The Mouse-To-Elephant Metabolic Curve: Historical Overview.

Although it is intuitive that large mammals need more food than smaller ones, it is not so obvious that, relative to their body mass, larger mammals consume less than smaller ones. In fact, on a per kg basis, the resting metabolic rate of a mouse is some 50 times higher than that of an elephant. The fact that metabolism could not be proportional to the mass of the animal was suggested by Sarrus and Rameaux in 1838. The first indication that oxygen consumption (or other indices of metabolic rate, Y) related to the animal body mass (M) according to an exponential of the type Y = a · Mb , where b was about 0.75, was presented by Max Kleiber in 1932. Two years later Samuel Brody had collected sufficient data to construct the first "mouse-to-elephant" metabolic curve. The physiological basis of the relationship has been the object of many hypotheses, often accompanied by a great deal of controversy. This historical essay traces the origin of the mouse-to-elephant metabolic function, recalling the earliest concepts of metabolism and its measurements to understand the body size dependency, which is still one of the most elusive phenomena in comparative physiology. A brief look at the metabolic scaling of nonmammalian organisms will be included to frame the mouse-to-elephant curve into a broader context and to introduce some interesting interpretations of the mammalian function. © 2023 American Physiological Society. Compr Physiol 13:4513-4558, 2023.

Breath-by-breath analysis of respiratory sinus arrhythmia in dogs.

Dogs differ greatly in size, heart (HR) and breathing rates (BR). In addition, they have a clear Respiratory Sinus Arrhythmia (RSA) at rest. Therefore, better than any other mammalian species, dogs offer an opportunity to test whether resting RSA varies with body weight, HR or BR. Sequences of inter-beat-intervals (IBI, ms) a few-minutes long were collected in twenty-three resting dogs of different sizes, together with pneumograms. IBI variability was quantified by standard time-domain criteria. From beat-to-beat instantaneous heart rate (hR, beats/min), RSA was the difference between inspiratory peak (hR-peak) and expiratory trough (hR-trough), in percent of mean HR. RSA averaged 40.1 % ±4.5, or more than three times that of humans, with large inter-animal variability. On average, RSA contributed 38 % of the total IBI variability. RSA did not differ between sexes and did not correlate with body weight. It had modest negative correlations with HR (P < 0.05) and BR (P < 0.05), and a very strong negative correlation with hR-trough (P < 0.001). In two separate dogs, during panting, RSA was absent. In the transition from resting to panting, RSA continued like at rest for several breaths, despite the tachypnea, underlying the importance of central mechanisms in the origin of RSA. In conclusion, RSA in dogs is very large and explains less than half of their sinus arrhythmia. Rather than HR, BR or hR-peak, changes in the vago-sympathetic control, represented by hR-trough, are the most likely source of variability of RSA among subjects.

Social interaction and the thermogenic response of chicken hatchlings.

The aggregation of two or more individuals of the same species (huddling) is common in mammals and birds, especially in the cold. The physical contact reduces the weight-specific body surface exposed to the environment, thus lowering heat loss and the thermogenic needs. This study investigated the possibility that the mere presence of a conspecific, in absence of physical contact, may by itself influence metabolic rate during cold. The oxygen consumption (Vo2) of pairs of chicken hatchlings was measured when the hatchlings were in isolation (individuals), together in the respirometer but kept separated by a grid (separated) or together in the respirometer free to huddle (together), in random order, in warm (ambient normothermia, 37.5 °C) and cold conditions (26 °C, 1 h). In warm, Vo2 did not differ significantly among individuals, separated and together (~ 1.03 ± 0.04 ml O2/min). During the whole cold period, Vo2 of individuals exceeded the value by 23.3 ± 3.1 ml of O2, significantly more than in separated (15.3 ± 2.0 ml O2, P<0.01) and together (13.9 ± 3.3 ml O2; P<0.001). Separated and together did not differ significantly. Vo2 in the cold averaged 149 ± 7% of the value measured in normothermia in isolated, 132 ± 5% in separated and 128 ± 7% in together. By the end of the cold-exposure, Vo2 averaged 166 ± 8% of normothermia in isolated, 146 ± 8% in separated and 140 ± 9% in together. In all cases, values of isolated significantly exceeded those of separated (P<0.01) and together (P<0.0001), while separated and together did not differ from each other (P>0.05; Two-way RM ANOVA). Hence, in this experimental model, social interaction without physical contact decreased the thermogenic response to cold as much as huddling did. Presumably, during the cold exposure, social interaction lowered the additional energetic cost of the stress of isolation.

Hypoxic hypometabolism in chicken embryos: conformism and downregulation.

Postnatally, during hypoxia the decrease in oxygen consumption ( [Formula: see text] ) can exceed what expected from the limitation in O2 availability, meaning that [Formula: see text] -downregulation exceeds O2-conformism. We questioned whether a similar phenomenon could occur prenatally, in chicken embryos at mid- (E11, out of 20.5 days) or near end- (E18) incubation. [Formula: see text] was measured with an open-flow system in the sequence of normoxia-normothermia (21% O2, 37 °C, 30 min), hypoxia in normothermia (Hx-NT, either 18, 15, 12 or 9% O2, 37 °C, 1 hour), hypoxia in hyperthermia (Hx-HT, up to 43 °C, 1 hour) and return to normoxia-normothermia (30 min). During Hx-NT [Formula: see text] invariably decreased in a [O2]-dependent fashion. The hypoxic drop in [Formula: see text] did not require a post-hypoxic payment of the O2-debt, implying that the decrease in [Formula: see text] reflected hypometabolism. [Formula: see text] did not differ significantly between Hx-HT and Hx-NT for [O2] = 15% or less, as expected by O2-conformism. Differently, with milder hypoxia (18% O2), [Formula: see text] during Hx-HT significantly exceeded that in Hx-NT, meaning that the value of [Formula: see text] in Hx-NT was not limited by O2 supply. We conclude that a phenomenon of hypoxic [Formula: see text] downregulation like that observed in postnatal mammals can occur also prenatally, in the chicken embryos. The mechanisms at the basis of the downregulation remain unresolved and could combine physiological and cellular processes.

Respiratory sinus arrhythmia during a mental attention task: the role of breathing-specific heart rate.

It is known that a mental attention task (MAT) can modify the magnitude of the increase in instantaneous heart rate (HR) with inspiration, or Respiratory Sinus Arrhythmia (RSA). Here, we asked whether the RSA changes were mediated by the changes in HR, breathing frequency (f) or HR/f ('breathing specific heart rate'). This latter reflects the degree of coupling between pulmonary blood and air flows, the optimization of which may be the function of RSA. RSA (computed as the difference between peak and trough instantaneous HR of each breath, in percent of mean HR) was measured breath-by-breath in 119 young men and women (19.6 ± 0.1 year old) during spontaneous breathing and during a MAT, which consisted in finger tapping at acoustic cues delivered in various patterns. During MAT, breathing became more rapid (+2.2 breaths/min, P < 0.001) and shallow (78% of rest, P < 0.001) and HR decreased slightly (-1 beats/min, P < 0.05). RSA dropped from 13.4 ± 0.7 to 11.6 ± 0.7% (P < 0.0001), because of the drop in the inspiratory peak of instantaneous HR, and so did HR/f, from 5.8 ± 0.2 to 4.9 ± 0.2 beats/breath (P < 0.0001).The results were very similar between genders. The magnitude of the changes in HR/f correlated linearly with those of RSA, so that those subjects who decreased HR/f the most also had the largest decrease in RSA and the few who increased HR/f during MAT also increased RSA. We conclude that this type of mental task changed RSA by a magnitude that depended on its effect on HR/f. The results support the concept that RSA is a central cardio-respiratory mechanism to ameliorate the matching between pulmonary blood and air flows, whether the ventilatory drive originates spontaneously or is under cortical influences.

Behavioral thermoregulation in avian embryos: Spectrum analysis of calls in warm and cold conditions.

During the last days of incubation vocalization is a form of communication between the avian embryo and the incubating parent. Commonly, embryonic calls increase when ambient temperature (Ta) deviates from the optimal range, but no information is available on whether the characteristics of the calls differ between warming and cooling. Rate of calls, power spectra (distribution of the call's energy among its frequency components) and spectrograms (time-frequency plots) were obtained in chicken embryos during the external pipping phase, in normothermia (38 °C), during progressive cooling to Ta = 27 °C (C) or progressive warming to Ta = 43 °C (W) over a short (30 min) or a long (150 min) period. Over the Ta range investigated, the embryo's oxygen consumption did not change significantly from normothermia. Number of calls, average and peak amplitudes of the power spectrum increased as cold or heat increased, according to power functions with exponents significantly higher during warming than during cooling. The spectrum frequency at peak amplitudes did not vary with Ta. Number of calls and characteristics of the power spectra (average amplitude, peak amplitude and frequency at peak amplitude) at five degrees above normothermia (43 °C) did not differ significantly from those at ten degrees below normothermia (27 °C), whether the changes in Ta occurred rapidly or slowly. The incidence of spectrograms with characteristics of 'distress' (progressive decrease in frequency with time) at 43 °C was similar to that at 27 °C. It is concluded that the vocalization of the chicken embryo has a stereotyped sonogram independent of the Ta directional changes, while the Ta-sensitivity of vocalization (changes in number of calls and amplitude per °C change in Ta) is much higher when Ta rises than when Ta drops.

Prenatal catch-up growth: A study in avian embryos.

Whether the growth of embryos after a period of stunt becomes accelerated (Catch-Up Growth, CUGr), as it occurs postnatally, has rarely been examined experimentally in any class of animals. Here, hypoxia or cold of different degrees and durations caused growth retardation in chicken embryos during the first or second week of incubation. On average, on the day of removal of the growth-inhibition, the weight of the experimental groups was 73% (wet) and 61% (dry) of control embryos, while near end-incubation (embryonic day E18) their weight averaged significantly more, respectively, 80% and 84% of controls (P < 0.001). When compared as function of developmental time, the post-intervention growth of experimental embryos was faster than that of controls. The faster growth was fully accounted for by their smaller weight at end-intervention, because embryonic growth is higher the smaller the weight. Hence, their growth was appropriate for their weight, rather than for their age. In fact, out of eight different models of growth based on age and weight (wet or dry) in various combination, the model based on embryonic wet weight at end-intervention, and weight alone, was the best predictor of the embryo's post-intervention growth. The oxygen consumption of the experimental embryos during CUGr was appropriate for their weight. In conclusion, in this experimental model of CUGr, the embryo's weight at the end of a stunt could fully predict and explain the rate of growth during the post-intervention recovery period.

How to breathe? Respiratory mechanics and breathing pattern.

On theoretical grounds any given level of pulmonary or alveolar ventilation can be obtained at various absolute lung volumes and through many combinations of tidal volume, breathing frequency and inspiratory and expiratory timing. However, inspection of specific cases of newborn and adult mammals at rest indicates that the breathing pattern reflects a principle of economy oriented toward minimal respiratory work. The mechanisms that permit optimization of respiratory cost are poorly understood; yet, it is their efficiency and coordination that permits pulmonary ventilation at rest to require only a minimal fraction of resting metabolism. The sensitivity of the breathing pattern to the mechanical properties implies that tidal volume, breathing rate, mean inspiratory flow or other ventilatory parameters cannot be necessarily considered indicators proportional to the central neural respiratory 'drive'. The broad conclusion is that the breathing pattern adopted by newborn and adult mammals is the one that produces the adequate alveolar ventilation with minimal cost, that is, in full recognition of the mechanical characteristics of the system.

The magnitude of respiratory sinus arrhythmia of a large mammal (the horse) is like that of humans.

Heart rate (FH) accelerates in inspiration and decelerates in expiration, a phenomenon known as Respiratory Sinus Arrhythmia (RSA). Although the presence of RSA has been documented in many species, how its magnitude compares among species is unknown. We asked whether the magnitude of RSA in a large mammal, the horse, differed from that of previously measured humans. From electrocardiogram and pneumography, the peaks and troughs of FH were identified breath-by-breath in four horses (Italian Saddlebred geldings) during resting wakefulness. RSA was computed as the peak-trough FH difference, in percent of mean FH. Horses had lower FH and respiratory frequency (FR) than humans, but similar FH/FR. RSA ranged between 6% and 15%, with an average of 9 ± 2%, not statistically different from the mean value in humans (12 ± 1%). Like in humans, in horses the FH/FR values below the mean had correspondingly lower RSA, while values above the mean had correspondingly higher RSA. If confirmed in other species, these results suggest that RSA is body size-independent. The correlation with FH/FR, rather than FH or FR, supports the view that RSA optimizes the coupling between pulmonary blood flow and ventilation.

Respiratory sinus arrhythmia in the immediate post-exercise period: correlation with breathing-specific heart rate.

BACKGROUND: Although the absolute values of pulmonary ventilation and cardiac output are similar, the designs of the respiratory and cardiovascular systems imply major differences in flow patterns, airflow being intermittent by comparison to the quasi-continuous pulmonary blood flow. PURPOSE: We hypothesized that respiratory sinus arrhythmia (RSA, difference in heart rate (fH) between inspiration and expiration, as percent of mean fH) ameliorates the inevitable differences between air- and blood-flow patterns. Specifically, we hypothesized RSA to correlate more closely to the ratio between fH and breathing frequency (fR) (fH/fR "breathing-specific heart rate", a proxy for cardio-respiratory coupling) than to either fH or fR alone. Hence, we designed protocols to change independently fH or fR. METHODS: We measured RSA breath-by-breath in 145 young men and women during spontaneous breathing, breathing under cues at different fR (to modify the denominator of fH/fR) and immediately post-exercise while breathing freely or by keeping fR as at rest (to modify the nominator of fH/fR). RESULTS: RSA had no significant correlation with fH, and a better correlation with fH/fR (r2 = 0.92) than with fR alone (r2 = 0.75); the variance of the Y values of the fH/fR-RSA correlation was ~ half that of the fR/RSA correlation (P < 0.002). CONCLUSIONS: We propose that the fH/fR-RSA relationship reflects a central process that ameliorates gas exchange against the difference between air- and blood-flow patterns. The neurological mechanisms are still conjectural. Measurements of RSA could offer a glimpse of the degree of cardio-respiratory central compensation in face of the inequality between blood flow and airflow.

Thermal tachypnea in avian embryos.

Many adult mammals and birds respond to high surrounding temperatures with thermal tachypnea - an increase in breathing frequency accompanied by shallow tidal volume, with minimal increase in oxygen consumption (V̇O2 ). This pattern favors heat dissipation by evaporative water loss (EWL) through the respiratory tract. We asked to what extent this response was apparent at the earliest stages of development, when pulmonary ventilation initiates. Measurements of pulmonary ventilation (V̇E; barometric technique), V̇O2  (open-flow methodology) and EWL (water scrubbers) were performed on chicken embryos at the earliest appearance of pulmonary ventilation, during the internal pipping stage. Data were collected, first, at the normal incubation temperature (37.5°C); then, ambient and egg temperatures were increased to approximately 44°C over a 2 h period. Other embryos of the same developmental stage (controls) were maintained in normothermia for the whole duration of the experiment. During heat exposure, the embryo's V̇O2  and carbon dioxide production increased little. In contrast, V̇E more than doubled (∼128% increase), entirely because of the large rise in breathing frequency (∼132% increase), with no change in tidal volume. EWL did not change significantly, probably because, within the egg, the thermal and water vapor gradients are almost nonexistent. We conclude that chicken embryos respond to a major heat load with tachypnea, like many adult mammals and birds do. Its appearance so early in development, although ineffective for heat loss, signifies that thermal tachypnea represents an important breathing response necessary to be functional from hatching.

Hematocrit of mammals (Artiodactyla, Carnivora, Primates) at 1500m and 2100m altitudes.

The rise in hematocrit (Hct) is one of the hallmarks of human acclimatization to high altitude and, in chronic conditions, reflects the hypoxia-induced polycythemia. However, it is not a uniform response among domestic species and it is not found in Andean camelids, species long adapted to high altitudes. Hence, we asked to what extent the polycythemia of humans is common among mammals. Hct data were collected from captive mammals of three orders (Primates, Artiodactyla, Carnivora), 70 specimens of 33 species at ∼1500m altitude (barometric pressure Pb=635mmHg) and 296 specimens of 64 species at ∼2100m (Pb=596mmHg), long-term residents at those altitudes. Sea level values and data in men and women at the corresponding altitudes were from a compilation of literature sources. At either altitude Hct was significantly higher than at sea level both in men and women; the increase (ΔHct) for genders combined averaged 3.4% (±0.7 SEM) at 1500m and 5.4% (±0.3) at 2100m. Differently, among the three mammalian orders studied a significant increase in Hct occurred only in females of Carnivora (at 1500m) and in males of Primates (at 2100m). The average ΔHct of all species combined was 0.8% (±0.7) at 1500m and 1.5% (±0.4) at 2100m, both significantly less than in humans (P<0.001). At 2100m the average ΔHct of nine species long adapted to high altitude was 0.4% (±1), significantly less than in non-adapted species (P<0.001). A polycythemic response like that of men and women at 2100m occurred in less than 10% of the mammals examined. We conclude that, at least for the altitudes studied, a minimal polycythemia is a general feature of both high-altitude adapted and non-adapted species, and the magnitude of the human response is exceptional among mammals.

Aerobic scope in chicken embryos.

We investigated the aerobic scope of chicken embryos, that is, the margin of increase of oxygen consumption ( [Formula: see text] ) above its normal value. [Formula: see text] was measured by an open-flow methodology at embryonic ages E3, E7, E11, E15, E19 and at E20 at the internal (IP) and external pipping (EP) phases, at the normal incubation temperature (Ta=38°C), in hypothermia (Ta=30°C) and in hyperthermia (Ta=41 and 44°C). In the cold, Q10 averaged ~2 at all ages, except in IP and EP when lower values (~1.5) indicated some degree of thermogenesis. In hyperthermia (38-44°C) Q10 was between 1 and 1.4. Hyperthermia had no significant effects on [Formula: see text] whether the results combined all ages or considered individual age groups, except in IP (in which [Formula: see text] increased 8% with 44°C) and EP embryos (+13%). After opening the air cell, which exposed the embryo to a higher O2 pressure, hyperthermic [Formula: see text] was significantly higher than in normothermia in E19 (+13%), IP (+22%) and EP embryos (+22%). We conclude that in chicken embryos throughout most of incubation neither heat nor oxygen availability limits the normal (normoxic-normothermic) values of [Formula: see text] . Only close to hatching O2-diffusion represents a limiting factor to the embryo's [Formula: see text] . Hence, embryos differ from postnatal animals for a nearly absent aerobic scope, presumably because their major sources of energy expenditure (growth and tissue maintenance) are constantly maximized.

The cessation of breathing in the chicken embryo during cold-hypometabolism.

The avian embryo toward end-incubation combines gas exchange through the chorioallantoic membrane (CAM) and pulmonary ventilation (V˙E). The main experiments examined breathing activity during cold-hypometabolism. Chicken embryos close to hatching were prepared for simultaneous measurements of oxygen consumption ( [Formula: see text] ) and carbon dioxide production ( [Formula: see text] ; open-flow methodology) and breathing frequency (f; barometric technique). As ambient (Ta) and egg temperature (Tegg) dropped, breathing eventually ceased at ∼18°C, when [Formula: see text] and [Formula: see text] were 22-28% of the normothermic values. With the eggshell experimentally covered to reduce CAM gas exchange breathing ceased at slightly lower [Formula: see text] and [Formula: see text] (17-18% of normothermia). Once breathing had stopped, egg exposure to hypoxia (10% or 5% O2) or hypercapnia (3% or 8% CO2) did not resume breathing, which recovered with re-warming. In normothermia, 10% O2 caused hypometabolism and tachypnea; differently, in 5% O2 [Formula: see text] dropped as much as with hypothermia and breathing stopped, to recover upon return in air. Correlation analysis among Ta, Tegg, [Formula: see text] , [Formula: see text] and f during cooling and re-warming indicated that f followed more closely the changes in [Formula: see text] and, especially, in [Formula: see text] than the changes in Ta or Tegg. Some considerations suggest that in this experimental model the cessation of breathing in hypothermia or severe hypoxia may be due to hypometabolism, while the lack of chemo-responses may have a different mechanistic basis.

The contribution of heart rate to the oxygen consumption of the chicken embryo during cold- or hypoxia-hypometabolism.

In embryos, cooling and hypoxia cause a decrease in oxygen consumption ( [Formula: see text] ); we asked what was the relative contribution of heart rate (HR) and of the 'not-HR' factor (the product of stroke volume and arterial-venous O2 difference) to the drop in [Formula: see text] . Data of HR (with subcutaneous electrodes) and [Formula: see text] (by an open-flow methodology) were collected simultaneously on chicken embryos close to end-incubation. Over the last four days of incubation (E16-E20) differences in HR contributed about 30% of the differences in resting [Formula: see text] among embryos. At E20, progressive cooling from 38 to 8°C decreased [Formula: see text] entirely because of the decrease in HR, with minimal compensation of the 'not-HR' component. The same pattern during cooling occurred in younger embryos (age E16), in E20 embryos simultaneously exposed to hypoxia (15% O2) and in E20 normoxic embryos which were incubated in hypoxia (15% O2). Differently, in E20 embryos in normothermia, progressive hypoxia (15%, 10% or 5% O2) lowered [Formula: see text] largely because of the reduction in the 'not-HR' component. We conclude that at end incubation during hypometabolism the changes in HR contribute very differently to the decrease in [Formula: see text] , from about the totality of it during cold to only about 10-20% during hypoxia, depending on its severity. It follows that during cold-hypometabolism, but not during hypoxic hypometabolism, the changes in HR are a good index of the changes in [Formula: see text] . The close relationship between [Formula: see text] and HR during cold-hypometabolism may permit estimates of the changes in [Formula: see text] from the changes in HR in infants undergoing therapeutic hypothermia.

Gender and the circadian pattern of body temperature in normoxia and hypoxia.

Circadian patterns are at the core of many physiological processes, and their disruption can have short- and long-term consequences. This essay focuses on one of the best known patterns, the daily oscillation of body temperature (Tb), and the possibility of its difference between genders. From human and animal studies globally considered, the tentative conclusion is reached that differences in Tb circadian pattern between genders are very small and probably limited to the timing of the rhythm, not to its amplitude. Such similarity between genders, despite the differences in hormonal systems, presumably testifies to the importance that the Tb circadian pattern plays in the economy of the organism and its survival against environmental challenges. The second part of the article presents some previously unpublished experimental data from behaving male and female rats during hypoxia in synchronized conditions. In adult rats hypoxia (10.5% O2 for three days) caused a profound drop of the Tb daily oscillations; by day 3 they were 55% (♀) and 22% (♂) of the normoxic amplitudes, with a statistically significant gender difference. In pre-puberty rats (26-day old) hypoxia caused a major disruption of the circadian pattern qualitatively similar to the adults but not different between genders. Hence, on the basis of this preliminary set of data, it seems that sex-hormones may be a factor in how the Tb daily pattern responds to hypoxia. The implications of the effects of hypoxia on the circadian patterns, and the possibility that such effects may differ between genders, are matters that could have biological and clinical implications and deserve further investigations.

Hematocrit and Hemoglobin Levels of Nonhuman Apes at Moderate Altitudes: A Comparison with Humans.

Mortola, Jacopo P. and DeeAnn Wilfong. Hematocrit and hemoglobin levels of nonhuman apes at moderate altitudes: a comparison with humans. High Alt Med Biol. 17:323-335, 2016.-We asked to what extent the hematologic response (increase in hematocrit [Hct] and in blood hemoglobin concentration [Hb]) of humans to altitude hypoxia was shared by our closest relatives, the nonhuman apes. Data were collected from 29 specimens of 7 species of apes at 2073 m altitude (barometric pressure Pb = 598 mm Hg); additional data originated from apes located at a lower altitude (1493 m, Pb = 639 mm Hg). The human altitude profiles of Hct and Hb between sea level and 3000 m were constructed from a compilation of literature sources that (all combined) comprised data sets of 10,000-12,000 subjects for each gender. These human data were binned for 0-250 m altitude (sea level) and for each 500 m of progressively higher altitudes. Values of Hb and Hct of both men and women were significantly higher than at sea level at the 1500 bin (1250-1750 m); hence, the altitude threshold for the human hematological responses must be between 1000 and 1500 m. In the nonhuman apes, no increase in Hct or Hb was apparent at 1500 m; at 2000 m, the increase was significant only for the Hb of females. At either altitude in the group of nonhuman apes, the increase in Hct was much less than in humans, and that of Hb was significantly less at 1500 m. We conclude that lack of, or minimal, hematopoietic response to moderate altitude can occur in mammalian species that are not genetically adapted to high altitudes. Polycythemia is not a common response to altitude hypoxia and, at least at moderate altitudes, the degree of the human response may represent the exception among apes rather than the rule.

The hypometabolic response to repeated or prolonged hypoxic episodes in the chicken embryo.

Hypoxia (hx) in embryos causes a drop in oxygen consumption ( [Formula: see text] ) that rapidly recovers upon return to normoxia. We asked whether or not this pattern varies with the embryo's hypoxic history. The [Formula: see text] of chicken embryos in the middle (E12) or at end-incubation (E19) was measured by an open-flow methodology during 15-min epochs of moderate (15% O2) or severe hx (10% O2). Each hx-epoch was repeated or alternated with air by various modalities (air-hx-air-hx-air-hx-air, air-2·hx-air-2·hx-air, air-5·hx-air), in randomized sequences. The hx drop in [Formula: see text] was larger with severe than with moderate hx; however, in either case, its magnitude was essentially independent of the preceding hx history. E19 embryos had hx drops in [Formula: see text] of the same magnitude whether their incubation was in air or in moderate hx from E4 to E19. A different protocol (air-12·hx-air) gave variable results; with moderate hx, the [Formula: see text] response was similar to that of the other hx regimes. Differently, with severe hx most embryos progressively decreased [Formula: see text] and eventually died. We interpret these data on the basis of what is known on the 'compensatory partitioning' between costs of growth and maintenance. With moderate hx presumably each episode caused an energy shortfall absorbed entirely by the blunted growth. Hypoxic events of this type, therefore, should have no long-term functional effects other than those related to the small birth weight. Differently, the aerobic energy shortfall with severe hypoxia probably impinged on some maintenance functions and became incompatible with survival.

Thinking about breathing: Effects on respiratory sinus arrhythmia.

Respiratory sinus arrhythmia (RSA), the increase and decrease in instantaneous heart rate (HR) with inspiration and expiration, is commonly evaluated as function of breathing frequency f. However, to the extent that RSA plays a role in the efficiency of gas exchange, it may be expected to correlate better with HR/f ('breathing specific heart rate') than with f, because the former is a better reflection of the cardio-respiratory coupling. We measured RSA breath-by-breath in 209 young men and women during spontaneous breathing and during volitional breathing under auditory cues at vastly different f. In either case, and for both genders, RSA correlated better with HR/f than with f. As HR/f increased so did RSA, in a linear manner. When compared on the basis of HR/f, RSA did not differ significantly between spontaneous and volitional breathing. It is proposed that RSA is a central mechanism that ameliorates the matching between the quasi-continuous pulmonary blood flow and the intermittent airflow, irrespective of the type of ventilatory drive (cortical or autonomic).

The cooling time of fertile chicken eggs at different stages of incubation.

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.