Journal of Applied Physiology Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

J Appl Physiol 97: 669-674, 2004; doi:10.1152/japplphysiol.00895.2003
8750-7587/04 $5.00
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (6)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kahraman, L.
Right arrow Articles by Thach, B. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kahraman, L.
Right arrow Articles by Thach, B. T.

Inhibitory effects of hyperthermia on mechanisms involved in autoresuscitation from hypoxic apnea in mice: a model for thermal stress causing SIDS

Levent Kahraman and Bradley T. Thach

Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110

Submitted 15 September 2003 ; accepted in final form 29 March 2004


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
The physiological mechanisms that might be involved in an association between heat stress and sudden infant death syndrome (SIDS) are obscure. We tested the hypothesis that a combination of acute hypoxia and elevated body temperature (TB) might prevent autoresuscitation from hypoxic apnea (AR). We exposed 21-day-old mice (total = 216) to hyperthermia (40.5–43.5°C), hypoxia, or a combination of the two. Neither hyperthermia alone (40.5–42.5°C) nor hypoxia alone was found to be lethal, but the combination produced failure to AR during the first hypoxic exposure with increasing frequency as TB increased. The ability to withstand multiple hypoxic exposures was also reduced as TB increased. In contrast, heat stress causing moderate TB increase (40.5°C) had no effect on survival. Increased TB (43.5°C) reduced gasping duration and number of gasps. It increased heart rate during anoxia but did not alter gasping rate. Furthermore, the oxygen-independent increase in heart rate observed before gasping failure was usually delayed until after the last gasp in hyperthermic animals. Mild dehydration occurred during TB elevation, but this did not appear to be a primary factor in AR failure. We conclude that a thermal stress, which by itself is nonlethal, frequently prevents AR from hypoxic apnea. This may be due, at least in part, to decreased gasp number and duration as well as to hyperthermia-related asynchrony of reflexes regulating heart and gasping frequencies during attempted AR.

hypoxic gasping; dehydration; hypoxic survival time; sudden infant death syndrome

SUDDEN INFANT DEATH SYNDROME (SIDS) occurs in infants during a relatively brief period of development with peak incidence at 2–3 mo of age. It has been suggested that thermal stress with or without actual increase in body temperature (TB) may be causal in many SIDS cases (6, 12). The primary evidence for this comes from epidemiological studies. These studies have found increased environmental temperature and/or history of heavy sweating in association with some SIDS cases (6, 26, 27). Despite this, the potential physiological mechanisms linking heat stress to SIDS are unclear.

Healthy infants have frequently been observed to autoresuscitate (AR) from prolonged apnea without apparent ill effects, indicating that this can be an important mechanism for surviving severe episodes of hypoxia (22, 32). Failure to AR from hypoxic apnea by gasping is well documented in SIDS cases, and it has been proposed that such failure could be a critical SIDS causal mechanism (21, 25). Examination of terminal recordings of infants dying of SIDS reveals that hypoxic apnea is followed by gasping, and yet AR fails during the first attempt. In contrast, infants with other diagnoses often have repeated successful AR attempts immediately before death (25).

It has previously been shown in 5-day-old rats that hyperthermia changes AR patterns and that, compared with control animals, death occurs more rapidly but only after repeated hypoxic exposures with repeated resuscitations (24). In contrast, Swiss Webster mice (21–23 days old) have been shown to be prone to AR failure during a relatively narrow window of development and after the first exposure to hypoxia, providing a model more closely resembling the AR failure occurring in SIDS (4, 10, 14, 15). In the present study, we tested four hypotheses in 21- to 23-day-old C57BL/6 mice, which are normally competent in AR. These hypotheses were the following: 1) moderate thermal stress sufficient to elevate TB does not impair AR, 2) TB values that are in and of themselves well tolerated can seriously impair AR, 3) AR failure during hyperthermia often occurs after the very first hypoxic exposure, 4) dehydration resulting from hyperthermia is a significant factor in AR failure, and 5) hyperthermia impairs heart rate- and gasping rate-regulating mechanisms that potentially contribute to successful AR.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
Animals.   Unanesthetized, 21- to 23-day-old, C57BL/6 weanling mice (Jackson Laboratories) were used in the experiments (n = 296). They were kept with their mothers until the time of the experiment. Animals were weighed before and after the experiment. These studies were approved by the Institutional Animal Studies Committee.

Protocol 1.   In these experiments, we studied the effects of different TB values on the number of times mice were able to AR after repeated hypoxic exposures. Each litter included randomly chosen animals that were allocated to each of three experimental groups: 1) hypoxia and hyperthermia, 2) hypoxia only, and 3) hyperthermia only control animals. Animals were not restrained. Colonic temperatures (TB) were continuously monitored via a copper-constantan thermocouple inserted ~1.5 cm into the rectum (model BAT-12, Sensortek, Clifton, NJ).

In the first experimental group (n = 102), hyperthermia was induced by an infrared heat source. Animals were heated at a rate of ~0.8 ± 0.1°C/min. The mean temperature of chamber wall was 43.9 ± 0.75°C. A continuous flow of room airflow (22°C) passed through the chamber at 2 l/min except during anoxia. Four target temperatures were studied: 40.5, 41.5, 42.5, and 43.5°C. Immediately after the target temperature was reached, hypoxic apnea was induced by sudden introduction of a 97% N2-3% CO2 gas mixture into the chamber at the same flow rate (9, 10, 14). Then a flow of 21% O2 (balance N2) was started at the onset of the apnea to allow for successful AR (10). In groups 1 and 2 once gasping ceased and eupneic respiration started, apnea was induced again before the animal was fully awake. This process was repeated until the animal failed to AR (10). Thus the survival rate (% successful AR) after the first episode and total number of successful ARs per animal were determined. The peak TB studied (43.5°C) was below hyperthermic seizure threshold, although it is close to the threshold documented in past studies of hyperthermia-induced seizures in rats and mice (13, 19, 20).

The second group (hypoxia only, n = 82) was exposed to anoxic gas mixture without preheating. As with the first group, the mice rapidly lost consciousness and became apneic, at which point a flow of room air was resumed. The third group consisted of animals heated to the various target temperatures and then promptly allowed to cool off (n = 58).

Protocol 2.   In these experiments, mice (n = 54) were warmed to a TB of 43.5°C and were exposed to continuous anoxia so that time to last gasp, which is a measure of an animal's tolerance to anoxia, could be measured (14, 24). During this second set of experiments, respiration was recorded using a semiquantitative plethysmograph closely similar to one previously used by our laboratory (16). A 20-ml cylindrical custom-made polypropylene chamber that covered most of the trunk of the animal was used. Latex sheets over both ends provided a seal so that pressure oscillations inside the chamber caused by respirations could be recorded. The pressure changes within the plethysmograph were detected by a differential pressure transducer and recorded on a chart recorder (Beckman Instruments, Schiller Park, IL). The electrocardiogram was recorded after subcutaneous placement of thoracic, fine-wire electrodes (38 gauge, Isomid, Belden, Chicago, IL) that were connected to a differential alternating-current microelectrode preamplifier (model P15, Grass Instrument, Chicago, IL). During these experiments, we gathered data on respiratory responses such as time to last gasp, number and frequency of gasps, as well as heart rate changes during the gasping period.

The heart rate data were analyzed to find the severity and the duration of bradycardia. As used in prior studies, the point at which heart rate increased to 60% of the baseline (averaged over 2 s) was used as an end point for some of the analyses (9, 10).

Statistics.   Categorical variables were analyzed by {chi}2 analysis. Unpaired t-test or ANOVA was used for continuous variables. A value of P < 0.05 was considered significant. Values are shown as means ± SE.


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 GRANTS
 REFERENCES
 
General characteristics of animals.   Weight and initial TB for animals studied in repeated hypoxia experiments were similar in test (hypoxia + hyperthermia) and control groups (Table 1).


View this table:
[in this window]
[in a new window]
  		Table 1. Baseline characteristics of animals studied during the first series of experiments (repeated hypoxic exposures)

 
Effect of thermal stress on dehydration.   Increased weight loss occurred in the hyperthermia groups (Table 1, Fig. 1). With increasing hyperthermia, there was a relative increase in weight loss (r = 0.87, P < 0.01; Fig. 1).



View larger version (11K):
[in this window]
[in a new window]
  		Fig. 1. Weight loss (% of initial body weight) during the experiments in animals studied at baseline colonic temperature and at high colonic temperatures. Increasing colonic temperature is positively correlated with increasing weight loss (r = +0.87). Error bars represent SE.

 
Effects of colonic temperature on survival.   AR was highly successful in control animals at normal colonic temperatures. Increased colonic temperature started affecting the survival rate adversely at a TB of 41.5°C in the hyperthermia and hypoxia group (Fig. 2). The first trial survival of mice exposed to heat and hypoxia varied with TB in a dose-dependent fashion (range 100–25%; P < 0.001). The number of hypoxic trials before AR failure occurred was also decreased in hyperthermic animals, and this also was dose dependent (P < 0.001; Fig. 3).



View larger version (21K):
[in this window]
[in a new window]
  		Fig. 2. Success in autoresusitation (AR; %survival) in the 3 experimental groups. Animals with colonic temperature ≥41.5°C had increased risk of failing the AR attempt after the first hypoxic exposure. Error bars represent SE. *P < 0.05.

 


View larger version (11K):
[in this window]
[in a new window]
  		Fig. 3. Number of successful AR with repeated hypoxic exposures in mice with normothermic and hyperthermic temperatures. Error bars represent SE. P < 0.001.

 
Significantly, hypoxic stress alone resulting in moderate elevation of TB (40.5°C) and increased weight loss had no effect on survival either during the first or multiple exposures (Figs. 2 and 3). There was no effect of sex on survival.

Effects of colonic temperature on gasping.   During the protocol 2 experiments using continuous anoxia, several significant differences were observed between the control and test animals (Fig. 4). The total number of gasps as well as time to last gasp were significantly decreased (P < 0.01) (Fig. 5). Notably, however, we did not find a significant difference in gasp frequency (Fig. 5; P = 0.32).



View larger version (17K):
[in this window]
[in a new window]
  		Fig. 4. Effects of elevated body temperature (TB) on the preterminal oxygen-independent increase in heart rate. A: tracings of respirations (Resp) and electrocardiogram (ECG) in a mouse with normal TB. The 2 traces at bottom are continuations of the 2 traces at top. Dots mark heart beats. G, gasps. B: hyperthermic mouse. Note increase in cardiac rate before last gasp in normothermic but not in hyperthermic mouse and prolonged gasping in the normothermic mouse.

 


View larger version (17K):
[in this window]
[in a new window]
  		Fig. 5. Number of gasps (A) and time to last gasp and gasp frequency (B) in control and hyperthemic (colonic temperature = 43.5°C) animals during continuous anoxia. Error bars represent SE. Number of gasps and time to last gasp were significantly different (*P < 0.01). Gasp frequency was not significantly different between the 2 groups (P = 0.32).

 
Heart rate changes in hyperthermic-hypoxic mice.   Baseline respiratory and heart rates were increased in hyperthermic compared with normothermic mice (253 ± 7.33 vs. 186 ± 6.04 breaths/min and 796 ± 15.95 vs. 692 ± 15.25 beats/min in hyperthermic and normothermic mice, respectively; P < 0.01). Hypoxic bradycardia at onset of hypoxic apnea was found to be less pronounced in hyperthermic mice (168 ± 12.95 vs. 260 ± 8.87 beats/min; P < 0.01; Fig. 6). Increases in heart rate after hypoxic apnea to at least 60% of prehypoxic levels were frequently observed in both normothermic and hyperthermic mice. However, this would more often occur before the last gasp in normothermic compared with hyperthermic mice, in which it usually occurred after the last gasp (P < 0.01; Fig. 7).



View larger version (12K):
[in this window]
[in a new window]
  		Fig. 6. Heart rates (HR) in normothermic and hyperthermic animals at various stages during hypoxia last gasp (LG). Error bars represent SE. *P < 0.01.

 


View larger version (16K):
[in this window]
[in a new window]
  		Fig. 7. Percentage of mice exposed to continuous anoxia in which heart rate increased after hypoxic apnea to ≥60% of control values [cardiac resuscitation (CR)]. This heart rate acceleration occurred in most mice irrespective of body temperature, but in cases where it did occur it was more often delayed until after the last gasp in hyperthermic than normothermic mice. *P < 0.01.

 

   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
GRANTS
 REFERENCES
 
Physiological mechanisms involved in AR have been studied for well over 300 years, and yet a role for AR in survival apart from the immediate perinatal period has, for the most part, been ignored. A departure from this thinking was the proposal of French et al. (7) that failure to AR from apnea might be causal in SIDS. More recently, it was proposed that thermal stress, even when not associated with increased TB, could be causal in SIDS; however, mechanisms whereby this could be fatal in the absence of overt heatstroke have remained largely obscure (6, 12). We chose to evaluate TB values below the seizure threshold in mice as appropriate in testing this model because infants frequently experience febrile seizures due to elevated TB, and these are considered benign (13). Accordingly, our ranges of TB used in this study are consistent with those experienced by many healthy infants.

Our findings are in several respects consistent with those of Sederevich and Fewell (24) in neonatal rats with respect to hyperthermia causing decreased gasping time, decreased number of gasps, and increased heart rate. We found increased susceptibility to repeated anoxic exposures as they did. However, in marked contrast to their findings, we have shown that young mice frequently fail to AR on the first exposure to anoxia when heat stressed. In several other respects, we were able to provide new information. We found the dehydration that occurs during the thermal exposure has little effect if any on survival. In addition, we found evidence of incoordination of cardiovascular and respiratory control during attempted AR when mice were overheated. Finally, we were able to show that moderate heat stress alone did not adversely effect AR, a finding contrary to what the thermal stress theory would predict in this model.

Probably the biggest factor contributing to the decreased number of ARs during repeated hypoxia is a progressive decrease in cardiac glycogen stores. These are essential for successful AR (4). In past work, it was found that cardiac glycogen is almost nil at the time of the last of several AR attempts (4). In mice, cardiac glycogen stores reach a nadir at 19–22 days (4). The increased susceptibility of 21-day-old Swiss mice to AR failure on first anoxic exposure, compared with other mouse strains, has been attributed to their exceptionally low cardiac glycogen at this stage of development (4). The mice used in the present study presumably reach a nadir in cardiac glycogen during this developmental period; however, as shown in our study, unlike Swiss mice, they are competent in AR at normal TB (15). Increased TB increases cardiac rate and would be expected to increase anaerobic metabolism in the C57BL/6 mice used in this study. Whether this would be sufficient to lower cardiac glycogen to levels normally occurring in same-aged Swiss mice is unclear. In any event, 21-day-old mice appear to be a better model than 5-day-old rats for heat stress-associated SIDS because, unlike deaths in infants due to other causes, SIDS infants die without evidence of prior successful ARs (21, 24).

One of the arguments that heat stress may be a major factor in SIDS is that a substantial number of SIDS infants are found wet with perspiration at death (12). It is well known that infants are particularly vulnerable to dehydration and hypovolemia when exposed to excessive environmental temperatures, yet the role of dehydration in heat-stressed SIDS infants has not been considered. The mice in the present study experienced mild dehydration during brief exposure to elevated ambient temperature. This can largely be attributed to their increased salivation and fur-wetting behavior (8, 28). Because AR is dependent on maintenance of a critical level of blood pressure, dehydration and associated hypovolemia and hypotension would be expected to impair AR competence (29). In the present study, dehydration was probably not a major factor in AR failure because mortality increased between 40.5 and 41.5°C TB, whereas weight loss did not change over this range. Furthermore, mild dehydration (5–10%) is generally well tolerated in infants. However, with longer heat exposures producing larger fluid losses, dehydration would be expected to play an increasingly important role in AR failure.

If cardiac and respiratory reflexes involved in AR were accelerated to the same degree during TB elevation, consistent with the thermal Q10 effect, one might expect that AR would still occur as TB increases, only at a faster rate (18). In fact, during maturation, although adult mice have a much shorter anoxic survival than infant mice, they are capable of AR during hypoxia equally well. This has been attributed to both increased heart rate and gasping frequency in the adult (9). Coordination of heart rate and gasping frequency appears to be crucial for successful AR during maturation (9). However, in the present case, with TB elevation, heart rate and gasping frequency during AR were not coordinated as they are during maturation because heart rate increased but gasping frequency did not. Hence, cardiovascular and respiratory reflexes were not equally affected by TB, and this may have prevented AR. Yet another example of incoordination of reflexes was evident in the preterminal heart rates. It is well documented that increasing heart rate once gasping has started is required for successful AR. Oxygen delivery to the arterial pacemaker, which produces an increase in heart rate, is provided by gasping (1). However, we like others (1, 2) observed an oxygen-independent increase in heart rate occurring late in the AR attempt. An increase in heart rate to 60% of control is usually associated with successful AR in mice when oxygen is made available at onset of the gasping phase (10, 14). Therefore, an oxygen-independent heart rate increase of this magnitude might be beneficial in AR. It is certain, however, that this would be of little or no benefit if it occurred after the last gasp.

Another and perhaps an even more important reason for AR failure in overheated, hypoxic mice may involve the different effects of heat and hypoxia on peripheral blood flow. It is well established that normal thermoregulation when TB increases is associated with increased blood flow to the skin and extremities (17, 30). In contrast, hypoxia decreases such blood flow (3, 5). This decrease is regarded as a protective reflex because the redistribution of blood flow serves to decrease cardiac work load while preserving blood flow to vital internal organs (3, 5). Just how these opposing vascular reflexes are regulated when hypoxia and hyperthermia coexist is unclear. A very rapid change from excessive peripheral vasodilation to vasoconstriction would be required to maintain blood pressure, and therefore any diminution or retardation of the hypoxic redistribution of blood flow could significantly impair AR.

Finally, recent studies indicate that glottic closure occurs immediately after a gasp (31). This in theory could be beneficial in successful AR. In any event, it is noteworthy that hyperthermia has been shown to markedly affect glottic closure-regulating mechanisms in immature species (11).

The thermal stress theory for SIDS, particularly that occurring in the absence of elevated TB, has yet to be proven. Our findings do not add support for the theory that moderate heat stress alone can cause AR failure. It does seem probable, however, that some deaths diagnosed as SIDS result, in part at least, from elevated TB resulting from increased environmental temperatures, febrile illnesses, overbundling, and prone sleeping position or a combination of these factors (23, 26, 27). In home-monitored SIDS deaths, gasping is present but bradycardia persists and AR is unsuccessful (21, 25). If an hypoxic event such as that associated with sleep apnea were to coincide with increased TB, then our findings that elevated TB can prevent AR in a manner similar to that occurring in SIDS would offer a plausible explanation for an association between heat stress and SIDS.

We conclude that an environmental thermal stress with moderate TB elevation has no effect on survival during AR but that further TB increase, which by itself is nonlethal, can often prevent AR from hypoxic apnea. The mechanism whereby thermal stress impairs AR may be related, at least in part, to decreased gasp number and duration as suggested previously (24). Our findings suggest that altered cardiorespiratory adaptations to hypoxia, including asynchrony of reflexes regulating heart rate and gasping frequency, may also be important in the adverse effects of hyperthermia on AR, whereas the effects of elevated TB on fluid loss appears to be less important.


   GRANTS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 GRANTS
REFERENCES
 
This research was funded by National Institute of Child Health and Human Development Grant HD-10993.


   FOOTNOTES
 

Address for reprint requests and other correspondence: B. T. Thach, Washington University School of Medicine, 660 S. Euclid, Campus Box 8208, St. Louis, MO 63110 (E-mail: thach{at}kids.wustl.edu).

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 

  1. Adolph EF. Regulations during survival without oxygen in infant mammals. Respir Physiol 7: 356–368, 1969.
  2. Bauer DJ. The effect of asphyxia upon the heart rate of rabbits at different ages. J Physiol 93: 90–103, 1938.
  3. Cohn HE, Sacks EJ, Heymann MA, and Rudolph AM. Cardiovascular responses of hypoxemia and acidemia in fetal lambs. Am J Obstet Gynecol 120: 817–824, 1974.
  4. Deshpande P, Khurana A, Hansen P, Wilkins D, and Thach BT. Failure of autoresuscitation in weanling mice: significance of cardiac glycogen and heart rate regulation. J Appl Physiol 87: 203–210, 1999.
  5. Fisher DJ and Ott E. Cardiac output and regional blood flows during hypoxaemia in unanaesthetized newborn lambs. J Dev Physiol 6: 485–494, 1983.
  6. Fleming PJ, Levine MR, Azaz Y, and Wigfield R. The development of themoregulation and interactions with the control of respiration in infants: possible relationship to sudden infant death. Acta Paediatr Scand Suppl 389: 57–59, 1993.
  7. French JW, Morgan BC, and Guntheroth WG. Infant monkeys—a model for crib death. Am J Dis Child 123: 480–484, 1972.
  8. Furuyama F. Thermal salivation and water economics among Wistar rat strains. Jpn J Vet Sci 50: 415–423, 1988.
  9. Gershan WM, Jacobi MS, and Thach BT. Maturation of cardiorespiratory interactions in spontaneous recovery from hypoxic apnea (autoresuscitation). Pediatr Res 28: 87–93, 1990.
  10. Gershan WM, Jacobi MS, and Thach BT. Mechanisms underlying induced autoresuscitation failure in BALB/c and SWR mice. J Appl Physiol 72: 677–685, 1992.
  11. Haraguchi S, Fung R, and Sasaki CT. Effect of hyperthermia on the laryngeal closure reflex: implications for the sudden infant death syndrome. Ann Otol Rhinol Laryngol 92: 24–28, 1983.
  12. Harper RM, Kinney HC, Fleming PJ, and Thach BT. Sleep influences on homeostatic functions: implications for sudden infant death syndrome. Respir Physiol 119: 123–132, 2000.
  13. Holtzman D, Obana K, and Olson J. Hyperthermia-induced seizures in the rat pup: a model for febrile convulsions in children. S Afr J Sci 213: 1034–1036, 1981.
  14. Jacobi MS, Gershan WM, and Thach BT. Mechanism of failure of recovery from hypoxic apnea by gasping in 17- to 23-day-old mice. J Appl Physiol 71: 1098–1105, 1991.
  15. Jacobi MS and Thach BT. Effect of maturation on spontaneous recovery from hypoxic apnea by gasping. J Appl Physiol 66: 2384–2390, 1989.
  16. Khurana A and Thach BT. Effects of upper airway stimulation on swallowing, gasping, and autoresuscitation in hypoxic mice. J Appl Physiol 80: 472–477, 1996.
  17. Kregel KC, Wall PT, and Gisolfi CV. Peripheral vascular responses to hyperthermia in the rat. J Appl Physiol 64: 582–2588, 1988.
  18. Krogh A. The quantitative relation between temperature and standard metabolism in animals. Intern Z Phys-Chem Biol 1: 491–508, 1914.
  19. Maxson SC. Febrile convulsions in inbred stains of mice susceptible and resistant to audiogenic seizures. Epilepsia 21: 637–645, 1980.
  20. McCaughran JA Jr and Schechter N. Experimental febrile convulsions: long-term effects of hyperthermia-induced convulsions in the developing rat. Epilepsia 23: 173–183, 1982.
  21. Poets LF, Meny RG, Chobanian MR, and Bouofiglo RE. Gasping and other cardiorespiratory patterns during sudden infant deaths. Pediatr Res 45: 350–355, 1999.
  22. Peiper A. Cerebral Function in Infancy and Childhood (2nd ed.). New York: Consultants Bureau, 1963, p. 373.
  23. Ponsonby A, Dwyer T, Gibbons LE, Cochrane JA, Jones ME, and McCall MJ. Thermal environment of sudden infant death syndrome: case control study. BMJ 304: 277–282, 1992.
  24. Serdarevich C and Fewell JE. Influence of core temperature on the time to last gasp and autoresuscitation from primary apnea during exposure to hypoxia in normal rat pups. J Appl Physiol 87: 1346–1353, 1999.
  25. Sridhar R, Thach BT, Kelly D, and Henslee J. Competency of autoresuscitation (AR) mechanisms in sudden infant death. Pediatr Pulmonol 36: 113–122, 200.
  26. Stanton AN. Overheating and cot death. Lancet 2: 1199–1201, 1984.
  27. Stanton AN, Scott DJ, and Downham MAPS. Is overheating a factor in some unexpected infant deaths? Lancet 1: 1054–1057, 1980.
  28. Stricker EM, Everett JC, and Porter REA. The regulation of body temperature by rats and mice in the heat: effects of desalivation and the presence of a water bath. Commun Behav Biol 2A: 113–119, 1968.
  29. Swann HG, Christian JJ, and Hamilton C. The process of anoxic death in newborn pups. Surg Gynecol Obstet 99: 5–8, 1954.
  30. Takamata A, Nose H, Mack GW, and Morimoto T. Control of total peripheral resistance during hyperthermia in rats. J Appl Physiol 69: 1087–1092, 1990.
  31. Thuot F, Lemaire D, Dorian D, Letourneau P, and Praud JP. Active glottal closure during anoxic gasping in lambs. Respir Physiol 128: 208–218, 2001.
  32. Thach BT, Jacob MS, and Gershan WM. Control of breathing during asphyxia and autoresuscitation. In: Developmental Neurobiology of Breathing, edited by Haddad G and Farber J. New York: Dekker, 1991, p. 681–699.



This article has been cited by other articles:


Home page
 J. Appl. Physiol.Home page
B. T. Thach
Some aspects of clinical relevance in the maturation of respiratory control in infants
J Appl Physiol, June 1, 2008; 104(6): 1828 - 1834.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
J. D. Pendlebury, R. J. A. Wilson, S. Bano, K. J. Lumb, J. M. Schneider, and S. U. Hasan
Respiratory Control in Neonatal Rats Exposed to Prenatal Cigarette Smoke
Am. J. Respir. Crit. Care Med., June 1, 2008; 177(11): 1255 - 1261.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
A. K. Curran, L. Xia, J. C. Leiter, and D. Bartlett Jr.
Elevated body temperature enhances the laryngeal chemoreflex in decerebrate piglets
J Appl Physiol, March 1, 2005; 98(3): 780 - 786.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (6)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kahraman, L.
Right arrow Articles by Thach, B. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kahraman, L.
Right arrow Articles by Thach, B. T.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2004 by the American Physiological Society.