Influence of hydration and airflow on thermoregulatory control in the heat

Exercise-heat exposure results in significant sweat losses due to large biophysical requirements for evaporative heat loss. Progressive body water losses will increase plasma tonicity and decrease blood volume (hypertonic–hypovolemia). The result is reduced dry and evaporative heat exchange through alterations in the core temperature threshold for initiation of skin blood flow and sweating as well as changes in the sensitivity of these thermo-effectors. Regulation of reduced sweating conserves body water, which reduces heat loss and increases exercise hyperthermia, but the magnitude of this effect is modified by environmental heat transfer capabilities. The focus of this paper is to (1) examine the major mechanisms by which hypohydration alters thermoregulatory responses in the heat, and (2) illustrate how important differences in environmental airflow characteristics between laboratory and field settings may modify these effects.     

Human thermoregulatory responses during prolonged walking in water at 25, 30 and 35°C

Eight healthy and physically well-trained male students exercised on a treadmill for 60 min while being immersed in water to the middle of the chest in a laboratory flowmill. The water velocity was adjusted so that the intensity of exercise correspond to 50% maximal oxygen uptake of each subject, and experiments were performed once at each of three water temperatures: 25, 30, 35°C, following a 30-min control period in air at 25°C, and on a treadmill in air at an ambient temperature of 25°C. Thermal states during rest and exercise were determined by measuring rectal and skin temperatures at various points, and mean skin temperatures were calculated. The intensity of exercise was monitored by measuring oxygen consumption, and heart rate was monitored as an indicator for cardiovascular function. At each water temperature, identical oxygen consumption levels were attained during exercise, indicating that no extra heat was produced by shivering at the lowest water temperature. The slight rise in rectal temperature during exercise was not influenced by the water temperature. The temperatures of skin exposed to air rose slightly during exercise at 25°C and 30°C water temperature and markedly at 35°C. The loss of body mass increased with water temperature indicating that both skin blood flow and sweating during exercise increased with the rise in water temperature. The rise in body temperature provided the thermoregulatory drive for the loss of the heat generated during exercise. Heart rate increased most during exercise in water at 35°C, most likely due to enhanced requirements for skin blood flow. Although such requirements were certainly smallest at 25°C water temperature, heart rate at this temperature was slightly higher than at 30°C suggesting reflex activation of sympathetic control by cold signals from the skin. There was a significantly greater increase in mean skin and rectal temperatures in subjects exercising on the treadmill in air, compared to those exercising in water at 25°C. Accepted: 22 May 1998     

The Cardiovascular Control of Heat Exchange: Consequences of Body Size

For blood flow to be an effective agent for the control of heatexchange, it must occur in a region of the body where conductionresistance in the tissues is relatively high, and in an environmentwhere external resistance to heat exchange is relatively low.If either of these conditions is not met, control of heat exchangeby blood flow is not possible. Very small reptiles should notbe able to control heat exchange by blood flow in any environment,unless they control blood flow specifically to appendages. Verylarge reptiles should be able to control heat exchange by bloodflow only under certain conditions, such as in water, very highwinds, or intense radiative heating. Otherwise, they shouldhave little control. An optimum body size should exist for areptile's ability to control heat exchange using blood flow.In air, this optimum body size for alligators appears to beabout 5 kg. Theoretically, the optimum size should be substantiallylarger than 5 kg for reptiles heating and cooling in water.     

A comparison of the immediate effects of moderate exercise in the late morning and late afternoon on core temperature and cutaneous thermoregulatory mechanisms

Twelve healthy male subjects each undertook two bouts of moderate exercise (70% VO2max for 30 minutes) in the morning (08:00) and late afternoon (18:00) at least 4 days apart. Measurements were made of heart rate, core (rectal) temperature, sternum skin temperature, and forearm skin blood flow during baseline conditions, during the bout of exercise, and throughout a 30-minute recovery period. Comparisons were made of the changes of heart rate, temperature, and skin blood flow produced by the exercise at the two times of day. Student t tests indicated that baseline values for core temperature (37.15 degrees C +/- 0.06 degrees C vs. 36.77 degrees C +/- 0.06 degrees C) and sternum temperature (33.60 degrees C +/- 0.29 degrees C vs. 32.70 degrees C + 0.38 degrees C) were significantly (p < .05) higher in the late afternoon than the early morning. Two-way analysis of variance (ANOVA) indicated that the increases in core and sternum temperatures during exercise were significantly less (p = .0039 and .0421, respectively) during the afternoon bout of exercise compared with the morning, even though the work loads, as determined by changes in heart rate, were not significantly different (p = .798) at the two times of testing. There were also tendencies for resting forearm skin blood flow to be higher in the afternoon than in the morning and for exercise to produce a more rapid rise in this variable in the afternoon. The possible mechanisms producing these responses to exercise are discussed in terms of those that are responsible for the normal circadian rhythm of core temperature. It is concluded that the body's ability to remove a heat load is less in the early morning, when the circadian system is in a "heat gain" mode, than in the late afternoon, when heat gain and "heat loss" modes are balanced more evenly.     

Cutaneous vascular responses to isometric handgrip exercise during local heating and hyperthermia.

The dramatic increase in skin blood flow and sweating observed during heat stress is mediated by poorly understood sympathetic cholinergic mechanisms. One theory suggests that a single sympathetic cholinergic nerve mediates cutaneous active vasodilation (AVD) and sweating via cotransmission of separate neurotransmitters, because AVD and sweating track temporally and directionally when activated during passive whole body heat stress. It has also been suggested that these responses are regulated independently, because cutaneous vascular conductance (CVC) has been shown to decrease, whereas sweat rate increases, during combined hyperthermia and isometric handgrip exercise. We tested the hypothesis that CVC decreases during isometric handgrip exercise if skin blood flow is elevated using local heating to levels similar to that induced by pronounced hyperthermia but that this does not occur at lower levels of skin blood flow. Subjects performed isometric handgrip exercise as CVC was elevated at selected sites to varying levels by local heating (which is independent of AVD) in thermoneutral and hyperthermic conditions. During thermoneutral isometric handgrip exercise, CVC decreased at sites in which blood flow was significantly elevated before exercise (-6.5 +/- 1.8% of maximal CVC at 41 degrees C and -10.5 +/- 2.0% of maximal CVC at 43 degrees C; P < 0.05 vs. preexercise). During isometric handgrip exercise in the hyperthermic condition, an observed decrease in CVC was associated with the level of CVC before exercise. Taken together, these findings argue against withdrawal of AVD to explain the decrease in CVC observed during isometric handgrip exercise in hyperthermic conditions.     

Circulation during hypoxia in birds

The effects of hypoxia on the avian cardiovascular system are reviewed. The avian cardiovascular system seems well adapted to deal with the stress of hypoxia. In general, birds are remarkably tolerant of hypoxia, with some species being capable of performing vigorous exercise at extreme altitude. During hypoxia at rest, the circulation maintains arterial pressure, increases cardiac output, and redistributes blood flow so oxygen delivery to the heart and brain is maintained. During exercise, further adjustments are required, since exercising muscle has large oxygen requirements. The mechanisms responsible for producing these circulatory changes are largely unknown. The transport steps that limit O2 delivery during hypoxia are also poorly understood.     

Regulation of the cutaneous circulation

In this symposium, a diversity of perspectives was focused on how blood flow to the skin is controlled. Thus, control of the cutaneous circulation by reflexes aimed at body temperature regulation, blood pressure regulation, and the reflexes attending muscular exercise was discussed in detail, as were the similarities and differences between control of cutaneous arterioles and arteriovenous anastomoses. A mechanistic treatment of interaction between adrenergic control of cutaneous blood vessels and their temperature brought physical factors and pharmacological approaches to the consideration of reflex control. Finally, the more slowly developing changes in the control of the skin circulation that accompany circadian rhythms, changes in blood volume or its distribution, physical training, and acclimatization were discussed. Because the cutaneous circulation has potentially large vascular conductance, blood flow, and blood volume, control of the resistance and compliance vessels within the skin has an importance well beyond that of tissue nutrition. Indeed, overall hemodynamics are dependent on how much blood flow and how much blood volume are distributed to skin. Consequently, reflex factors, physical factors, and their interaction all have roles of importance with respect to exchange of heat with environment as well as maintenance of blood pressure, cardiac output, and blood flow to other tissues.     

Hemodynamic responses to heat stress in the resting and exercising human leg: insight into the effect of temperature on skeletal muscle blood flow

Heat stress increases limb blood flow and cardiac output (Q) in humans, presumably in sole response to an augmented thermoregulatory demand of the skin circulation. Here we tested the hypothesis that local hyperthermia also increases skeletal muscle blood flow at rest and during exercise. Hemodynamics, blood and tissue oxygenation, and muscle, skin, and core temperatures were measured at rest and during exercise in 11 males across four conditions of progressive whole body heat stress and at rest during isolated leg heat stress. During whole body heat stress, leg blood flow (LBF), Q, and leg (LVC) and systemic vascular conductance increased gradually with elevations in muscle temperature both at rest and during exercise (r(2) = 0.86-0.99; P < 0.05). Enhanced LBF and LVC were accompanied by reductions in leg arteriovenous oxygen (a-vO(2)) difference and increases in deep femoral venous O(2) content and quadriceps tissue oxygenation, reflecting elevations in muscle and skin perfusion. The increase in LVC occurred despite an augmented plasma norepinephrine (P < 0.05) and was associated with elevations in muscle temperature (r(2) = 0.85; P = 0.001) and arterial plasma ATP (r(2) = 0.87; P < 0.001). Isolated leg heat stress accounted for one-half of the increase in LBF with severe whole body heat stress. Our findings suggest that local hyperthermia also induces vasodilatation of the skeletal muscle microvasculature, thereby contributing to heat stress and exercise hyperemia. The increased limb muscle vasodilatation in these conditions of elevated muscle sympathetic vasoconstrictor activity is closely related to the rise in arterial plasma ATP and local tissue temperature.     

Muscle blood flow is not reduced in humans during moderate exercise and heat stress

The effect of heat stress on circulation in an exercising leg was determined using one-legged knee extension and two-legged bicycle exercise, both seated and upright. Subjects exercised for three successive 25-min periods wearing a water-perfused suit: control [CT, mean skin temperature (Tsk) = 35 degrees C], hot (H, Tsk = 38 degrees C), and cold (C, Tsk = 31 degrees C). During the heating period, esophageal temperature increased to a maximum of 37.91, 39.35, and 39.05 degrees C in the three types of exercise, respectively. There were no significant changes in pulmonary O2 uptake (VO2) throughout the entire exercise period with either one or two legs. Leg blood flow (LBF), measured in the femoral vein of one leg by thermodilution, remained unchanged between CT, H, and C periods. Venous plasma lactate concentration gradually declined over time, and no trend for an increased lactate release during the heating period was found. Similarly, femoral arteriovenous O2 difference and leg VO2 remained unchanged between the three exercise periods. Although cardiac output (acetylene rebreathing) was not significantly higher during H, there was a tendency for an increase of 1 and 2 l/min in one- and two-legged exercise, respectively, which could account for part of the increase in total skin blood flow during heating (gauged by changes in forearm blood flow). Because LBF was not reduced during exercise and heat stress in these experiments, the additional increase in skin blood flow must have been met by redistribution of blood away from vascular beds other than active skeletal muscle.     

Physiological Responses Of Birds To Flight And Running

1. The energy required for sustained physical activity in flying and running birds is obtained from fatty acids mobilized from adipose stores under the influence of hormones. There is some evidence that glucagon, insulin and growth hormone may be involved in this process. 2. Energy expenditure can increase up to 14 times and 12 times resting values in flying and running birds, respectively. Energy expenditure varies only slightly over the normal range of flight speeds in individual species, but in running birds there is a linear correlation between oxygen consumption and speed. The slope of this relationship is an inverse function of body weight and indicates the energy cost of transport in ml O₂.kg^-1.m^-1. 3. Increased oxygen demands by the working muscles are met by increased ventilation and circulation. Increased oxygen delivery by the blood is achieved by rises in cardiac output and oxygen extraction. Cardiac stroke volume changes relatively little and the increased cardiac output results mainly from an increase in heart rate. Regional blood distribution during exercise may be determined not only by the demands of the locomotory muscles but also by the need to increase heat loss from the skin and respiratory tract. 4. Ventilatory movements during flight are frequently synchronized in a I:I fashion with wing movements. Increased ventilation during flight and running may be stimulated, not only by the need for increased gas exchange, but also in order to raise heat loss by respiratory evaporation. Thermal hyperventilation carries a risk of CO, washout from the lungs and consequent blood alkalosis. The risk is minimized in some species by appropriate alterations in the rate and depth of breathing, which help to confine excess ventilation to the respiratory dead space. 5. Metabolic heat produced during exercise is either lost from the respiratory linings and the skin, or stored by the body with a resultant rise in body temperature. Changes in peripheral blood perfusion and active regulation of the feathers may assist cutaneous heat loss. Respiratory evaporation usually accounts for less than 30% of the total heat loss, even at high air temperatures, and becomes progressively less efficient at higher exercise intensities. At high air temperatures and high exercise intensities, most of the metabolic heat is stored, and exercise duration is limited as the body temperature approaches the upper lethal limit.     

Skin blood flow influences near-infrared spectroscopy-derived measurements of tissue oxygenation during heat stress.

Near-infrared (NIR) spectroscopy is a noninvasive optical technique that is increasingly used to assess muscle oxygenation during exercise with the assumption that the contribution of skin blood flow to the NIR signal is minor or nonexistent. We tested this assumption in humans by monitoring forearm tissue oxygenation during selective cutaneous vasodilation induced by locally applied heat (n = 6) or indirect whole body heating (i.e., heating subject but not area surrounding NIR probes; n = 8). Neither perturbation has been shown to cause a measurable change in muscle blood flow or metabolism. Local heating (approximately 41 degrees C) caused large increases in the NIR-derived tissue oxygenation signal [before heating = 0.82 +/- 0.89 optical density (OD), after heating = 18.21 +/- 2.44 OD; P < 0.001]. Similarly, whole body heating (increase internal temperature 0.9 degrees C) also caused large increases in the tissue oxygenation signal (before heating = -0.31 +/- 1.47 OD, after heating = 12.48 +/- 1.82 OD; P < 0.001). These increases in the tissue oxygenation signal were closely correlated with increases in skin blood flow during both local heating (mean r = 0.95 +/- 0.02) and whole body heating (mean r = 0.89 +/- 0.04). These data suggest that the contribution of skin blood flow to NIR measurements of tissue oxygenation can be significant, potentially confounding interpretation of the NIR-derived signal during conditions where both skin and muscle blood flows are elevated concomitantly (e.g., high-intensity and/or prolonged exercise).     

Recent advances in temperature regulation during exercise in humans

This paper describes first the dynamics of heat transfer from active muscle to the body core and then the physiological regulatory mechanisms that act to modify the rates of heat transfer from core to skin and from skin to environment. After this, nonthermal factors influencing the regulatory mechanisms are described, emphasizing the importance of body fluid status and its influence on the temperature regulatory mechanisms. The control of cutaneous vasomotor and venomotor tone is the shared effector loop of both the blood pressure and temperature regulatory systems; during exercise these systems interact, with the former system predominating when mutually exclusive demands exist. The importance of blood volume is emphasized again in a final discussion of the effects of improved physical condition on the temperature regulatory system.     

The effects of head cooling on endurance and neuroendocrine responses to exercise in warm conditions

The present study investigated the effects of head cooling during endurance cycling on performance and the serotonergic neuroendocrine response to exercise in the heat. Subjects exercised at 75 % VO(2max) to volitional fatigue on a cycle ergometer at an ambient temperature of 29+/-1.0 degrees C, with a relative humidity of approximately 50 %. Head cooling resulted in a 51 % (p<0.01) improvement in exercise time to fatigue and Borg Scale ratings of perceived exertion were significantly lower throughout the exercise period with cooling (p<0.01). There were no indications of peripheral mechanisms of fatigue either with, or without, head cooling, indicating the importance of central mechanisms. Exercise in the heat caused the release of prolactin in response to the rise in rectal temperature. Head cooling largely abolished the prolactin response while having no effect on rectal temperature. Tympanic temperature and sinus skin temperature were reduced by head cooling and remained low throughout the exercise. It is suggested that there is a co-ordinated response to exercise involving thermoregulation, neuroendocrine secretion and behavioural adaptations that may originate in the hypothalamus or associated areas of the brain. Our results are consistent with the effects of head cooling being mediated by both direct cooling of the brain and modified cerebral artery blood flow, but an action of peripheral thermoreceptors cannot be excluded.     

Effects of ATP-induced leg vasodilation on VO2 peak and leg O2 extraction during maximal exercise in humans

During maximal whole body exercise VO2 peak is limited by O2 delivery. In turn, it is though that blood flow at near-maximal exercise must be restrained by the sympathetic nervous system to maintain mean arterial pressure. To determine whether enhancing vasodilation across the leg results in higher O2 delivery and leg VO2 during near-maximal and maximal exercise in humans, seven men performed two maximal incremental exercise tests on the cycle ergometer. In random order, one test was performed with and one without (control exercise) infusion of ATP (8 mg in 1 ml of isotonic saline solution) into the right femoral artery at a rate of 80 microg.kg body mass-1.min-1. During near-maximal exercise (92% of VO2 peak), the infusion of ATP increased leg vascular conductance (+43%, P<0.05), leg blood flow (+20%, 1.7 l/min, P<0.05), and leg O2 delivery (+20%, 0.3 l/min, P<0.05). No effects were observed on leg or systemic VO2. Leg O2 fractional extraction was decreased from 85+/-3 (control) to 78+/-4% (ATP) in the infused leg (P<0.05), while it remained unchanged in the left leg (84+/-2 and 83+/-2%; control and ATP; n=3). ATP infusion at maximal exercise increased leg vascular conductance by 17% (P<0.05), while leg blood flow tended to be elevated by 0.8 l/min (P=0.08). However, neither systemic nor leg peak VO2 values where enhanced due to a reduction of O2 extraction from 84+/-4 to 76+/-4%, in the control and ATP conditions, respectively (P<0.05). In summary, the VO2 of the skeletal muscles of the lower extremities is not enhanced by limb vasodilation at near-maximal or maximal exercise in humans. The fact that ATP infusion resulted in a reduction of O2 extraction across the exercising leg suggests a vasodilating effect of ATP on less-active muscle fibers and other noncontracting tissues and that under normal conditions these regions are under high vasoconstrictor influence to ensure the most efficient flow distribution of the available cardiac output to the most active muscle fibers of the exercising limb.     

Hydration effects on thermoregulation and performance in the heat

During exercise, sweat output often exceeds water intake, producing a water deficit or hypohydration. The water deficit lowers both intracellular and extracellular fluid volumes, and causes a hypotonic-hypovolemia of the blood. Aerobic exercise tasks are likely to be adversely effected by hypohydration (even in the absence of heat strain), with the potential affect being greater in hot environments. Hypohydration increases heat storage by reducing sweating rate and skin blood flow responses for a given core temperature. Hypertonicity and hypovolemia both contribute to reduced heat loss and increased heat storage. In addition, hypovolemia and the displacement of blood to the skin make it difficult to maintain central venous pressure and thus cardiac output to simultaneously support metabolism and thermoregulation. Hyperhydration provides no advantages over euhydration regarding thermoregulation and exercise performance in the heat.     

Redistribution of blood within the body is important for thermoregulation in an ectothermic vertebrate (<Emphasis Type="Italic">Crocodylus porosus</Emphasis>)

Changes in blood flow are a principal mechanism of thermoregulation in vertebrates. Changes in heart rate will alter blood flow, although multiple demands for limited cardiac output may compromise effective thermoregulation. We tested the hypothesis that regional differences in blood flow during heating and cooling can occur independently from changes in heart rate. We measured heart rate and blood pressure concurrently with blood flow in the crocodile, Crocodylus porosus. We measured changes in blood flow by laser Doppler flowmetry, and by injecting coloured microspheres. All measurements were made under different heat loads, with and without blocking cholinergic and β-adrenergic receptors (autonomic blockade). Heart rates were significantly faster during heating than cooling in the control animals, but not when autonomic receptors were blocked. There were no significant differences in blood flow distribution between the control and autonomic blockade treatments. In both treatments, blood flow was directed to the dorsal skin and muscle and away from the tail and duodenum during heating. When the heat source was switched off, there was a redistribution of blood from the dorsal surface to the duodenum. Blood flow to the leg skin and muscle, and to the liver did not change significantly with thermal state. Blood pressure was significantly higher during the autonomic blockade than during the control. Thermal time constants of heating and cooling were unaffected by the blockade of autonomic receptors. We concluded that animals partially compensated for a lack of differential heart rates during heating and cooling by redistributing blood within the body, and by increasing blood pressure to increase flow. Hence, measures of heart rate alone are insufficient to assess physiological thermoregulation in reptiles.     

Effects of exercise and heat stress on regional blood flow in pregnant sheep

Radioactive microspheres were used to measure cardiac output and blood flow to most major tissues, including those in the pregnant uterus, in late-pregnant ewes at rest and during treadmill exercise (approximately 3-fold increase in metabolic rate for 30 min) in thermoneutral (TN) (dry bulb temperature (Tdb) = 13 degrees C, wet bulb temperature (Twb) = 10 degrees C) and mildly hot (MH) (Tdb = 40 degrees C, Twb = 27 degrees C) environments. Exercise caused major increases in blood flow to respiratory muscles, nonrespiratory limb muscles, and adipose tissue, and flow was decreased to some gastrointestinal tissues, spleen, pancreas, and to placental and nonplacental tissues in the pregnant uterus. Heat exposure had relatively little effect on these exercise-induced changes, except that flow was further increased in the respiratory muscles. Results are compared with those of a similar study on nonpregnant sheep in which changes in muscle, skin, and visceral flows during exercise were attenuated by heat exposure. It is suggested that redistribution of blood flow from the pregnant uterus, which in resting ewes took 22% of cardiac output, is a significant buffer against the potentially deleterious effects of combined exercise and heat stress on blood flow to exercising muscles and thermoregulatory tissues.     

Selective brain cooling: a multiple regulatory mechanism

The mechanism of selective brain cooling (SBC) allows the brain to remain cooler than the rest of the body. This paper aims to provide new ideas to better understand SBC, emphasizing how it works, how it is controlled and what its role is. There are two distinct types of SBC in homeotherms: (1) using precooling of arterial blood destined for the brain, with cool venous blood returning from the nose and head skin, (2) using venous blood to cool the brain directly. There is a common mechanism of control of SBC intensity. Reduced sympathetic activity leads to simultaneous dilation of the angular oculi veins, supplying the intracranial heat exchangers, and constriction of the facial veins, supplying the heart. Therefore, SBC is enhanced during heat exposure, endurance exercise, relaxed wakefulness and NREM sleep, and vanishes in the cold and during emotional distress. SBC is a multifunctional effector mechanism: it protects the brain from heat damage; it intensifies in dehydrated mammals, thereby saving water; it helps exercising animals delay exhaustion; it might thermally modulate alertness; it is used in diving animals to drop cerebral temperature much below its normal level, expanding diving capacity and protecting the brain from asphyxic damage. Altogether, SBC integrates both thermal and non-thermal regulatory functions.     

Heat stress and age: Skin blood flow and body temperature

1. 1. The ability to increase skin blood flow is an important mechanism for transferring heat from the body core to the skin for dissipation.

2. 2. During exercise, skin blood flow is typically 20–40% lower in men and women aged 55 and over (compared with 20–30 years old) at a given body core temperature. Yet criterion measures of heat tolerance (changes in core temperature, heat storage) often show minimal or no age-related alterations. From a series of studies conducted in our laboratory over the past 5 years, the following conclusions can be drawn.

3. 3. When fit healthy older subjects are matched with younger subjects of the same gender, size and body composition, V_O2max, acclimation state, and hydration level, age-related differences in skin blood flow are evident. However, these differences often do not translate into “poorer” heat tolerance or higher core temperatures.

4. 4. The larger core-to-skin thermal gradient maintained by the older individuals allows for effective heat transfer at lower skin blood flows.

5. 5. Furthermore, there is an increased coefficient of variation for thermoregulatory response variables with increasing age.

6. 6. Despite differences in the mechanisms underlying thermoregulation, true thermal tolerance is less a function of chronological age than of functional capacity and physiological health status.

7. 7. While this conclusion is based primarily on cross-sectional studies, it is supported by the results of more recent studies using multiple regression analyses.

8. 8. Implicit in this conclusion is the notion that thermal tolerance, at any age, is a modifiable individual characteristic.

A study of the pharmacologic control of blood flow to acute skin flaps using xenon washout. Part I

This study was undertaken to understand the control mechanisms differentiating circulation to normal skin and acute skin flaps. The approach was to compare the effects of systemic vasoactive drugs on skin blood flow in rats in acute skin flaps and identical areas of control skin. With this model it was felt that systemic changes would affect both areas equally and any difference in response would be due to vascular control mechanisms unique to the flap. Xenon washout by percutaneous injection was chosen to measure blood flow. The results of over 8000 observations in these studies were: 1. Vasodilation enhances blood flow and flap survival. 2. Vasoconstriction decreases blood flow. 3. Depletion of sympathetic nerve terminals enhances blood flow and flap survival. 4. The acute flap is less sensitive to systemic alpha-agonists than control skin. 5. The acute flap is less sensitive to vasodilators acting at the receptor-site level than control skin. 6. Total sympathetic denervation does not occur. 7. Biologic increases in area of flap survival did occur in drug dose ranges predicted by xenon washout measurements in this model. These findings indicate that the vessels in an acutely raised skin flap have a greater vasospastic tone than is optimal for maximum nutrient blood flow. One explanation consistent with these findings is offered in which the mechanism responsible for this tone is the release of catecholamines from the sympathetic nerve terminals after the flap has been raised.