parallel decreases in VE and VO2, thereby maintaining VE/VO2. Hypoxia resulted in a hyperventilation achieved with the same relative decrease in VO2 and increase in VE in both normothermic and hypothermic rats. The results suggest that 1) the changes in metabolic rate and VE during hypothermia reflect a direct effect of cold and, 2) because of similar levels of hypoxic hyperventilation in the hypothermic and normothermic rats, relative to metabolic rate, respiratory gain has not been depressed in hypothermic rats.

Dual effect of aminophylline on the ventilatory response to hypoxia in the rat.

Male Hooded Wistar rats were exposed to three five-minute periods of hypoxia in which they breathed a gas mixture comprising 7% O2 and 93% N2. Before the second and third hypoxic exposures rats were injected (i.m.) with aminophylline (an adenosine antagonist) at a dose of 15 mg.kg-1. In control animals, hypoxia caused an increase in ventilation which was greater during the first than during the fifth minute of hypoxia. Each injection of aminophylline significantly increased ventilation in air-breathing rats. However, the first dose of the drug did not significantly alter the hypoxic ventilatory response. The second dose of aminophylline had two effects on ventilation during hypoxia. It reduced the ventilatory response during the first minute of hypoxia, and also prevented the fall in ventilation between the first and fifth minute of exposure. Ethylenediamine injections had no effect on ventilation or the responses to hypoxia. The results suggest that adenosine has a dual role in respiratory control during hypoxia, one excitatory and the other inhibitory. Although previous studies have already identified such roles for adenosine, the present study may represent the first time in which these have been demonstrated in a single animal model.

Respiratory responses to combined hypoxia and hypothermia in rats after posterior hypothalamic lesions.

Urethane-anaesthetised rats were exposed to hypoxia (7% O2 in N2) for 5 min periods while body core temperature (Tbc) was maintained within the normal range (37-38 degrees C) using an abdominal heat exchanger. Animals were exposed to hypoxia and after placement of electrolytic lesions in either the anterior (n = 6) or posterior hypothalamus (n = 6). Neither lesion altered respiration while rats breathed air at either Tbc. At normal Tbc, rats responded to hypoxia with increased ventilation throughout the exposure period. This response was unchanged by lesions in either location. At reduced Tbc rats responded to hypoxia with an initial increase in ventilation followed by depression to below air-breathing levels. This depressive response was unchanged after anterior hypothalamic lesions but eliminated after posterior hypothalamic lesions. It is concluded that neurons either originating in the posterior hypothalamus, or passing through it, play a role in the interaction between cold and hypoxia which leads to inhibition of respiration.

Phrenicotomy in the rat: acute changes in blood gases, pH and body temperature.

Adult male rats were used to compare blood gases, pH and body temperature (Tb) before and after acute bilateral phrenicotomy. Under anaesthesia a femoral artery was catheterised and ties were placed round the phrenic nerves of seven rats (PNX group), while in five rats the ties were placed in the vicinity of the phrenic nerves (SHAM group). Twenty-four hours after surgery arterial blood samples were collected during quiet wakefulness (QW) and grooming (G), before and 1 h after the ties were pulled, and analysed for PO2, PCO2 and pH. No changes were detected in the SHAM samples taken before and after the ties were pulled. In the PNX group a significant decrease in Tb occurred (QW, 0.6 degrees C; G, 1.5 degrees C). Following PNX PaO2 decreased by 11.2 mmHg (QW) and 10.0 mmHg (G); PaCO2 increased by 2.6 mmHg (QW) and 2.4 mmHg (G) and pH fell by 0.04 (QW) and 0.03 (G). All changes except in PaCO2 (QW) were significant. It is concluded that the changes in Tb, blood gases and pH which follow phrenicotomy in the rat are due to an increase in dead space ventilation (VD) and a small reduction in alveolar ventilation (VA) associated with a faster, shallower pattern of breathing.

Body temperature effects on hypoxic and hypercapnic responses in awake rats.

During surgery under pentobarbital sodium anesthesia, 20 rats had heat exchange devices implanted into their abdominal cavity. After recovery, 14 rats underwent two sets of trials, one in which body core temperature (Tbc) was lowered to 34.5-35.5 degrees C and another in which Tbc was raised to 40.5-41.5 degrees C. Rats breathed air and hypoxic (15, 11, and 7% O2 in N2) and hypercapnic (2, 4, and 6% CO2 in air) gas mixtures. Respiratory responses were measured using a barometric method and compared with data from the same rats breathing the gas mixtures at normal Tbc (37.5-38.5 degrees C) before surgery. The six remaining rats served as controls (Tbc unchanged). Lowering Tbc increased respiration in air, whereas heating had no effect. Hypothermia and severe hypoxia combined to inhibit respiration when compared with breathing air at lowered Tbc or low O2 at normal Tbc. The CO2 response slope became steeper when Tbc was raised, suggesting an increased CO2 sensitivity. Possible sites for the hypothermia-hypoxia interaction and the hyperthermia-hypercapnia interaction are discussed.

Alteration in breathing of the awake rat after laryngeal and diaphragmatic muscle paralysis.

The respiratory rate (f), tidal volume (VT) and ventilation (V) were measured in 3 groups of rats: 10 rats before and after cutting both recurrent laryngeal nerves (RLNX), 10 rats before and after bilateral phrenicotomy (PNX) and 5 sham transected (SHAMX) rats. All rats were exposed to air and gas mixtures, deficient in O2 and/or enriched with CO2. The barometric method was used to measure ventilatory parameters. The sham operation did not affect breathing pattern or ventilation. In RLNX rats, breathing the various gas mixtures exhibited no changes in V because f uniformly increased as VT declined. Therefore, loss of the neural control of the respiratory functions of the larynx in awake rats exposed to selected gas mixtures has no untoward effects on alveolar ventilation. Changes in ventilation of PNX rats, compared with SHAMX rats, depends on the gas composition breathed. With increasing severity of hypoxia and/or hypercapnia, PNX rats show a marked reduction in alveolar ventilation over that of the SHAMX rats. Thus, when the diaphragm is no longer able to participate in ventilatory responses, gas exchange is likely to become deficient.

A vagally mediated response to metabolic acidosis in anesthetized rabbits.

Pentobarbital sodium-anesthetized rabbits received 10-min infusions of acetic, lactic, or propionic acid delivered via a catheter to the right atrium at a rate of 1 mmol/min (n = 14). Arterial [H+] increased by 35.8 +/- 7.6 (SD) nmol/l, a decrease in pH of 0.27 +/- 0.04. By the end of the infusion period respiratory frequency (f), tidal volume (VT), and minute ventilation (V) had increased by 15.5 +/- 6.2 breaths/min, 7.3 +/- 2.7 ml, and 0.86 +/- 0.34 l/min, respectively. Arterial PCO2 (PaCO2) increased initially, but isocapnia was established during the latter half of the infusion (delta PaCO2 = 0.4 +/- 2.0 Torr). Bilateral cervical vagotomy eliminated the f response to acid infusions (n = 9, delta f = 0.6 +/- 2.4 breaths/min). The increase in VT (12.6 +/- 3.1 ml) was greater, but that in V (0.39 +/- 0.11 l/min) was less than in intact animals (P less than 0.05). PaCO2 remained elevated throughout the infusion (delta PaCO2 = 5.5 +/- 2.6 Torr), resulting in a greater rise in arterial [H+] (delta[H+]a = 53.6 +/- 6.6 nmol/l, delta pHa = -0.37 +/- 0.04). It is concluded that vagal afferents play a role in the f response to acute metabolic acidosis in rabbits.

Changes in ventilation, breathing pattern and acid-base balance of conscious rabbits following intravenous almitrine.

Five conscious rabbits each received a single injection of almitrine bismesylate via a marginal ear vein. Measurements were made of ventilation and breathing pattern using a barometric method, and blood gases, pH and lactate concentration ([Lac]) were measured from arterial blood samples throughout the hour following the injection. Almitrine caused an immediate increase in ventilation through an increase in tidal volume (VT), frequency (f) showing a small decline. After 15 min f increased to above control level and VT declined. Slower, deeper breathing was reinstated by 40 min post-injection. Large changes in blood gases occurred in the first 15 min, with PO2 raised by 30 Torr and PCO2 lowered by 20 Torr. These recovered to be within 10 and 7.5 Torr of control at the end of 1 h. [Lac] increased steeply at first, then declined towards control levels. The acid-base situation was mixed, comprising a respiratory alkalosis, resulting from CO2 washout, and a metabolic acidosis from high [Lac]. These results are discussed in the context of assessing the primary and secondary effects of almitrine and recognition of the possibility that the drug may act at more than one site to alter respiration.

Ventilation and acid-base balance in awake dogs exposed to heat and CO2.

Some awake quiet dogs pant at cool ambient temperature (Ta) and some do not pant even when acutely exposed to heat. The purpose of the study was to determine whether this puzzling variability in respiratory behavior diminished during prolonged heat. The contributions of thermal and CO2 drives to respiratory adaptations were also examined. Five awake dogs acclimated to 20 degrees C were studied before and 2 and 48 h following exposure to 30-31 degrees C. Rectal temperature did not change; the important thermal stimulus, even at 48 h, appeared to be the increase in peripheral temperature. Variability between nonpanting and panting persisted over 48 h. On the average, ventilation (VE) doubled during heat, largely due to increased dead space ventilation. Nonpanting dogs at cool Ta decreased the threshold of the ventilatory response to CO2. A panting dog at cool Ta changed its slope of the ventilatory response from negative to positive. During hypercapnia in acute heat, ventilatory pattern changed so that frequency increased and tidal volume decreased for a given VE. By 48 h of heat, the ventilatory response to CO2 returned to control in only two dogs, but the ventilatory pattern during hypercapnia returned to control in four dogs. Since thermal stimuli remained unchanged at 48 h, adaptations of respiratory control may have been related to progressive adjustments of strong ions and acid-base balance.

Effects of decortication and carotid sinus nerve section on ventilation of the rat.

The effect on ventilation of exposure to hypoxic, hypercapnic and hypoxic/hypercapnic gas mixtures was studied before and after functional decortication of intact rats and rats in which the carotid chemoreceptors had been disconnected. Unanaesthetized rats responded to both hypoxia and hypercapnia with an increase in minute ventilation (V) through increases in both frequency (f) and tidal volume (VT). Decortication led to a greater V response to CO2. This was through an effect on f, rather than VT. Carotid sinus nerve section (CSNS) caused a lessening in the V response to gas mixtures, f and VT being equally affected. Decortication, following CSNS, increased the V response but this time through increased VT rather than f. This effect on VT was not specific to any particular gas mixture. It is concluded that the carotid body chemoreceptors, together with the bulbopontine rate controller, influence the response to CO2. It is further suggested that this integration takes place in the reticular formation and is normally under some degree of inhibition from the cerebral cortex.

Effect of a constant arterial CO2 tension on respiratory pattern in hear-stressed sheep.

Sheep were exposed in a climate chamber to a hot humid environment under two conditions: breathing atmospheric air and breathing air enriched with CO2. Measurements were made of rectal temperature (Tre), respiratory frequency (fR), mean arterial pressure (BP), heart rate (fH), and arterial O2 tension (PO2), CO2 tension (PCO2), and pH; depth of breathing was also estimated. Tre increased at a similar rate under both conditions. When breathing air, sheep exhibited rapid shallow panting followed by slower deeper (second phase) breathing during which they became severely hypocapnic and alkalotic. When the sheep breathed CO2-enriched air at a rate allowing normocapnia to be maintained, fR was lower and the depth of breathing greater, but the sequence of changes in respiratory activity was similar to that with air breathing. BP, fH, and PO2 each increased to a similar extent under both conditions. It is concluded that the normal biphasic panting response to severe heat stress in sheep is largely independent of arterial PCO2.

The respiratory frequency response to carbon dioxide inhalation in conscious rabbits.

1. The respiratory responses to CO(2) inhalation were measured in New Zealand White rabbits. Prior to testing, the rabbits either received drinking water ad libitum (C), or were subjected to 72 hr water deprivation (WD). The rabbits were tested in a climatic chamber at either 20 degrees C, (C20, WD20) or 30 degrees C (C30, WD30).2. CO(2) exposure caused increases in both tidal volume (V(T)) and minute volume (V(E)). The direction and magnitude of changes in respiratory frequency (f), however, were dependent upon treatment.3. Linear regressions were drawn for f vs.% CO(2) in inhaled gas. Treatment C20 showed zero slope, treatment C30 a large negative slope, and treatments WD20 and WD30 a significant positive slope.4. The slopes of the regression lines obtained from plotting f vs.% CO(2) were plotted against their intercepts for each rabbit under each treatment condition. This yielded a highly significant linear regression from which it could be concluded that the frequency response to CO(2) exposure is dependent upon the initial frequency when the rabbits are breathing air.5. It is suggested that frequency is shifted during hypercapnia towards an optimal value which is dependent upon the existing% CO(2) in the inspired gas.6. Comparison of the results obtained for the rabbit with results reported for the conscious dog and sheep suggest that a similar relationship may hold for these species.

Responses of conscious rabbits to CO2 at ambient temperatures of 5, 20, and 35 degrees C.

Conscious rabbits were exposed to atmospheric air or to 6% CO2 in air at ambient temperatures (Ta) of 5, 20 and 35 degrees C. Measurements were made of rectal temperature (Tre), metabolic rate (MR), respiratory frequency (f), tidal volume (VT), and minute volume (VE). CO2 exposure did not affect Tre at any Ta and only affected MR at 35 degrees C when it caused an increase. At each Ta hypercapnia caused an increase in VT and a decrease in f. At 5 degrees C VE was increased by CO2, at 35 degrees C VE decreased, and at 20 degrees C the results were variable. The data were examined in the light of theories relating to the relative contributions of inputs from brain stem and from pulmonary stretch receptors, in response to body temperature and CO2 partial pressure. It was concluded that hypercapnia stimulates an increase in VT via the brain stem, whereas at the same time removing a hypocapnic drive which, along with central thermal inputs, stimulates f.

Blood gas changes during panting in a small East African antelope, the dik-dik.

Five adult male dik-dik (Madoqua kirkii) were exposed in a climatic chamber to an air temperature of 45 degrees C. Measurements were made of rectal temperature (Tre) and respiratory frequency (f) and arterial blood samples taken before and during heat exposure were analyzed for pH, PCO2 and PO2. During exposure, Tre and f increased in all animals. In the first 80 min dik-dik displayed thermal tachypnea and minor changes in blood gases. Continued exposure lead to hyperpnea accompanied by a fall in PaCO2 and a rise in pH. PaCO2 at first fell and then increased toward or above control levels. The dik-dik did not display second phase breathing. This observation confirms that second phase breathing is not essential to the development of respiratory alkalosis. The main conclusion of the study is that the dik-dik, unlike another heat-adapted antelope, the wildebeest (Taylor, Robertshaw, and Hoffmann. Am. J. Physiol. 217:907-910, 1969), is unable to resist alkalosis during heat stress.