The interaction of the upper airway and thermo-metabolism on respiratory rhythm during non-REM sleep in the developing lamb.

This study investigates the role of metabolic rate and of vagal airway mechanisms in sustaining rhythmic breathing in the developing lamb. Fifteen lambs were prepared, at 2 days of age under fluothane anaesthesia, for sequential studies at 4, 14, 30, 45, and 55 days of age. At each age they were maintained at an ambient temperature of 5, 10, 15, 20, 25 and 30 degrees C for at least one hour before measurements were made during N-REM sleep. In 6 lambs at 4 days and in all lambs at older ages the upper airway was by-passed (by opening a tracheal window) for 10-15 minutes at each ambient temperature. Oxygen consumption was unaffected by upper airway by-pass and there were no consistent changes in mean breathing frequency or amplitude, with the exception of shifts to panting at warm ambient temperatures. Breathing pattern was unaffected by upper airway by-pass in lambs at 4 days of age, but at older ages loss of regularity of breathing frequently occurred (up to 47% of 30 days-old lambs at 25 degrees C). This was related to the fall in oxygen consumption with age and to basal values at thermoneutrality, and coincided with lower respiratory rates and increased use of expiratory laryngeal braking. Periodic breathing (and apnea) of a fixed cycle length (9.3 +/- 0.36 s) was a common feature (62%) of the observed breathing dysrhythmia. In young lambs high metabolic rate sustained high frequency rhythmic breathing which was unaffected by upper airway by-pass.(ABSTRACT TRUNCATED AT 250 WORDS)     

The control of thermoregulation in the developing lamb during slow wave sleep

This study investigates the mechanisms involved in adjusting metabolic rate in response to acute changes in ambient temperature close to thermoneutrality during postnatal development. Twelve lambs were prepared for sequential studies at 4, 14, 30, 45 and 55 days of age. During each study they were maintained at ambient temperatures of 5, 10, 15, 20, 25 and 30 degrees C for at least 1 h and until a slow wave sleep epoch was established. Eight lambs completed all studies. In these there was a significant fall in oxygen consumption with age which was independent of ambient temperature. This effect was closely related to a decrease in plasma triiodothyronine concentration that was greatest between 4- and 14-days old lambs and was not associated with a change in the plasma concentration of thyrotrophin or thyroxine. In 4-days old lambs oxygen consumption was increased at ambient temperatures of 5 and 10 degrees C by non-shivering thermogenesis, whilst in 14- and 30-days old lambs this effect was achieved by shivering. On the basis of significant changes in oxygen consumption and/or the occurrence of shivering (lower critical temperature) and panting (upper critical temperature) we have shown that there is a fall in both upper and lower critical temperature with age and a widening of the thermoneutral zone. This was associated with a decrease in the plasma cortisol concentration and heart rate as measured at thermoneutrality, whilst rectal temperature increased from 4 to 30 days of age. The other 4 lambs, 3 of which died between 7 and 17 days of age, had low plasma triiodothyronine concentrations when studied at 4 and/or 14 days of age and their oxygen consumption at thermoneutrality was significantly lower than the normal group at 14 days. Shivering thermogenesis occurred at an earlier age and control of body temperature was less effective. It is concluded that triiodothyronine has an important role in the control of metabolic rate in the developing lamb even to meet modest changes in ambient temperature, and possibly directly in survival.     

Pituitary adenylate cyclase-activating polypeptide maintains neonatal breathing but not metabolism during mild reductions in ambient temperature

Mild reductions in ambient temperature dramatically increase the mortality of neonatal mice deficient in pituitary adenylate cyclase-activating polypeptide (PACAP), with the majority of animals succumbing in the second postnatal week. During anesthesia-induced hypothermia, PACAP(-/-) mice at this age are also vulnerable to prolonged apneas and sudden death. From these observations, we hypothesized that before the onset of genotype-specific mortality and in the absence of anesthetic, the breathing of PACAP-deficient mice is more susceptible to mild reductions in ambient temperature than wild-type littermates. To test this hypothesis, we recorded breathing in one group of postnatal day 4 PACAP+/+, (+/-), and (-/-) neonates (using unrestrained, flow-through plethysmography) and metabolic rate in a separate group (using indirect calorimetry), both of which were exposed acutely to ambient temperatures slightly below (29 degrees C), slightly above (36 degrees C), or at thermoneutrality (32 degrees C). At 32 degrees C, the breathing frequency of PACAP(-/-) neonates was significantly less than PACAP+/+ littermates. Reducing the ambient temperature to 29 degrees C caused a significant suppression of tidal volume and ventilation in both PACAP+/- and (-/-) animals, while the tidal volume and ventilation of PACAP+/+ animals remained unchanged. Genotype had no effect on the ventilatory responses to ambient warming. At all three ambient temperatures, genotype had no influence on oxygen consumption or body temperature. These results suggest that during mild reductions in ambient temperature, PACAP is vital for the preservation of neonatal tidal volume and ventilation, but not for metabolic rate or body temperature.     

Thyroarytenoid muscle activity during hypoxia in awake lambs

It is generally accepted that hypoxia in early life results in active laryngeal braking of expiratory airflow via the recruitment of glottic adductor muscles. We examined the electromyogram expiratory activity of the thyroarytenoid muscle in seven 11- to 18-day-old awake nonsedated lambs exposed to an inspired O2 fraction of 0.08 for 18 min. The lambs breathed through a face mask and a pneumotachograph. During baseline prehypoxic breathing, the thyroarytenoid muscle was largely inactive in each awake lamb. Unexpectedly, no recruitment of the thyroarytenoid muscle was recorded during hypoxia in any of the seven lambs; simultaneous examination of the flow-volume curves revealed an absence of expiratory airflow braking. Also unexpectedly, marked expiratory activity of the thyroarytenoid muscle was recorded, with each expiration occurring within less than 10 s after the return to room air. The resulting delay of expiration was apparent in the flow-volume loops. Thus, in awake 11- to 18-day-old lambs, 1) active expiratory glottic adduction is absent during hypoxia and 2) a return from hypoxia to room air results in prolonged expiration as well as active glottic adduction that controls end-expiratory lung volume.     

Metabolic rate and thermoregulation in two species of tuco-tuco, Ctenomys talarum and Ctenomys australis (Caviomorpha, Octodontidae)

1. Resting metabolic rate and body temperature in function of ambient temperature were determined for two species of Ctenomys. 2. Oxygen consumption was lowest between 25 and 30 degrees C and was 0.946 +/- 0.030 and 0.968 +/- 0.022 in Ctenomys talarum (from Mar de Cobo and Necochea, respectively). Resting metabolic rate was 0.343 +/- 0.053 at 30 C in C. australis. 3. Mean rectal temperature at thermoneutrality was 36.1 +/- 0.13 and 37.3 +/- 0.17 in C. talarum and C. australis, respectively. 4. Limited thermoregulation occurred in C. talarum down to 20 degrees C but C. australis maintained body temperature down to 10 degrees C. 5. Both species of tuco-tucos became hyperthermic at ambient temperatures above thermoneutrality.     

Metabolism during normoxia, hyperoxia, and recovery in newborn rats.

Aerobic metabolism (oxygen consumption, VO2, and carbon dioxide production, VCO2) has been measured in newborn rats at 2 days of age during normoxia, 30 min of hyperoxia (100% O2) and an additional 30 min of recovery in normoxia at ambient temperatures of 35 degrees C (thermoneutrality) or 30 degrees C. In normoxia, at 30 degrees C VO2 was higher than at 35 degrees C. With hyperoxia, VO2 increased in all cases, but more so at 30 degrees C (+20%) than at 35 degrees C (+9%). Upon return to normoxia, metabolism readily returned to the prehyperoxic value. The results support the concept that the normoxic metabolic rate of the newborn can be limited by the availability of oxygen. At temperatures below thermoneutrality the higher metabolic needs aggravate the limitation in oxygen availability, and the positive effects of hyperoxia on VO2 are therefore more apparent.     

Increased oxygen consumption associated with breathing activity in fetal lambs

To examine the relationship between fetal O2 consumption and fetal breathing movements, we measured O2 consumption, umbilical blood flow, and cardiovascular and blood gas data before, during, and after fetal breathing movements in conscious chronically catheterized fetal lambs. During fetal breathing movements, O2 consumption increased by 30% from a control value of 7.7 +/- 0.7 (SE) ml X min-1 X kg-1. Umbilical blood flow was 210 +/- 21 ml X min-1 X kg-1 before fetal breathing movements; in 9 of 16 samples it increased by 52 +/- 12 ml X min-1 X kg-1, while in the other 7 it decreased by 23 +/- 9 ml X min-1 X kg-1. Umbilical arterial and venous O2 partial pressures and pH fell during fetal breathing movements, and the fall was greater when umbilical blood flow was decreased. Partial CO2 pressure rose in both vessels, and again the increase was greatest when umbilical blood flow fell during fetal breathing movements. Also associated with a fall in umbilical blood flow was the transition from low-amplitude irregular to large-amplitude regular fetal breathing movements. It is concluded that fetal breathing movements increase fetal O2 demands and are associated with a transient deterioration in fetal blood gas status, which is most severe during large-amplitude breathing movements.     

Influence of sleep on the cardiovascular and metabolic responses to a decrease in ambient temperature in lambs

Experiments were done on seven lambs between the ages of 10 and 24 days to investigate the effects of sleep on the cardiovascular and metabolic responses to a decrease in ambient temperature. Each lamb was anesthetized and instrumented for recordings of electrocorticogram, electro-oculogram, and nuchal electromyograms and measurements of cardiac output, systemic and pulmonic pressures and hemoglobin oxygen saturations as well as body core temperature. No sooner than three days after surgery, measurements were made during periods of quiet wakefulness, quiet sleep and active sleep at ambient temperatures of 25 degrees C and 18 degrees C. Decreasing the environmental temperature from 25 degrees C to 18 degrees C elicited a similar thermogenic response during quiet wakefulness, quiet sleep and active sleep as evidenced by an increase in total body oxygen consumption. The increased metabolic oxygen demand was met by an increase in systemic oxygen transport as well as by an increase in total body oxygen extraction. Since shivering was absent during active sleep, it is likely that nonshivering thermogenesis played a major role in the metabolic response. Our data provide evidence that sleep does not significantly alter the cardiovascular and metabolic responses to a modest decrease in ambient temperature in young lambs.     

Thermoregulation in rats during early postnatal maturation: importance of nitric oxide

Experiments were carried out to determine the role of nitric oxide in mediating autonomic and behavioral thermoregulatory control in rat pups on postnatal days 1-2, 5-6, and 10-11. For an experiment, each pup received a subcutaneous injection of vehicle, NG-nitro-D-arginine methyl ester (D-NAME; 100 mg/kg), or NG-nitro-L-arginine methyl ester (L-NAME; 100 mg/kg) before being placed in a metabolic chamber or in a thermocline with a linear temperature gradient of 23 to 43 degrees C. In the metabolic chamber, oxygen consumption and core temperature were measured as ambient temperature was decreased from 40 to 15 degrees C over a 60-min period. Decreasing ambient temperature elicited an increase in oxygen consumption in all age groups that received vehicle or d-NAME. The lower critical temperature and peak oxygen consumption upon exposure to cold after vehicle were 41 +/- 10 ml x kg(-1) x min(-1) at 30 degrees C, 43 +/- 12 ml x kg(-1) x min(-1) at 28 degrees C, and 55 +/- 11 ml x kg(-1) x min(-1) at 25 degrees C in the 1- to 2-, 5- to 6-, and 10- to 11-day-old pups, respectively. Administration of L-NAME abolished the oxygen consumption response to cold in the 1- to 2- and 5- to 6-day-old pups and significantly attenuated the oxygen consumption response to cold in the 10- to 11-day-old pups. Selected ambient temperature in the thermocline was not significantly affected by prior administration of D-NAME or L-NAME compared with vehicle. Thus our data provide evidence that the nitric oxide system plays a role in mediating autonomic but not behavioral thermoregulatory control in rat pups during early postnatal maturation.     

Dynamics of breathing in the hypoxic awake lamb

Newborn mammals respond to hypoxia with an immediate hyperventilation that is rapidly dampened. Changes in mechanical properties of the respiratory system during hypoxia have been considered an important reason for this fall in minute ventilation (VE). We have studied the dynamic mechanical behavior of the respiratory system in eight unanesthetized intact newborn lambs (mean age 2 days) during normoxia and hypoxia (FIO2 = 0.08). Mouth pressure (P), airflow (V), and volume (V) were recorded while lambs were breathing through a leak-proof face mask and a pneumotachograph. Active compliance (C') and resistance (R') of the respiratory system were computed from P developed during an inspiratory effort against airway closure at end expiration and V and V of the preceding breaths. Tidal expiratory V-V curves were analyzed to estimate the elevation in functional residual capacity (FRC) over resting volume (Vr). After hypoxia, there was an immediate increase in VE in the first 2 min, from 0.49 to 1.13 l.kg-1.min-1, followed by a rapid decrease to 0.80. After 8 min of hypoxia, C' was unchanged. The inspiratory R' decreased during hypoxia, probably reflecting a drop in inspiratory laryngeal resistance. The expiratory V-V curves during hypoxia showed considerable braking, often with a double peak in expiratory V. This pattern was only occasionally seen during normoxia. In animals with a linear segment of the expiratory V-V curves the FRC-Vr difference could be calculated and averaged 1.93 ml/kg during normoxia and 3.47 during hypoxia. The recoil P of the respiratory system at end expiration was 0.75 cmH2O during normoxia vs. 1.63 cmH2O during hypoxia (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

The energetics of the common mole rat Cryptomyś, a subterranean eusocial rodent from Zambia

Body temperature, oxygen consumption, respiratory and cardiac activity and body mass loss were measured in six females and four males of the subterranean Zambian mole rat Cryptomys sp. (karyotype 2 n=68), at ambient temperatures between 10 and 35°C. Mean body temperature ranged between 36.1 and 33.2°C at ambient temperatures of 32.5–10°C and was lower in females (32.7°C) than in males (33.9°C) at ambient temperatures of 10°C but dit not differ at thermoneutrality (32.5°C). Except for body temperature, mean values of all other parameters were lowest at thermoneutrality. Mean basal oxygen consumption of 0.76 ml O₂·g^-1· h^-1 was significantly lower than expected according to allometric equations and was different in the two sexes (females: 0.82 ml O₂·g^-1·h^-1, males: 0.68 ml O₂·g¹·h^-1) but was not correlated with body mass within the sexes. Basal respiratory rate of 74·min^-1 (females: 66·min¹, males: 87·min^-1) and basal heart rate of 200·min^-1 (females: 190·min^-1, males: 216·min^-1) were almost 30% lower than predicted, and the calculated thermal conductance of 0.144 ml O₂·g^-1·h¹·°C^-1 (females; 0.153 ml O₂·g^-1·h^-1·°C^-1, males: 0.131 ml O₂·g^-1·h^-1·°C^-1) was significantly higher than expected. The body mass loss in resting mole rats of 8.6–14.1%·day^-1 was high and in percentages higher in females than in males. Oxygen consumption and body mass loss as well as respiratory and cardiac activity increased at higher and lower than thermoneutral temperatures. The regulatory increase in O₂ demand below thermoneutrality was mainly saturated by increasing tidal volume but at ambient temperatures <15°C, the additional oxygen consumption was regulated by increasing frequency with slightly decreasing tidal volume. Likewise, the additional blood transport capacity was mainly effected by an increasing stroke volume while there was only a slight increase of heart frequency. In an additional field study, temperatures and humidity in different burrow systems have been determined and compared to environmental conditions above ground. Constant temperatures in the nest area 70 cm below ground between 26 and 28°C facilitate low resting metabolic rates, and high relative humidity minimizes evaporative water loss but both cause thermoregulatory problems such as overheating while digging. In 13–16 cm deep foraging tunnels, temperature fluctuations were higher following the above ground fluctuations with a time lag. Dominant breeding females had remarkably low body temperatures of 31.5–32.3°C at ambient temperatures of 20°C and appeared to be torpid. This reversible hypothermy and particular social structure involving division of labour are discussed as a strategy reducing energy expenditure in these eusocial subterranean animals with high foraging costs.Abbreviations BMR basal metabolic rate - br breath - C thermal conductance - HR neart rate - LD light/dark - M _b body mass - MR metabolic rate - OP oxygen pulse - PCO₂ partial pressure of carbon dioxide - PO₂ partial pressure of oxygen - RMR resting metabolic rate - RR respiratory rate - T _a ambient temperature - T _b body temperature - TNZ thermal neural zone - O₂ oxygen consumption     

Ventilatory accommodation of oxygen demand and respiratory water loss in a large bird,the emu (Dromaius novaehollandiae), and a re-examination of ventilatory allometry for birds

Ventilation was studied in the emu, a large flightless bird of mass 40kg, within the range of ambient temperatures from-5 to 45°C. Data for the emu and 21 other species were used to calculate allometric relationships for resting ventilatory parameters in birds (breath frequency=13.5 mass^-0.314; tidal volume=20.7 mass^1.0). At low ambient temperatures the ventilatory system must accommodate the increased metabolic demand for oxygen. In the emu this was achieved by a combination of increased tidal volume and increased oxygen extraction. Data from emus sitting and standing at-5°C, when metabolism is 1.5x and 2.6x basal metabolic rate, respectively, indicate that at least in the emu an increase in oxygen extraction can be stimulated by low temperature independent of oxygen demand. At higher ambient temperatures ventilation was increased to facilitate respiratory water loss. The emu achieved this by increased respiratory frequency. At moderate heat loads (30–35°C) tidal volume fell. This is usually interpreted as a mechanism whereby respiratory water loss can be increased without increasing parabronchial ventilation. At 45°C tidal volume increased; however, past studies have shown that CO₂ washout is minimal under these conditions. The mechanism whereby this is possible is discussed.Abbreviations BMR basal metabolic rate - BTPS body temperature, ambient pressure, saturated - EO ₂ oxygen extraction - EWL evaporative water loss - f _R ventilation frequency - RH relative humidity - RHL respiratory heat loss - SEM standard error of the mean - SNK student-Newman-Keuls multiple range test - STPD standard temperature and pressure, dry - T _a ambient temperatures(s) - T _b body temperature(s) - T _ex expired air temperature(s) - T _rh chamber excurrent air temperature - V _J ventilation - VO₂ oxygen consumption - V _T tidal volume - V/Q air ventilation to blood perfusion ratio     

Homeostatic responses to caloric restriction: influence of background metabolic rate.

The biological responses to caloric restriction (CR) are generally examined in rats with elevated metabolic rates due to being housed at ambient temperatures (T(a)) below the zone of thermoneutrality. We determined the physiological and behavioral responses to 2 wk of 30-40% CR in male FBNF1 rats housed in cool (T(a) = 12 degrees C) or thermoneutral (TMN; T(a) = 30 degrees C) conditions. Rats were instrumented with telemetry devices and housed continuously in home-cage calorimeters for the entire experiment. At baseline, rats housed in cool T(a) had reduced rate of weight gain; thus a mild CR (5%) group at thermoneutrality for weight maintenance was also studied. Rats housed in cool T(a) exhibited elevated caloric intake (cool = 77 +/- 1; TMN = 54 +/- 2 kcal), oxygen consumption (Vo(2); cool = 9.9 +/- 0.1; TMN = 5.5 +/- 0.1 ml/min), mean arterial pressure (cool = 103 +/- 1; TMN = 80 +/- 2 mmHg), and heart rate (cool = 374 +/- 3; TMN = 275 +/- 4 beats/min). Cool-CR rats exhibited greater CR-induced weight loss (cool = -62 +/- 3; TMN = -42 +/- 3 g) and reductions in Vo(2) (cool = -2.6 +/- 0.1; TMN = -1.5 +/- 0.1 ml/min) but similar CR-induced reductions in heart rate (cool = -59 +/- 1; TMN= -51 +/- 7 beats/min). CR had no effect on arterial blood pressure or locomotor activity in either group. Unexpectedly, weight maintenance produced significant reductions in Vo(2) and heart rate. At thermoneutrality, a single day of refeeding effectively abolished CR-induced reductions in Vo(2) and heart rate. The results reveal that rats with low or high baseline metabolic rate exhibit comparable compensatory reductions in Vo(2) and heart rate and suggest that T(a) can be used to modulate the metabolic background on which the more prolonged effects of CR can be studied.     

Cardiovascular and metabolic responses to fasting and thermoneutrality are conserved in obese Zucker rats

The primary purpose of the study was to test the hypothesis that reduced leptin signaling is necessary to elicit the cardiovascular and metabolic responses to fasting. Lean (Fa/?; normal leptin receptor; n = 7) and obese (fa/fa; mutated leptin receptor; n = 8) Zucker rats were instrumented with telemetry transmitters and housed in metabolic chambers at 23 degrees C (12:12-h light-dark cycle) for continuous (24 h) measurement of metabolic and cardiovascular variables. Before fasting, mean arterial pressure (MAP) was higher (MAP: obese = 103 +/- 3; lean = 94 +/- 1 mmHg), whereas oxygen consumption (VO(2): obese = 16.5 +/- 0.3; lean = 18.6 +/- 0.2 ml. min(-1). kg(-0.75)) was lower in obese Zucker rats compared with their lean controls. Two days of fasting had no effect on MAP in either lean or obese Zucker rats, whereas VO(2) (obese = -3.1 +/- 0.3; lean = -2.9 +/- 0.1 ml. min(-1). kg(-0.75)) and heart rate (HR: obese = -56 +/- 4; lean = -42 +/- 4 beats/min) were decreased markedly in both groups. Fasting increased HR variability both in lean (+1.8 +/- 0.4 ms) and obese (+2.6 +/- 0.3 ms) Zucker rats. After a 6-day period of ad libitum refeeding, when all parameters had returned to near baseline levels, the cardiovascular and metabolic responses to 2 days of thermoneutrality (ambient temperature 29 degrees C) were determined. Thermoneutrality reduced VO(2) (obese = -2.4 +/- 0.2; lean = -3.3 +/- 0.2 ml. min(-1). kg(-0.75)), HR (obese = -46 +/- 5; lean = -55 +/- 4 beats/min), and MAP (obese = -13 +/- 6; lean = -10 +/- 1 mmHg) similarly in lean and obese Zucker rats. The results indicate that the cardiovascular and metabolic responses to fasting and thermoneutrality are conserved in Zucker rats and suggest that intact leptin signaling may not be requisite for the metabolic and cardiovascular responses to reduced energy intake.     

Regulation of end-expiratory lung volume during sleep in premature infants

To investigate the regulation of end-expiratory lung volume (EEV) in premature infants, we recorded airflow, tidal volume, diaphragm electromyogram (EMG), and chest wall displacement during sleep. In quiet sleep, EEV during breathing was 10.8 +/- 3.6 (SD) ml greater than the minimum volume reached during unobstructed apneas. In active sleep, no decrease in EEV was observed during 28 of 35 unobstructed apneas. Breaths during quiet sleep had a variable extent of expiratory airflow retardation (braking), and inspiratory interruption occurred at substantial expiratory flow rates. During active sleep, the expiratory flow-volume curve was nearly linear, proceeding nearly to the volume axis at zero flow, and diaphragm EMG activity terminated near the peak of mechanical inspiration. Expiratory duration (TE) and inspiratory duration (TI) were significantly shortened in quiet sleep vs. active sleep although tidal volume was not significantly different. In quiet sleep, diaphragmatic braking activity and shortened TE combined to maintain EEV during breathing substantially above relaxation volume. In active sleep, reduced expiratory braking and prolongation of TE resulted in an EEV that was close to relaxation volume. We conclude that breathing strategy to regulate EEV in premature infants appears to be strongly influenced by sleep state.     

Effects of expiratory resistive loading on the sensation of dyspnea

To determine whether an increase in expiratory motor output accentuates the sensation of dyspnea (difficulty in breathing), the following experiments were undertaken. Ten normal subjects, in a series of 2-min trials, breathed freely (level I) or maintained a target tidal volume equal to (level II) or twice the control (level III) at a breathing frequency of 15/min (similar to the control frequency) with an inspiratory load, an expiratory load, and without loads under hyperoxic normocapnia. In tests at levels II and III, end-expiratory lung volume was maintained at functional residual capacity. A linear resistance of 25 cmH2O.1(-1).s was used for both inspiratory and expiratory loading; peak mouth pressure (Pm) was measured, and the intensity of dyspnea (psi) was assessed with a visual analog scale. The sensation of dyspnea increased significantly with the magnitude of expiratory Pm during expiratory loading (level II: Pm = 9.4 +/- 1.5 (SE) cmH2O, psi = 1.26 +/- 0.35; level III: Pm = 20.3 +/- 2.8 cmH2O, psi = 2.22 +/- 0.48) and with inspiratory Pm during inspiratory loading (level II: Pm = 9.7 +/- 1.2 cmH2O, psi = 1.35 +/- 0.38; level III: Pm = 23.9 +/- 3.0 cmH2O, psi = 2.69 +/- 0.60). However, at each level of breathing, neither the intensity of dyspnea nor the magnitude of peak Pm during loading was different between inspiratory and expiratory loading. The augmentation of dyspnea during expiratory loading was not explained simply by increases in inspiratory activity. The results indicate that heightened expiratory as well as inspiratory motor output causes comparable increases in the sensation of difficulty in breathing.     

Effects of augmented respiratory muscle pressure production on locomotor limb venous return during calf contraction exercise.

We determined effects of augmented inspiratory and expiratory intrathoracic pressure or abdominal pressure (Pab) excursions on within-breath changes in steady-state femoral venous blood flow (Qfv) and net Qfv during tightly controlled (total breath time = 4 s, duty cycle = 0.5) accessory muscle/"rib cage" (DeltaPab <2 cmH2O) or diaphragmatic (DeltaPab >5 cmH2O) breathing. Selectively augmenting inspiratory intrathoracic pressure excursion during rib cage breathing augmented inspiratory facilitation of Qfv from the resting limb (69% and 89% of all flow occurred during nonloaded and loaded inspiration, respectively); however, net Qfv in the steady state was not altered because of slight reductions in femoral venous return during the ensuing expiratory phase of the breath. Selectively augmenting inspiratory esophageal pressure excursion during a predominantly diaphragmatic breath at rest did not alter within-breath changes in Qfv relative to nonloaded conditions (net retrograde flow = -9 +/- 12% and -4 +/- 9% during nonloaded and loaded inspiration, respectively), supporting the notion that the inferior vena cava is completely collapsed by relatively small increases in gastric pressure. Addition of inspiratory + expiratory loading to diaphragmatic breathing at rest resulted in reversal of within-breath changes in Qfv, such that >90% of all anterograde Qfv occurred during inspiration. Inspiratory + expiratory loading also reduced steady-state Qfv during mild- and moderate-intensity calf contractions compared with inspiratory loading alone. We conclude that 1) exaggerated inspiratory pressure excursions may augment within-breath changes in femoral venous return but do not increase net Qfv in the steady state and 2) active expiration during diaphragmatic breathing reduces the steady-state hyperemic response to dynamic exercise by mechanically impeding venous return from the locomotor limb, which may contribute to exercise limitation in health and disease.     

Respiratory changes induced by prolonged laryngeal stimulation in awake piglets

To examine the role of the laryngeal reflex in modulating cardiorespiratory function, we stimulated the superior laryngeal nerves (SLN) bilaterally in unanesthetized, chronically instrumented piglets (n = 10, age 5-14 days). The SLN were placed in cuff electrodes and wires were exteriorized in the neck for stimulation. A cannula placed in the aorta was used for blood pressure recording and arterial blood sampling. During each experiment, 1-2 days after surgery, ventilation was recorded using whole-body plethysmography, and electroencephalogram and electrocardiogram were recorded after acute subcutaneous electrode placement. After base-line recordings, the SLN were electrically stimulated for 1 h. During this period, mean respiratory frequency decreased by 40-75% and apneas of 10-15 s were regularly interspersed between single breaths or clusters of breaths. Periods of breathing were always associated with opening of the eyes and generally with head and body movements, an awakening that occurred every 10-15 s. At 1 h into the stimulus period, minute ventilation had decreased by 57 +/- 7% (mean +/- SE), arterial partial pressure of O2 (PaO2) by 68 +/- 3 Torr, and arterial partial pressure of CO2 (PaCO2) had increased by 19 +/- 2 Torr. Throughout the entire stimulus period, mean blood pressure and average heart rate were maintained within 12% of base line. We suggest that: low-threshold SLN afferents exert primarily respiratory effects and only minor cardiovascular effects; breathing during laryngeal reflex activation is sustained by an arousal system; and the laryngeal reflex does not pose an imminent threat to the unanesthetized, awake, young animal.     

Energetics and thermoregulation during digging in the rodent tuco-tuco (Ctenomys talarum)

For subterranean rodents, searching for food by extension of the tunnel system and maintenance of body temperature are two of the most important factors affecting their life underground. In this study we assess the effect of ambient temperature on energetics and thermoregulation during digging in Ctenomys talarum. We measured VO2 during digging and resting at ambient temperature (Ta) below, within, and above thermoneutrality. Digging metabolic rate was lowest at Ta within the thermoneutral zone and increased at both lower and higher temperatures, but body temperature (Tb) remained constant at all Tas. Below thermoneutrality, the cost of digging and thermoregulation are additive. Heat production for thermoregulation would be compensated by heat produced as a by-product of muscular activity during digging. Above thermoneutrality, conduction would be an important mechanism to maintain a constant Tb during digging.     

Effects of naloxone on breathing movements during hypercapnia in the fetal lamb

To determine whether endogenous opioids influence the fetal breathing response to CO2 we have investigated the effect of the opiate antagonist, naloxone on the incidence, rate, and amplitude of breathing movements during hypercapnia in fetal lambs in utero. In 20 experiments in six pregnant sheep (130-145 days gestation) hypercapnia was induced by giving the ewe 4-6% CO2-18% O2 in N2 to breathe for 60 min. After 30 min of hypercapnia either naloxone (13 experiments) or saline (7 experiments) was infused intravenously for the remaining 30 min. During hypercapnia breath amplitude increased from 5.8 +/- 0.5 to 9.1 +/- 1.2 mmHg (P less than 0.001), and infusion of naloxone was associated with a further significant increase to 15.7 +/- 1.2 mmHg (P less than 0.001). Naloxone had no effect on the incidence or rate of breathing movements during hypercapnia. After hypercapnia there was a significant decrease in the incidence of fetal breathing movements in the naloxone group (14.7 +/- 3.2%). Infusion of saline during hypercapnia had no effect on incidence, rate, or amplitude of fetal breathing movements. These results suggest that endogenous opioids act to suppress or limit breath amplitude during hypercapnia but do not affect rate or incidence of breathing movements.