THERMOREGULATION AND SET POINT. BPK 422: Physiological Basis of Temperature Regulation By: Edwin Leung () & Lily Gan () Fall 2015 December 2, 2015

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THERMOREGULATION AND SET POINT BPK 422: Physiological Basis of Temperature Regulation By: Edwin Leung () & Lily Gan () Fall 2015 December 2, 2015

SUPPORTING POINT HYPOTHESIS Core temperatures are defended at a set point 1

Humans immersed in warm and cool baths Examining the presence of a core neutral thermal zone in humans 6 healthy male subjects Immersed in warm water (38.8 + 0.8ºC) on 26 occasions and in cool water (28 + 1.0ºC) on 13 occasions Cabanac and Massonnet, 1977 2

Humans immersed in warm and cool baths No dead band between shivering and sweating responses Equilibrated between hyperthermia and hypothermia and thermal neutrality is virtual No dead band seen in goats (Jessen and Clough, 1973) Cabanac and Massonnet, 1977 3

Amine injections into unanesthetized cats Adjustable set points in fevers Unanesthetized cats Implanted Collison cannula into left lateral ventricle to administer injections Substances injected: pyrogens Typhoid AB vaccine (contains Salmonella typhi and paratyphi) Shigella dysenteriae Adrenaline bitartrate Noradrenaline bitartrate 5-hydroxytryptamine (5-HT) creatinine sulphate Feldberg and Myers, 1964 4

Amine injections into unanesthetized cats Pyrogens and 5-HT increased rectal temperature Adrenaline and noradrenaline decreased rectal temperature The set point temperature can be shifted decreased warmsensitive and increased coldsensitive thermoreceptor activities reduced heat loss and increased heat production (Eisenman, 1969) Feldberg and Myers, 1964 5

Thermoreceptor activities in response to temperature changes Temperature regulation in urethane-anesthetized dogs Recordings between anterior commissure and optic chiasma Hypothalamic temperature varied by water perfusion technique (heating and cooling cycles) Rectal temperature (Tre) monitored by thermistor probe and maintained within range of 38-39ºC Hardy et al., 1964 6

Thermoreceptor activities in response to temperature changes Between 88 neurons: 60% temperature insensitive 32% warm sensitive Increased activity with heating Decreased activity with cooling 8% cold sensitive Increased activity with cooling Decreased activity with heating Hardy et al., 1964 7

Thermoreceptor activities in response to temperature changes 60% temperature insensitive Same two types of neurons recorded throughout hypothalamus in different species with consistent proportions: ~70% temperature insensitive and ~20% warm sensitive neurons (Boulant and Dean, 1986) In neuronal models, synaptic inputs from temperature insensitive neurons served as a steady-state reference signal for set point (Boulant and Dean, 1986) Hardy et al., 1964 8

OPPOSING COUNTERPOINT HYPOTHESIS Core temperatures are not defended at a set point, but rather in a null zone 9

Underwater cycle ergometer 9 male subjects exercised on an underwater cycle ergometer at 50% of their relative max work rate Immersed in water to chin level (28ºC) Measured forehead sweat rate Found core temperature (Tcore) at which sweating ceased and shivering commenced significantly different Concluded there is a null zone 0.59 + 0.23ºC for esophageal temperature (Tes) and 0.57 + 0.2ºC for rectal temperature (Tre) Mekjavic et al., 1991 10

Underwater cycle ergometer - limitations Failure to cool Tes and Tre in a constant rate Indirect skin temperature (Tsk) measurement Augment cutaneous constriction to sweating threshold Did not take possible acclimation into consideration Mekjavic et al., 1991 11

Induced hypothermia 8 male subjects Day 1: slow cooling rate (0.7 + 0.1ºC/ hr) Day 2: fast cooling rate (1.7 + 0.4ºC/hr) 8 female subjects Day 1 only: fast cooling rate Core hyperthermia induced by forced air warming, hypothermia induced by central venous infusion of cold lactated ringer s solution Constant Tsk near 36.7ºC Found null zone threshold range between sweating and shivering ~1.3 + 0.6ºC Lopez et al., 1994 12

Induced hypothermia - limitations Failed to match subjects according to weight Affects rate at which Tcore is cooled (White et al., 1992) Male outlier results removed Due to lower weight and body fat Threshold deviated by ~3 standard deviations Other potential limitations Threshold variations Fitness level Hydration status Matching subjects (height, weight, body fat) Lopez et al., 1994 13

Conclusion Core temperatures are defended at a set point and not in a null zone Studies have shown that thermoreceptors and thermoregulatory responses are according to changes in Tcore to maintain a set point Fevers demonstrate an adjustable set point Evidence supporting a null zone may have a lack of matched subjects, failed to consider acclimation status and didn t maintain constant Tsk through direct measurements Therefore, we support our point hypothesis in that core temperatures are defended at a set point 14

References Boulant, J. A., & Dean, J. B. (1986). Temperature Receptors in the Central Nervous System. Annual Review of Physiology, 48(1), 639-654. Cabanac, M., & Massonnet, B. (1977). Thermoregulatory Responses as a Function of Core Temperature in Humans. The Journal of Physiology, 265(3), 587-596. Eisenman, J. S. (1969). Pyrogen-Induced Changes in the Thermosensitivity of Septal and Preoptic Neurons. American Journal of Physiology--Legacy Content, 216(2), 330-334. Feldberg, W., & Myers, R. D. (1964). Effects on Temperature of Amines Injected into the Cerebral Ventricles. A New Concept of Temperature Regulation. The Journal of Physiology, 173(2), 226-237. Hardy, J. D., Hellon, R. F., & Sutherland, K. (1964). Temperature Sensitive Neurones in the Dog's Hypothalamus. The Journal of Physiology, 175(2), 242-253. Jessen, C., & Clough, D. P. (1973). Evaluation of Hypothalamic Thermosensitivity by Feedback Signals. Pflügers Archiv, 345(1), 43-59. Lopez, M., Sessler, D. I., Walter, K., Emerick, T., & Ozaki, M. (1994). Rate and Gender Dependence of the Sweating, Vasoconstriction, and Shivering thresholds in Humans. Anesthesiology, 80(4), 780-788. Mekjavic, I. B., Sundberg, C. J., & Linnarsson, D. (1991). Core Temperature "Null Zone". Journal of Applied Physiology, 71(4), 1289-1295. White, M. D., Ross, W. D., & Mekjavic, I. B. (1992). Relationship Between Physique and Rectal Temperature Cooling Rate. Undersea Biomedical Research, 19(2), 121-130. 15