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J Appl Physiol 101: 655-663, 2006. First published March 24, 2006; doi:10.1152/japplphysiol.00210.2006
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INVITED REVIEW

HIGHLIGHTED TOPIC
A Physiological Systems Approach to Human and Mammalian Thermoregulation

Components and mechanisms of thermal hyperpnea

Matthew D. White

Laboratory for Exercise and Environmental Physiology, School of Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada


   ABSTRACT
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 ABSTRACT
PHYSIOLOGICAL COMPONENTS OF...
 PROPOSED MECHANISMS OF THERMAL...
 RATIONALE FOR THE EXISTENCE...
 SUMMARY AND CONCLUSIONS
 REFERENCES
 
The pattern of breathing during a hyperthermia-induced hyperventilation varies across different species. Thermal tachypnea is a first phase panting response adopted during hyperthermia when tidal volume is minimized and the frequency of breathing is maximized. Blood-gas tensions and pH are maintained during this hyperventilation, and the associated heat loss helps the animal regulate its body temperature. A second pattern of breathing adopted in hyperthermia is thermal hyperpnea; this response is the focus of this review. This form of hyperventilation is evident after an increase in core temperature and it is apparent in humans. Increases of tidal volume as well as frequency of breathing are evident during this response that results in a respiratory alkalosis. The cause of thermal hyperpnea is not resolved; evidence of the potential mechanisms underlying this response support that modulators of the response act in either a multiplicative or additive manner with body temperatures. The details of the designs and methodologies of the studies supporting or refuting these two views are discussed. A physiological rationale for thermal hyperpnea is presented in which it is suggested this response serves a heat-loss role and contributes to selective brain cooling in hyperthermic humans. Ongoing research in this area is focused on resolving the mechanisms underlying thermal hyperpnea and its contribution to cranial thermoregulation. The direct application of this research is for the care of febrile and hyperthermic patients.

panting; pulmonary ventilation; thermal tachypnea; selective brain cooling

THE FOCUS OF THIS REVIEW is twofold. The first is to give a description of the thermal hyperpnea pattern of breathing that can be adopted during a hyperthermia-induced hyperventilation, and the second is to give a review of studies addressing the potential mechanisms underlying this response. This review is restricted to a discussion of the potential independent effects or interactions of the known principal peripheral and central modulators of pulmonary ventilation with body or tissue temperatures in humans and other homeothermic animals. The objective of the review is to demonstrate an emerging view that pulmonary ventilation is an important heat-loss response for cranial thermoregulation in hyperthermic humans.

The review is divided into three main sections followed by a summary and conclusions. The first section gives a description of the changes to pulmonary ventilation during hyperthermia and describes thermal hyperpnea as a pattern of breathing adopted after an elevation in core temperature (Tc). The second section reviews the potential mechanisms of thermal hyperpnea, and the third section presents a rationale for the existence of this hyperthermic-induced increase pulmonary ventilation in humans.


   PHYSIOLOGICAL COMPONENTS OF PULMONARY VENTILATION DURING HYPERTHERMIA
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Pulmonary ventilation during hyperthermia at rest.   In resting humans (36), nonhuman primates (12, 44), and horses (4, 50, 61, 63), an elevation in Tc by ~1°C induces a hyperventilation, whereas Tc increases of less than ~1°C do not influence pulmonary ventilation (22, 42, 92). For humans this response was first illustrated by Haldane (36) and subsequently by others (11, 19, 20, 34, 46, 55, 79, 85, 93) to induce a hyperventilation relative to metabolic needs. For hyperthermic humans, the prominent changes include significant elevations in both the respiratory exchange ratio and pulmonary ventilation when simultaneous O2 consumption increases can be less pronounced or absent (Fig. 1).


Figure 1
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  		Fig. 1. Mean pulmonary ventilation, metabolic, and heart rate responses for 7 male subjects. At minute 20 the elevations of core temperatures were ~1.5°C above resting normothermic levels. b·min–1, Beats/min. Reprinted from Ref. 11, with the kind permission of Springer Science and Business Media.

 
The magnitude of this response is seen with an elevation of human rectal temperature by ~1.0°C, and it gives an increase of both pulmonary ventilation by ~35% and of venous blood pH from ~7.38 to 7.46 (34). Coupled to these two changes are decreases in both plasma bicarbonate from ~25.5 to 22.3 meq/l and arterial CO2 partial pressure (PaCO2) from ~44 to 33 Torr (34). With an increase in tympanic temperature by ~2.3°C, end-tidal CO2 partial pressure (PETCO2) decreased by a greater amount from 37 to 30.8 Torr (85). In an extreme case, when rectal temperature increased to 39.2°C, the blood pH increased to ~7.6 and PaCO2 decreased to ~20 Torr (46). In resting volunteers rendered hyperthermic, other known modulators of pulmonary ventilation, including plasma norepinephrine (8) and potassium (18, 32, 53), remain at concentrations close to resting normothermic levels. Collectively, the evidence supports that at rest an elevation in Tc during hyperthermia can directly increase pulmonary ventilation

The magnitude of this increase in pulmonary ventilation is more pronounced for an increasing Tc relative to a stable but elevated Tc (5, 6, 55, 85). The site of Tc measurement employed complicates expression of the size of this hyperventilation because rectal temperature gives a more sluggish response than tympanic, esophageal, or cranial temperatures (58, 60). Depending on whether the Tc is stable or increasing, and on the site of Tc measurement, an elevation of Tc from a resting level by 1.0 to 2.0°C gives a typical sensitivity of pulmonary ventilation from ~2.0 to ~4.0 l·min–1·°C–1 (11, 34, 90).

Pulmonary ventilation and exercise-induced hyperthermia.   How exercise ventilation is controlled is not entirely resolved, and several reflexes contributing to this hyperventilation have been reviewed in detail (51). A problem that remains is that some of the principal variables known to influence pulmonary ventilation at rest appear to be dissociated from increases in exercise ventilation. Despite multifold increases of pulmonary ventilation during exercise, PaCO2, arterial O2 partial pressure (PaO2), and arterial pH remain relatively constant at preexercise levels during low- to moderate-intensity exercise. During high-intensity exercise, there is an additional disproportionate increase pulmonary ventilation relative to metabolic needs (24), and a hyperventilation is evident with PaCO2 and PaO2 changes contrary to that expected. Although there is a decrease in plasma pH during high-intensity exercise, this is not obligatory for this response. This is evidenced with muscle glycogen depletion studies during exercise that demonstrated a dissociation between the ventilatory breakaway and decreases in blood pH (40). Other potential metabolic modulators of exercise ventilation include plasma potassium (76) and norepinephrine (51), which each increase proportionately to pulmonary ventilation during exercise. Evidence also supports that the concomitant increase of Tc during work or exercise (73) is an additional stimulus to exercise ventilation, and this follows from several studies (15, 19, 25, 77).

Petersen and Vejby-Christensen (77), Dempsey et al. (25), Cotes (19), as well as Chu et al. (15) have each demonstrated an influence of body temperature on exercise ventilation. Attenuation (25) or prevention (15, 19, 25, 77) of an exercise-induced elevation in Tc suppresses pulmonary ventilation and reduces the fall in PaCO2 (Fig. 2A). This temperature-induced suppression of pulmonary ventilation is also evident during low-intensity exercise (15). Nybo and Nielsen (74) further this view for exercise at ~57% of maximal O2 uptake. They showed that a hyperthermia superimposed on the normal exercise-induced elevation in esophageal temperature increased exercise ventilation by an additional 40% (Fig. 2B).


Figure 2
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  		Fig. 2. A: effect of limiting the rise in rectal temperature (Temp) in humans on pulmonary ventilation and arterial CO2 tension during prolonged submaximal work at ~65% maximal oxygen uptake (VO2 max). {circ}, Control condition; bullet, with a water perfused suit used to cool subjects and limit the increase in rectal temperature. Tsk, skin temperature. The figure is used with permission from Birkhauser-Verlag (25). B: effect of a hyperthermia on PaCO2 and pulmonary ventilation during a steady-state submaximal exercise at ~57% VO2 max. *Significantly different from 10-min value; P < 0.05. {dagger}Significantly different from control, P < 0.05. Detail from figure originally published in Ref. 74 by Blackwell Publishing; used with permission.

 
Tc is positively correlated to increases in pulmonary ventilation during exercise (93). However, similar positive correlations are evident between metabolic modulators and pulmonary ventilation (51), plus limb movement alone can induce increases in pulmonary ventilation (26). These two examples underline the difficulty of demonstrating an independent influence of Tc on exercise ventilation. As discussed above, it appears that temperature-induced increases in pulmonary ventilation are more readily demonstrated at rest (Fig. 1). Tc is also positively correlated to pulmonary ventilation during hyperthermia at rest, when plasma norepinephrine and potassium are at normothermic values (8, 18, 32, 53) and there are no limb movements.

Patterns of breathing during hyperthermia.   A hyperthermia-induced increase in pulmonary ventilation can include two distinct patterns of breathing. They are thermal tachypnea or thermal hyperpnea (47, 56, 62, 82). Thermal tachypnea is a panting response (83) with an elevated functional residual capacity, a high frequency of breathing often exceeding 200–300 breaths/min, and a reduced tidal volume (56, 82). Once initiated, thermal tachypnea gives a preferential ventilation of the upper airways and nasal turbinates. During this pattern of ventilation there is a maintenance of blood-gas tensions and pH (87). In contrast, thermal hyperpnea is a pattern of ventilation that is only evident with an increase in Tc. For thermal hyperpnea, relative to the respective values for thermal tachypnea, tidal volume is increased and frequency of breathing is reduced. These changes to the breathing pattern lead to a hyperventilation of the alveoli, an arterial hypocapnia, and respiratory alkalosis (62, 82). Thermal tachypnea and thermal hyperpnea breathing patterns are not mutually exclusive, and several mammals display both patterns of breathing (82). For humans, hyperthermia gives a hyperventilation that exceeds metabolic activity. This results in a hypocapnia and respiratory alkalosis (11, 36, 46, 85). It follows for humans that this temperature-induced increase in pulmonary ventilation is best described as a thermal hyperpnea or a second-phase panting.

Patterns of breathing have been studied during both passively and actively induced hyperthermia. For humans during passively induced hyperthermia, the increase of pulmonary ventilation is due to moderate elevations in breathing frequency (2, 34, 78, 90), and these can be combined with moderate elevations in tidal volume (2, 11, 34). Similarly, with an actively induced hyperthermia, the increases in pulmonary ventilation are from elevations of both tidal volume and frequency of breathing (84). Sancheti and White (84) show in their Fig. 3 that increases of pulmonary ventilation during incremental exercise are first accounted for by tidal volume at lower Tc and then by frequency of breathing at higher Tc. The potential mechanism(s) underlying this thermal hyperpnea are reviewed in the next section.


Figure 3
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  		Fig. 3. Mean tidal volume (VT) and frequency of respiration (f) for 7 men expressed as a function of esophageal temperatures (Toes) during incremental seated cycle exercise from rest to the point of exhaustion. Indicated in the figure are mean ± SE esophageal temperatures at the mean VT plateau point and the mean f threshold. Reprinted from Ref. 11, with the kind permission of Springer Science and Business Media (11).

 

   PROPOSED MECHANISMS OF THERMAL HYPERPNEA
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Both surface skin and core or hypothalamic temperatures participate in regulation of first-phase panting or thermal tachypnea in mammals (38, 41, 56, 82). The mechanisms of this response are discussed by Robertshaw (83). Still unresolved are the mechanism(s) accounting for the second phase panting response or thermal hyperpnea. This has been investigated in humans and other mammals that do not demonstrate thermal tachypnea during hyperthermia (82). Results from these studies support the idea that body temperatures and modulators ventilation either interact to give a multiplicative effect or act independently to give an additive effect on pulmonary ventilation. The evidence supporting or refuting these two hypotheses is presented in the following paragraphs together with a discussion of some limitations of the methods employed in these investigations.

Multiplicative effects of hypercapnia, hypoxia, and Tc?   Advocates of the multiplicative hypothesis indicate there is an interaction of the modulators of pulmonary ventilation with body tissue temperatures. This is reasoned to be in the periphery at the carotid and/or aortic bodies and/or at central sites of chemosensitivity, possibly on or near the ventral surface of the medulla oblongata (VMS), is the putative site of central chemoreception (68, 70). Studies in humans examining ventilation responses to hypercapnia and hypoxia, with and without body warming, have supported an interaction of these modulators of ventilation with Tc (15).

Several studies in humans (2, 20, 72) indicate that the pulmonary ventilation response to an elevated inspired fraction of CO2 (FICO2) is increased by ~1.5- to 2.0-fold during hyperthermia. This response depends on the degree of Tc elevation and on the inspired partial pressure of O2. Similar to a temperature-induced increase of the pulmonary ventilation response to CO2 at rest, exercise ventilation of hyperthermic individuals was increased in proportion to the elevation of FICO2 across a physiological range of its values (65, 91). This hyperventilation is evident in hot climates during exercise (39), and it can be also associated to an increased ventilation response to CO2 during light to moderate (65, 91) and heavy exercise intensities (91). However, other studies demonstrate no changes (52) or decreases (17, 69) of the ventilation response to CO2 during exercise. This suggests the influence of an elevated FICO2 on exercise ventilation remains to be resolved.

Similarly to ventilation responses to elevations of inspired CO2 during hyperthermia at rest or during exercise, whole body hypoxia and hyperthermia were investigated for their influence on pulmonary ventilation. Relative to normothermic rest, the dynamic hypoxic ventilation response was significantly elevated as judged by the A-shape parameter after elevations of rectal temperature by 0.4 and 1.4°C (72). A similar result was recently shown by Chu et al. (15) when the steady-state ventilation response to isocapnic hypoxia was diminished in a normothermic (Tc {approx} 37.0°C) relative to a hyperthermic (Tc {approx} 38.5°C) light exercise session.

The results above and below from whole body pulmonary ventilation response tests must be expressed with the known limitation that these are not a direct estimate of the responses to hypercapnia (21) or hypoxia. This follows from potential influences that would dissociate the measured stimulus (e.g., PaCO2 or PaO2) and actual stimulus at the chemosensitive tissues. For hypercapnic tests these include that both the cerebral blood flow and bicarbonate (intracellular fluid or extracellular fluid) increase significantly after elevations in FICO2 (23). Each of these changes would alter the central pH stimulus. Also for a hypercapnic test the relationship between PaCO2 and pH is closer to a logarithmic than linear relationship, and this needs to be considered when assessing slope of the respiratory tolerance curve to CO2 (86). Similar reasoning applies for ventilation responses to hypoxia, but examples are not given here.

Additive effects of hypercapnia, hypoxia, and Tc?   Proponents of the additive hypothesis (35) suggest that chemical modulators act independently from temperature-induced changes of pulmonary ventilation. In this context, peripheral and central chemoreceptors act as thermosensors inducing a hyperventilation at a given PaCO2 and arterial pH or PaO2. At rest during a hyperoxic hypercapnic rebreathing test, Vejby-Christensen and Petersen (89, 90) and House and Holmes (45) each showed no change in the slope of the ventilation response curve to CO2 and an additive effect of a raised body temperature on pulmonary ventilation. Cotes (19), in multiple trials for a single volunteer exercising at a submaximal intensity, illustrated an additive effect of elevated Tc on pulmonary ventilation at fixed levels of PETCO2. As well, at four submaximal exercise intensities, rectal temperature was suggested to give an additive, "nonchemical" stimulus to pulmonary ventilation (16).

The additive hypothesis is further supported by a multitude of studies, focused on identifying chemosensitive sites in the medulla oblongata (for reviews, see Refs. 9, 31). Several studies indicated cooling of the VMS suppressed pulmonary ventilation (9, 14, 68), supporting the temperature sensitivity of these tissues that are thought to house the central chemoreceptors (68, 70). This was also illustrated with heating of the ventral respiratory group tissue to 40°C that gave fictive respiratory frequency that was two to four times that at 30°C (88).

In humans, direct cooling or heating of the VMS or medulla oblongata is not feasible. But in monkeys (Macaca cyclopis) heating of the medulla oblongata or spinal cord gave thermolytic heat-loss responses and an approximate doubling of the frequency of breathing, whereas the hypothalamic temperature was unchanged or decreased after the onset of these heat-loss responses (13). Likewise in the monkey, cooling of the medulla oblongata or spinal cord invoked thermogenic responses, a reduction of the frequency of breathing by ~50%, and increases in hypothalamic temperature (12). Hiley (44) showed similar-magnitude increases in the frequency of breathing in the baboon (Papio cynocephalus) and chimpanzee (Pan satyrus) at dry-bulb temperatures of 40°C with a Tc elevated from a resting value by ~0.7–1.4°C. However, for these two preceding studies (12, 44), limitations were inherent in each experimental design because whole body or localized temperature changes influence chemosensitive tissue perfusion. As a consequence, the level of stimulation by modulators of pulmonary ventilation would be changed in these tissues. Despite the limitations of these studies, they provide support to the view that globally heating or cooling the medulla oblongata and spinal cord invokes an elevation in pulmonary ventilation. As well it demonstrates that some primates respond to hyperthermia with an increased frequency of breathing in an apparent thermoregulatory response.

For pentobarbital-anesthetized and mechanically ventilated cats, Cherniack et al. (14) addressed this preceding concern of uncontrolled temperature variations in chemosenstive tissues (12, 44). The goal of their study was to examine the effects of focal temperature changes of the superficial "chemoceptive" areas of the ventral surface of the medulla on respiratory output parameters at different levels of alveolar PCO2. A supplementary outcome of their study demonstrated temperature changes of the intermediate area of the VMS evoked proportionate changes of phrenic nerve firing rates with local alveolar PCO2 at fixed values from ~24 to ~49 Torr and local temperature at stable levels from ~25 to ~42°C (Fig. 4).


Figure 4
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  		Fig. 4. Effect of temperature of intermediate area of the ventral surface of the medulla oblongata, at different alveolar PCO2 (PACO2), on phrenic amplitude (Phr ampl) of a vagotomized, anesthetized cat on constant artificial ventilation. rel, Relative. The figure is used with permission from Blackwell Publishing (14).

 
Their findings indicated the temperature of intermediate area of the VMS and PCO2 (and PO2, not shown) have independent, additive effects on rates of phrenic nerve discharge. Cherniack et al.’s study (14) lends support to the view that VMS modulation of pulmonary ventilation is in part a consequence of temperature-induced changes in central chemosensitive tissues at a fixed PCO2. This outcome of a centrally modulated additive signal from temperature (14) was supported by evidence from sheep that retained a normal hyperthermia-induced increase in pulmonary ventilation after chronic carotid body denervation (37).

For centrally induced changes in pulmonary ventilation (14, 37), it remains to be determined whether this is a direct effect of temperature or whether it is a function of the changes in the tissue’s transduction of the CO2/H+ signal. Recently, cells in the rat retrotrapezoid nucleus were indicated to have a CO2 sensitivity, supporting the idea that these tissues juxtaposed to the VMS are the site of the central chemoreceptors (67, 70). The retrotrapezoid nucleus would appear to provide the tissues where the signal transduction pathway for this central temperature influence on pulmonary ventilation can be resolved.

Thermal receptor characteristics of peripheral chemoreceptors.   Directly heating (7, 64) and cooling (30, 64) the isolated carotid body in cats gave proportionate changes to their rates of discharge as illustrated in Fig. 5A.


Figure 5
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  		Fig. 5. A: effects of different temperatures on the discharge frequency of single chemoreceptor fibers from the cat carotid body. The values in a, b, and c are temperatures in °C. The ordinate scales in a and c are linear and in b the ordinate scale is logarithmic (33). B: dynamic and static frequency responses with changes in the temperature of chemosensitive tissues between 38 and 42°C in 2°C steps. The tissues were from the cat’s carotid body in vitro with a flow of 1.5–3 ml/min with physiological saline (pH = 7.44) and the superfusate saline was equilibrated with 50% O2 in N2. Both figures are used with permission from the American Physiological Society (31).

 
Eyzaguirre and colleagues (29, 31, 33) and later Zaputa and colleagues (1, 57, 94) have reported a temperature dependence of carotid body rates of discharge. These include for carotid body firing rates a high Q10 of ~75 in vitro (33) and a Q10 of ~3 in vivo (31). This gives empirical support that these tissues act like thermosensors, since changing their temperatures influences their firing rates and this would presumably lead to proportionate changes of pulmonary ventilation. An Arrhenius plot for the logarithm of the cat carotid chemoreceptor discharge frequencies (in vivo) and the reciprocal of absolute temperatures were linear and gave an apparent energy of activation that was not influenced by varying either PCO2 from 3.2 to 5.5% or local PO2 (64). Also using an Arrhenius plot in vitro studies for superfused, excised carotid bodies (33) supported that there is a rate-limiting chemical reaction or reaction(s) in these tissues that is temperature dependent. Unlike for whole body studies, hyperoxia suppressed and each of hypoxia, 6% CO2 with normal pH (~7.43), and 6% CO2 with decreased pH (~6.5) increased in vitro carotid body discharge rates. These in vitro experiments with a ~25-fold greater Q10 value and influences of blood gases and pH were stated to more likely reflect the chemoreceptor sensing elements temperature and responses (64).

The differences between the whole body (64) and in vitro (33) studies of carotid body firing rates were reasoned in part to be due to the secondary local effects of temperature in the animal. These temperature influences include, among others, a change in the affinity of hemoglobin for O2 and of variations of local vascular tone. Each of these influences would change the homeostasis and discharge frequencies of carotid body cells, giving lower temperature effects on discharge frequencies for the whole animal compared with those reported in vitro. These results emphasize, as was evident for studies of the VMS (14), the need to account for local effects of temperature on these chemosensitive tissues when working to deduce the potential influences of temperature on their discharge frequencies.

Another characteristic of peripheral chemoreceptors that support their function as thermosensors is the frequency response of the carotid bodies following step changes in their temperature (Fig. 5B). These responses (31) are the same as that of temperature-sensitive neurons, with a dynamic overshoot followed by diminished but elevated frequency, the latter of which is indicative of a static temperature-induced response (43).


   RATIONALE FOR THE EXISTENCE OF THERMAL HYPERPNEA IN HUMANS
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Chemoregulation, thermoregulation, and selective brain cooling.   As shown by Cabanac and White (11) during passive warming and White et al. (84, 93) during active warming, until human Tc reaches a threshold body temperature does not appear to influence pulmonary ventilation. At suprathreshold Tc a thermal hyperpnea is evident and respiratory alkalosis develops (11, 84, 93). The question that becomes apparent is why chemoregulation is apparently abandoned after an elevation in Tc during passive body warming or during exercise in humans or other homeotherms. Entin et al.’s (27, 28) results support the idea that an elevation in Tc is a greater stimulus to ventilation than is the inhibition brought on by the simultaneous hyperventilation-induced hypocapnia. This allows a hyperventilation that increases heat loss of the upper airways, despite PaCO2 decreasing to values at which pulmonary ventilation is normally inhibited (80).

Selective brain cooling (SBC) is a decrease of intracranial below trunk temperature when an animal becomes hyperthermic. SBC has been widely studied and full reviews of this response are available in the literature (10, 49, 71). A synopsis of SBC is described here to allow a rationale to be presented for the existence of thermal hyperpnea as a heat-loss effector response in humans who do not adopt a first-phase panting or thermal tachypnea.

The principal heat-loss mechanisms for SBC include heat loss from the surface of the cranium, elevations of respiratory evaporative heat loss, and countercurrent heat exchange between the arterial supply to and venous drainage from the cranium. This countercurrent heat exchange is usually in the cavernous sinus, and it is evident in mammals with or without a carotid rete (3, 4). This response was originally recognized as a thermoprotective response for the cranial tissues, but an emerging view (48, 54) is that SBC is also a water-conservation response. This is because it would appear that lowering brain temperature decreases secretions of fluids employed in whole body (e.g., sweat) or respiratory evaporative heat loss (e.g., airway mucus), and this conserves water for the animal. As well, it appears from studies of free-ranging animals that SBC is possibly abandoned during a fight-or-flight response when venous drainage bypasses the carotid rete in a sympathetically mediated response (48, 66).

For hyperthermic humans similar mechanisms as outlined above are reasoned to give cranial cooling (10), but the existence of SBC in humans is not without opposition. There are contrary views on cardiovascular mechanisms thought to underlie SBC (74, 75). Respiratory heat loss in humans can, however, increase to 46% of total cephalic heat loss, even during light activity with a low pulmonary ventilation (81). This suggests that thermal hyperpnea and respiratory evaporative heat loss from the upper airways give an important heat-loss avenue for human cranial thermoregulation. This is supported by direct evidence illustrating that even small changes in upper airway ventilation at rest gave a local human selective brain cooling (59). In the study by Mariak and colleagues (59), the cribriform plate cooled at ~5.0°C/h when a patient was asked to breathe intensively for 3 min and at ~6.0°C/h after an endotracheal extubation (59). This evidence supports the idea that heat loss of this magnitude from the upper airways, at a site juxtaposed to the hypothalamus, which is the principal integrative tissue in thermoregulation, merits further consideration in the models of human thermoregulation. In this context, it is suggested the physiological function of thermal hyperpnea for humans is to act as a heat-loss effector response to provide an additional means for cranial cooling during hyperthermia.


   SUMMARY AND CONCLUSIONS
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 ABSTRACT
 PHYSIOLOGICAL COMPONENTS OF...
 PROPOSED MECHANISMS OF THERMAL...
 RATIONALE FOR THE EXISTENCE...
 SUMMARY AND CONCLUSIONS
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Hyperthermia can induce an elevation of pulmonary ventilation. In humans this is accounted for by increases in both tidal volume and frequency of breathing. This pattern of breathing is a thermal hyperpnea and it is markedly different from the first phase panting or thermal tachypnea response.

During rest or exercise a consequence of thermal hyperpnea is a respiratory alkalosis when chemoregulation is abandoned and a thermally driven increase of pulmonary ventilation is adopted.

The mechanisms accounting for thermal hyperpnea appear to include interactions of blood gases and pH with body temperatures; however, a direct additive influence of temperature on this response is also possible. To allow resolution of the mechanism(s) accounting for thermal hyperpnea, future protocols need to account for local effects of temperature if the goal is to illustrate an independent influence of temperature on chemosensitive tissues.

Hyperthermia and an elevated Tc give an increase of pulmonary ventilation and greater heat loss from the upper airways, despite PaCO2 decreasing to values at which pulmonary ventilation is normally inhibited.

Small increases in upper airway ventilation give a local selective brain cooling in humans.

Future studies are needed to clarify the potential of pulmonary ventilation as a heat-loss response involved in human cranial thermoregulation. This appears to have important applications for hyperthermic and febrile patients.


   FOOTNOTES
 

Address for reprint requests and other correspondence: M. D. White, Laboratory for Exercise and Environmental Physiology, 8888 University Dr., School of Kinesiology, Simon Fraser Univ., Burnaby, British Columbia, Canada V5A 1S6 (e-mail: matt{at}sfu.ca)


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