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Biomedical subjects

William K Milsom

Publications and source records attributed to William K Milsom.

At least 19 recordsLinked to original sources
PubMed2006

Ventilatory roll off during sustained hypercapnia is gender specific in pekin ducks.

The objective of the present study was to examine the relative roles of peripheral versus central mechanisms in producing ventilatory adjustments in pekin ducks during prolonged (5 h) hypercapnia (5% inspired CO2), and to determine whether these adjustments differed between male and female ducks. After 20 min of CO2 exposure, intact ducks increased total ventilation (VE) 2.5-3-fold above control values, due to large increases (approximately 200%) in tidal volume (VT) and slightly smaller increases (approximately 140%) in breathing frequency (fR). This response was accompanied by respiratory acidosis (pHa fell from approximately 7.46 to approximately 7.41) and hypercapnia (PaCO2 increased from approximately 35 to approximately 40 Torr). In males, VE fell progressively thereafter due exclusively to a fall in fR, in parallel with a rapid partial recovery of pH (to 7.44) while PaCO2 continued to climb (to approximately 42 Torr). In females, VE remained elevated during hypercapnia, and no pH recovery occurred. This suggests that a respiratory decline resulting from acid-base compensation (probably due to HCO3- mobilization) occurred in males but not in females. Bicarbonate mobilization, and thus pH compensation, may have been reduced in females due to the CaCO3 requirements of eggshell formation. In males, the acute ventilatory response was reduced slightly by denervation of the carotid bodies or intrapulmonary chemoreceptors, but there was no effect of denervation of either receptor group on the responses to prolonged CO2. We conclude that pH compensation triggered by constant or increasing PaCO2, acting at central chemoreceptors, likely mediates the respiratory adjustments seen in male pekin ducks during hypercapnia. Furthermore, we suggest that this ventilatory response be considered a gender-specific hypercapnic ventilatory roll off, in the context of the various time domains of the hypercapnic ventilatory response.

Adaptation, Physiological↗
PubMed2006

Control of breathing in anuran amphibians.

The primary role of the respiratory system is to ensure adequate tissue oxygenation, eliminate carbon dioxide and help to regulate acid-base status. To maintain this homeostasis, amphibians possess an array of receptors located at peripheral and central chemoreceptive sites that sense respiration-related variables in both internal and external environments. As in mammals, input from these receptors is integrated at central rhythmogenic and pattern-forming elements in the medulla in a manner that meets the demands determined by the environment within the constraints of the behavior and breathing pattern of the animal. Also as in mammals, while outputs from areas in the midbrain may modulate respiration directly, they do not play a significant role in the production of the normal respiratory rhythm. However, despite these similarities, the breathing patterns of the two classes are different: mammals maintain homeostasis of arterial blood gases through rhythmic and continuous breathing, whereas amphibians display an intermittent pattern of aerial respiration. While the latter is also often rhythmic, it allows a degree of fluctuation in key respiratory variables that has led some to suggest that control is not as tight in these animals. In this review we will focus specifically on recent advances in studies of the control of ventilation in anuran amphibians. This is the group of amphibians that has attracted the most recent attention from respiratory physiologists.

Animals↗
PubMed2006

Flying high: a theoretical analysis of the factors limiting exercise performance in birds at altitude.

The ability of some bird species to fly at extreme altitude has fascinated comparative respiratory physiologists for decades, yet there is still no consensus about what adaptations enable high altitude flight. Using a theoretical model of O(2) transport, we performed a sensitivity analysis of the factors that might limit exercise performance in birds. We found that the influence of individual physiological traits on oxygen consumption (Vo2) during exercise differed between sea level, moderate altitude, and extreme altitude. At extreme altitude, haemoglobin (Hb) O(2) affinity, total ventilation, and tissue diffusion capacity for O(2) (D(To2)) had the greatest influences on Vo2; increasing these variables should therefore have the greatest adaptive benefit for high altitude flight. There was a beneficial interaction between D(To2) and the P(50) of Hb, such that increasing D(To2) had a greater influence on Vo2 when P(50) was low. Increases in the temperature effect on P(50) could also be beneficial for high flying birds, provided that cold inspired air at extreme altitude causes a substantial difference in temperature between blood in the lungs and in the tissues. Changes in lung diffusion capacity for O(2), cardiac output, blood Hb concentration, the Bohr coefficient, or the Hill coefficient likely have less adaptive significance at high altitude. Our sensitivity analysis provides theoretical suggestions of the adaptations most likely to promote high altitude flight in birds and provides direction for future in vivo studies.

Adaptation, Physiological↗
PubMed2006

The role of branchial and orobranchial O2 chemoreceptors in the control of aquatic surface respiration in the neotropical fish tambaqui (Colossoma macropomum): progressive responses to prolonged hypoxia.

The present study examined the role of branchial and orobranchial O(2) chemoreceptors in the cardiorespiratory responses, aquatic surface respiration (ASR), and the development of inferior lip swelling in tambaqui during prolonged (6 h) exposure to hypoxia. Intact fish (control) and three groups of denervated fish (bilateral denervation of cranial nerves IX+X (to the gills), of cranial nerves V+VII (to the orobranchial cavity) or of cranial nerves V alone), were exposed to severe hypoxia (Pw(O)2=10 mmHg) for 360 min. Respiratory frequency (fr) and heart rate (fh) were recorded simultaneously with ASR. Intact (control) fish increased fr, ventilation amplitude (V(AMP)) and developed hypoxic bradycardia in the first 60 min of hypoxia. The bradycardia, however, abated progressively and had returned to normoxic levels by the last hour of exposure to hypoxia. The changes in respiratory frequency and the hypoxic bradycardia were eliminated by denervation of cranial nerves IX and X but were not affected by denervation of cranial nerves V or V+VII. The V(AMP) was not abolished by the various denervation protocols. The fh in fish with denervation of cranial nerves V or V+VII, however, did not recover to control values as in intact fish. After 360 min of exposure to hypoxia only the intact and IX+X denervated fish performed ASR. Denervation of cranial nerve V abolished the ASR behavior. However, all (control and denervated (IX+X, V and V+VII) fish developed inferior lip swelling. These results indicate that ASR is triggered by O(2) chemoreceptors innervated by cranial nerve V but that other mechanisms, such as a direct effect of hypoxia on the lip tissue, trigger lip swelling.

Adaptation, Physiological↗
PubMed2005

Regulation of ventilation in the caiman (Caiman latirostris): effects of inspired CO2 on pulmonary and upper airway chemoreceptors.

In order to study the relative roles of receptors in the upper airways, lungs and systemic circulation in modulating the ventilatory response of caiman (Caiman latirostris) to inhaled CO2, gas mixtures of varying concentrations of CO2 were administered to animals breathing through an intact respiratory system, via a tracheal cannula by-passing the upper airways (before and after vagotomy), or via a cannula delivering gas to the upper airways alone. While increasing levels of hypercarbia led to a progressive increase in tidal volume in animals with intact respiratory systems (Series I), breathing frequency did not change until the CO2 level reached 7%, at which time it decreased. Despite this, at the higher levels of hypercarbia, the net effect was a large and progressive increase in total ventilation. There were no associated changes in heart rate or arterial blood pressure. On return to air, there was an immediate change in breathing pattern; breathing frequency increased above air-breathing values, roughly to the same maximum level regardless of the level of CO2 the animal had been previously breathing, and tidal volume returned rapidly toward resting (baseline) values. Total ventilation slowly returned to air breathing values. Administration of CO2 via different routes indicated that inhaled CO2 acted at both upper airway and pulmonary CO2-sensitive receptors to modify breathing pattern without inhibiting breathing overall. Our data suggest that in caiman, high levels of inspired CO2 promote slow, deep breathing. This will decrease dead-space ventilation and may reduce stratification in the saccular portions of the lung.

Alligators and Crocodiles↗
PubMed2005

Dipalmitoylphosphatidylcholine is not the major surfactant phospholipid species in all mammals.

Pulmonary surfactant, a complex mixture of lipids and proteins, lowers the surface tension in terminal air spaces and is crucial for lung function. Within an animal species, surfactant composition can be influenced by development, disease, respiratory rate, and/or body temperature. Here, we analyzed the composition of surfactant in three heterothermic mammals (dunnart, bat, squirrel), displaying different torpor patterns, to determine: 1) whether increases in surfactant cholesterol (Chol) and phospholipid (PL) saturation occur during long-term torpor in squirrels, as in bats and dunnarts; 2) whether surfactant proteins change during torpor; and 3) whether PL molecular species (molsp) composition is altered. In addition, we analyzed the molsp composition of a further nine mammals (including placental/marsupial and hetero-/homeothermic contrasts) to determine whether phylogeny or thermal behavior determines molsp composition in mammals. We discovered that like bats and dunnarts, surfactant Chol increases during torpor in squirrels. However, changes in PL saturation during torpor may not be universal. Torpor was accompanied by a decrease in surfactant protein A in dunnarts and squirrels, but not in bats, whereas surfactant protein B did not change in any species. Phosphatidylcholine (PC)16:0/16:0 is highly variable between mammals and is not the major PL in the wombat, dunnart, shrew, or Tasmanian devil. An inverse relationship exists between PC16:0/16:0 and two of the major fluidizing components, PC16:0/16:1 and PC16:0/14:0. The PL molsp profile of an animal species is not determined by phylogeny or thermal behavior. We conclude that there is no single PL molsp composition that functions optimally in all mammals; rather, surfactant from each animal is unique and tailored to the biology of that animal.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2005

Effects of two protocols of intermittent hypoxia on human ventilatory, cardiovascular and cerebral responses to hypoxia.

We determined the ventilatory, cardiovascular and cerebral tissue oxygen response to two protocols of normobaric, isocapnic, intermittent hypoxia. Subjects (n = 18, male) were randomly assigned to short-duration intermittent hypoxia (SDIH, 12% O2 separated by 5 min of normoxia for 1 h) or long-duration intermittent hypoxia (LDIH, 30 min of 12% O2). Both groups had 10 exposures over a 12 day period. The hypoxic ventilatory response (HVR) was measured before each daily intermittent hypoxia exposure on days 1, 3, 5, 8, 10 and 12. The HVR was measured again 3 and 5 days after the end of intermittent hypoxia. During all procedures, ventilation, blood pressure, heart rate, arterial oxyhaemoglobin saturation and cerebral tissue oxygen saturation were measured. The HVR increased throughout intermittent hypoxia exposure regardless of protocol, and returned to baseline by day 17 (day 1, 0.84 +/- 0.50; day 12, 1.20 +/- 1.01; day 17, 0.95 +/- 0.58 l min(-1) %S(aO2)(-1); P < 0.01). The change in systolic blood pressure sensitivity (r = +0.68; P < 0.05) and the change in diastolic blood pressure sensitivity (r = +0.73; P < 0.05) were related to the change in HVR, while the change in heart rate sensitivity was not (r = +0.32; NS). The change in cerebral tissue oxygen saturation sensitivity to hypoxia was less on day 12, and returned to baseline by day 17 (day 1, -0.51 +/- 0.13; day 12, -0.64 +/- 0.18; day 17, -0.51 +/- 0.13; P < 0.001). Acute exposure to SDIH increased mean arterial pressure (+5 mmHg; P < 0.01), but LDIH did not (P > 0.05). SDIH and LDIH had similar effects on the ventilatory and cardiovascular response to acute progressive hypoxia and hindered cerebral oxygenation. Our findings indicate that the vascular processes required to control blood flow and oxygen supply to cerebral tissue in a healthy human are hindered following exposure to 12 days of isocapnic intermittent hypoxia.

Adaptation, Physiological↗
PubMed2005

Reciprocal modulation of O2 and CO2 cardiorespiratory chemoreflexes in the tambaqui.

This study examined the effect of acute hypoxic and hypercapnic cardiorespiratory stimuli, superimposed on existing cardiorespiratory disturbances in tambaqui. In their natural habitat, these fish often encounter periods of hypoxic hypercapnia that can be acutely exacerbated by water turnover. Tambaqui were exposed to periods of normoxia, hypoxia, hyperoxia and hypercapnia during which, externally oriented O2 and CO2 chemoreceptors were further stimulated, by administration into the inspired water of sodium cyanide and CO2-equilibrated water, respectively. Hyperoxic water increased the sensitivity of the NaCN-evoked increase in breathing frequency (f(R)) and decrease in heart rate. Hypoxia and hypercapnia attenuated the increase in f(R) but, aside from blood pressure, did not influence the magnitude of NaCN-evoked cardiovascular changes. Water PO2 influenced the magnitude of the CO2-evoked cardiorespiratory changes and the sensitivity of CO2-evoked changes in heart rate and blood flow. The results indicate that existing respiratory disturbances modulate cardiorespiratory responses to further respiratory challenges reflecting both changes in chemosensitivity and the capacity for further change.

Animals↗
PubMed2004

Evolutionary trends in airway CO2/H+ chemoreception.

In many species of air-breathing vertebrates CO2-sensitive airway receptors play an important role in ventilatory control. In ectotherms, olfactory receptors often inhibit breathing and prolong breath holding when environmental CO2 levels are high. CO2/H+ sensitive pulmonary receptors (intra pulmonary chemoreceptors (IPC) and pulmonary stretch receptors (PSR)) regulate breathing patterns in all vertebrates in a manner that reduces dead space ventilation and enhances the efficiency of CO2 excretion under conditions of environmental hypercarbia, and/or reduces CO2 loss from hyperventilation. The greater CO2 sensitivity of IPC may allow them to also serve as a venous CO2 receptor (at least transiently when levels of metabolically produced CO2 begin to rise), prevent alkalosis during hyperpnea/polypnea, and may have contributed to the evolution of the extremely thin air/blood barrier and increased diffusion capacity associated with the rigid avian lung. The presence of all three receptor groups with different degrees of CO2 sensitivity in most reptiles, however, gives rise to what appear to be anomalous responses to environmental CO2.

Biological Evolution↗
PubMed2004

The effect of O2 and CO2 on the dive behavior and heart rate of lesser scaup ducks (Aythya affinis): quantification of the critical PaO2 that initiates a diving bradycardia.

Lesser scaup ducks were trained to dive for short and long durations following exposure to various gas concentrations to determine the influence of oxygen (O2) and carbon dioxide (CO2) on diving behavior and heart rate. Compared with normoxia, hyperoxia (50% O2) significantly increased the duration of long dives, whereas severe hypoxia (9% O2) significantly decreased the duration of both short and long dives. Hypercapnia (5% CO2) had no effect on dive duration. Surface intervals were not significantly altered by the oxygen treatments, but significantly increased following CO2 exposure. Heart rate during diving was unaffected by hyperoxia and hypercapnia, but gradually declined in long dives after severe hypoxia. Thus, our results suggest that during the majority of dives, O2 and CO2 levels in lesser scaup ducks are managed through changes in diving behavior without any major cardiovascular adjustments, but below a threshold PaO2, a bradycardia is evoked to conserve the remaining oxygen for hypoxia sensitive tissues. A model of oxygen store utilization during voluntary diving was developed to estimate the critical PaO2 below which bradycardia is initiated (approximately 26 mmHg) and predicted that this critical PaO2 would be reached 19s into a dive after exposure to severe hypoxia, which corresponded exactly with the time of initiation of bradycardia in the severe hypoxia trials.

Analysis of Variance↗
PubMed2004

Pontine influences on respiratory control in ectothermic and heterothermic vertebrates.

Respiratory rhythm generators appear both evolutionarily and developmentally as paired segmental rhythm generators in the reticular formation, associated with the motor nuclei of cranial nerves V, VII, IX, X, and XII. Those associated with the Vth and VIIth motor nuclei are "pontine" in origin and in fishes that employ a buccal suction/force pump for breathing the primary pair of respiratory rhythm generators are associated with the trigeminal nuclei. In amphibians, while the basic respiratory pump remains the same, the dominant site of respiratory rhythm generation has been assumed by the facial, glossopharyngeal and vagal motor nuclei. In reptiles, birds and mammals, in general there is a switch to an aspiration pump driven by thoraco-lumbar muscles innervated by spinal nerves. In these groups, the critical sites necessary for respiratory rhythmogenesis now sit near the ponto-medullary border, in the parafacial region (which may underlie expiratory-dominated, intercostal-abdominal breathing in non-mammalian tetrapods) and in a more caudal region, the preBotzinger complex (which may underlie inspiratory-dominated diaphragmatic breathing in mammals).

Animals↗
PubMed2004

Pontine influences on breathing: an overview.

Historical and contemporary views of the functional organization of the lateral pontine regions influencing breathing are reviewed. In vertebrates, the rhombencephalon generates a breathing rhythm and detailed motor pattern that persist throughout life. Key to this process is an essentially continuous column of neurons extending from the spino-medullary border through the ventrolateral medulla, continuing through the ventral pons and arcing into the dorsolateral medulla. Comparative neuroanatomy and physiology indicate this is a richly interconnected network divided into serial, functionally distinct compartments. Serial compartmentalization of pontomedullary structures related to breathing also reflects the developmental segmentation of the rhombencephalon. However, with migration of cell groups such as the facial nucleus from the pons to the medulla during ontogeny, the boundaries of the adult pons are sometimes difficult to precisely define. Accordingly, a working definition of rostral and caudal pontine boundaries for adult mammals is depicted.

Animals↗
PubMed2004

Cardiorespiratory reflexes and aquatic surface respiration in the neotropical fish tambaqui (Colossoma macropomum): acute responses to hypercarbia.

We examined the cardiorespiratory responses to 6 h of acute hypercarbia (1, 2.5, and 5% CO(2)) in intact and gill-denervated (bilateral denervation of branchial branches of cranial nerves IX and X) tambaqui, Colossoma macropomum. Intact fish exposed to 1 and 2.5% CO(2) increased respiratory frequency ( f(R)) and ventilation amplitude ( V(AMP)) slowly over a 1- to 3-h period. Denervated fish did not show this response, suggesting that tambaqui possess receptors in the gills that will produce excitatory responses to low levels of hypercarbia (1 and 2.5% CO(2)) if the exposure is prolonged. The cardiac response to stimulation of these receptors with this level of CO(2) was a tachycardia and not a bradycardia. During exposure to 5% CO(2), intact fish increased f(R) and V(AMP), and showed a pronounced bradycardia after 1 h. After 2 h, the heart rate ( f(H)) started to increase, but returned to control values after 6 h. In denervated fish, the increase in f(R) was abolished. The slow increase in V(AMP) and the bradycardia were not abolished, suggesting that these changes arose from extra-branchial receptors. Neither intact nor denervated fish developed the swelling of the lower lip or performed aquatic surface respiration, even after 6 h, suggesting that these are unique responses to hypoxia and not hypercarbia.

Analysis of Variance↗
PubMed2004

The thermogenesis of digestion in rattlesnakes.

Some snakes have a feeding regime characterized by the infrequent ingestion of relatively large meals, causing impressive increments in post-prandial metabolism. Metabolism remains elevated for many days, while digestion proceeds, resulting in considerable investment of time and energy. Snakes actively adjust thermoregulatory behavior to raise their body temperature during digestion, exhibiting a post-prandial thermophilic response that accelerates digestion at the expense of higher metabolic rates. In the present study, we investigated the possibility that endogenously derived heat, originating as a byproduct of the post-prandial increase in metabolism, could itself contribute to the elevated body temperature during digestion in the South American rattlesnake Crotalus durissus. We assessed heat production, at a constant environmental temperature, by taking infrared (IR) images of snakes during fasting and after being fed meals varying from 10% to 50% of their own body masses. Our results show clearly that digesting rattlesnakes have significantly increased body temperatures, even when precluded from adjusting their thermoregulatory behavior. The feeding-derived thermogenesis caused the surface body temperature of rattlesnakes to increase by 0.9-1.2 degrees C, a temperature change that will significantly affect digestive performance. The alterations in body temperature following feeding correlated closely with the temporal profile of changes in post-prandial metabolism. Moreover, the magnitude of the thermogenesis was greater for snakes fed large meals, as was the corresponding metabolic response. Since IR imaging only assesses surface temperatures, the magnitude of the thermogenesis and the changes in deep core temperature could be even more pronounced than is reported here.

Animals↗
PubMed2003

Hypothermia-induced respiratory arrest and recovery in neonatal rats.

To examine the changes in breathing that occur during progressive hypothermia and rewarming in neonatal rats, we cooled and rewarmed rat pups during the first 6 days of life. During cooling, breathing stopped when rectal temperature (Tr) fell below 10.7+/-0.24 degrees C, and recovered spontaneously during rewarming when Tr reached 13.3+/-0.38 degrees C, regardless of age. During cooling, breathing frequency declined progressively, whereas tidal volume increased until Tr fell below 15 degrees C whence it declined to, but never below, normothermic levels. These data support suggestions that failure occurs at the level of the central rhythm generator for breathing and is not due to an inability to sustain the level of motor output. During rewarming, following respiratory arrest, the pattern of change was reversed, but with a significant thermal hysteresis, resulting in slower breathing and cardiac frequencies at any given rectal temperature during rewarming. There were no effects of age observed over the range studied on the changes in respiratory variables associated with hypothermia or rewarming. Breathing restarted spontaneously on rewarming with no evidence that gasping was required to initiate this process. The overall breathing pattern was episodic during the early stages of rewarming, however, suggesting that the respiratory rhythm is only periodically expressed during the initial stages of recovery from hypothermia.

Animals↗
PubMed2003

Effects of afferent input on the breathing pattern continuum in the tambaqui (Colossoma macropomum).

This study used a decerebrate and artificially-ventilated preparation to examine the roles of various afferent inputs in breathing pattern formation in the tambaqui (Colossoma macropomum). Three general breathing patterns were observed: (1) regular breathing; (2) frequency cycling and (3) episodic breathing. Under normoxic, normocapnic conditions, 50% of control fish exhibited regular continuous breathing and 50% exhibited frequency cycling. Denervation of the gills and oro-branchial cavity promoted frequency cycling. Central denervation of the glossopharyngeal and vagus nerves produced episodic breathing. Regardless of the denervation state, hyperoxia produced either frequency cycling or episodic breathing while hypoxia and hypercarbia shifted the pattern to frequency cycling and continuous breathing. We suggest that these breathing patterns represent a continuum from continuous to episodic breathing with waxing and waning occupying an intermediate stage. The data further suggest that breathing pattern is influenced by both specific afferent input from chemoreceptors and generalised afferent input while chemoreceptors specific for producing changes in breathing pattern may exist in fish.

Afferent Pathways↗
PubMed2003

Apneusis follows disruption of NMDA-type glutamate receptors in vagotomized ground squirrels.

The influences of N-methyl-D-aspartate (NMDA) type glutamate receptor antagonism, by (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine maleate (MK-801), on breathing pattern and ventilatory chemoresponses, were assessed in anaesthetized vagotomized spontaneously breathing golden-mantled ground squirrels, Spermophilus lateralis. MK-801 was administered by either bilateral pressure micro-injection into a region of the rostral dorsolateral pons, containing the medial and lateral Parabrachial and Kölliker-Fuse nuclei (the Parabrachial complex, PbC), or by systemic injection. Both treatments induced apneusis. These data indicate that functional NMDA receptor-mediated processes located within the PbC terminate inspiration and actively prevent apneusis in vagotomized ground squirrels. Although both hypercapnia and hypoxia stimulated breathing during the apneusis, the responses were generally slight. The breathing frequency component of the hypercapnic ventilatory response was completely eliminated supporting the hypothesis that the PbC is an integral component of the control network for CO(2) chemoreflex responses. Differences in the results of systemic versus PbC MK-801 illustrate that NMDA receptor-mediated processes outside the PbC do influence ventilation. Our data also show that such processes outside the PbC lengthen both inspiration and expiration in this species, slowing ventilation, and are necessary for the expression of the hypoxic ventilatory response.

Animals↗