Circadian temperature and cortisol rhythms during a constant routine are phase-delayed in hypersomnic winter depression.

Circadian temperature, cortisol, and thyroid-stimulating hormone (TSH) rhythms during a constant routine were assessed in 6 female controls and 6 female patients with hypersomnic winter depression (seasonal affective disorder, SAD) before and after morning bright light treatment. After sleep was standardized for 6 days, the subjects were sleep-deprived and at bed rest for 27 hours while rectal temperature, cortisol, and TSH levels were assessed. The minimum of the fitted rectal temperature rhythm was phase-delayed in the SAD group compared to the controls 5:42 AM vs. 3:16 AM (p < .005); with bright light treatment, the minimum advanced from 5:42 AM to 3:36 AM (p = .06). The minimum of the cortisol rhythm was phase-delayed in the SAD group compared to the control group, 12:11 AM vs. 10:03 PM (P < .05); with bright light treatment, the minimum advanced from 12:11 AM to 10:38 PM (P = .06) [corrected]. The acrophase of the TSH rhythm was not significantly phase-delayed in SAD subjects compared to control, though the trend appeared to be toward a phase-delay (p = .07). After bright light therapy, the TSH acrophase was not significantly different in the SAD subjects; the trend was a phase-advance (p = .09). Overall, the data suggest that circadian rhythms are phase-delayed relative to sleep in SAD patients and that morning bright light phase-advances those rhythms.

Sleep deprivation alters body temperature dynamics to mild cooling and heating not sweating threshold in women.

Sleep deprivation alters thermoregulatory responses. We used control of skin temperature to produce mild thermal challenge, both cool (32 degrees C) and warm (38 degrees C), and recorded esophageal and rectal temperatures, sweat rate and forearm blood flow in six healthy young women at rest. We discovered that after one night of sleep deprivation (1) both mean esophageal and rectal temperatures were reduced, (2) the mean threshold for sweating was not altered, and (3) there was no direct indication that skin blood flow was set at different levels with skin temperature neutral or cool. Peripheral vasodilation was attenuated when skin temperature was held at 38 degrees C. Following this period of mild hyperthermia, esophageal and rectal temperatures decreased much more rapidly in sleep-deprived subjects when skin temperature was cooled and held constant at 32 degrees C. We conclude that sleep-deprived women lose heat rapidly in response to a mild cooling stimulus. Sleep-deprived humans may be more vulnerable to heat loss with reduced ability to warm even at temperatures thought to be associated with thermal comfort.

Influence of tissue compressibility on calibration for strain-gauge plethysmography.

Strain gauges employed in plethysmography for determination of limb blood flow tend to counter the expansion of the limb during venous occlusion. Traditionally a mechanical calibration is performed in situ to compensate for tissue compressibility. Greenfield, Whitney, and Mowbray stated that, otherwise, large errors would result (Br. Med. Bull. 19: 101-109, 1963). Nonetheless, not all of the recent reports on skin blood flow in humans have been based on a calibration procedure that corrects for tissue compressibility. To evaluate the significance of this problem, we developed a new strain-gauge holder that made possible frequent, reproducible, stretching of a single-strand Whitney gauge in situ. We compared the apparent sensitivity thus obtained to electrical or bench mechanical determinations. We independently determined tissue compressibility by recording limb circumference as tension in a circumferential tube was varied. Both techniques showed that tissue compressibility is a small source of error (5%) and that compressibility decreases during occlusion. Therefore the cumbersome holder and potential artifacts associated with the traditional technique need not be tolerated. We also investigated the consequences of nonuniform tension distribution and temperature changes; practical considerations for dealing with these are discussed.

Reproducibility of the vascular response to heating in human skin.

Blood flow in human skin increases enormously in response to direct heating. If local skin temperature is held above 42 degrees C, blood flow eventually stabilizes at a level beyond which other influences, barring change in blood pressure, can produce no further increase. If this maximal level is a reproducible characteristic of an individual's cutaneous vasculature, it could be useful in comparing individuals; for example, in their response to hyperthermia. Our experiments were carried out to discover whether the maximal response of the vasculature of the skin of the forearm can be reproduced within reasonable limits and, also, to clarify the time course of the response. We used water sprayed over the surface of the forearms of 10 subjects to hold skin temperature above 42 degrees C for 60 min. During the last 10 min of heating, forearm blood flow (via venous occlusion plethysmography) was stable, at a level ranging from 16 to 38 ml.min-1.100 ml-1. This level, normalized to a blood pressure of 100 mmHg, was reproduced in a given individual on four or five occasions, with an average coefficient of variation of 10%. The response was 77 +/- 11% (SD) complete after 20 min of heating. Elapsed time at 90% of the final value was 35 +/- 9 (SD) min. We conclude that the maximal forearm blood flow response to local heating is a reproducible characteristic of the cutaneous vasculature with potential utility in the scaling of responses between and within individuals.

Control of skin blood flow in the neutral zone of human body temperature regulation.

In humans, matching of heat loss and heat production in the "neutral" zone, defined operationally in terms of a range of skin temperatures (Tsk), is accomplished by regulation of skin blood flow (SkBF). Our studies were designed to reveal the characteristics of control of SkBF [from measurements of forearm blood flow (FBF)] in this zone. We controlled the temperature of water sprayed on most of the body of supine men and women at 33 or 35 degrees C in a square-wave pattern (15 min at each temperature) or a step pattern (60 min at 33 degrees C separated by short periods at 35 degrees C). FBF followed Tsk (0.5 ml.min-1.degrees C-1). Esophageal temperature changed approximately 0.11 degrees C with each 2 degrees C change in Tsk, falling with Tsk increase and vice versa. Little influence on FBF, < 0.1 ml.min-1.100 ml-1. degrees C-1, was observed when only the forearm was sprayed with 33 and 35 degrees C water. We conclude that SkBF control in the 33-35 degree C range of Tsk is dominated by the feedforward reflex influence of Tsk on SkBF. The reflex response overcompensates for the effect of Tsk on thermal balance in the neutral zone, so that equilibrium core temperature has an inverse relationship to Tsk.

Plasma renin activity and forearm blood flow in paraplegic humans.

We recently found that paraplegic humans respond to hyperthermia with subnormal increase in skin blood flow (SkBF), based on measurements of forearm blood flow (FBF). Is this inhibition of SkBF a defect in thermoregulation or a cardiovascular adjustment necessary for blood pressure control? Since high resting plasma renin activity (PRA) is found in unstressed individuals with spinal cord lesions and since PRA increases during hyperthermia in normal humans, we inquired whether the renin-angiotensin system is responsible for the attenuated FBF in hyperthermic resting paraplegics. Five subjects, 28-47 yr, with spinal transections (T1-T10), were heated in water-perfused suits. Blood samples for PRA determinations were collected during a control period and after internal temperature reached approximately 38 degrees C. Some subjects with markedly attenuated FBF had little or no elevation of PRA; those with the best-developed FBF response exhibited the highest PRA. Clearly, circulating angiotensin is not the agent that attenuates SkBF. Rather, increased activity of the renin-angiotensin system may be a favorable adaptation that counters the locally mediated SkBF increase in the lower body and thus allows controlled active vasodilation in the part of the body subject to centrally integrated sympathetic effector outflow.

Reproducibility of core temperature threshold for sweating onset in humans.

The control of sweating in humans has been described quantitatively in terms of skin and core temperatures (Tsk and Tcore, respectively). However, the precision with which features of the relationship between sweat rate and Tcore at a given Tsk can be reproduced in the short term is not known. We focused on the threshold Tcore. We held Tsk at 38 degrees C until sweating began for two periods separated by a period of cooling with Tsk at 32 degrees C in six men and three women. The esophageal temperature (Tes) at which sweating began was invariably lower in the second period of heating (average difference 0.09 degree C; maximum 0.17 degree C). Also, the rate of rise in Tes was invariably higher (average 148%) during the second period of heating. Thus, although a threshold cannot be reproduced within the error of Tes measurement, the consistency and small magnitude of the downward shift recommend our protocol as a practical method for evaluating other influences on thermoregulation, provided that the effects are big enough to be seen against a background of an expected small decrease. From the fundamental point of view, the consistency of the downward displacement has provocative implications, e.g., the rate of change in Tcore influences sweating or thermosensitive units in slow-responding thermal compartments contribute to the Tcore input signal.

Maximal skin blood flow is decreased in elderly men.

When subjected to total body heating and exercise, skin blood flow does not increase as much in elderly as in young subjects. It is not known whether this age-related decline is due to the autonomic dysfunction that develops in the elderly or to changes at the level of the blood vessels of the skin. We used local heating of the forearm to quantify the intrinsic ability of the cutaneous vasculature to dilate in seven young men (avg age 31 yr) and seven elderly men (avg age 71 yr). A water spray was used to maintain a neutral skin temperature of 32-35 degrees C for > 10 min, followed by 60 min of a 42 degrees C skin temperature to induce maximal skin blood flow. Forearm blood flow was measured by venous occlusion plethysmography with a mercury-in-Silastic circumference gauge. At the neutral skin temperature, forearm blood flows in the elderly subjects were comparable to those in the young subjects: 3.0 +/- 0.5 vs. 2.8 +/- 1.0 ml.min-1 x 100 ml-1. During the last 10 min of heating, however, blood flows were much lower in the elderly than in the young subjects: 11.1 +/- 2.7 vs. 19.9 +/- 5.2 ml.min-1 x 100 ml-1 (P = 0.002). We conclude that aging results in a reduction of the maximal conductance of the cutaneous vasculature.

Sweat rate vs. forearm blood flow during lower body negative pressure.

Skin blood flow is inhibited when hyperthermia and added hypovolemic stresses are superimposed. We tested the hypothesis that part of this inhibition is a reduced drive for cutaneous active vasodilatation (AVD) with sweat rate (SR) taken as an indirect measure of the efferent drive for cutaneous AVD. We also inquired whether SR itself changes with redistribution of blood volume. Six healthy supine men were subjected to lower body negative pressure (LBNP) after heating in water-perfused suits increased esophageal temperatures (Tes) to a mean of 37.2 degrees C and at least doubled SR and forearm vascular conductance (FVC). Heating continued throughout LBNP and recovery. Sweat rate did not decrease with LBNP onset, although SR-Tes slopes during LBNP were reduced 28% from control. In four subjects the SR-Tes slope did not recover when LBNP was discontinued. These observations suggest that SR is not an effector of the low-pressure baroreflex. In contrast to SR, FVC abruptly fell 22% at the onset of LBNP. Thereafter, FVC-Tes slopes near zero or less occurred. The major effector for FVC inhibition with LBNP appears to be the neural vasoconstrictor system. A minor component due to reduced drive for cutaneous AVD probably occurs as well.

Unaltered norepinephrine-heart rate relationship in exercise with exogenous heat.

We measured plasma norepinephrine (NE) concentration, an index of sympathetic nervous activity, and epinephrine (E), an index of adrenal medulla activity, in six normal young men during mild to severe exercise, with and without superimposed heat stress. The primary objective was to observe whether the normally close relationship between heart rate and log NE concentration in upset when heart rate at a given work load is increased by heat stress. Exercise, beginning at 50 W, was graded in 50-W increments lasting 10 min each up to 200 W, which lasted 5-10 min. Each subject went through the protocol twice, once with skin temperature kept low by a water-perfused suit and then with skin temperature raised to 38 degrees C. Exogenous heart stress raised log circulating NE concentration in proportion to the rise in heart rate at a given work load so that the usual relationship between these variables, previously observed during other stresses, was preserved. In contrast to some other stresses, heat stress had no added effect on E concentration, indicating that this stress during exercise raises sympathetic neural activity (as reflected in the rise in NE) without stimulating additional adrenal release of E.

Effects of dehydration on thermoregulatory responses of horses during low-intensity exercise.

Effects of dehydration on thermoregulatory and metabolic responses were studied in six horses during 40 min of exercise eliciting approximately 40% of maximal O2 consumption and for 30 min after exercise. Horses were exercised while euhydrated (C), 4 h after administration of furosemide (FDH; 1.0 mg/kg i.v.) to induce isotonic dehydration, and after 30 h without water (DDH) to induce hypertonic dehydration. Cardiac output was significantly lower in FDH (144.1 +/- 8.0 l/min) and in DDH (156.6 +/- 6.9 l/min) than in C (173.1 +/- 6.2 l/min) after 30 min of exercise. When DDH, FDH, and C values were compared, dehydration resulted in higher temperatures in the middle gluteal muscle (41.9 +/- 0.3, 41.1 +/- 0.2, and 40.6 +/- 0.2 degrees C, respectively) and pulmonary artery (40.8 +/- 0.3, 40.1 +/- 0.2, and 39.7 +/- 0.2 degrees C, respectively). Temperatures in the superficial thoracic vein and subcutaneous sites on the neck and back and peak sweating rates on the neck and back were not significantly different in DDH and C. In view of higher core temperatures during exercise after dehydration and decrease in cardiac output without concomitant increases in peripheral temperatures or reduced sweating rates, we conclude that the impairment of thermoregulation was primarily due to decreased transfer of heat from core to periphery.

Cystic fibrosis, vasoactive intestinal polypeptide, and active cutaneous vasodilation.

The transmitter substance for the active cutaneous vasodilation that accompanies sweating during hyperthermia in humans is unknown. Hökfelt et al. (Nature Lond. 284: 515-521, 180) hypothesized that it is vasoactive intestinal polypeptide (VIP) that is cotransmitted with acetylcholine. Heinz-Erian et al. (Science Wash. DC 229: 1407-1408, 1985) reported that VIP innervation is sparse in the skin of persons with cystic fibrosis (CF). A corresponding attenuation of active vasodilation in these subjects would be evidence that VIP is involved in this effector mechanism of human thermor-regulation. Immunocytochemical analysis of skin biopsies from four men with CF confirmed that VIP innervation was sparse. We also analyzed immunoreactivity for calcitonin gene-related peptide (CGRP; normal), substance P (normal), and neuropeptide Y (low). VIP-immunoreactive Merkel cells were abnormal. Despite sparse VIP-immunoreactive innervation, our CF subjects' cutaneous vascular responses to hyperthermia were normal. Because VIP was not completely absent, this evidence is insufficient to rule out VIP as the vasodilator transmitter. However, the CGRP and substance P innervation we observed could mean that release of one or both of these peptides was the mechanism of the fully developed active cutaneous vasodilation.

Does acute hypoxemia blunt sympathetic activity in hyperthermia?

Sympathetic alpha-adrenergic function is depressed by hypoxemia per se; does addition of another sympathoexcitatory stimulus elicit normal responses in other sympathetic effector pathways? We activated by hyperthermia four sympathetic pathways: alpha-adrenergic [norepinephrine (NE) release], beta-adrenergic [plasma renin activity (PRA)], cholinergic (sweating), and peptidergic (active vasodilation). In the first test, five normothermic men were exposed to hypoxemia for 10 min (control), then hypoxemia plus heat for 30 min, and then heat with normoxia for 8-10 min over a continuous 48- to 50-min period. Heating was controlled with a water-perfused suit. Time courses and magnitudes of heat-induced increments in body temperature, forearm blood flow, and sweat rate were normal during hypoxemia and unaffected by switching to normoxia. Hypoxemia exaggerated increases in plasma NE, epinephrine, PRA, and heart rate but had no additional effects on blood pressure. In a second 50-min test (2 men) with normoxic control (10 min), heating plus normoxia (20 min), and heating plus hypoxemia (20 min), effects of hypoxemia on all variables were as in the first test. Thus, acute moderate hypoxemia did not blunt active cutaneous vasodilation or sweating and exaggerated increases in catecholamines and heart rate, indicating maintained peripheral autonomic function.

Independence of brain and tympanic temperatures in an unanesthetized human.

Temperature within the brain and the esophagus and at the tympanum were obtained in a 12-yr-old male in a series of experiments that began 8 days after surgery for implantation of a drainage catheter. Fanning the face did reduce tympanic temperature but not temperature in the brain; brain temperatures followed esophageal temperatures. In long-term monitoring, temperature in the lateral ventricle was 0.5 degree C above esophageal temperature and 0.2 degree C below that in white matter 1 cm above, with the offsets fixed throughout the overnight cycle. All temperatures went through similar excursions when the face was excluded from fanning applied to the body. These observations highlight the fact that in humans the defense against hyperthermia takes advantage of cooling distributed over the entire skin surface.

Dissipation of metabolic heat in the horse during exercise.

Horses were exercised at 40, 65, and 90% of their maximum O2 uptake (VO2max) until moderately fatigued (approximately 38, 15, and 9 min, respectively) to assess heat loss through different routes. Approximately 4,232, 3,195, and 2,333 kcal of heat were generated in response to exercise at these intensities. Of this, approximately 7, 16, and 20% remained as stored heat 30 min postexercise. Respiratory heat loss, estimated from the temperature difference between blood in the pulmonary and carotid arteries and the cardiac output, was estimated to be 30, 19, and 23% of the heat produced during exercise at the three intensities. The kinetics of the increases in muscle and blood temperature were similar, with the greatest change in temperature occurring in muscle (+3.8, 5.2, and 6.1 degrees C after exercise at 40, 65, and 90% of VO2max, respectively). The temperature of blood in the superficial thoracic vein was approximately 2 degrees C below that of arterial blood at rest. This difference had increased to approximately 3 degrees C during the last minute of exercise. The rate of sweating at sites on the back and neck increased with exercise intensity to a common peak of approximately 40 ml.m-2.min-1. If complete evaporation had occurred, water loss in response to exercise (estimated to be 12, 10, and 7.7 liters for the different intensities of exercise) greatly surpassed that required for dissipation of the metabolic heat load.

Effect of facial cooling on tympanic temperature.

BACKGROUND: In clinical practice, tympanic temperature is used as an estimate of body temperature. Theoretically, temperature recorded directly from the tympanum reflects the temperature of arterial blood circulating to the brain. However, some studies do not support this connection. Ear-based thermometers in clinical use, commonly called tympanic thermometers, detect heat emission from the aural canal and tympanum. Dissociation of core body temperature and tympanic temperature would suggest that factors other than arterial blood perfusion affect tympanic temperature. METHODS: In a controlled laboratory experiment with four adult volunteers, esophageal and tympanic temperatures were recorded repeatedly at 2-minute intervals during whole-body heating and cooling. Facial cooling, produced by a small electrical fan, was used in three subjects. RESULTS: The gradient between tympanic and esophageal temperature was inconsistent across subjects, with tympanic temperature both higher and lower than esophageal temperature. Correlations between esophageal and tympanic temperature varied widely across subjects. Fanning the face produced a decrease in tympanic temperature without an accompanying decline in esophageal temperature. CONCLUSIONS: Facial cooling in the form of fanning altered the relationship between tympanic and esophageal temperature. This result suggests the possible lowering of tympanic temperature by cooled facial venous blood flow. Use of tympanic temperature in circumstances in which facial temperature may be different from that of other regions of the body deserves further study.

Shivering following cardiac surgery: predictive factors, consequences, and characteristics.

BACKGROUND: Shivering is common after cardiac surgery and may evoke harmful hemodynamic changes. Neither those changes nor factors increasing probability of shivering are well defined. OBJECTIVES: (1) To identify factors linked with risk of shivering by comparing age, weight, body surface area, gender, intraoperative details, anesthetics, postoperative temperatures, hemodynamics, and therapeutics in shivering vs nonshivering patients. (2) To describe temperatures, hemodynamics, therapeutics, myocardial oxygen consumption correlates (rate-pressure product, heart rate, systemic vascular resistance) in shivering and nonshivering groups, and shivering and nonshivering periods. (3) To characterize the electromyogram to determine whether the tremor is cold-induced. METHODS: A descriptive design with a time series component was used to study a convenience sample of 10 shivering and 10 nonshivering adults for 4 hours during early recovery from cardiac surgery. Pulmonary artery and skin (facial, calf, trunk) temperature were measured every 60 seconds; heart rate and arterial pressure, every 15 minutes; cardiac output, 3 times. Electromyogram was recorded intermittently. Medications and treatments were noted. RESULTS: Lower skin temperature was significantly related to shivering risk. Heart rate was significantly higher initially in shiverers and remained higher by 13.6 beats per minute. Significantly more nitroprusside was used to control arterial pressure before than after shivering. No significant differences were noted between groups in core temperature, age, weight, body surface area, anesthesia type, intraoperative temperature; or surgery, circulatory bypass, or cardiac cross-clamp duration. The electromyogram pattern during shivering was typical of that produced by cold. CONCLUSIONS: These results suggest that true shivering occurs after cardiac surgery. Skin, but not core, temperature and elevated heart rate predict shivering. Shivering may be more likely in hemodynamically unstable patients.

Effect of the 30 degree lateral recumbent position on pulmonary artery and pulmonary artery wedge pressures in critically ill adult cardiac surgery patients.

BACKGROUND: Despite demonstrated benefits of lateral positioning, critically ill patients may require prolonged supine positioning to obtain reproducible hemodynamic measurements. OBJECTIVES: TO determine the effect of 30 degree right and left lateral positions on pulmonary artery and pulmonary artery wedge pressures after cardiac surgery in critically ill adult patients. METHODS: An experimental repeated-measures design was used to study 35 patients with stable hemodynamics after cardiac surgery. Subjects were randomly assigned to 1 of 2 position sequences. Pulmonary artery and pulmonary artery wedge pressures were measured in each position. RESULTS: Measurements obtained from patients in the 30 degree left lateral position differed significantly (all Ps < .05) from measurements obtained from patients in the supine position for pulmonary artery systolic, end-diastolic, and mean pressures. Pulmonary artery wedge pressures did not differ significantly; however, data were available from only 17 subjects. The largest mean difference in pressures between the 2 positions was 2.0 +/- 2.1 mm Hg for pulmonary artery systolic pressures, whereas maximum differences for end-diastolic and pulmonary artery wedge pressures were 1.4 +/- 2.7 mm Hg and 1.6 +/- 2.4 mm Hg, respectively. Clinically significant position-related changes in pressure occurred in 12 (2.1%) of 581 pressure pairs. Clinically significant changes occurred in end-diastolic pressure in 2 subjects and in pulmonary artery wedge pressure in 1 subject. CONCLUSIONS: In patients with stable hemodynamics during the first 12 to 24 hours after cardiac surgery, measurements of pulmonary artery and pulmonary artery wedge pressures obtained in the 30 degree lateral and supine positions are clinically interchangeable.