Corticospinal and spinal excitability during peripheral or central cooling in humans.

Cold exposure can impair fine and gross motor control and threaten survival. Most motor task decrement is due to peripheral neuromuscular factors. Less is known about cooling on central neural factors. Corticospinal and spinal excitability were determined during cooling of the skin (Tsk) and core (Tco). Eight subjects (four female) were actively cooled in a liquid perfused suit for 90 min (2 °C inflow temperature), passively cooled for 7 min, and then rewarmed for 30 min (41 °C inflow temperature). Stimulation blocks included 10 transcranial magnetic stimulations [eliciting motor evoked potentials (MEPs) which indicate corticospinal excitability], 8 trans-mastoid electrical stimulations [eliciting cervicomedullary evoked potentials (CMEPs) which indicate spinal excitability] and 2 brachial plexus electrical stimulations [eliciting maximal compound motor action potentials (Mmax)]. These stimulations were delivered every 30 min. Cooling for 90 min reduced Tsk to 18.2 °C while Tco did not change. At the end of rewarming Tsk returned to baseline while Tco decreased by 0.8 °C (afterdrop) (P < 0.001). Metabolic heat production was higher than baseline at the end of passive cooling (P = 0.01), and 7 min into rewarming (P = 0.04). MEP/Mmax remained unchanged throughout. CMEP/Mmax increased by 38% at end cooling (although increased variability at this time rendered the increase insignificant, P = 0.23) and 58% at end warming when Tco was 0.8 °C below baseline (P = 0.02). Cooling increased spinal excitability but not corticospinal excitability. Cooling may decrease cortical and/or supraspinal excitability which is compensated for by increased spinal excitability. This compensation is key to providing a motor task and survival advantage.

Shivering endurance and fatigue during cold water immersion in humans.

An important component of survival time during cold exposure is shivering endurance. Nine male and three female healthy and fit subjects [mean (SD) age 24.8 (6.3) years, body mass 71.7 (13.2) kg, height 1.75 (0.10) m, body fat 22.7 (7.4)%] were immersed to the upper chest level in cold water for periods ranging from 105 to 388 min on two occasions to test a prediction of shivering endurance. The water was cooled from 20 to 8 degrees C during the first 15 min of immersion and subsequently rewarmed (<20 degrees C) to elicit a near constant submaximal shivering response. The data were divided according to moderate (M) and high (H) levels of shivering intensity. Respective mean total immersion times were 250 (75) and 199 (80) min ( P=0.086) at different average shivering intensities of 61 (10) and 69 (8)% relative to maximal shivering ( P<0.001). Blood plasma glucose concentration increased during the immersion [from 3.44 (0.54) pre- to 3.94 (0.60) mmol x l(-1) post-immersion ( P=0.037)] and levels were higher during M ( P=0.012). When compared to a model prediction of shivering endurance, shivering activity continued well beyond the predicted endurance times in 18 out of the 24 trials. The average rates of oxygen consumption over the entire immersion period were lower ( P=0.002) during M [0.93 (0.20) l x min(-1)] compared to H [1.05 (0.21) l x min(-1)), and while these rates did not change during the last 90 min of immersion, there was an increase in fat oxidation. There were no trial differences in the average esophageal (T(es)) and mean skin temperatures during the entire immersion period (36.0 and 18.0 degrees C, respectively), yet T(es) decreased ( P=0.003) approximately 0.4 degrees C during the last 90 min of immersion. When the shivering intensity was normalized to account for this decrease, a significant downward trend of approximately 17% x h(-1) in the normalized shivering intensity was found after the predicted end of shivering endurance. These results suggest that shivering drive, and not shivering intensity per se, decreased during the latter stages of the immersion. Underlying mechanisms such as fatigue and habituation for this diminishing cold sensitivity are discussed.

Emergency treatment of hypothermia.

This review considers several recent concepts regarding aetiology and treatment of accidental hypothermia. The importance and effectiveness of shivering heat production in the attenuation and reversal of hypothermia is described. Immediately following removal from cold stress, the patient is in danger of a deteriorating condition that may be due to collapse of arterial pressure and/or continued decrease of core temperature. Several controversies are discussed. It is advised that, when possible, patients should be actively but gently warmed as soon as possible (especially if arrival at the emergency department will take greater than 45 min). Extra time should be taken to check for life signs before cardiopulmonary resuscitation is initiated. Chest compressions should proceed at regular normothermic rates and care should be taken to not overventilate the patient. In the emergency department, several factors should be considered before deciding on a treatment regimen. These factors include level of consciousness, cardiovascular stability, core temperature and the direction of change of core temperature. It may be advantageous to transport the more severely hypothermic patient to a more advanced care facility even though transport time may be greater.

Measurement and prediction of peak shivering intensity in humans.

Prediction equations of shivering metabolism are critical to the development of models of thermoregulation during cold exposure. Although the intensity of maximal shivering has not yet been predicted, a peak shivering metabolic rate (Shivpeak) of five times the resting metabolic rate has been reported. A group of 15 subjects (including 4 women) [mean age 24.7 (SD 6) years, mean body mass 72.1 (SD 12) kg, mean height 1.76 (SD 0.1) m, mean body fat 22.3 (SD 7)% and mean maximal oxygen uptake (VO2max) 53.2 (SD 9) ml O2.kg-1.min-1] participated in the present study to measure and predict Shivpeak. The subjects were initially immersed in water at 8 degrees C for up to 70 min. Water temperature was then gradually increased at 0.8 degree C.min-1 to a value of 20 degrees C, which it was expected would increase shivering heat production based on the knowledge that peripheral cold receptors fire maximally at approximately this temperature. This, in combination with the relatively low core temperature at the time this water temperature was reached, was hypothesized would stimulate Shivpeak. Prior to warming the water from 8 to 20 degrees C, the oxygen consumption was 15.1 (SD 5.5) ml.kg-1.min-1 at core temperatures of approximately 35 degrees C. After the water temperature had risen to 20 degrees C, the observed Shivpeak was 22.1 (SD 4.2) ml O2.kg-1.min-1 at core and mean skin temperatures of 35.2 (SD 0.9) and 22.1 (SD 2.2) degrees C, respectively. The Shivpeak corresponded to 4.9 (SD 0.8) times the resting metabolism and 41.7 (SD 5.1)% of VO2max. The best fit equation predicting Shivpeak was Shivpeak (ml O2.kg-1.min-1) = 30.5 + 0.348 x VO2max (ml O2.kg-1.min-1) - 0.909 x body mass index (kg.m-2) - 0.233 x age (years); (P = 0.0001; r2 = 0.872).

Prehospital treatment of hypothermia.

This article considers several issues regarding cold stress, development of hypothermia, and prehospital care of the hypothermic patient. Advice is given on the use of clinical impressions and functional characteristics to determine the level of hypothermia. Response to cold water immersion is characterized as short-term (cold shock response), midterm (loss of performance), and long-term (development of hypothermia). Circum-rescue collapse is the dramatic worsening condition of the patient just before, during, or after rescue from cold stress. After rescue, the treatment priorities are to arrest the fall in core temperature, establish a steady, safe rewarming rate while maintaining the stability of the cardiorespiratory system, and provide sufficient physiological support.

Moderate exercise increases the post exercise resting warm thermoregulatory response thresholds.

BACKGROUND: The purpose of this study was to evaluate the effect of exercise on the subsequent post-exercise core temperature thresholds for vasodilation and sweating. METHODS: On two separate days, with 6 subjects (3 males and 3 females), a whole-body water-perfused suit decreased mean skin temperature until the threshold for vasoconstriction was demonstrated. Mean skin temperature was then slowly increased (approximately 5.0 degrees C x h(-1)) until thresholds for vasodilation and sweating were clearly established. Subjects were cooled by decreasing water temperature until both esophageal and mean skin temperatures returned to near baseline values. Subjects then either performed 15 min of cycle ergometry (60% V(O2max)) followed by 30 min of recovery (Exercise), or remained seated with no exercise for 45 min (Control). Subjects were then cooled again until the onset of cutaneous vasoconstriction followed by a second warming period. The core temperature thresholds for vasodilation and sweating increased significantly by 0.49 degrees C and 0.19 degrees C post-exercise, respectively (p < 0.05). In order to compare thresholds between conditions in which both esophageal and mean skin temperatures were changing, we mathematically compensated for changes in skin temperatures using the established linear cutaneous contribution of skin to the control of vasodilation and sweating (10%). RESULTS: The calculated core temperature threshold (at a designated skin temperature of 36.0 degrees C) for vasodilation increased significantly from 36.56 +/- 0.12 degrees C to 37.11 +/- 0.21 degrees C post-exercise (p < 0.01). Likewise, the sweating threshold increased from 36.79 +/- 0.18 degrees C to 37.05 +/- 0.23 degrees C postexercise (p < 0.01). In contrast, sequential measurements, without exercise, demonstrate a time-dependent decrease (0.18 degrees C) in the sweating threshold, with no difference in the vasodilation threshold. CONCLUSION: These data indicate that exercise has a prolonged effect by increasing the post-exercise thresholds for both warm thermoregulatory responses.

Cold stress, near drowning and accidental hypothermia: a review.

This paper reviews literature on the topic of cold stress, near-drowning and hypothermia, written mainly since the last review of this type in this journal. The main effects of cold stress, especially in cold water immersion, include the "cold shock" response, local cooling causing decrements in physical and mental performance, and ultimately core cooling as hypothermia occurs. The section on cold-water submersion (near-drowning) includes discussion regarding the various mechanisms for brain and body cooling during submersion. The mechanisms for cold-induced protection of the anoxic brain are discussed with attention given to decreased brain temperature and the Q10 principle, the mammalian dive reflex and a newly considered mechanism; cold-induced changes in neurotransmitter release (i.e., glutamate and dopamine). The section on the post-cooling period includes the post-rescue collapse and subsequent rewarming strategies used in the field, during emergency transport or in medical facilities. Recent research on topics such as inhalation warming, body-to-body warming, radio wave therapy, warm water immersion, exercise, body cavity lavage, and cardiopulmonary bypass is reviewed. Information on new methods of warming, including arteriovenous anastomoses (AVA) warming (by application of heat- with or without negative pressure application-to distal extremities in an effort to increase AVA blood flow), forced-air warming, and peripheral vascular extracorporeal warming, are discussed.

Immersion of distal arms and legs in warm water (AVA rewarming) effectively rewarms mildly hypothermic humans.

INTRODUCTION: Active rewarming of hypothermic victims for field use, and where transport to medical facilities is impossible, might be the only way to restore deep body temperature. In active rewarming in warm water, there has been a controversy concerning whether arms and legs should be immersed in the water or left out. Further, it has been suggested in the Royal Danish Navy treatment regime, that immersion of hands, forearms, feet, and lower legs alone might accomplish rapid rates of rewarming (AVA rewarming). METHODS: On three occasions, six subjects (one female) were cooled in 8 degrees C water, to an esophageal temperature of 34.3+/-0.8 (+/-SD) degrees C. After cooling the subjects were warmed by shivering heat production alone, or by immersing the distal extremities (hands, forearms, feet and lower legs) in either 42 degrees C or 45 degrees C water. RESULTS: The post cooling afterdrop in esophageal temperature was decreased by both 42 degrees C and 45 degrees C water immersion (0.4+/-0.2 degrees C) compared with the shivering alone procedure (0.6+/-0.4 degrees C; p < 0.05). The subsequent rate of rewarming was significantly greater with 45 degrees C water immersion (9.9+/-3.2 degrees C x h(-1)) than both 42 degrees C water immersion (6.1+/-1.2 degrees C x h(-1)) and shivering alone (3.4+/-1.5 degrees C x h(-1); p < 0.05). CONCLUSION: The extremity rewarming procedure was experienced by the subjects as the most comfortable as the rapid rise in deep body temperature shortened the period of shivering. During the extremity rewarming procedures the rectal temperature lagged considerably behind the esophageal and aural canal (via indwelling thermocouple) temperatures. Thus large gradients may still exist between body compartments even though the heart is warmed.

Changes in exercise and post-exercise core temperature under different clothing conditions.

This study evaluates the effect of different levels of insulation on esophageal (Tes) and rectal (Tre) temperature responses during and following moderate exercise. Seven subjects completed three 18-min bouts of treadmill exercise (75% VO2max, 22 degrees C ambient temperature) followed by 30 min of recovery wearing either: (1) jogging shoes, T-shirt and shorts (athletic clothing); (2) single-knit commercial coveralls worn over the athletic clothing (coveralls); or (3) a Canadian Armed Forces nuclear, bacteriological and chemical warfare protective overgarment with hood, worn over the athletic clothing (NBCW overgarment). Tes was similar at the start of exercise for each condition and baseline Tre was approximately 0.4 degree C higher than Tes. The hourly equivalent rate of increase in Tes during the final 5 min of exercise was 1.8 degrees C, 3.0 degrees C and 4.2 degrees C for athletic clothing, coveralls and NBCW overgarment respectively (P < 0.05). End-exercise Tes was significantly different between conditions [37.7 degrees C (SEM 0.1 degree C), 38.2 degrees C (SEM 0.2 degree C and 38.5 degrees C (SEM 0.2 degree C) for athletic clothing, coveralls and NBCW overgarment respectively)] (P < 0.05). No comparable difference in the rate of temperature increase for Tre was demonstrated, except that end-exercise Tre for the NBCW overgarment condition was significantly greater (0.5 degree C) than that for the athletic clothing condition. There was a drop in Tes during the initial minutes of recovery to sustained plateaus which were significantly (P < 0.05) elevated above pre-exercise resting values by 0.6 degree C, 0.8 degree C and 1.0 degree C, for athletic clothing, coveralls, and NBCW overgarment, respectively. Post-exercise Tre decreased very gradually from end-exercise values during the 30-min recovery. Only the NBCW overgarment condition Tre was significantly elevated (0.3 degree C) above the athletic clothing condition (P < 0.05). In conclusion, Tes is far more sensitive in reflecting the heat stress of different levels of insulation during exercise and post-exercise than Tre. Physiological mechanisms are discussed as possible explanations for the differences in response.

The effect of dynamic exercise on resting cold thermoregulatory responses measured during water immersion.

The purpose of this study was to evaluate the effect of exercise on the subsequent post-exercise thresholds for vasoconstriction and shivering measured during water immersion. On 2 separate days, seven subjects (six males and one female) were immersed in water (37.5 degrees C) that was subsequently cooled at a constant rate of approximately 6.5 degrees C x h(-1) until the thresholds for vasoconstriction and shivering were clearly established. Water temperature was then increased to 37.5 degrees C. Subjects remained immersed for approximately 20 min, after which they exited the water, were towel-dried and sat in room air (22 degrees C) until both esophageal temperature and mean skin temperature (Tsk) returned to near-baseline values. Subjects then either performed 15 min of cycle ergometry (at 65% maximal oxygen consumption) followed by 30 min of recovery (Exercise), or remained seated with no exercise for 45 min (Control). Subjects were then cooled again. The core temperature thresholds for both vasoconstriction and shivering increased significantly by 0.2 degrees C Post-Exercise (P < 0.05). Because the Tsk at the onset of vasoconstriction and shivering was different during Pre- and Post-Exercise Cooling, we compensated mathematically for changes in skin temperatures using the established linear cutaneous contribution of skin to the control of vasoconstriction and shivering (20%). The calculated core temperature threshold (at a designated skin temperature of 32.0 degrees C) for vasoconstriction increased significantly from 37.1 (0.3) degrees C to 37.5 ( 0.3) degrees C post-exercise (P < 0.05). Likewise, the shivering threshold increased from 36.2 (0.3) degrees C to 36.5 (0.3) degrees C post-exercise (P < 0.05). In contrast to the post-exercise increase in cold thermal response thresholds, sequential measurements demonstrated a time-dependent similarity in the Pre- and Post-Control thresholds for vasoconstriction and shivering. These data indicate that exercise has a prolonged effect on the post-exercise thresholds for both cold thermoregulatory responses.

Prediction of shivering heat production from core and mean skin temperatures.

Prediction formulae of shivering metabolism (Mshiv) are critical to the development of models of thermoregulation for cold exposure, especially when the extrapolation of survival times is required. Many such formulae, however, have been calibrated with data that are limited in their range of core temperatures (Tc), seldom involving values of less than 36 degrees C. Certain recent studies of cold-water immersion have reported Tc as low as 33.25 degrees C. These data comprise measurements of Tc (esophageal) and mean skin temperature (Ts), and metabolism from 14 males [mean (SD); age = 28 (5) years; height = 1.78 (0.06) m; body mass = 77.7 (6.9) kg; body fat (BF) = 18.4 (4.5)%] during immersion in water as cold as 8 degrees C for up to 1 h and subsequent self-rewarming via shivering under dry blanketed conditions. The data contain 3343 observations with mean (SD) Tc and Ts of 35.92 (0.93) degrees C and 23.4 (8.9) degrees C, respectively, and have been used to re-examine the prediction of Mshiv. Rates of changes of these temperatures were not used in the analysis. The best fit of the formulae, which are essentially algebraic constructs with and without setpoints, are those with a quadratic expression involving Ts. This is consistent with the findings of Benzinger (1969) who demonstrated that the thermosensitivity of skin is parabolic downwards with temperature peaking near a value of 20 degrees C. Formulae that included a multiplicative interaction term between Tc and Ts did not predict as well. The best prediction using 37 degrees C and 33 degrees C as the Tc and Ts setpoints, respectively, was found with BF as an attenuation factor: Mshiv (W x m(-2)) = [155.5 x (37- Tc) + 47.0 x (33 - Ts) - 1.57 x (33 - Ts)2]/(%BF)(0.5).

Design and evaluation of a portable rigid forced-air warming cover for prehospital transport of cold patients.

Forced-air warming is promising for use during transport of cold patients. However, the current soft covers may be easily damaged in the nonhospital environment. Two rigid covers were designed to direct heat to the torso and thighs. Five subjects (one female) were heated with an AC powered heater (Bair Hugger 505, Augustine) and either a soft cover or the rigid covers (with heat input at the head or abdomen). Compared to the soft cover, the rigid cover (with heat input at the abdomen) provided similar heat delivery but a higher mean skin temperature. We conclude that the portable rigid covers are efficient for treatment of cold victims during pre-hospital transport.

Moderate exercise increases postexercise thresholds for vasoconstriction and shivering.

The purpose of this study was to evaluate the effect of exercise on the subsequent postexercise thresholds for vasoconstriction and shivering. On two separate days, with six subjects (3 women), a whole body water-perfused suit slowly decreased mean skin temperature (approximately 7.0 degreesC/h) until thresholds for vasoconstriction and shivering were clearly established. Subjects were then rewarmed by increasing water temperature until both esophageal and mean skin temperatures returned to near-baseline values. Subjects either performed 15 min of cycle ergometry (65% maximal O2 consumption) followed by 30 min of recovery (Exercise) or remained seated with no exercise for 45 min (Control). Subjects were then cooled again. We mathematically compensated for changes in skin temperatures by using the established linear cutaneous contribution of skin to the control of vasoconstriction and shivering (20%). The calculated core temperature threshold (at a designated skin temperature of 30.0 degreesC) for vasoconstriction increased significantly from 36.64 +/- 0.20 to 36.89 +/- 0.22 degreesC postexercise (P < 0.01). Similarly, the shivering threshold increased from 35.73 +/- 0.13 to 36.13 +/- 0.12 degreesC postexercise (P < 0.01). In contrast, sequential measurements, without exercise, demonstrate a time-dependent decrease in both the vasoconstriction (0.10 degreesC) and shivering (0.12 degreesC) thresholds. These data indicate that exercise has a prolonged effect by increasing the postexercise thresholds for both cold thermoregulatory responses.

Ethanol ingestion prolongs orthostatic intolerance in hyperthermic humans.

BACKGROUND: Both ethanol ingestion and hyperthermia contribute to orthostatic intolerance (OI). HYPOTHESIS: Since ethanol has been cited as a major risk factor for hyperthermia-related deaths, we hypothesized that ethanol exacerbates OI induced by hyperthermia. METHODS: There were seven subjects (four males, three females) rendered hyperthermic (esophageal temperature = 39 degrees C) in a 40 degrees C water bath on two separate days: Condition 1) Control (juice ingestion); and Condition 2) Ethanol [ethanol (1 ml x kg(-1) body mass) and juice ingestion]. To test for OI, 5-min supine periods were followed by 5-min 63 degrees head-up tilts prior to and following immersion. BPs, heart rate and esophageal temperatures were monitored throughout the experiments. RESULTS: For first and second post-immersion tilts, mean arterial BP (MAP) during tilting increased by 5.9 +/- 3.6 (SE) and 9.8 +/- 2.6 mm Hg in the control condition, while it decreased by 7.9 +/- 5.8 and 0.6 +/- 4.3 mm Hg in the ethanol condition. This gave significantly lower MAP (ethanol vs. control) of 63.6 +/- 3.1 vs. 71.8 +/- 4.5 mm Hg (p < 0.05) for the first and 79.6 +/- 2.3 vs. 86.7 +/- 4.4 mm Hg (p < 0.05) for the second post-immersion tilts. These values were all significantly less (p < 0.05) than normothermic tilted values of 94.7 +/- 4.7 mm Hg in the ethanol and 93.6 +/- 2.9 mm Hg in the control condition. Prior to warm water immersion, subjects tolerated all head-up tilts. In the control condition, only one subject experienced orthostatic intolerance following the first post-heating tilt and no intolerance was experienced following 30 min post-heating. However, during the ethanol condition, 4 subjects experienced orthostatic intolerance following the first tilt with episodes of intolerance lasting as long as 80 min (8 supine/tilt cycles). CONCLUSION: Ethanol ingestion prolonged and increased the magnitude of OI in hyperthermic subjects. This may at least partly explain why ethanol is a major risk factor in hyperthermia-related deaths.

The convective afterdrop component during hypothermic exercise decreases with delayed exercise onset.

HYPOTHESIS: Following cold water immersion, the post-cooling decrease in esophageal temperature (Tes) (i.e., afterdrop) is 3 times greater during exercise than during shivering, presumably due to increased muscular blood flow and convective core-to-periphery heat loss with exercise (J. Appl. Physiol. 63:2375, 1987). We felt that if exercise were to commence once the afterdrop period during shivering is complete, the threat of a further decrease in Tes (i.e., a second afterdrop) during the subsequent exercise would be minimized because much of the convective capacity for core cooling would already be dissipated. METHODS: Six subjects were each cooled three times in 8 degrees C water, until Tes decreased to 35.3 +/- 0.7 degrees C, and rewarmed by either shivering alone, exercise, or exercise commencing once a shivering afterdrop period was complete. RESULTS: The initial afterdrop was greater during Exercise only (1.1 +/- 0.4 degrees C) than Shivering only (0.35 +/- 0.3 degrees C) and Shivering-Exercise (0.45 +/- 0.2 degrees C) (p < 0.05). In contrast, exercise caused a secondary afterdrop of only 0.38 +/- 0.3 degrees C during Shivering-Exercise (p < 0.05). The initial rewarming rate during Exercise only (3.45 degrees C.h-1) was greater than the initial (2.7 degrees C.h-1) and second (2.4 degrees C.h-1) rewarming rates during Shivering-Exercise (p < 0.05), but not significantly greater than during Shivering only (2.99 degrees C.h-1) (p < 0.1). DISCUSSION: It is likely that during the Shivering-Exercise protocol, continued blood flow to shivering muscles: a) contributes to the initial afterdrop, and thus b) diminishes the convective capacity (or heat sink) available for further cooling during subsequent exercise.

Recovery of a 62-year-old man from prolonged cold water submersion.

Recovery from prolonged cold water submersion is well documented in children but rare in adults. In the few adult cases reported, significant body cooling occurred (rectal temperature ranging from 22 degrees to 32 degrees C) and the victims were relatively young (< 40 years). We report a case of a 62-year-old man who was submersed in 2 degrees to 3 degrees C water for 15 minutes (time from initial submersion to intubation = 22 minutes). At the time of rescue, he had no vital signs, received prehospital Advanced Life Support, and was transported to hospital. On arrival at hospital, the patient remained in full cardiopulmonary arrest with an agonal ECG rhythm and had an initial pH of 6.77. Initial rectal temperature was near normal (36 degrees C) but subsequently dropped to 33 degrees C. The patient was resuscitated, rewarmed by forced-air warming, and treated for acute myocardial infarction, pulmonary edema, and generalized seizures. He was discharged after 27 days with minor neurologic abnormalities. Given the near-normal initial rectal temperature, preferential brain cooling may have been at least partially responsible for the positive neurologic outcome.

Clonidine decreases vasoconstriction and shivering thresholds, without affecting the sweating threshold.

PURPOSE: This study was conducted to test the hypothesis that clonidine produces a dose-dependent increase in the sweating threshold and dose-dependent decreases in vasoconstriction and shivering thresholds. METHODS: Six healthy subjects (two female) were studied on four days after taking clonidine in oral doses of either 0 (control), 3, 6 or 9 micrograms.kg-1. The order followed a balanced design in a double-blind fashion. Oesophageal temperature and mean skin temperature (from 12 sites) were measured. Subjects were seated in 37 degrees C water which was gradually warmed until sweating occurred (sweat rate increased above 50 g.m-2.h-1). The water was then cooled gradually until thresholds for vasoconstriction (onset of sustained decrease in fingertip blood flow) and shivering (sustained elevation in metabolism) were determined. Thresholds were then referred to as the core temperature, adjusted to a designated mean skin temperature of 33 degrees C. RESULTS: High dose clonidine similarly decreased the adjusted core temperature thresholds for vasoconstriction by 1.16 +/- 0.30 degrees C and for shivering by 1.63 +/- 0.23 degrees C (P < 0.01). The dose response effects were linear for both cold responses with vasoconstriction and shivering thresholds decreasing by 0.13 +/- 0.05 and 0.19 +/- 0.09 degree C.microgram-1 respectively (P < 0.0001). The sweating threshold was unaffected by clonidine, however the interthreshold range between sweating and vasoconstriction thresholds increased from control (0.19 +/- 0.48 degree C) to high dose clonidine (1.31 +/- 0.54 degrees C). CONCLUSION: The decreases in core temperature thresholds for cold responses and increased interthreshold range are consistent with the effects of several anaesthetic agents and opioids and is indicative of central thermoregulatory inhibition.

Reflex tracheal smooth muscle contraction and bronchial vasodilation evoked by airway cooling in dogs.

Cooling intrathoracic airways by filling the pulmonary circulation with cold blood alters pulmonary mechanoreceptor discharge. To determine whether this initiates reflex changes that could contribute to airway obstruction, we measured changes in tracheal smooth muscle tension and bronchial arterial flow evoked by cooling. In nine chloralose-anesthetized open-chest dogs, the right pulmonary artery was cannulated and perfused; the left lung, ventilated separately, provided gas exchange. With the right lung phasically ventilated, filling the right pulmonary circulation with 5 degrees C blood increased smooth muscle tension in an innervated upper tracheal segment by 23 +/- 6 (SE) g from a baseline of 75 g. Contraction began within 10 s of injection and was maximal at approximately 30s. The response was abolished by cervical vagotomy. Bronchial arterial flow increased from 8 +/- 1 to 13 +/- 2 ml/min, with little effect on arterial blood pressure. The time course was similar to that of the tracheal response. This response was greatly attenuated after cervical vagotomy. Blood at 20 degrees C also increased tracheal smooth muscle tension and bronchial flow, whereas 37 degrees C blood had little effect. The results suggested that alteration of airway mechanoreceptor discharge by cooling can initiate reflexes that contribute to airway obstruction.