Hyperemic flow heterogeneity within the calf, foot, and forearm measured with continuous arterial spin labeling MRI

Arterial spin labeling (ASL) is a noninvasive magnetic resonance imaging (MRI) technique for microvascular blood flow measurement. We used a continuous ASL scheme (CASL) to investigate the hyperemic flow difference between major muscle groups in human extremities. Twenty-four healthy subjects with no evidence of vascular disease were recruited. MRI was conducted on a 3.0 Tesla Siemens Trio whole body system with a transmit/receive knee coil. A nonmagnetic orthopedic tourniquet system was used to create a 5-min period of ischemia followed by a period of hyperemic flow (occlusion pressure = 250 mmHg). CASL imaging, lasting from 2 min before cuff inflation to 3 min after cuff deflation, was performed on the midcalf, midfoot, and midforearm in separate sessions from which blood flow was quantified with an effective temporal resolution of 16 s. When muscles in the same anatomic location were compared, hyperemic flow was found to be significantly higher in the compartments containing muscles known to have relatively higher slow-twitch type I fiber compositions, such as the soleus muscle in the calf and the extensors in the forearm. In the foot, the plantar flexors exhibited a slightly delayed hyperemic response relative to that of the dorsal compartment, but no between-group flow difference was observed. These results demonstrate that CASL is sensitive to flow heterogeneity between diverse muscle groups and that nonuniform hyperemic flow patterns following an ischemic paradigm correlate with relative fiber-type predominance.     

Altered thresholds for thermoregulatory sweating and vasodilatation in anorexia nervosa.

The changes in peripheral (hand) blood flow that occurred when deep body temperature was raised were measured in 13 patients with anorexia nervosa and 13 control subjects. The relation between blood flow and core temperature was shifted to the left in the patients with anorexia, with the onset of vasodilatation occurring at lower core and mean skin temperatures: no significant differences in the slopes of the responses were evident. The onset of thermal sweating occurred at lower core and mean skin temperatures in the patients with anorexia than in the controls. After ingestion of a high-energy liquid meal core temperature increased in the patients, and this was accompanied by a significant rise in peripheral blood flow in most cases. A similar meal in the normal subjects was followed by either no change in core temperature or a slight fall, and no consistent change in peripheral blood flow. These findings suggest that the lowering of thresholds for thermoregulatory sweating and vasodilatation may be a contributory factor to the abnormally low core temperature of patients with anorexia and may also explain some of their common complaints relating to feelings of warmth in the hands and feet after meals.     

Challenging the sleep homeostat does not influence the thermoregulatory system in men: evidence from a nap vs. sleep-deprivation study

The purpose of our study was to understand the relationship between the components of the three-process model of sleepiness regulation (homeostatic, circadian, and sleep inertia) and the thermoregulatory system. This was achieved by comparing the impact of a 40-h sleep deprivation vs. a 40-h multiple nap paradigm (10 cycles with 150/75 min wakefulness/sleep episodes) on distal and proximal skin temperatures, core body temperature (CBT), melatonin secretion, subjective sleepiness, and nocturnal sleep EEG slow-wave activity in eight healthy young men in a "controlled posture" protocol. The main finding of the study was that accumulation of sleep pressure increased subjective sleepiness and slow-wave activity during the succeeding recovery night but did not influence the thermoregulatory system as measured by distal, proximal, and CBT. The circadian rhythm of sleepiness (and proximal temperature) was significantly correlated and phase locked with CBT, whereas distal temperature and melatonin secretion were phase advanced (by 113 +/- 28 and 130 +/- 30 min, respectively; both P < 0.005). This provides evidence for a primary role of distal vasodilatation in the circadian regulation of CBT and its relationship with sleepiness. Specific thermoregulatory changes occur at lights off and on. After lights off, skin temperatures increased and were most pronounced for distal; after lights on, the converse occurred. The decay in distal temperature (vasoconstriction) was significantly correlated with the disappearance of sleep inertia. These effects showed minor and nonsignificant circadian modulation. In summary, the thermoregulatory system seems to be independent of the sleep homeostat, but the circadian modulation of sleepiness and sleep inertia is clearly associated with thermoregulatory changes.     

Local vascular responses affecting blood flow in postural tachycardia syndrome

Postural tachycardia syndrome (POTS) is defined by orthostatic intolerance associated with abnormal upright tachycardia. Some patients have defective peripheral vasoconstriction and increased calf blood flow. Others have increased peripheral arterial resistance and decreased blood flow. In 14 POTS patients (13-19 yr) evenly subdivided among low-flow POTS (LFP) and high-flow POTS (HFP) we tested the hypothesis that myogenic, venoarteriolar, and reactive hyperemic responses are abnormal. We used venous occlusion plethysmography to measure calf venous pressure and blood flow in the supine position and when the calf was lowered by 40 cm to evoke myogenic and venoarteriolar responses and during venous hypertension by 40-mmHg occlusion to evoke the venoarteriolar response. We measured calf reactive hyperemia with plethysmography and cutaneous laser-Doppler flowmetry. Baseline blood flow in LFP was reduced compared with HFP and control subjects (0.8 +/- 0.2 vs. 4.4 +/- 0.5 and 2.7 +/- 0.4 ml.min-1.100 ml-1) but increased during leg lowering (1.2 +/- 0.5 ml.min-1. 100 ml-1) while decreasing in the others. Baseline peripheral arterial resistance was increased in LFP and decreased in HFP compared with control subjects (39 +/- 13 vs. 15 +/- 3 and 22 +/- 5 mmHg.ml-1. 100 ml. min) but decreased to 29 +/- 13 mmHg.ml-1.100 ml. min in LFP during venous hypertension. Resistance increased in the other groups. Maximum calf hyperemic flow and cutaneous flow were similar in all subjects. The duration of hyperemic blood flow was curtailed in LFP compared with either control or HFP subjects (plethysmographic time constant = 20 +/- 2 vs. 29 +/- 4 and 28 +/- 4 s; cutaneous time constant = 60 +/- 25 vs. 149 +/- 53 s in controls). Local blood flow regulation in low-flow POTS is impaired.     

Attenuation of sleep propensity, core hypothermia, and peripheral heat loss after temazepam tolerance

If changes in thermoregulation mediate sleepiness induced by sedative/hypnotics, then a reduction in the soporific efficacy (tolerance) of these agents may be accompanied by a concomitant reduction in their thermoregulatory effects. We compared the thermoregulatory and soporific effects of acute temazepam (30 mg at 1400) in 11 young male subjects before and immediately after 7 consecutive days of temazepam (30 mg). Subjects lay supine (0800-2030), while foot (T(ft)) and rectal (T(c)) temperatures were recorded. Sleep onset latency (SOL) was measured hourly using 20-min multiple sleep latency tests. Relative to placebo, temazepam significantly reduced both T(c) and SOL (-0.31 degrees C and 14.1 min) while increasing T(ft) (3.39 degrees C). A significant tolerance developed after the week of temazepam, with a mean reduction in soporific efficacy of 4.0 +/- 0.8 min. This was accompanied by a concomitant attenuation in both T(c) (-0.16 degrees C) and T(ft) (1.44 degrees C). Furthermore, SOL was temporally related to T(ft) and the maximum rate of decline in T(c) before and after tolerance. Together, these results indicate that the thermoregulatory system may be functionally involved in the regulation of sleepiness.     

Regional Blood Flow in the Upper Extremity during and after Exposure to Acute Normobaric Hypoxia

Cardiovascular indices were analyzed in young healthy males exposed to normobaric hypoxia (breathing a gas mixture containing 10% O₂ for 16 min). There was a marked variation in individual responses. A linear relationship was observed between the individual blood oxygen saturation at the end of exposure and the baseline muscle blood flow (MBF). Moreover, blood oxygen saturation decreased in subjects with an initially high forearm MBF and remained unchanged or even slightly increased in subjects with a low forearm MBF. After hypoxic exposure (10–15 min), the MBF continued to decrease, venous capacity increased, and postocclusion hyperemic response decreased. It is suggested that hypoxic exposure activates the neuroreflex mechanisms regulating the peripheral blood flow and that the peripheral vascular response to acute hypoxia depends largely on the baseline blood flow in skeletal muscles.     

Plateau in muscle blood flow during prolonged exercise in miniature swine

Cardiovascular, metabolic, and thermoregulatory responses were studied in eight male miniature swine during a prolonged treadmill run. Each animal underwent 8-10 wk of exercise training, thoracic surgery, and 3 wk of retraining before the experimental run. This regimen enabled the animals to run at 65% of the heart rate range (210-220 beats/min) for approximately 100 min. Skin wetting and a fan were used to cool the pigs during the run. Regional blood flow was significantly altered with the onset of exercise; however, hindlimb muscle and total gastrointestinal blood flow were unchanged throughout the exercise period. Compared with 5-min values, heart rate and cardiac output were significantly elevated by 17 beats/min and 31 ml.min-1.kg-1 at 60 min and by 20 beats/min and 33 ml.min-1.kg-1 at end exercise, respectively. Core temperatures increased between 5 and 30 min of exercise (39.4 vs. 39.9 degrees C) but then remained unchanged to the end of exercise. Mean arterial pressure, O2 consumption, and blood lactate did not change during the exercise bout. These data indicate that limiting increases in core temperature during prolonged exercise was associated with a plateau in active muscle blood flow.     

Effect of blood viscosity on oxygen transport in residual stenosed artery following angioplasty

The effect of blood viscosity on oxygen transport in a stenosed coronary artery during the postangioplasty scenario is studied. In addition to incorporating varying blood viscosity using different hematocrit (Hct) concentrations, oxygen consumption by the avascular wall and its supply from vasa vasorum, nonlinear oxygen binding capacity of the hemoglobin, and basal to hyperemic flow rate changes are included in the calculation of oxygen transport in both the lumen and the avascular wall. The results of this study show that oxygen transport in the postangioplasty residual stenosed artery is affected by non-Newtonian shear-thinning property of the blood viscosity having variable Hct concentration. As Hct increases from 25% to 65%, the diminished recirculation zone for the increased Hct causes the commencement of pO(2) decrease to shift radially outward by approximately 20% from the center of the artery for the basal flow, but by approximately 10% for the hyperemic flow at the end of the diverging section. Oxygen concentration increases from a minimum value at the core of the recirculation zone to over 90 mm Hg before the lumen-wall interface at the diverging section for the hyperemic flow, which is attributed to increased shear rate and thinner lumen boundary layer for the hyperemic flow, and below 90 mm Hg for the basal flow. As Hct increases from 25% to 65%, the average of pO(2,min) beyond the diverging section drops by approximately 25% for the basal flow, whereas it increases by approximately 15% for the hyperemic flow. Thus, current results with the moderate stenosed artery indicate that reducing Hct might be favorable in terms of increasing O(2) flux and pO(2,min), in the medial region of the wall for the basal flow, while higher Hct is advantageous for the hyperemic flow beyond the diverging section. The results of this study not only provide significant details of oxygen transport under varying pathophysiologic blood conditions such as unusually high blood viscosity and flow rate, but might also be extended to offer implications for drug therapy related to blood-thinning medication and for blood transfusion and hemorrhage.     

Aerobic run training improves brachial artery flow-mediated dilation

The purpose of this study was to assess the relationship between aerobic exercise training and brachial artery flow-mediated dilation (FMD) in healthy subjects. Healthy controls (HC) and aerobically-trained (T) subjects were studied with high-resolution vascular ultrasound at baseline, and during a 5-minute period of hyperemia following forearm cuff occlusion. Training was defined by self-reported participation in recreational or competitive run training. Forearm cuff occlusion was held at 200 mm Hg for 5 minutes. At baseline, both brachial artery flow and diameter were greater in T than in HC (p < 0.05). Resting heart rate was lower in T than in HC (p < 0.05). Peak hyperemic flow (15 seconds postocclusion) was significantly greater in T than in HC (HC; 539 +/- 75 ml x min(-1) vs. T; 832 +/- 103 ml x min(-1), p < 0.05) and correlated well with V(.-)O2peak (r = 0.67, p = 0.008). Flow-mediated dilation was significantly greater in T vs. HC throughout the 5-minute postocclusion phase (p < 0.05). Maximal brachial artery dilation was greater in T than in HC (HC; 3 +/- 1% of baseline vs. T; 8 +/- 3% of baseline; p < 0.05) and moderately correlated with V(.-)O2peak (r = 0.55, p < 0.05). These data suggest that the greater FMD observed in trained subjects may be due, in part, to an augmentation of peak hyperemic flow.     

Reflex control of cutaneous vasoconstrictor system is reset by exogenous female reproductive hormones.

To determine whether cardiovascular influences of exogenous female steroid hormones include effects on reflex thermoregulatory control of the adrenergic cutaneous vasoconstrictor system, we conducted ramp decreases in skin temperature (T(sk)) in eight women in both high- and low (placebo)-progesterone/estrogen phases of oral contraceptive use. With the use of water-perfused suits, T(sk) was held at 36 degrees C for 10 min (to minimize initial vasoconstrictor activity) and was then decreased in a ramp, approximately 0.2 degrees C/min for 12-15 min. Subjects rested supine for 30-40 min before each experiment, and the protocol was terminated before the onset of shivering. Skin blood flow was monitored by laser-Doppler flowmetry and arterial pressure by finger photoplethysmography. In all experiments, cutaneous vasoconstriction began immediately with the onset of cooling, and cutaneous vascular conductance (CVC) decreased progressively with decreasing T(sk). Regression analysis of the relationship of CVC to T(sk) showed no difference in slope between phases (low-hormone phase: 17.67 +/- 5.57; high-hormone phase: 17.40 +/- 8.00 %baseline/ degrees C; P > 0.05). Additional studies involving local blockade confirmed this response as being solely due to the adrenergic vasoconstrictor system. Waking oral temperature (T(or)) was significantly higher on high-hormone vs. low-hormone days (36.60 +/- 0.11 vs. 36.37 +/- 0.09 degrees C, respectively; P < 0.02). Integrative analysis of CVC in terms of simultaneous values for T(sk) and T(or) showed that the cutaneous vasoconstrictor response was shifted in the high-hormone phase such that a higher T(or) was maintained throughout cooling (P < 0.05). Thus reflex thermoregulatory control of the cutaneous vasoconstrictor system is shifted to higher internal temperatures by exogenous female reproductive hormones.     

Effect of occluded venous return on core temperature during cold water immersion

Recent studies using inanimate and animal models suggest that the afterdrop observed upon rewarming from hypothermia is based entirely on physical laws of heat flow without involvement of the returning cooled blood from the limbs. During the investigation of thermoregulatory responses to cold water immersion (15 degrees C), blood flow to the limbs (minimized by the effects of hydrostatic pressure and vasoconstriction) was occluded in 17 male subjects (age, 29.0 +/- 3.3 yr). Comparisons of rectal (Tre) and esophageal temperature (Tes) responses were made during the 5 min before occlusion, during the 10-min occlusion period, and for 5 min immediately after the release of the cuffs (postocclusion). In the preocclusion phase, Tre and Tes showed similar cooling rates. The occlusion of blood flow to the extremities significantly arrested the cooling of Tes (P less than 0.05) with little effect on Tre. Upon release of the pressure cuffs, the returning extremity blood flow resulted in an increased rate of cooling, that was three times greater at the esophageal site (-0:149 +/- 0.052 vs. -0.050 +/- 0.026 degrees C.min-1). These results suggest that the cooled peripheral circulation, minimized during cold water immersion, may dramatically affect esophageal temperature and the complete neglect of the circulatory component to the afterdrop phenomenon is not warranted.     

Effects of encouraged water drinking on thermoregulatory responses after 20 days of head-down bed rest in humans

We tested the hypothesis that encouraged water drinking according to urine output for 20 days could ameliorate impaired thermoregulatory function under microgravity conditions. Twelve healthy men, aged 24 ± 1.5 years (mean ± SE), underwent −6° head-down bed rest (HDBR) for 20 days. During bed rest, subjects were encouraged to drink the same amount of water as the 24-h urine output volume of the previous day. A heat exposure test consisting of water immersion up to the knees at 42°C for 45 min after a 10 min rest (baseline) in the sitting position was performed 2 days before the 20-day HDBR (PRE), and 2 days after the 20-day HDBR (POST). Core temperature (tympanic), skin temperature, skin blood flow and sweat rate were recorded continuously. We found that the −6° HDBR did not increase the threshold temperature for onset of sweating under the encouraged water drinking regime. We conclude that encouraged water drinking could prevent impaired thermoregulatory responses after HDBR.     

Nitric oxide synthase inhibition does not alter the reactive hyperemic response in the cutaneous circulation.

Reactive hyperemia is the sudden rise in blood flow after release of an arterial occlusion. Currently, the mechanisms mediating this response in the cutaneous circulation are poorly understood. The purpose of this study was to 1). characterize the reactive hyperemic response in the cutaneous circulation and 2). determine the contribution of nitric oxide (NO) to reactive hyperemia. Using laser-Doppler flowmetry, we characterized reactive hyperemia after 3-, 5-, 10-, and 15-min arterial occlusions in 10 subjects. The total hyperemic response was calculated by taking the area under the curve (AUC) of the hyperemic response minus baseline skin blood flow (SkBF) [i.e., total hyperemic response = AUC - [baseline SkBF as %maximal cutaneous vascular conductance (CVC(max) x duration of hyperemic response in s]]. For the characterization protocol, the total hyperemic response significantly increased as the period of ischemia increased from 5 to 15 min (P < 0.05). However, the 3-min response was not significantly different from the 5-min response. In the NO contribution protocol, two microdialysis fibers were placed in the forearm skin of eight subjects. One site served as a control and was continuously perfused with Ringer solution. The second site was continuously perfused with 10 mM NG-nitro-l-arginine methyl ester (l-NAME) to inhibit NO synthase. CVC was calculated as flux/mean arterial pressure and normalized to maximal blood flow (28 mM sodium nitroprusside). The total hyperemic response in control sites was not significantly different from l-NAME sites after a 5-min occlusion (3261 +/- 890 vs. 2907 +/- 531% CVC(max. s). Similarly, total hyperemic responses in control sites were not different from l-NAME sites (9155 +/- 1121 vs. 9126 +/- 1088% CVC(max. s) after a 15-min arterial occlusion. These data suggest that NO does not directly mediate reactive hyperemia and that NO is not produced in response to an increase in shear stress in the cutaneous circulation.     

Cutaneous and subcutaneous blood flow during general anaesthesia

The vasodilator effect of anaesthetic agents on cutaneous vessels has often been investigated. In contrast, although subcutaneous tissue is concerned with metabolism and thermoregulation, the effects of anaesthesia on subcutaneous blood flow have not been well documented. The purpose of this study was to determine the magnitude of changes in cutaneous and subcutaneous blood flow during general anaesthesia in Man. Anaesthesia was induced with flunitrazepam in 15 patients before facial plastic surgery. Blood flow was estimated using heat thermal clearance (HC). Two HC sensors in different areas allowed the measurement of superficial and deep HC. Systolic (SABP), diastolic (DABP) and mean arterial blood pressure (MABP), heart rate (HR), and rectal and mean skin temperature were also recorded. After induction of anaesthesia, HR increased significantly (p less than 0.05) whereas SABP, DABP and MABP remained unchanged. The rectal-toe temperature gradient fell from 6.3 +/- 4.1 degrees C to 3.4 +/- 1.1 degrees C (p less than 0.01) suggesting a reduction in vasomotor tone. Superficial HC increased from 0.37 +/- 0.06 to 0.42 +/- 0.08 W.m-1.degrees C-1 (p less than 0.05) whereas deep HC decreased from 0.33 +/- 0.07 to 0.31 +/- 0.09 W.m-1.degrees C-1 (NS) and returned to the control value thereafter. Rectal temperature and mean skin temperature were unchanged. The changes in deep HC are similar to those previously observed in muscle during induction of anaesthesia. Our results show that anaesthesia mainly affects cutaneous blood flow, without any significant change in subcutaneous blood flow during the early phase of anaesthesia in human beings.     

Rapid blunting of sympathetic vasoconstriction in the human forearm at the onset of exercise.

The purpose of this study was to test the hypothesis that sympathetic vasoconstriction is rapidly blunted at the onset of forearm exercise. Nine healthy subjects performed 5 min of moderate dynamic forearm handgrip exercise during -60 mmHg lower body negative pressure (LBNP) vs. without (control). Beat-by-beat forearm blood flow (Doppler ultrasound), arterial blood pressure (finger photoplethysmograph), and heart rate were collected. LBNP elevated resting heart rate by approximately 45%. Mean arterial blood pressure was not significantly changed (P = 0.196), but diastolic blood pressure was elevated by approximately 10% and pulse pressure was reduced by approximately 20%. At rest, there was a 30% reduction in forearm vascular conductance (FVC) during LBNP (P = 0.004). The initial rapid increase in FVC with exercise onset reached a plateau between 10 and 20 s of 126.6 +/- 4.1 ml. min(-1). 100 mmHg(-1) in control vs. only 101.6 +/- 4.1 ml. min(-1). 100 mmHg(-1) in LBNP (main effect of condition, P = 0.003). This difference was quickly abolished during the second, slower phase of adaptation in forearm vascular tone to steady state. These data are consistent with a rapid onset of functional sympatholysis, in which local substances released with the onset of muscle contractions impair sympathetic neural vasoconstrictor effectiveness.     

Free fatty acids/triglycerides increase ocular and subcutaneous blood flow

Elevated plasma free fatty acids (FFA) induce skeletal muscle insulin resistance and impair endothelial function. The aim of this study was to characterize the acute hemodynamic effects of FFA in the eye and skin. A triglyceride (Intralipid 20%, 1.5 ml/min)/heparin (bolus: 200 IU; constant infusion rate: 0.2 IU. kg(-1). min(-1)) emulsion or placebo was administered to 10 healthy subjects. Measurements of pulsatile choroidal blood flow with laser interferometry, retinal blood flow with the blue field entoptic technique, peak systolic and end diastolic blood velocity (PSV, EDV) in the ophthalmic artery with Doppler sonography, and subcutaneous blood flow with laser Doppler flowmetry were performed during an euglycemic somatostatin-insulin clamp over 405 min. Plasma FFA/triglyceride elevation induced a rise in pulsatile choroidal blood flow by 25 +/- 3% (P < 0.001) and in retinal blood flow by 60 +/- 23% (P = 0.0125). PSV increased by 27 +/- 8% (P = 0.001), whereas EDV was not affected. Skin blood flow increased by 149 +/- 38% (P = 0.001). Mean blood pressure and pulse rate remained unchanged, whereas pulse pressure amplitude increased by 17 +/- 5% (P = 0.019). Infusion of heparin alone had no hemodynamic effect in the eye or skin. In conclusion, FFA/triglyceride elevation increases subcutaneous and ocular blood flow with a more pronounced effect in the retina than in the choroid, which may play a role for early changes of ocular perfusion in the insulin resistance syndrome.     

Dose-dependent effects of endotoxin on human sleep

The role of the central nervous system in the host response to infection and inflammation and modulation of these responses by the hypothalamic-pituitary-adrenal system are well established. In animals, activation of host defense mechanisms increases non-rapid eye movement (NREM) sleep amount and intensity, which, in turn, are thought to support host defense, or the body's ability to defend itself against challenges to its immune system. In humans, the evidence is conflicting. Therefore, we investigated the effects of three placebo-controlled doses of endotoxin on host response, including nocturnal sleep in healthy volunteers. Administered before nocturnal sleep onset, endotoxin dose dependently increased rectal temperature, heart rate, and the plasma levels of tumor necrosis factor (TNF)-alpha, soluble TNF receptors, interleukin (IL)-1 receptor antagonist, IL-6, and cortisol. The lowest dose reliably increased circulating levels of cytokines and soluble cytokine receptors, but it did not affect rectal temperature, heart rate, or cortisol. This subtle host defense activation increased deep NREM sleep amount, often referred to as slow-wave sleep (stages 3 and 4), and intensity (delta power). Conversely, the highest dose of endotoxin disrupted sleep. Whereas it is well established that the endocrine and thermoregulatory systems are very sensitive to endotoxin, this study shows that human sleep-wake behavior is even more sensitive to activation of host defense mechanisms.     

Cerebral O2 metabolism and cerebral blood flow in humans during deep and rapid-eye-movement sleep

It could be expected that the various stages of sleep were reflected in variation of the overall level of cerebral activity and thereby in the magnitude of cerebral metabolic rate of oxygen (CMRO2) and cerebral blood flow (CBF). The elusive nature of sleep imposes major methodological restrictions on examination of this question. We have now measured CBF and CMRO2 in young healthy volunteers using the Kety-Schmidt technique with 133Xe as the inert gas. Measurements were performed during wakefulness, deep sleep (stage 3/4), and rapid-eye-movement (REM) sleep as verified by standard polysomnography. Contrary to the only previous study in humans, which reported an insignificant 3% reduction in CMRO2 during sleep, we found a deep-sleep-associated statistically highly significant 25% decrease in CMRO2, a magnitude of depression according with studies of glucose uptake and reaching levels otherwise associated with light anesthesia. During REM sleep (dream sleep) CMRO2 was practically the same as in the awake state. Changes in CBF paralleled changes in CMRO2 during both deep and REM sleep.     

Modification of cutaneous vasodilator response to heat stress by daytime exogenous melatonin administration

In humans, the nocturnal fall in internal temperature is associated with increased endogenous melatonin and with a shift in the thermoregulatory control of skin blood flow (SkBF), suggesting a role for melatonin in the control of SkBF. The purpose of this study was to test whether daytime exogenous melatonin would shift control of SkBF to lower internal temperatures during heat stress, as is seen at night. Healthy male subjects (n = 8) underwent body heating with melatonin administration (Mel) or without (control), in random order at least 1 wk apart. SkBF was monitored at sites pretreated with bretylium to block vasoconstrictor nerve function and at untreated sites. Cutaneous vascular conductance, calculated from SkBF and arterial pressure, sweating rate (SR), and heart rate (HR) were monitored. Skin temperature was elevated to 38 degrees C for 35-50 min. Baseline esophageal temperature (Tes) was lower in Mel than in control (P < 0.01). The Tes threshold for cutaneous vasodilation and the slope of cutaneous vascular conductance with respect to Tes were also lower in Mel at both untreated and bretylium-treated sites (P < 0.05). The Tes threshold for the onset of sweating and the Tes for a standard HR were reduced in Mel. The slope of the relationship of HR, but not SR, to Tes was lower in Mel (P < 0.05). These findings suggest that melatonin affects the thermoregulatory control of SkBF during hyperthermia via the cutaneous active vasodilator system. Because control of SR and HR are also modified, a central action of melatonin is suggested.