The contribution of carotid rete variability to brain temperature variability in sheep in a thermoneutral environment

The degree of variability in the temperature difference between the brain and carotid arterial blood is greater than expected from the presumed tight coupling between brain heat production and brain blood flow. In animals with a carotid rete, some of that variability arises in the rete. Using thermometric data loggers in five sheep, we have measured the temperature of arterial blood before it enters the carotid rete and after it has perfused the carotid rete, as well as hypothalamic temperature, every 2 min for between 6 and 12 days. The sheep were conscious, unrestrained, and maintained at an ambient temperature of 20-22 degrees C. On average, carotid arterial blood and brain temperatures were the same, with a decrease in blood temperature of 0.35 degrees C across the rete and then an increase in temperature of the same magnitude between blood leaving the rete and the brain. Rete cooling of arterial blood took place at temperatures below the threshold for selective brain cooling. All of the variability in the temperature difference between carotid artery and brain was attributable statistically to variability in the temperature difference across the rete. The temperature difference between arterial blood leaving the rete and the brain varied from -0.1 to 0.9 degrees C. Some of this variability was related to a thermal inertia of the brain, but the majority we attribute to instability in the relationship between brain blood flow and brain heat production.     

A test of biochemical symmorphosis in a heterothermic tissue: bluefin tuna white muscle

Selective brain cooling (SBC) is defined as a brain temperature cooler than the temperature of arterial blood from the trunk. Surrogate measures of arterial blood temperature have been used in many published studies on SBC. The use of a surrogate for arterial blood temperature has the potential to confound proper identification of SBC. We have measured brain, carotid blood, and rectal temperatures in conscious sheep exposed to 40, 22, and 5 degrees C. Rectal temperature was consistently higher than arterial blood temperature. Brain temperature was consistently cooler than rectal temperature during all exposures. Brain temperature only fell below carotid blood temperature during the final few hours of 40 degrees C exposure and not at all during the 5 degrees C exposure. Consequently, using rectal temperature as a surrogate for arterial blood temperature does not provide a reliable indication of the status of the SBC effector. We also show that rapid suppression of SBC can result if the animals are disturbed.     

Absence of selective brain cooling in unrestrained baboons exposed to heat

To test whether baboons are capable of implementing selective brain cooling, we measured, every 5 min, the temperature in their hypothalamus, carotid arterial bloodstream, and abdominal cavity. The baboons were unrestrained and exposed to 22 degrees C for 7 days and then to a cyclic environment with 15 degrees C at night and 35 degrees C during the day for a further 7 days. During the latter 7 days some of the baboons also were exposed to radiant heat during the day. For three days, during heat exposure, water was withheld. At no time was the hypothalamus cooler than carotid arterial blood, despite brain temperatures above 40 degrees C. With little variation, the hypothalamus was consistently 0.5 degrees C warmer than arterial blood. At high body temperatures, the hypothalamus was sometimes cooler than the abdomen. Abdominal temperature was more variable than arterial blood and tended to exceed arterial blood temperature at higher body temperatures. Hypothalamic temperature cooler than a warm abdomen is not evidence for selective brain cooling. In species that can implement selective brain cooling, the brain is most likely to be cooler than carotid arterial blood when an animal is hyperthermic, during heat exposure, and also dehydrated and undisturbed by human presence. When we exposed baboons to high ambient temperatures while they were water deprived and undisturbed, they never implemented selective brain cooling. We conclude that baboons cannot implement selective brain cooling and can find no convincing evidence that any primate species can do so.     

Dehydration increases the magnitude of selective brain cooling independently of core temperature in sheep

By cooling the hypothalamus during hyperthermia, selective brain cooling reduces the drive on evaporative heat loss effectors, in so doing saving body water. To investigate whether selective brain cooling was increased in dehydrated sheep, we measured brain and carotid arterial blood temperatures at 5-min intervals in nine female Dorper sheep (41 +/- 3 kg, means +/- SD). The animals, housed in a climatic chamber at 23 degrees C, were exposed for nine days to a cyclic protocol with daytime heat (40 degrees C for 6 h). Drinking water was removed on the 3rd day and returned 5 days later. After 4 days of water deprivation, sheep had lost 16 +/- 4% of body mass, and plasma osmolality had increased from 290 +/- 8 to 323 +/- 9 mmol/kg (P < 0.0001). Although carotid blood temperature increased during heat exposure to similar levels during euhydration and dehydration, selective brain cooling was significantly greater in dehydration (0.38 +/- 0.18 degrees C) than in euhydration (-0.05 +/- 0.14 degrees C, P = 0.0008). The threshold temperature for selective brain cooling was not significantly different during euhydration (39.27 degrees C) and dehydration (39.14 degrees C, P = 0.62). However, the mean slope of lines of regression of brain temperature on carotid blood temperature above the threshold was significantly lower in dehydrated animals (0.40 +/- 0.31) than in euhydrated animals (0.87 +/- 0.11, P = 0.003). Return of drinking water at 39 degrees C led to rapid cessation of selective brain cooling, and brain temperature exceeded carotid blood temperature throughout heat exposure on the following day. We conclude that for any given carotid blood temperature, dehydrated sheep exposed to heat exhibit selective brain cooling up to threefold greater than that when euhydrated.     

Brain thermal inertia,but no evidence for selective brain cooling,in free-ranging western grey kangaroos (<Emphasis Type="Italic">Macropus fuliginosus</Emphasis>)

Marsupials reportedly can implement selective brain cooling despite lacking a carotid rete. We measured brain (hypothalamic) and carotid arterial blood temperatures every 5 min for 5, 17, and 63 days in spring in three free-living western grey kangaroos. Body temperature was highest during the night, and decreased rapidly early in the morning, reaching a nadir at 10:00. The highest body temperatures recorded occurred sporadically in the afternoon, presumably associated with exercise. Hypothalamic temperature consistently exceeded arterial blood temperature, by an average 0.3°C, except during these afternoon events when hypothalamic temperature lagged behind, and was occasionally lower than, the simultaneous arterial blood temperature. The reversal in temperatures resulted from the thermal inertia of the brain; changes in the brain to arterial blood temperature difference were related to the rate of change of arterial blood temperature on both heating and cooling (P < 0.001 for all three kangaroos). We conclude that these data are not evidence for active selective brain cooling in kangaroos. The effect of thermal inertia on brain temperature is larger than might be expected in the grey kangaroo, a discrepancy that we speculate derives from the unique vascular anatomy of the marsupial brain.     

Adaptive heterothermy and selective brain cooling in arid-zone mammals

Adaptive heterothermy and selective brain cooling are regarded as important thermal adaptations of large arid-zone mammals. Adaptive heterothermy, a process which reduces evaporation by storing body heat, ought to be enhanced by ambient heat load and by water deficit, but most mammals studied fail to show at least one of those attributes. Selective brain cooling, the reduction of brain temperature below arterial blood temperature, is most evident in artiodactyls, which possess a carotid rete, and traditionally has been considered to protect the brain during hyperthermia. The development of miniature ambulatory data loggers for recording body temperature allows the temperatures of free-living wild mammals to be measured in their natural habitats. All the African ungulates studied so far, in their natural habitats, do not exhibit adaptive heterothermy. They have low-amplitude nychthemeral rhythms of temperature, with mean body temperature over the night exceeding that over the day. Those with carotid retes (black wildebeest, springbok, eland) employ selective brain cooling but zebra, without a rete, do not. None of the rete ungulates, however, seems to employ selective brain cooling to prevent the brain overheating during exertional hyperthermia. Rather, they use it at rest, under moderate heat load, we believe in order to switch body heat loss from evaporative to non-evaporative routes.     

Temperature difference between the body core and arterial blood supplied to the brain during hyperthermia or hypothermia in humans

 A vascular heat transfer model is developed to simulate temperature decay along the carotid arteries in humans, and thus, to evaluate temperature differences between the body core and arterial blood supplied to the brain. Included are several factors, including the local blood perfusion rate, blood vessel bifurcation in the neck, and blood vessel pairs on both sides of the neck. The potential for cooling blood in the carotid artery by countercurrent heat exchange with the jugular veins and by radial heat conduction to the neck surface was estimated. Cooling along the common and internal carotid arteries was calculated to be up to 0.87 °C during hyperthermia by high environmental temperatures or muscular exercise. This model was also used to evaluate the feasibility of lowering the brain temperature effectively by placing ice pads on the neck and head surface or by wearing cooling garments during hypothermia treatment for brain injury or other medical conditions. It was found that a 1.1 °C temperature drop along the carotid arteries is possible when the neck surface is cooled to 0 °C. Thus, the body core temperature may not be a good indication of the brain temperature during hyperthermia or hypothermia. Received: 10 January 2002 / Accepted: 7 May 2002 This research was supported by a UMBC Summer Faculty Fellowship.     

Competition for cool nasal blood between trunk and brain in hyperthermic goats

An influence of brain and trunk temperatures controlled independently of each other by means of artificial heat exchangers, on the intensity of natural selective brain cooling (SBC) was studied in 6 conscious goats. Intensity of SBC was markedly enhanced by increasing brain temperature. On the other hand, a rise of trunk temperature with the cerebral temperature clamped at 39 degrees C or 40 degrees C, reduced SBC intensity in spite of a simultaneous increase in the respiratory evaporative heat loss. When brain temperature was clamped at 41 degrees C, the magnitude of SBC was essentially independent of trunk temperature. These results suggest that during hyperthermia a competition exists between trunk and brain for cool nasal blood.     

REM sleep related increase in brain temperature: a physiologic problem

The roles of metabolic heat production, arterial blood flow and temperature in the genesis of the brain temperature increase related to REM sleep occurrence in several mammalian species are discussed on the basis of available experimental evidence. The experimental data show that only changes in arterial blood flow and temperature consistently underlie the rise in brain temperature in presence (cat) or absence (rabbit) of the carotid rete. The alteration of cardiovascular regulation in REM sleep is the remote cause of such rise. The proximate causes are decrease in carotid blood supply and increase in vertebral blood supply to the brain and related depression of systemic and selective brain cooling.     

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.     

Angularis oculi vein blood flow modulates the magnitude but not the control of selective brain cooling in sheep

To investigate the role of the angularis oculi vein (AOV) in selective brain cooling (SBC), we measured brain and carotid blood temperatures in six adult female Dorper sheep. Halfway through the study, a section of the AOV, just caudal to its junction with the dorsal nasal vein, was extirpated on both sides. Before and after AOV surgery, the sheep were housed outdoors at 21-22°C and were exposed in a climatic chamber to daytime heat (40°C) and water deprivation for 5 days. In sheep outdoors, SBC was significantly lower after the AOV had been cut, with its 24-h mean reduced from 0.25 to 0.01°C (t(5) = 3.06, P = 0.03). Carotid blood temperature also was lower (by 0.28°C) at all times of day (t(5) = 3.68, P = 0.01), but the pattern of brain temperature was unchanged. The mean threshold temperature for SBC was not different before (38.85 ± 0.28°C) and after (38.85 ± 0.39°C) AOV surgery (t(5) =0.00, P = 1.00), but above the threshold, SBC magnitude was about twofold less after surgery. SBC after AOV surgery also was less during heat exposure and water deprivation. However, SBC increased progressively by the same magnitude (0.4°C) over the period of water deprivation, and return of drinking water led to rapid cessation of SBC in sheep before and after AOV surgery. We conclude that the AOV is not the only conduit for venous drainage contributing to SBC in sheep and that, contrary to widely held opinion, control of SBC does not involve changes in the vasomotor state of the AOV.     

Integration of jugular venous return and circle of Willis in a theoretical human model of selective brain cooling.

A three-dimensional mathematical model was developed to examine the induction of selective brain cooling (SBC) in the human brain by intracarotid cold (2.8 degrees C) saline infusion (ICSI) at 30 ml/min. The Pennes bioheat equation was used to propagate brain temperature. The effect of cooled jugular venous return was investigated, along with the effect of the circle of Willis (CoW) on the intracerebral temperature distribution. The complete CoW, missing A1 variant (mA1), and fetal P1 variant (fP1) were simulated. ICSI induced moderate hypothermia (defined as 32-34 degrees C) in the internal carotid artery (ICA) territory within 5 min. Incorporation of the complete CoW resulted in a similar level of hypothermia in the ICA territory. In addition, the anterior communicating artery and ipsilateral posterior communicating artery distributed cool blood to the contralateral anterior and ipsilateral posterior territories, respectively, imparting mild hypothermia (35 and 35.5 degrees C respectively). The mA1 and fP1 variants allowed for sufficient cooling of the middle cerebral territory (30-32 degrees C). The simulations suggest that ICSI is feasible and may be the fastest method of inducing hypothermia. Moreover, the effect of convective heat transfer via the complete CoW and its variants underlies the important role of CoW anatomy in intracerebral temperature distributions during SBC.     

Brain, blood and rectal temperature during whole body cooling

To determine if rectal temperature is an adequate index of brain temperature during changing thermal conditions, we measured rectal, cerebral cortical, and carotid arterial blood temperatures simultaneously during whole body cooling in adult cats. The mean steady state rectal, brain and carotid arterial temperatures at the onset of cooling were: 39.2 +/- 0.2, 38.5 +/- 0.2, and 38.3 +/- 0.3 degrees C, respectively. Rectal temperature decreased faster than both brain and arterial blood, while only a small temperature difference was observed between brain and arterial blood, brain always exceeding blood. Rectal temperature cannot be considered an adequate index of brain temperature. Carotid arterial temperature is a better estimate of brain temperature.     

Selective Brain Cooling Reduces Water Turnover in Dehydrated Sheep

In artiodactyls, arterial blood destined for the brain can be cooled through counter-current heat exchange within the cavernous sinus via a process called selective brain cooling. We test the hypothesis that selective brain cooling, which results in lowered hypothalamic temperature, contributes to water conservation in sheep. Nine Dorper sheep, instrumented to provide measurements of carotid blood and brain temperature, were dosed with deuterium oxide (D₂O), exposed to heat for 8 days (40◦C for 6-h per day) and deprived of water for the last five days (days 3 to 8). Plasma osmolality increased and the body water fraction decreased over the five days of water deprivation, with the sheep losing 16.7% of their body mass. Following water deprivation, both the mean 24h carotid blood temperature and the mean 24h brain temperature increased, but carotid blood temperature increased more than did brain temperature resulting in increased selective brain cooling. There was considerable inter-individual variation in the degree to which individual sheep used selective brain cooling. In general, sheep spent more time using selective brain cooling, and it was of greater magnitude, when dehydrated compared to when they were euhydrated. We found a significant positive correlation between selective brain cooling magnitude and osmolality (an index of hydration state). Both the magnitude of selective brain cooling and the proportion of time that sheep spent selective brain cooling were negatively correlated with water turnover. Sheep that used selective brain cooling more frequently, and with greater magnitude, lost less water than did conspecifics using selective brain cooling less efficiently. Our results show that a 50kg sheep can save 2.6L of water per day (~60% of daily water intake) when it employs selective brain cooling for 50% of the day during heat exposure. We conclude that selective brain cooling has a water conservation function in artiodactyls.     

Duration of induced seizures during selective pharyngeal brain cooling]

Whole body hypothermia can be used to treat the injured brain (e.g. after hypoxic events). Side effects include hemodynamic instability, coagulopathy and infection. Because of these side effects it appears reasonable to cool the brain selectively (selective brain cooling, SBC) without changing the core temperature. A new animal model was used to demonstrate SBC from the pharynx and to examine effects of SBC on the duration of pharmacologically induced seizure activity. Sprague-Dawley rats (n=18, 12 successful experiments) were sedated and mechanically ventilated. Invasive blood pressure monitoring was instituted and blood gases were drawn to evaluate the arterial blood gas status. Electrical brain activity was recorded using a microneedle in the extracellular compartment of the rat brain cortex. Cooled water was circulated through a small tubing into and out of the pharynx of the animals. The cortical as well as the rectal temperature were recorded. After the injection of a single dose of bicuculline (1 mg/kg i.v.) per animal the duration of the induced seizure activity was measured and compared with the temperature prior to the induction of seizure activity. The cortical blood flow (CBF) was detected using intra tissue Doppler signals in the rat cortex in the same location as the EP-study. The influence of a brain temperature reduction between 36.5 degrees to 31.5 degrees C on the seizure duration was examined. There was a positive correlation between the seizure duration and the cortical temperature (r=0.64). Also the CBF was increased during seizure activity (p=0.02) and the increase correlated weakly with cortical temperature (r=0.18). The core temperature remained in the normothermic range (36.9+/-0.7 degrees C) Conclusion: The duration of induced seizures correlates with local brain temperature. In the future further studies should examine the efficiency of induced (selective) brain cooling to treat prolonged seizure activity.     

Posthatching development of the rete ophthalmicum in relation to brain temperature of mallard ducks (anas platyrhynchos)

In posthatching mallard ducks (Anas platyrhynchos), brain cooling improves with growth. To determine whether this may be correlated with growth-related changes in morphology of the rete ophthalmicum, we studied the development of this rete in immature mallards from hatching to 29 days of age. We found that the number of arteries and veins was fixed at hatching. The rete continued to grow, however, in length and vessel diameter during body and brain growth. The vascular surface area for heat exchange in the rete therefore also increased with body and brain mass. The increase in retial heat-exchange area was faster than the simultaneous increase in brain mass. The increase in body-to-brain temperature difference (delta T) described previously occurred nearly in direct proportion to heat-exchange area, such that the ratio of delta T to exchange area was nearly constant at about 0.1 degrees C per mm2 during growth. It is concluded that the increase in heat-exchange area of the rete ophthalmicum plays a major role in the development of brain cooling capacity of posthatching ducks.     

Heat loss from the human head during exercise

Evaporative and convective heat loss from head skin and expired air were measured in four male subjects at rest and during incremental exercise at 5, 15, and 25 degrees C ambient temperature (Ta) to verify whether the head can function as a heat sink for selective brain cooling. The heat losses were measured with an open-circuit method. At rest the heat loss from head skin and expired air decreased with increasing Ta from 69 +/- 5 and 37 +/- 18 (SE) W (5 degrees C) to 44 +/- 25 and 26 +/- 7 W (25 degrees C). At a work load of 150 W the heat loss tended to increase with increasing Ta: 119 +/- 21 (head skin) and 82 +/- 5 W (respiratory tract) at 5 degrees C Ta to 132 +/- 27 and 103 +/- 12 W at 25 degrees C Ta. Heat loss was always higher from the head surface than from the respiratory tract. The heat losses, separately and together (total), were highly correlated to the increasing esophageal temperature at 15 and 25 degrees C Ta. At 5 degrees C Ta on correlation occurred. The results showed that the heat loss from the head was larger than the heat brought to the brain by the arterial blood during hyperthermia, estimated to be 45 W per 1 degree C increase above normal temperature, plus the heat produced by the brain, estimated to be up to 20 W. The total heat to be lost is therefore approximately 65 W during a mild hyperthermia (+1 degrees C) if brain temperature is to remain constant.(ABSTRACT TRUNCATED AT 250 WORDS)     

Finite-element simulation of cooling of realistic 3-D human head and neck

Rapid cooling of the brain in the first minutes following the onset of cerebral ischemia is a potentially attractive preservation method. This computer modeling study was undertaken to examine brain-cooling profiles in response to various external cooling methods and protocols, in order to guide the development of cooling devices suitable for deployment on emergency medical vehicles. The criterion of successful cooling is taken to be the attainment of a 33 degrees C average brain temperature within 30 min of treatment. The transient cooling of an anatomically correct realistic 3-D head and neck with realistically varying local tissue properties was numerically simulated using the finite-element method (FEM). The simulations performed in this study consider ice packs applied to head and neck as well as using a head-cooling helmet. However, it was found that neither of these cooling approaches satisfies the 33 degrees C temperature within 30 min. This central conclusion of insubstantial cooling is supported by the modest enhancements reported in experimental investigations of externally applied cooling. The key problem is overcoming the protective effect of warm blood perfusion, which reaches the brain via the uncooled carotid arterial supply and effectively blocks the external cooling wave from advancing to the core of the brain. The results show that substantial cooling could be achieved in conjunction with neck cooling if the blood speed in the carotid artery is reduced from normal by a factor of 10. The results suggest that additional cooling means should be explored, such as cooling of other pertinent parts of the human anatomy.     

Brain temperature and limits on transcranial cooling in humans: quantitative modeling results

Selective brain cooling (SBC) of varying strengths has been demonstrated in a number of mammals and appears to play a role in systemic thermoregulation. Although primates lack obvious specialization for SBC, the possibility of brain cooling in humans has been debated for many years. This paper reports on the use of mathematical modeling to explore whether surface cooling can control effectively the temperature of the human cerebrum. The brain was modeled as a hemisphere with a volume of 1.33 1 and overlying layers of cerebrospinal fluid, skull, and scalp. Each component was assigned appropriate dimensions, physical properties and physiological characteristics that were determined from the literature. The effects of blood flow and of thermal conduction were modeled using the steady-state form of the bio-heat equation. Input parameters included core (arterial) temperature: normal (37°C) or hyperthermic (40°C), air temperature: warm (30°C) or hot (40°C), and sweat evaporation rate: 0, 0.25, or 0.50 l · m⁻² · h⁻¹. The resulting skin temperatures of the model ranged from 31.8°C to 40.2°C, values which are consistent with data obtained from the literature. Cerebral temperatures were generally insensitive to surface conditions (air temperature and evaporation rate), which affected only the most superficial level of the cerebrum (≤1.5 mm) The remaining parenchymal temperatures were 0.2–0.3°C above arterial temperatures, regardless of surface conditions. This held true even for the worst-case conditions combining core hyperthermia in a hot environment with zero evaporative cooling. Modeling showed that the low surface-to-volume ratio, low tissue conductivity, and high rate of cerebral perfusion combine to minimize the potential impact of surface cooling, whether by transcranial venous flow or by conduction through intervening layers to the skin or mucosal surfaces. The dense capillary network in the brain assures that its temperature closely follows arterial temperature and is controlled through systemic thermoregulation independent of head surface temperature. A review of the literature reveals several independent lines of evidence which support these findings and indicate the absence of functionally significant transcranial venous flow in either direction. Given the fact that humans sometimes work under conditions which produce face and scalp temperatures that are above core temperature, a transcranial thermal link would not necessarily protect the brain, but might instead increase its vulnerability to environmentally induced thermal injury. Accepted: 11 March 1998     

Improved preferential tumor hyperthermia with regional heating and systemic blood cooling: a balanced heat transfer method

Absorption of power in large body volumes can occur with some approaches used for hyperthermia treatment of cancer. A systemic heat absorption rate exceeding the heat dissipation rate can lead to systemic temperature elevation that limits the magnitude and duration of application of power and hence the degree of preferential tumor temperature rise. We describe a hyperthermia approach consisting of regional electromagnetic power absorption and extracorporeal blood cooling with regulation of both systemic heat absorption and dissipation rates ("balanced heat transfer"). A test of this approach in five dogs with nonperfused tumor models demonstrated intratumoral temperatures greater than 42 degrees C, while systemic temperature remained at 33 degrees C and visceral temperatures within the heated region equilibrated between 33 and 42 degrees C. Solutions of the bioheat transfer equation were obtained for a simplified model with a tumor perfusion rate lower than surrounding normal tissue perfusion rate. In this model, the use of arterial blood temperatures less than 37 degrees C allowed higher power densities to be used, for given normal tissue temperatures, than when arterial temperature was greater than or equal to 37 degrees C. As a result, higher intratumoral temperatures were predicted. Control of arterial blood temperature using extracorporeal cooling may thus (1) limit systemic temperature rise produced by regional heating devices and (2) offer a means of improving intratumoral temperature elevations.