Ventilatory response of the diamondback water snake,Natrix rhombifera to hypoxia, hypercapnia and increased oxygen demand

Summary Simultaneous measurements of ventilatory frequency, tidal volume, O₂ uptake, CO₂ output and cardiac frequency were made in the diamondback water snake,Natrix rhombifera while breathing hypoxic (15% to 5% O₂ in N₂) or hypercarbic (2% to 10% CO₂ and 21% O₂ in N₂) gases. The snakes responded to hypoxia by increasing tidal volume and decreasing ventilatory frequency resulting in little change in ventilation (50% increase at 5% inspired O₂), or O₂ uptake and only a light increase in CO₂ output. Hypercarbia to 4.2% inspired CO₂ resulted in a slight hyperventilation but ventilation was depressed at 6.3% inspired CO₂ and became erratic at higher concentrations. The resting rate of O₂ uptake was maintained throughout hypercapnia. Heart rate increased during hypoxia and decreased during hypercapnia. Cutaneous O₂ uptake increased during extreme hypoxia (5% inspired O₂) and cutaneous CO₂ output increased during hypercapnia, probably due to changes in the body-to-ambient gas gradients (Crawford and Schultetus, 1970). Both pulmonary oxygen uptake and ventilation were dramatically increased immediately following 10–15 min experimental dives. The increased ventilation was achieved primarily through an increased tidal volume.     

Separate and combined effects of temperature and hypoxia on breathing pattern in the domestic fowl

Summary Minute ventilation (V _E), tidal volume (V _T), respiratory frequency (f) and clavicular air sac gas composition were measured in conscious domestic fowl breathing air and hypoxic gas mixtures at neutral (18±1°C) and raised (33±1°C) air temperatures. Increases inV _E caused by inhalation of 10%, 8% or 6.5% O₂ in N₂, respectively, were independent of temperature although at each level the absoluteV _E was ca. 21·min⁻¹ greater in the panting birds. Changes in respiratory pattern during hypoxia were markedly dependent on temperature. At 18°C almost all of the increasedV _E resulted from increasedf. At 33°C hypoxia led to a strong suppression off and increase inV _T. It is concluded that hyperthermia and hypoxia are additive and non-interactive in their effects on ventilatory drive, in agreement with previously reported effects of hypercapnia and physical exercise on breathing in panting fowl.     

Responses to heat stress in two species of Australian quail,Coturnix pectoralis andCoturnix chinensis

Summary Stubble quail and King quail are both native to Australia although Stubble quail extend into more arid environments than do King quail. In this study, the responses of body temperature (T _b), heart rate (f _h), respiration rate (f _r) and rates of gular flutter (f _g) were measured in response to ambient temperatures (T _a) ranging from 20 °C to 50 °C. Both species exhibited hyperthermia atT _a in excess of 38–39 °C although both species maintainedT _b lower thanT _a atT _a above 42 °C. Respiration rate remained relatively constant until the onset of panting, just prior to the commencement of gular flutter. The onset of panting and gular flutter in both species was relatively sudden and occurred at a meanT _a of 38.1 °C for Stubble quail (meanT _b of 42.5 °C) and a significantly higherT _a of 40.9 °C but similar meanT _b of 42.1 °C for King quail. Gular flutter appeared to occur synchronously with respiration and showed some tendency to increase withT _b. The percentage of time spent in gular flutter showed a direct increase withT _b. Heart rate tended to decrease with increasingT _a in King quail while remaining relatively constant in Stubble quail. However, the relationship was not consistent and a great deal of variability existed between individuals. The two species are similar in their responses to heat stress and in general these responses do not reflect their different natural habitats.Symbols f _h heart rate - f _r respiratory rate - f _g rate of gular fluttering     

Breathing, locomotion and everything in-between. Proceedings of a symposium held at the 2nd International Congress of Respiratory Science. Bad Honnef, Germany. August 9-13, 2009

In the chick embryo at day 3, gas exchange occurs by diffusion and oxygen consumption (V?_O2) does not depend on the cardiovascular convection of O₂. Whether or not this is the case in hypoxia is not known and represents the aim of the study. The heart of chicken embryos at 72 h (stage HH18) was filmed through a window of the eggshell by a camera attached to a microscope. Stroke volume was estimated from the changes in heart silhouette between systole and diastole. V?_O2was measured by a closed system methodology. In normoxia, a decrease in temperature (T) from 39 to 31 °C had parallel depressant effects on V?_O2and HR. At 39 °C, a progressive decrease in O₂ lowered V?_O2; HR was maintained until the O₂ threshold of ～ 15%. In severe hypoxia (4% O₂) V?_O2and HR were, respectively, ～ 12% and ～ 62% of normoxia. At 32 °C the hypoxic threshold for HR was significantly lower. During constant hypoxia (7% O₂) V?_O2did not respond to T, while the HR response was preserved. Stroke volume changed little with changes in T or O₂, except at 6 and 4% O₂, when it decreased by ～ 20 and 30%. In embryos growth-retarded because of incubation in chronic hypoxia, V?_O2and HR responses to T and hypoxia were similar to those of normal embryos. We conclude that in the early embryo during hypoxia cardiovascular O₂ convection is not responsible for the drop in V?_O2. The generalised hypometabolic response, in combination with the extremely small cardiac V?_O2, probably explains the minor effects of hypoxia on cardiac activity.     

Dietary fatty acid composition influences tissue lipid profiles and regulation of body temperature in Japanese quail

Many avian species reduce their body temperature (T _b) to conserve energy during periods of inactivity, and we recently characterized how ambient temperature (T _a) and nutritional stress interact with one another to influence physiologically controlled hypothermic responses in Japanese quail (Coturnix japonica). In the present study, we examined how the fatty acid (FA) composition of the diet influences the FA composition of phospholipids in major organs and how these affect controlled hypothermic responses and metabolic rates in fasted birds. For 5 weeks prior to fasting, quail were fed a standard diet and gavaged each morning with 0.7 ml of water (control), or a vegetable oil comprising saturated fatty acids (SFA; coconut oil), or unsaturated fatty acids (UFA; canola oil). Birds were then fasted for 4 days at a T _a of 15°C. We found that, while fasting, both photophase and scotophase T _b decreased significantly more in the SFA treatment group than in the control group; apparently the former down-regulated their T _b set point. This deeper hypothermic response was correlated with changes in the phospholipid composition of the skeletal muscle and liver, which contained significantly more oleic acid (18:1) and less arachidonic acid (20:4), respectively. Our data imply that these two FAs may be associated with thermoregulation.     

Functional acclimation of Japanese quail to simulated high-altitude

Summary Japanese quail,Coturnix coturnix japonica, which were acclimated to a simulated altitude of 6100 m for six weeks were compared with control quail maintained at sea level. Body weight initially decreased in both groups, and by the end of six weeks the altitude quail weighed an average of 8% less than the control quail (Fig. 1). Compared with the controls, the altitude birds exhibited mean increases in hematocrit ratio and blood hemoglobin concentration of 31 and 37% respectively (Fig. 2). Blood volume was 36% higher in the altitude acclimated quail, while plasma volume was unchanged (Fig. 3). Exposure to chronic hypoxia resulted in hypertrophy of the right ventricle, while left ventricular mass was unchanged (Fig. 4). Rates of O₂ consumption (VO₂) at 5°C were continuously recorded as ambient PO₂ was slowly reduced from 155 to 30 torr. VO₂ was significantly higher at any given PO₂ in the altitude quail (Fig. 5). Exposure to reduced PO₂ resulted in a significantly greater decrease in body temperature in the control quail than in the altitude acclimated birds (Fig. 6).     

Decreases in Amino Acid and Acetylcholine Metabolism During Hypoxia

Abstract: Hypoxia impairs brain function by incompletely defined mechanisms. Mild hypoxia, which impairs memory and judgment, decreases acetylcholine (ACh) synthesis, but not the levels of ATP or the adenylate energy charge. However, the effects of mild hypoxia on the synthesis of the glucosederived amino acids [alanine, aspartate, γ-amino butyric acid (GABA), glutamate, glutamine, and serine] have not been characterized. Thus, we examined the incorporation of [U-¹⁴C]glucose into these amino acids and ACh during anemic hypoxia (injection of NaNO₂), hypoxic hypoxia (15 or 10% O₂), and hypoxic hypoxia plus hypercarbia (15 or 10% O₂ with 5% CO₂). In general, the synthesis of the amino acids and of ACh declined in parallel with each type of hypoxia we studied. For example, anemic hypoxia (75 mg/kg of NaNO₂) decreased the incorporation of [U-¹⁴C]glucose into the amino acids and into ACh similarly. [Percent inhibition: ACh (57.4), alanine (34.4), aspartate (49.2), GABA (61.9). glutamine (59.2), glutamate (51.0), and serine (36.7)]. A comparison of several levels (37.5, 75, 150, 225 mg/kg of NaNO₂) of anemic hypoxia showed a parallel decrease in the flux of glucose into ACh and into the amino acids whose synthesis depends on mitochondrial oxidation: GABA (r= 0.98), glutamate (r= 0.99), aspartate (r= 0.96), and glutamine (r= 0.97). The synthesis of the amino acids not dependent on mitochondrial oxidation did not correlate as well with changes in ACh metabolism: serine (r= 0.68) and alanine (r= 0.76). The decreases in glucose incorporation into ACh and into the amino acids with hypoxic hypoxia (15% or 10% O₂) or hypoxic hypoxia with 5% CO₂ were very similar to those with the two lowest levels of anemic hypoxia. Thus, any explanation of the brain's sensitivity to a decrease in oxygen availability must include the alterations in the metabolism of the amino acid neurotransmitters as well as ACh.     

Biochemical and morphological effects of hypoxic environment on human embryonic stem cells in long-term culture and differentiating embryoid bodies

The mammalian reproductive tract is known to contain 1.5–5.3% oxygen (O₂), but human embryonic stem cells (hESCs) derived from preimplantation embryos are typically cultured under 21% O₂ tension. The aim of this study was to investigate the effects of O₂ tension on the long-term culture of hESCs and on cell-fate determination during early differentiation. hESCs and embryoid bodies (EBs) were grown under different O₂ tensions (3, 12, and 21% O₂). The expression of markers associated with pluripotency, embryonic germ layers, and hypoxia was analyzed using RTPCR, immunostaining, and Western blotting. Proliferation, apoptosis, and chromosomal aberrations were examined using BrdU incorporation, caspase-3 immunostaining, and karyotype analysis, respectively. Structural and morphological changes of EBs under different O₂ tensions were comparatively examined using azan- and hematoxylineosin staining, and scanning and transmission electron microscopy. Mild hypoxia (12% O₂) increased the number of cells expressing Oct4/Nanog and reduced BrdU incorporation and aneuploidy. The percentage of cells positive for active caspase-3, which was high during normoxia (21% O₂), gradually decreased when hESCs were continuously cultured under mild hypoxia. EBs subjected to hypoxia (3% O₂) exhibited well-differentiated microvilli on their surface, secreted high levels of collagen, and showed enhanced differentiation into primitive endoderm. These changes were associated with increased expression of Foxa2, Sox17, AFP, and GATA4 on the EB periphery. Our data suggest that mild hypoxia facilitates the slow mitotic division of hESCs in long-term culture and reduces the frequency of chromosomal abnormalities and apoptosis. In addition, hypoxia promotes the differentiation of EBs into extraembryonic endoderm.     

Effects of oxygen fraction in inspired air on force production and electromyogram activity during ergometer rowing

Six male rowers rowed maximally for 2500 m in ergometer tests during normoxia (fractional concentration of oxygen in inspired air, F _IO₂ 0.209), in hyperoxia (F _IO₂ 0.622) and in hypoxia (F _IO₂ 0.158) in a randomized single-blind fashion. Oxygen consumption (V˙O₂), force production of strokes as well as integrated electromyographs (iEMG) and mean power frequency (MPF) from seven muscles were measured in 500-m intervals. The iEMG signals from individual muscles were summed to represent overall electrical activity of these muscles (sum-iEMG). Maximal force of a stroke (F _max) decreased from the 100% pre-exercise maximal value to 67 (SD 12)%, 63 (SD 15)% and 76 (SD 13)% (P<0.05 to normoxia, ANOVA) and impulse to 78 (SD 4)%, 75 (SD 14)% and 84 (SD 7)% (P<0.05) in normoxia, hypoxia and hyperoxia, respectively. A strong correlation between F _max and V˙O₂ was found in normoxia but not in hypoxia and hyperoxia. The mean sum-iEMG tended to be lower (P<0.05) in hypoxia than in normoxia but hyperoxia had no significant effect on it. In general, F _IO₂ did not affect MPF of individual muscles. In conclusion, it was found that force output during ergometer rowing was impaired during hypoxia and improved during hyperoxia when compared with normoxia. Moreover, the changes in force output were only partly accompanied by changes in muscle electrical activity as sum-iEMG was affected by hypoxic but not by hyperoxic gas. The lack of a significant correlation between F _max and V˙O₂ during hypoxia and hyperoxia may suggest a partial uncoupling of these processes and the existence of other limiting factors in addition to V˙O₂. Accepted: 2 June 1997     

Opioidergic Modulation of Ventilatory Response to Sustained Hypoxia in Obese Zucker Rats

Objective: To determine whether altered central and/or peripheral opioidergic mechanisms contribute to the altered ventilatory response to sustained hypoxia in obese Zucker rats. Research Methods and Procedures: Eight lean (176 ± 8 [SEM] g) and eight obese (225 ± 12 g) Zucker rats were studied at 6 weeks of age. Pulmonary ventilation (V?_E), tidal volume (V_T), and breathing frequency (f) at rest and in response to sustained (30 minutes) hypoxic (10% O₂) challenges were measured on three separate occasions by the barometric method after the randomized, blinded administration of equal volumes of saline (control), naloxone methiodide (N_M; 5 mg/kg, peripheral opioid antagonist), or naloxone hydrochloride (N_HCl; 5 mg/kg, peripheral and central opioid antagonist). Results: Administration of N_M and N_HCl in lean animals had no effect on V?_E either at rest or during 30 minutes of sustained exposure to hypoxia. Similarly, N_M failed to alter V?_E in obese rats. In contrast, N_HCl significantly (p < 0.05) increased V?_E and V_T both at rest and during 2 to 10 minutes of hypoxic exposure in obese rats. After 20 to 30 minutes of hypoxic exposure, V_T remained elevated with N_HCl, but the earlier elevation of V?_E seemed to be attenuated due to a decrease in f at 20 minutes of exposure to hypoxia. Discussion: Thus, endogenous opioids modulate both resting V?_E and the ventilatory response to sustained hypoxia in obese, but not in lean, Zucker rats by acting specifically on opioid receptors located within the central nervous system.     

Body temperature regulation during acclimation to cold and hypoxia in rats

Extreme environmental conditions present challenges for thermoregulation in homoeothermic organisms such as mammals. Such challenges are exacerbated when two stressors are experienced simultaneously and each stimulus evokes opposing physiological responses. This is the case of cold, which induces an increase in thermogenesis, and hypoxia, which suppresses metabolism conserving oxygen and preventing hypoxaemia. As an initial approach to understanding the thermoregulatory responses to cold and hypoxia in a small mammal, we explored the effects of acclimation to these two stressors on the body temperature (T_b) and the daily and ultradian T_b variations of Sprague-Dawley rats. As T_b is influenced by sleep-wake cycles, these T_b variations reflect underlying adjustments in set-point and thermosensitivity. The T_b of rats decreased precipitously during initial hypoxic exposure which was more pronounced in cold (T_b=33.4±0.13) than in room temperature (T_b=35.74±0.17) conditions. This decline was followed by an increase in T_b stabilising at a new level ~0.5 °C and ~1.4 °C below normoxic values at room and cold temperatures, respectively. Daily T_b variations were blunted during hypoxia with a greater effect in the cold. Ultradian T_b variations exhibited daily rhythmicity that disappeared under hypoxia, independent of ambient temperature. The adjustments in T_b during hypoxia and/or cold are in agreement with the hypothesis that an initial decrease in the T_b set-point is followed by its partial re-establishment with chronic hypoxia. This rebound of the T_b set-point might reflect cellular adjustments that would allow animals to better deal with low oxygen conditions, diminishing the drive for a lower T_b set-point. Cold and hypoxia are characteristic of high altitude environments. Understanding how mammals cope with changes in oxygen and temperature will shed light into their ability to colonize new environments along altitudinal clines and increase our understanding of how T_b is regulated under stimuli that impose contrasting physiological constraints.     

Cardiac responses to stress and activity in the armoured legless lizard Ophisaurus apodus: Comparison with snake and tortoise

• 1.1. Heart rate (HR) was measured during and after stress and activity in the armoured legless lizard Ophisaurus apodus, the snake Natrix natrix and the tortoise Testudo hermanni, at different body temperatures T_b. These are discussed in relation to field T_b, defensive behaviour and published V́O₂.
• 2.2. Ophisaurus apodus used passive defence, including hemipenis or cloacal sac eversion and prolonged immobility after release. This was correlated with a low degree of tachycardia, bradycardia at low T_b, low metabolism and armour.
• 3.3. Defence behaviour was T_b-dependent in wild T. hermanni, with passive withdrawal into the shell at low T_b, and active struggling at high T_b. The degree of tachycardia was lower at low T_b.
• 4.4. Standard and active oxygen pulse OP were insensitive to T_b in O. apodus and N. natrix, and their SOP was lower than tetrapod lizards. Factorial scope of HR was reduced at 35°C, just above the activity T_b range of these species.
• 5.5. Recovery of HR after activity in T. hermanni was much more rapid than in the squamates, and of similar duration to recovery after stress. It is suggested that tortoises do not utilize anaerobic metabolism during activity.

     

The effects of intermittent exposure to hypoxia during endurance exercise training on the ventilatory responses to hypoxia and hypercapnia in humans

The present study was performed to investigate the effects of a combination of intermittent exposure to hypoxia during exercise training for short periods on ventilatory responses to hypoxia and hypercapnia (HVR and HCVR respectively) in humans. In a hypobaric chamber at a simulated altitude of 4,500 m (barometric pressure 432 mmHg), seven subjects (training group) performed exercise training for 6 consecutive days (30 min · day⁻¹), while six subjects (control group) were inactive during the same period. The HVR, HCVR and maximal oxygen uptake (V˙O_{2 max}) for each subject were measured at sea level before (pre) and after exposure to intermittent hypoxia. The post exposure test was carried out twice, i.e. on the 1st day and 1 week post exposure. It was found that HVR, as an index of peripheral chemosensitivity to hypoxia, was increased significantly (P < 0.05) in the control group after intermittent exposure to hypoxia. In contrast, there was no significant increase in HVR in the training group after exposure. The HCVR in both groups was not changed by intermittent exposure to hypoxia, while V˙O_{2 max} increased significantly in the training group. These results would suggest that endurance training during intermittent exposure to hypoxia depresses the increment of chemosensitivity to hypoxia, and that intermittent exposure to hypoxia in the presence or absence of exercise training does not induce an increase in the chemosensitivity to hypercapnia in humans. Accepted: 18 March 1998     

Body temperature responses of Great Tits Parus major to handling in the cold

Animals typically respond to stressful stimuli such as handling by increasing core body temperature. However, small birds in cold environments have been found to decrease body temperature (T_b) when handled over longer periods, although there are no data extending beyond the actual handling event in such birds. We therefore measured both the initial T_b decrease during ringing and standardized T_b sampling, and subsequent recovery of T_b after this handling protocol in wild Great Tits Parus major roosting in nestboxes in winter. Birds reduced their T_b by 2.3 °C during c. 4 min of handling. When birds were returned to their nestboxes after handling, T_b decreased by a further 1.9 °C over c. 2 min, reaching a T_b of 34.6 °C before taking 20 min to rewarm to 2.5 °C above their initial T_b. The T_b reduction during handling could be a consequence of increased heat loss rate from disrupted plumage insulation, whereas T_b reduction after handling might reflect reduced heat production. These are important factors to consider when handling small birds in the cold.     

Ventilatory and metabolic responses of a bat,Phyllostomus discolor,to hypoxia and CO2: implications for the allometry of respiratory control

The ventilatory and metabolic responses of lesser spear-nosed bats to hypoxia and hypercapnia were measured to determine whether these corresponded to preliminary allometries and a positive relationship between hypoxic ventilatory threshold andP ₅₀. Ventilatory responses of lesser spear-nosed bats to 3, 5 and 7% CO₂ differed significantly from ventilation on air and each other. The magnitude of their ventilatory response to CO₂ is consistent with the prediction of a smaller ventilatory response to hypercapnia in small compared to large mammals [ ; Williams et al. (1994)]. Among 12, 10 and 8% O₂ treatments only the ventilatory response to 8% O₂ differed significantly from ventilation on air or the other treatments. Metabolic rate was significantly reduced at both 10 and 8% O₂. The hypoxic ventilatory response of these bats does not support the prediction of a greater response in small compared to large mammals [ ; Boggs and Tenney (1984)]. Their metabolic response is consistent with the hypoxic hypometabolism typical of small mammals, though not of comparable magnitude. The response, expressed as percent change in convection requirement ( ), is also less than that observed in other small mammals. This relative insensitivity to hypoxia may be associated with this bat's unusually high affinity hemoglobin (P₅₀=27.5 torr).     

Respiratory and cardiovascular responses to acute hypoxia and hyperoxia in internally pipped chicken embryos

During the first day of hatching, the developing chicken embryo internally pips the air cell and relies on both the lungs and chorioallantoic membrane (CAM) for gas exchange. Our objective in this study was to examine respiratory and cardiovascular responses to acute changes in oxygen at the air cell or the rest of the egg during internal pipping. We measured lung (V·_O2lung) and CAM (V·_O2CAM) oxygen consumption independently before and after 60 min exposure to combinations of hypoxia, hyperoxia, and normoxia to the air cell and the remaining egg. Significant changes in V·_O2total were only observed with combined egg and air cell hypoxia (decreased V·_O2total) or egg hyperoxia and air cell hypoxia (increased V·_O2total). In response to the different O₂ treatments, a change in V·_O2lung was compensated by an inverse change in V·_O2CAM of similar magnitude. To test for the underlying mechanism, we focused on ventilation and cardiovascular responses during hypoxic and hyperoxic air cell exposure. Ventilation frequency and minute ventilation (V_E) were unaffected by changes in air cell O₂, but tidal volume (V_T) increased during hypoxia. Both V_T and V_E decreased significantly in response to decreased P_CO2. The right-to-left shunt of blood away from the lungs increased significantly during hypoxic air cell exposure and decreased significantly during hyperoxic exposure. These results demonstrate the internally pipped embryo's ability to control the site of gas exchange by means of altering blood flow between the lungs and CAM.     

Thermoregulatory changes in the cold induced by physical training in humans

It has previously been demonstrated that metabolic heat production (M˙) during cold exposure at rest was related to maximal oxygen uptake (O_2max). Consequently, an increase in O_2max could allow an increase M˙ in the cold. The aim of the present study was therefore to test this hypothesis. Eight male volunteers undertook interval training (periods of 25% V˙O_2max of 30-s duration and 110% V˙O_2max of 60-s duration until exhaustion, five times a week over 8 weeks) to increase V˙O_2max. Both before and after this physical training, they were subjected to a 10^∘, 5^∘ and 1^∘C 2-h cold air test in a climatic chamber. During the cold exposure, rectal temperature (T _re), tympanic temperature (T _ty), mean skin temperature () and M˙ were measured as well as the time to onset of shivering (t) and body temperatures () at t. The results showed that physical training involved an increase in O_2max (14%–15%, P < 0.05). During the cold exposure, T _re was higher after training both at 10^∘,5^∘ and 1^∘C (P < 0.05) whereas were not significantly changed. However, an increase in the sensitivity of the thermoregulatory system was attested by a decreased t at higher These slight physiological changes found after training were not related to the increases in V˙O_2max. In conclusion, this study demonstrated that interval training induced slight thermoregulatory changes unrelated to changes in V˙O_2max and it suggested that M˙ during cold exposure could be related mainly to the level of V˙O_2max observed before training, since increases in V˙O_2max did not modify M˙. Accepted: 8 April 1998     

Influence of initial respiratory status on the short-and long-term activity of the trout red blood cell β-adrenergic Na+/H+ exchanger

The effects of ambient O₂ partial pressure and CO₂ partial pressure on the intensity of rainbow trout (Oncorhynchus mykiss) red blood cell -adrenergic Na⁺/H⁺ exchange were investigated. This was accomplished in vitro by continuously monitoring whole blood extracellular pH, partial pressures of O₂ and CO₂ and by measuring red blood cell water content and Na⁺ concentration before and 30 min after the addition of a catecholamine mixture (final nominal concentrations: 250 nmol·l^-1 adrenaline and 20 nmol·l^-1 noradrenaline). The experiments were performed under six different initial conditions combining two ambient partial pressures of CO₂ (1.50 and 6.75 torr) and three ambient partial pressures of O₂ (15, 30 and 150 torr). The activation of red blood cell Na⁺/H⁺ exchange (as indicated by marked reductions of whole blood pH) was followed by transient reductions in blood partial pressures of CO₂ and O₂ (2 min) resulting from the shift of the CO₂/HCO₃ ^- equilibrium within the cell and the subsequent binding of O₂ to the haemoglobin. The initial reduction in blood CO₂ partial pressure was followed by a rise reflecting the titration of plasma HCO₃ ^- by extruded H⁺. At low partial pressure of CO₂ (1.50 torr) there was a pronounced stimulatory effect of hypoxia on the initial intensity of the extracellular acidification (5 min), whereas at high CO₂ partial pressure (6.75 torr) hypoxia actually lowered the extent of the initial acidification. In all cases, Na⁺/H⁺ exchange activation was accompanied by increases in cell water content and red blood cell Na⁺ levles when measured 30 min after addition of catecholamines. Both hypercapnia and hypoxia increased the magnitude of these changes although the largest changes in cell water content and Na⁺ levels were observed under hypercapnic conditions. Thus, the long-term activity (as determined by measuring cell water and Na⁺ levels) of the Na⁺/H⁺ exchanger was enhanced both by hypercapnia and hypoxia regardless of the initial CO₂ partial pressure. The initial activity (5 min), on the other hand, although stimulated by hypercapnia was influenced by hypoxia in opposing directions depending upon the initial CO₂ partial pressure of the blood.Abbreviations RBC red blood cell(s) - Hb haemoglobin - pHe extracellular pH - P _bCO₂ blood partial pressure of CO₂ - P _bO₂ blood partial pressure of O₂     

Cecal microbial transplantation attenuates hyperthyroid-induced thermogenesis in Mongolian gerbils

Endothermic mammals have a high energy cost to maintain a stable and high body temperature (T_b, around 37°C). Thyroid hormones are a major regulator for energy metabolism and T_b. The gut microbiota is involved in modulating host energy metabolism. However, whether the interaction between the gut microbiota and thyroid hormones is involved in metabolic and thermal regulations is unclear. We hypothesized that thyroid hormones via an interaction with gut microbiota orchestrate host thermogenesis and T_b. l -thyroxine-induced hyperthyroid Mongolian gerbils (Meriones unguiculatus) increased resting metabolic rate (RMR) and T_b, whereas Methimazole-induced hypothyroid animals decreased RMR. Both hypothyroid and hyperthyroid animals differed significantly in faecal bacterial community. Hyperthyroidism increased the relative abundance of pathogenic bacteria, such as Helicobacter and Rikenella, and decreased abundance of beneficial bacteria Butyricimonas and Parabacteroides, accompanied by reduced total bile acids and short-chain fatty acids. Furthermore, the hyperthyroid gerbils transplanted with the microbiota from control donors increased type 2 deiodinase (DIO2) expression in the liver and showed a greater rate of decline of both serum T3 and T4 levels and, consequently, a more rapid recovery of normal RMR and T_b. These findings indicate that thyroid hormones regulate thermogenesis depending on gut microbiota and colonization with normal microbiota by caecal microbial transplantation attenuates hyperthyroid-induced thermogenesis. This work reveals the functional consequences of the gut microbiota-thyroid axis in controlling host metabolic physiology and T_b in endotherms.