We asked whether or not the thermal characteristics of fertile avian eggs changed throughout incu... more We asked whether or not the thermal characteristics of fertile avian eggs changed throughout incubation. The cooling and warming times, expressed by the time constant τ of the egg temperature response to a rapid change in ambient temperature, were measured in fertile chicken eggs at early (E7), intermediate (E11) and late (E20) stages of embryonic development. Same measurements were conducted on eggs emptied of their content and refilled with water by various amounts. The results indicated that (1) the τ of a freshly laid egg was ~50 min; (2) τ decreased linearly with the drop in egg water volume; (3) the dry eggshell had almost no thermal resistance but its wet inner membrane contributed about one-third to the stability of egg temperature; (4) the egg constituents (yolk, albumen and embryonic tissues) and the chorioallantoic circulation had no measurable effect on τ; (5) the presence of an air pocket equivalent in volume to the air cell of fertile eggs reduced τ by about 3 min (E7), 5 min (E11) and 11 min (E20). Hence, in response to warming the egg τ at E20 was slightly shorter than at E7. In response to cooling, the egg τ at E20 was similar to, or longer than, E7 because embryonic thermogenesis (evaluated by measurements of oxygen consumption during cold) offset the reduction in τ introduced by the air cell. In conclusion, until the onset of thermogenesis the thermal behavior of a fertile egg is closely approximated by that of a water-filled egg with an air volume equivalent to the air cell. It is possible to estimate the cooling τ of avian eggs of different species from their weight and incubation time.
Journal of applied physiology (Bethesda, Md. : 1985), 2000
Body temperature (T(b)) of rat pups (7-9 days old) raised under a 12:12-h light-dark (L-D) regime... more Body temperature (T(b)) of rat pups (7-9 days old) raised under a 12:12-h light-dark (L-D) regimen (L: 0700-1900, D: 1900-0700) was consistently higher in D than in L by approximately 1.1 degrees C. We tested the hypothesis that the L-D differences in T(b) were accompanied by differences in the set point of thermoregulation. Measurements were performed on rat pups at 7-9 days after birth. O(2) consumption (VO(2)) and CO(2) production (VCO(2)) were measured with an open-flow method during air breathing, as ambient temperature (T(a)) was decreased from 40 to 15 degrees C at the constant rate of 0.5 degrees C/min. At T(a) >/=33 degrees C, VO(2) was not significantly different between L and D, whereas VCO(2) was higher in L, suggesting a greater ventilation. Over the 33 to 15 degrees C range the VO(2) values in D exceeded those in L by approximately 30%. Specifically, the difference was contributed by differences in thermogenesis at T(a) = 30 to 20 degrees C. As T(a) was decreased, t...
The primary aim of this study was to establish whether or not embryonic hypoxia selectively affec... more The primary aim of this study was to establish whether or not embryonic hypoxia selectively affects the growth of specific organs. Chicken embryos were incubated either in normoxia (Nx) or in hypoxia (15% O 2 from embryonic day E5, Hx). The length of the beak and third toe (as indexes of skeletal growth) and the weights of internal organs (eyes, brain, heart, lungs, liver, kidneys, stomach, and intestines) were collected at E14, E17, E19, and E20. Hypoxia reduced embryonic body weight (BW). At any given age, the specific weight (organ weight/BW) of some organs in Hx was higher, and that of others was lower, than in Nx. However, almost all differences disappeared when organ weights were compared as function of BW, rather than at fixed chronological ages. The important exception was the chorioallantoic membrane (CAM), the mass of which in Hx developed out of proportion. In a third group of embryos, hypoxic until E14 and normoxic thereafter, there was no post-hypoxic catch-up growth, differently from what known to occur postnatally. A possible interpretation is that catch-up growth does not depend on the age of the embryo but on its BW. In conclusion, at least in the chicken embryo and for the level of hypoxia tested, hypoxia has no selective effects on the growth of specific organs, except for the CAM. Qualitative differences in the weight response to hypoxia among organs observed at any given age can be explained largely by the effects of the blunted growth on the growth trajectory of the individual organs.
Canadian Journal of Physiology and Pharmacology, Feb 13, 2011
The barometric method is a common technique for measurements of pulmonary ventilation in unrestra... more The barometric method is a common technique for measurements of pulmonary ventilation in unrestrained animals. It basically consists of recording the changes in chamber pressure generated during breathing. In fact, as the air inspired is warmed and humidified from the ambient to the pulmonary values, the total pressure in the animal chamber increases; the opposite occurs in expiration. The present commentary is an introduction to this method, briefly reviewing its historical development, the conceptual pitfalls, and potential sources of errors during practical applications.
We questioned to what extent changes in temperature could affect the newborn's ventilator... more We questioned to what extent changes in temperature could affect the newborn's ventilatory inhibition provoked by lung inflation, or Hering-Breüer (HB) inflation reflex. Conscious newborn rats (3-4 d old) were studied in a double chamber airflow plethysmograph at ambient temperatures of 32 degrees C (slightly below their thermoneutrality), 24 degrees C (cold), and 36 degrees C (warm). At these ambient temperatures, the corresponding body temperatures averaged 35.4, 31.0, and 37 degrees C. The HB reflex was triggered by negative body surface pressures of 5 or 10 cm H2O, and quantified as the duration of the expiratory time during the maintained inflation, either in absolute values or in relation to the control expiratory time. In cold the HB reflex decreased to 80%, and in warm it increased to 150%, of the values measured at 32 degrees C. Oxygen consumption, measured by an open flow system, averaged 59, 47, and 29 mL x kg(-1) x min(-1) at, respectively, 24, 32, and 36 degrees C. In cold, the ventilatory response to hypoxia (10% O2) was almost absent, that to hypercapnia (5% CO2) was greater, and that to hypoxia and hypercapnia combined was less than in warm. We conclude that in newborn rats the strength of the vagal inhibition on breathing, evaluated in the form of the HB reflex, is sensitive to temperature, becoming stronger as temperature increases. One contributing factor is the temperature-induced change in metabolic rate, whereas the role of temperature-induced changes in ventilatory chemosensitivity is variable. The strong temperature-dependency of the neonatal HB reflex implies that in newborns exposed to a warm environment breathing is more susceptible to inhibitory inputs.
1. Hypoxia is known to decrease thermogenesis. We set out to determine whether this is accompanie... more 1. Hypoxia is known to decrease thermogenesis. We set out to determine whether this is accompanied by alterations in the brown adipose tissue, which is a major source of non-shivering thermogenesis. 2. Measurements were performed on 25- and 64-day-old rats, after 4 days of hypoxia (10% inspired O2), and on approximately 3.5-month-old rats in hypobaric hypoxia since birth, at an ambient temperature of 25 degrees C. 3. All hypoxic rats had higher haematocrit and lower body mass than corresponding controls. 4. In the 25-day-old rats, hypoxia had minimal and non significant effects on brown adipose tissue mass, proteins and DNA concentration. The content of the mitochondrial uncoupling protein thermogenin, evaluated by immunoblot after electrophoretic separation, relative to the cytoskeleton actin (UCP/Act), was not significantly altered. 5. In 25-day-old rats exposed for 4 days to cold (ambient temperature = 7-9 degrees C), brown adipose tissue was hyperplastic, with increased UCP/Act; hypoxia did not appreciably alter the response to cold. 6. In the 2-month-old rats, after 4 days of hypoxia UCP/Act was reduced to about 40% of control. 7. In the 3.5-month-old rats maintained in hypoxia since birth, brown adipose tissue mass was reduced in proportion to body mass, with little effect on total proteins and DNA; UCP/Act was decreased to about 50% of control. 8. We conclude that chronic hypoxia had a minimal effect on brown adipose tissue total proteins and DNA content. However, the uncoupling protein content can be greatly reduced, depending upon age and duration of hypoxia.
Saiki, Chikako, and Jacopo P. Mortola. Effect of 2,4dinitrophenol on the hypometabolic response t... more Saiki, Chikako, and Jacopo P. Mortola. Effect of 2,4dinitrophenol on the hypometabolic response to hypoxia of conscious adult rats. J. Appl. Physiol. 83(2): 537-542, 1997.-During acute hypoxia, a hypometabolic response is commonly observed in many newborn and adult mammalian species. We hypothesized that, if hypoxic hypometabolism were entirely a regulated response with no limitation in O 2 availability, pharmacological uncoupling of the oxidative phosphorylation should raise O 2 consumption (V O 2 ) by similar amounts in hypoxia and normoxia. Metabolic, ventilatory, and cardiovascular measurements were collected from conscious rats in air and in hypoxia, both before and after intravenous injection of the mitochondrial uncoupler 2,4-dinitrophenol (DNP). In hypoxia (10% O 2 breathing, 60% arterial O 2 saturation), V O 2 , as measured by an open-flow technique, was less than in normoxia (,80%). Successive DNP injections (6 mg/kg, 4 times) progressively increased V O 2 in both normoxia and hypoxia by similar amounts. Body temperature slightly increased in normoxia, whereas it did not change in hypoxia. The DNP-stimulated V O 2 during hypoxia could even exceed the control normoxic value. A single DNP injection (17 mg/kg iv) had a similar metabolic effect; it also resulted in hypotension and a drop in systemic vascular resistance. We conclude that pharmacological stimulation of V O 2 counteracts the V O 2 drop determined by hypoxia and stimulates V O 2 not dissimilarly from normoxia. Hypoxic hypometabolism is likely to reflect a regulated process of depression of thermogenesis, with no limitation in cellular O 2 availability. cellular hypoxia; hypoxic ventilatory response; oxidative phosphorylation; oxygen consumption; uncoupling agents
Seifert, Erin L., and Jacopo P. Mortola. Light-dark differences in the effects of ambient tempera... more Seifert, Erin L., and Jacopo P. Mortola. Light-dark differences in the effects of ambient temperature on gaseous metabolism in newborn rats. J Appl Physiol 88: 1853-1858, 2000.-Body temperature (T b ) of rat pups (7-9 days old) raised under a 12:12-h light-dark (L-D) regimen (L: 0700-1900, D: 1900-0700) was consistently higher in D than in L by ϳ1.1°C. We tested the hypothesis that the L-D differences in T b were accompanied by differences in the set point of thermoregulation. Measurements were performed on rat pups at 7-9 days after birth. O 2 consumption (V O 2 ) and CO 2 production (V CO 2 ) were measured with an open-flow method during air breathing, as ambient temperature (T a ) was decreased from 40 to 15°C at the constant rate of 0.5°C/min. At T a Ն33°C, V O 2 was not significantly different between L and D, whereas V CO 2 was higher in L, suggesting a greater ventilation. Over the 33 to 15°C range the V O 2 values in D exceeded those in L by ϳ30%. Specifically, the difference was contributed by differences in thermogenesis at T a ϭ 30 to 20°C. As T a was decreased, the critical temperature at which V O 2 began to rise was lower in L. We conclude that the higher T b of rat pups in D is accompanied by a higher set point for thermoregulation and a greater thermogenesis. These results are consistent with the idea that, in newborns, endogenous changes in the set point of thermoregulation contribute to the circadian oscillations of T b .
We investigated the vocalization and the thermogenic responses to cold during hypoxia in chicken ... more We investigated the vocalization and the thermogenic responses to cold during hypoxia in chicken hatchlings during the first postnatal day. Calls were quantified in number and sound characteristics (amplitude and frequency); the change in oxygen (O 2 ) consumption, measured by an open-flow methodology, represented thermogenesis. The cold challenge consisted of a decrease in ambient temperature (Ta) from ϳ39 to 28°C, in steps of 2°C, or an acute exposure to ϳ28°C, either in normoxia or hypoxia (10% O 2 ). Hypoxia lowered thermogenesis and the critical Ta, suggesting a decrease in the set point for thermoregulation. The vocalization response to cold was rapid; did not progress with the duration or intensity of the cold stimulus; was similar in very young (Ͻ8 hr old) and older (12-24 hr) hatchlings despite their differences in thermogenic capacity; and was essentially unaffected by hypoxia. We conclude that the hatchling's vocalization in the cold follows a stereotyped pattern not related to the thermogenic regulation of body temperature. The dissociation between vocalization and thermogenesis might carry some advantage in conditions of cold and hypoxia.
Mortola, Jacopo P., and Lina Naso. Thermogenesis in newborn rats after prenatal or postnatal hypo... more Mortola, Jacopo P., and Lina Naso. Thermogenesis in newborn rats after prenatal or postnatal hypoxia. J. Appl. Physiol. 85(1): 84-90, 1998.-Oxygen consumption (V O 2 ) was measured in normoxia as ambient temperature (T a ) was lowered from 40 to 15°C, at the rate of 0.5°C/min (thermoneutrality ϳ33°C). In 2-day-old rats born in hypoxia after hypoxic gestation, the T a -V O 2 relationship was as in controls; their interscapular brown adipose tissue (IBAT) was hypoplastic (less proteins and DNA), with lower concentration of the mitochondrial uncoupling protein thermogenin. In 8-day-old rats exposed to hypoxia postnatally (day 2 to day 8), at any T a below thermoneutrality V O 2 was higher than in controls; also, in this group IBAT was hypoplastic with decreased thermogenin. Additional measurements under various experimental conditions indicated that the increased thermogenic capacity was not explained by the smaller body mass and increased blood oxygen content or by the eventuality of intermittent cold stimuli during the chronic hypoxia. On the other hand, chronic hypercapnia (3% CO 2 in normoxia, from day 2 to day 8) also resulted in increased normoxic thermogenesis. We conclude that chronic hypoxia in the perinatal period 1) reduces IBAT mass and thermogenin concentration and 2) can increase the newborn's thermogenic capacity because of stress-related mechanisms not specific to hypoxia. brown adipose tissue; hypercapnia; perinatal hypoxia; uncoupling protein thermogenin; undernourishment 8750-7587/98 $5.00
This communication describes the application of the barometric technique to the measurements of t... more This communication describes the application of the barometric technique to the measurements of the breathing pattern (tidal volume and breathing rate) and pulmonary ventilation (V E ) in chicken embryos and hatchlings. The chamber-plethysmograph was separated into two sections, an animal compartment, maintained at incubation temperature, and a recording compartment kept at a lower temperature. In the case of the embryos, the eggshell itself represented the animal compartment. The hatchlings were accommodated into a "nest" compartment. A flow-through system permitted simultaneous measurements of oxygen consumption (V O 2 ) and carbon dioxide production. Values of breathing rate corresponded to those counted visually in hatchlings while resting in the incubator, and data of restingV E were similar to those obtained by airflow plethysmography, a more invasive technique applicable only to the hatchlings. At rest, the ventilatory equivalent (V E /V O 2 ) of the hatchlings was similar to that reported for adult birds, while in embryos it was much lower. Hypoxia (15 and 10% O 2 ) and hypercapnia (2 and 4% CO 2 ) caused hyperventilation (increase inV E /V O 2 ), both in the hatchlings and in the embryos, these latter using hypometabolism as the main approach to hyperventilate in hypoxia. We conclude that the barometric technique can be adapted to the study of breathing andV E responses in avian embryos and hatchlings.
In mammals, biological time keeping is organised with a hierarchical and pyramidal structure, und... more In mammals, biological time keeping is organised with a hierarchical and pyramidal structure, under the control of the master clock in the suprachiasmatic hypothalamic nuclei (SCN). Body temperature (Tb) and metabolic rate have robust circadian patterns, and probably represent primary variables controlled closely by the SCN. From the data of studies in animals (mostly rats) and humans, it appears that the most common effect of prolonged hypoxia is to decrease, and in some cases to abolish, the amplitudes of the daily oscillations, irrespective of the state of arousal or activity level. On the other hand, the evidence is that hypoxia causes only minimal and transient perturbation of the period of the rhythm. The fact that hypoxia modifies the circadian oscillations of variables as important as body temperature and metabolism leads to the expectation that the daily rhythms of many other functions are perturbed by hypoxia, according to their link to the primary variables. The data currently available, although sparse and fragmentary, support this view. It is speculated that the alterations of the normal circadian oscillations can contribute to many common symptoms during sustained hypoxia, from sleep fragmentation, to malaise and loss of appetite.
We asked whether hypoxia and hypercapnia, singly or combined, affect the lung volume-dependent ve... more We asked whether hypoxia and hypercapnia, singly or combined, affect the lung volume-dependent ventilatory inhibition [Hering-Breuer (HB) reflex] in newborn rats. Conscious rats 2, 5, and 8 days old were breathing in a flow plethysmograph. Mean lung volume was increased by applying a negative body surface pressure of 6 or 12 cmH2O. HB reflex was quantified as the inhibitory ratio (IR) of the apnea during the inflation expiratory time (TEinfl) to the control expiratory time (TEc), i.e., IR = TEinfl/TEc. In normoxia-normocapnia (control), IR with 6 cmH2O was approximately 8-12 at all ages and approximately doubled with inflation at 12 cmH2O. In hypoxia (HPX; 10% O2) or hypercapnia (HPCN; 3% CO2), IR decreased at 8 days, whereas it did not differ from the control value at 2 and 5 days. In HPX + HPCN, IR decreased at all ages. In HPX (at both 6- and 12-cmH2O inflations), in HPCN (6 cmH2O), or in HPX + HPCN (6 and 12 cmH2O), IR decreased significantly more at 8 days than at 2 days. Metabolic rate, simultaneously measured, decreased during HPX or HPX + HPCN by a similar amount at all ages. The ventilatory response to HPX or to HPCN was significantly more pronounced at 8 days than at 2 days. We conclude that, during the early postnatal development of the rat, HPX or HPCN, singly or combined, reduces the HB reflex inhibition in the oldest pups, with minimal or no effects in the youngest. These developmental differences cannot be explained by differences in metabolic drive on ventilation but are contributed to by differences in chemosensitivity.
We measured the metabolic component of heat (Hmet) of avian eggs by thermography.In the first hal... more We measured the metabolic component of heat (Hmet) of avian eggs by thermography.In the first half of incubation Hmet was not significant.Later in incubation Hmet was significant and correlated with the embryos VO2.Thermography can verify the progression of embryo's incubation and estimate its VO2.In eggs, the metabolic activities of the developing embryo produce heat (H) that is dissipated in various forms, including radiation. Given that much of the total heat radiated by an egg (Htot) is heat acquired passively, we asked whether it was possible to detect the fraction produced metabolically (Hmetab) and the extent of its correlation with the embryo's metabolic rate. In chicken and duck eggs at various incubation ages, under standardized experimental conditions of heat conduction and convection, Hmetab was measured by thermography as the difference in Htot between fertile and sterile eggs. Then, Hmetab was correlated to the embryo's oxygen consumption (V̇O2), measured by an open-circuit methodology. Heat loss by water evaporation was found to be less than 3% of the total. During the first half of incubation Hmetab was too small to be significantly separated from Htot. In the second half of incubation Hmetab was significant, represented 30–50% of the total energy consumed and correlated linearly with V̇O2 for a good fraction of incubation. We conclude that under standardized conditions of heat conduction and convection, in the second half of incubation thermography offers a simple tool not only to verify the progression of the embryo's incubation but also to estimate its metabolic rate.
Comparative Developmental Physiology -Contributions, Tools, and Trends is a collection of thirtee... more Comparative Developmental Physiology -Contributions, Tools, and Trends is a collection of thirteen articles selected from topics discussed at the meeting 'New Directions in Developmental Physiology', held in Texas in 2002. The chapters cover quite different subjects, in seemingly casual order, ranging from theoretical or almost philosophical essays to modeling and experimental details. As neither the book nor the individual chapters have summaries, I will briefly allude to their content in this review.
We asked whether or not the thermal characteristics of fertile avian eggs changed throughout incu... more We asked whether or not the thermal characteristics of fertile avian eggs changed throughout incubation. The cooling and warming times, expressed by the time constant τ of the egg temperature response to a rapid change in ambient temperature, were measured in fertile chicken eggs at early (E7), intermediate (E11) and late (E20) stages of embryonic development. Same measurements were conducted on eggs emptied of their content and refilled with water by various amounts. The results indicated that (1) the τ of a freshly laid egg was ~50 min; (2) τ decreased linearly with the drop in egg water volume; (3) the dry eggshell had almost no thermal resistance but its wet inner membrane contributed about one-third to the stability of egg temperature; (4) the egg constituents (yolk, albumen and embryonic tissues) and the chorioallantoic circulation had no measurable effect on τ; (5) the presence of an air pocket equivalent in volume to the air cell of fertile eggs reduced τ by about 3 min (E7), 5 min (E11) and 11 min (E20). Hence, in response to warming the egg τ at E20 was slightly shorter than at E7. In response to cooling, the egg τ at E20 was similar to, or longer than, E7 because embryonic thermogenesis (evaluated by measurements of oxygen consumption during cold) offset the reduction in τ introduced by the air cell. In conclusion, until the onset of thermogenesis the thermal behavior of a fertile egg is closely approximated by that of a water-filled egg with an air volume equivalent to the air cell. It is possible to estimate the cooling τ of avian eggs of different species from their weight and incubation time.
Journal of applied physiology (Bethesda, Md. : 1985), 2000
Body temperature (T(b)) of rat pups (7-9 days old) raised under a 12:12-h light-dark (L-D) regime... more Body temperature (T(b)) of rat pups (7-9 days old) raised under a 12:12-h light-dark (L-D) regimen (L: 0700-1900, D: 1900-0700) was consistently higher in D than in L by approximately 1.1 degrees C. We tested the hypothesis that the L-D differences in T(b) were accompanied by differences in the set point of thermoregulation. Measurements were performed on rat pups at 7-9 days after birth. O(2) consumption (VO(2)) and CO(2) production (VCO(2)) were measured with an open-flow method during air breathing, as ambient temperature (T(a)) was decreased from 40 to 15 degrees C at the constant rate of 0.5 degrees C/min. At T(a) >/=33 degrees C, VO(2) was not significantly different between L and D, whereas VCO(2) was higher in L, suggesting a greater ventilation. Over the 33 to 15 degrees C range the VO(2) values in D exceeded those in L by approximately 30%. Specifically, the difference was contributed by differences in thermogenesis at T(a) = 30 to 20 degrees C. As T(a) was decreased, t...
The primary aim of this study was to establish whether or not embryonic hypoxia selectively affec... more The primary aim of this study was to establish whether or not embryonic hypoxia selectively affects the growth of specific organs. Chicken embryos were incubated either in normoxia (Nx) or in hypoxia (15% O 2 from embryonic day E5, Hx). The length of the beak and third toe (as indexes of skeletal growth) and the weights of internal organs (eyes, brain, heart, lungs, liver, kidneys, stomach, and intestines) were collected at E14, E17, E19, and E20. Hypoxia reduced embryonic body weight (BW). At any given age, the specific weight (organ weight/BW) of some organs in Hx was higher, and that of others was lower, than in Nx. However, almost all differences disappeared when organ weights were compared as function of BW, rather than at fixed chronological ages. The important exception was the chorioallantoic membrane (CAM), the mass of which in Hx developed out of proportion. In a third group of embryos, hypoxic until E14 and normoxic thereafter, there was no post-hypoxic catch-up growth, differently from what known to occur postnatally. A possible interpretation is that catch-up growth does not depend on the age of the embryo but on its BW. In conclusion, at least in the chicken embryo and for the level of hypoxia tested, hypoxia has no selective effects on the growth of specific organs, except for the CAM. Qualitative differences in the weight response to hypoxia among organs observed at any given age can be explained largely by the effects of the blunted growth on the growth trajectory of the individual organs.
Canadian Journal of Physiology and Pharmacology, Feb 13, 2011
The barometric method is a common technique for measurements of pulmonary ventilation in unrestra... more The barometric method is a common technique for measurements of pulmonary ventilation in unrestrained animals. It basically consists of recording the changes in chamber pressure generated during breathing. In fact, as the air inspired is warmed and humidified from the ambient to the pulmonary values, the total pressure in the animal chamber increases; the opposite occurs in expiration. The present commentary is an introduction to this method, briefly reviewing its historical development, the conceptual pitfalls, and potential sources of errors during practical applications.
We questioned to what extent changes in temperature could affect the newborn's ventilator... more We questioned to what extent changes in temperature could affect the newborn's ventilatory inhibition provoked by lung inflation, or Hering-Breüer (HB) inflation reflex. Conscious newborn rats (3-4 d old) were studied in a double chamber airflow plethysmograph at ambient temperatures of 32 degrees C (slightly below their thermoneutrality), 24 degrees C (cold), and 36 degrees C (warm). At these ambient temperatures, the corresponding body temperatures averaged 35.4, 31.0, and 37 degrees C. The HB reflex was triggered by negative body surface pressures of 5 or 10 cm H2O, and quantified as the duration of the expiratory time during the maintained inflation, either in absolute values or in relation to the control expiratory time. In cold the HB reflex decreased to 80%, and in warm it increased to 150%, of the values measured at 32 degrees C. Oxygen consumption, measured by an open flow system, averaged 59, 47, and 29 mL x kg(-1) x min(-1) at, respectively, 24, 32, and 36 degrees C. In cold, the ventilatory response to hypoxia (10% O2) was almost absent, that to hypercapnia (5% CO2) was greater, and that to hypoxia and hypercapnia combined was less than in warm. We conclude that in newborn rats the strength of the vagal inhibition on breathing, evaluated in the form of the HB reflex, is sensitive to temperature, becoming stronger as temperature increases. One contributing factor is the temperature-induced change in metabolic rate, whereas the role of temperature-induced changes in ventilatory chemosensitivity is variable. The strong temperature-dependency of the neonatal HB reflex implies that in newborns exposed to a warm environment breathing is more susceptible to inhibitory inputs.
1. Hypoxia is known to decrease thermogenesis. We set out to determine whether this is accompanie... more 1. Hypoxia is known to decrease thermogenesis. We set out to determine whether this is accompanied by alterations in the brown adipose tissue, which is a major source of non-shivering thermogenesis. 2. Measurements were performed on 25- and 64-day-old rats, after 4 days of hypoxia (10% inspired O2), and on approximately 3.5-month-old rats in hypobaric hypoxia since birth, at an ambient temperature of 25 degrees C. 3. All hypoxic rats had higher haematocrit and lower body mass than corresponding controls. 4. In the 25-day-old rats, hypoxia had minimal and non significant effects on brown adipose tissue mass, proteins and DNA concentration. The content of the mitochondrial uncoupling protein thermogenin, evaluated by immunoblot after electrophoretic separation, relative to the cytoskeleton actin (UCP/Act), was not significantly altered. 5. In 25-day-old rats exposed for 4 days to cold (ambient temperature = 7-9 degrees C), brown adipose tissue was hyperplastic, with increased UCP/Act; hypoxia did not appreciably alter the response to cold. 6. In the 2-month-old rats, after 4 days of hypoxia UCP/Act was reduced to about 40% of control. 7. In the 3.5-month-old rats maintained in hypoxia since birth, brown adipose tissue mass was reduced in proportion to body mass, with little effect on total proteins and DNA; UCP/Act was decreased to about 50% of control. 8. We conclude that chronic hypoxia had a minimal effect on brown adipose tissue total proteins and DNA content. However, the uncoupling protein content can be greatly reduced, depending upon age and duration of hypoxia.
Saiki, Chikako, and Jacopo P. Mortola. Effect of 2,4dinitrophenol on the hypometabolic response t... more Saiki, Chikako, and Jacopo P. Mortola. Effect of 2,4dinitrophenol on the hypometabolic response to hypoxia of conscious adult rats. J. Appl. Physiol. 83(2): 537-542, 1997.-During acute hypoxia, a hypometabolic response is commonly observed in many newborn and adult mammalian species. We hypothesized that, if hypoxic hypometabolism were entirely a regulated response with no limitation in O 2 availability, pharmacological uncoupling of the oxidative phosphorylation should raise O 2 consumption (V O 2 ) by similar amounts in hypoxia and normoxia. Metabolic, ventilatory, and cardiovascular measurements were collected from conscious rats in air and in hypoxia, both before and after intravenous injection of the mitochondrial uncoupler 2,4-dinitrophenol (DNP). In hypoxia (10% O 2 breathing, 60% arterial O 2 saturation), V O 2 , as measured by an open-flow technique, was less than in normoxia (,80%). Successive DNP injections (6 mg/kg, 4 times) progressively increased V O 2 in both normoxia and hypoxia by similar amounts. Body temperature slightly increased in normoxia, whereas it did not change in hypoxia. The DNP-stimulated V O 2 during hypoxia could even exceed the control normoxic value. A single DNP injection (17 mg/kg iv) had a similar metabolic effect; it also resulted in hypotension and a drop in systemic vascular resistance. We conclude that pharmacological stimulation of V O 2 counteracts the V O 2 drop determined by hypoxia and stimulates V O 2 not dissimilarly from normoxia. Hypoxic hypometabolism is likely to reflect a regulated process of depression of thermogenesis, with no limitation in cellular O 2 availability. cellular hypoxia; hypoxic ventilatory response; oxidative phosphorylation; oxygen consumption; uncoupling agents
Seifert, Erin L., and Jacopo P. Mortola. Light-dark differences in the effects of ambient tempera... more Seifert, Erin L., and Jacopo P. Mortola. Light-dark differences in the effects of ambient temperature on gaseous metabolism in newborn rats. J Appl Physiol 88: 1853-1858, 2000.-Body temperature (T b ) of rat pups (7-9 days old) raised under a 12:12-h light-dark (L-D) regimen (L: 0700-1900, D: 1900-0700) was consistently higher in D than in L by ϳ1.1°C. We tested the hypothesis that the L-D differences in T b were accompanied by differences in the set point of thermoregulation. Measurements were performed on rat pups at 7-9 days after birth. O 2 consumption (V O 2 ) and CO 2 production (V CO 2 ) were measured with an open-flow method during air breathing, as ambient temperature (T a ) was decreased from 40 to 15°C at the constant rate of 0.5°C/min. At T a Ն33°C, V O 2 was not significantly different between L and D, whereas V CO 2 was higher in L, suggesting a greater ventilation. Over the 33 to 15°C range the V O 2 values in D exceeded those in L by ϳ30%. Specifically, the difference was contributed by differences in thermogenesis at T a ϭ 30 to 20°C. As T a was decreased, the critical temperature at which V O 2 began to rise was lower in L. We conclude that the higher T b of rat pups in D is accompanied by a higher set point for thermoregulation and a greater thermogenesis. These results are consistent with the idea that, in newborns, endogenous changes in the set point of thermoregulation contribute to the circadian oscillations of T b .
We investigated the vocalization and the thermogenic responses to cold during hypoxia in chicken ... more We investigated the vocalization and the thermogenic responses to cold during hypoxia in chicken hatchlings during the first postnatal day. Calls were quantified in number and sound characteristics (amplitude and frequency); the change in oxygen (O 2 ) consumption, measured by an open-flow methodology, represented thermogenesis. The cold challenge consisted of a decrease in ambient temperature (Ta) from ϳ39 to 28°C, in steps of 2°C, or an acute exposure to ϳ28°C, either in normoxia or hypoxia (10% O 2 ). Hypoxia lowered thermogenesis and the critical Ta, suggesting a decrease in the set point for thermoregulation. The vocalization response to cold was rapid; did not progress with the duration or intensity of the cold stimulus; was similar in very young (Ͻ8 hr old) and older (12-24 hr) hatchlings despite their differences in thermogenic capacity; and was essentially unaffected by hypoxia. We conclude that the hatchling's vocalization in the cold follows a stereotyped pattern not related to the thermogenic regulation of body temperature. The dissociation between vocalization and thermogenesis might carry some advantage in conditions of cold and hypoxia.
Mortola, Jacopo P., and Lina Naso. Thermogenesis in newborn rats after prenatal or postnatal hypo... more Mortola, Jacopo P., and Lina Naso. Thermogenesis in newborn rats after prenatal or postnatal hypoxia. J. Appl. Physiol. 85(1): 84-90, 1998.-Oxygen consumption (V O 2 ) was measured in normoxia as ambient temperature (T a ) was lowered from 40 to 15°C, at the rate of 0.5°C/min (thermoneutrality ϳ33°C). In 2-day-old rats born in hypoxia after hypoxic gestation, the T a -V O 2 relationship was as in controls; their interscapular brown adipose tissue (IBAT) was hypoplastic (less proteins and DNA), with lower concentration of the mitochondrial uncoupling protein thermogenin. In 8-day-old rats exposed to hypoxia postnatally (day 2 to day 8), at any T a below thermoneutrality V O 2 was higher than in controls; also, in this group IBAT was hypoplastic with decreased thermogenin. Additional measurements under various experimental conditions indicated that the increased thermogenic capacity was not explained by the smaller body mass and increased blood oxygen content or by the eventuality of intermittent cold stimuli during the chronic hypoxia. On the other hand, chronic hypercapnia (3% CO 2 in normoxia, from day 2 to day 8) also resulted in increased normoxic thermogenesis. We conclude that chronic hypoxia in the perinatal period 1) reduces IBAT mass and thermogenin concentration and 2) can increase the newborn's thermogenic capacity because of stress-related mechanisms not specific to hypoxia. brown adipose tissue; hypercapnia; perinatal hypoxia; uncoupling protein thermogenin; undernourishment 8750-7587/98 $5.00
This communication describes the application of the barometric technique to the measurements of t... more This communication describes the application of the barometric technique to the measurements of the breathing pattern (tidal volume and breathing rate) and pulmonary ventilation (V E ) in chicken embryos and hatchlings. The chamber-plethysmograph was separated into two sections, an animal compartment, maintained at incubation temperature, and a recording compartment kept at a lower temperature. In the case of the embryos, the eggshell itself represented the animal compartment. The hatchlings were accommodated into a "nest" compartment. A flow-through system permitted simultaneous measurements of oxygen consumption (V O 2 ) and carbon dioxide production. Values of breathing rate corresponded to those counted visually in hatchlings while resting in the incubator, and data of restingV E were similar to those obtained by airflow plethysmography, a more invasive technique applicable only to the hatchlings. At rest, the ventilatory equivalent (V E /V O 2 ) of the hatchlings was similar to that reported for adult birds, while in embryos it was much lower. Hypoxia (15 and 10% O 2 ) and hypercapnia (2 and 4% CO 2 ) caused hyperventilation (increase inV E /V O 2 ), both in the hatchlings and in the embryos, these latter using hypometabolism as the main approach to hyperventilate in hypoxia. We conclude that the barometric technique can be adapted to the study of breathing andV E responses in avian embryos and hatchlings.
In mammals, biological time keeping is organised with a hierarchical and pyramidal structure, und... more In mammals, biological time keeping is organised with a hierarchical and pyramidal structure, under the control of the master clock in the suprachiasmatic hypothalamic nuclei (SCN). Body temperature (Tb) and metabolic rate have robust circadian patterns, and probably represent primary variables controlled closely by the SCN. From the data of studies in animals (mostly rats) and humans, it appears that the most common effect of prolonged hypoxia is to decrease, and in some cases to abolish, the amplitudes of the daily oscillations, irrespective of the state of arousal or activity level. On the other hand, the evidence is that hypoxia causes only minimal and transient perturbation of the period of the rhythm. The fact that hypoxia modifies the circadian oscillations of variables as important as body temperature and metabolism leads to the expectation that the daily rhythms of many other functions are perturbed by hypoxia, according to their link to the primary variables. The data currently available, although sparse and fragmentary, support this view. It is speculated that the alterations of the normal circadian oscillations can contribute to many common symptoms during sustained hypoxia, from sleep fragmentation, to malaise and loss of appetite.
We asked whether hypoxia and hypercapnia, singly or combined, affect the lung volume-dependent ve... more We asked whether hypoxia and hypercapnia, singly or combined, affect the lung volume-dependent ventilatory inhibition [Hering-Breuer (HB) reflex] in newborn rats. Conscious rats 2, 5, and 8 days old were breathing in a flow plethysmograph. Mean lung volume was increased by applying a negative body surface pressure of 6 or 12 cmH2O. HB reflex was quantified as the inhibitory ratio (IR) of the apnea during the inflation expiratory time (TEinfl) to the control expiratory time (TEc), i.e., IR = TEinfl/TEc. In normoxia-normocapnia (control), IR with 6 cmH2O was approximately 8-12 at all ages and approximately doubled with inflation at 12 cmH2O. In hypoxia (HPX; 10% O2) or hypercapnia (HPCN; 3% CO2), IR decreased at 8 days, whereas it did not differ from the control value at 2 and 5 days. In HPX + HPCN, IR decreased at all ages. In HPX (at both 6- and 12-cmH2O inflations), in HPCN (6 cmH2O), or in HPX + HPCN (6 and 12 cmH2O), IR decreased significantly more at 8 days than at 2 days. Metabolic rate, simultaneously measured, decreased during HPX or HPX + HPCN by a similar amount at all ages. The ventilatory response to HPX or to HPCN was significantly more pronounced at 8 days than at 2 days. We conclude that, during the early postnatal development of the rat, HPX or HPCN, singly or combined, reduces the HB reflex inhibition in the oldest pups, with minimal or no effects in the youngest. These developmental differences cannot be explained by differences in metabolic drive on ventilation but are contributed to by differences in chemosensitivity.
We measured the metabolic component of heat (Hmet) of avian eggs by thermography.In the first hal... more We measured the metabolic component of heat (Hmet) of avian eggs by thermography.In the first half of incubation Hmet was not significant.Later in incubation Hmet was significant and correlated with the embryos VO2.Thermography can verify the progression of embryo's incubation and estimate its VO2.In eggs, the metabolic activities of the developing embryo produce heat (H) that is dissipated in various forms, including radiation. Given that much of the total heat radiated by an egg (Htot) is heat acquired passively, we asked whether it was possible to detect the fraction produced metabolically (Hmetab) and the extent of its correlation with the embryo's metabolic rate. In chicken and duck eggs at various incubation ages, under standardized experimental conditions of heat conduction and convection, Hmetab was measured by thermography as the difference in Htot between fertile and sterile eggs. Then, Hmetab was correlated to the embryo's oxygen consumption (V̇O2), measured by an open-circuit methodology. Heat loss by water evaporation was found to be less than 3% of the total. During the first half of incubation Hmetab was too small to be significantly separated from Htot. In the second half of incubation Hmetab was significant, represented 30–50% of the total energy consumed and correlated linearly with V̇O2 for a good fraction of incubation. We conclude that under standardized conditions of heat conduction and convection, in the second half of incubation thermography offers a simple tool not only to verify the progression of the embryo's incubation but also to estimate its metabolic rate.
Comparative Developmental Physiology -Contributions, Tools, and Trends is a collection of thirtee... more Comparative Developmental Physiology -Contributions, Tools, and Trends is a collection of thirteen articles selected from topics discussed at the meeting 'New Directions in Developmental Physiology', held in Texas in 2002. The chapters cover quite different subjects, in seemingly casual order, ranging from theoretical or almost philosophical essays to modeling and experimental details. As neither the book nor the individual chapters have summaries, I will briefly allude to their content in this review.
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