Guttural pouches, brain temperature and exercise in horses

Selective brain cooling (SBC) is defined as the lowering of brain temperature below arterial blood temperature. Artiodactyls employ a carotid rete, an anatomical heat exchanger, to cool arterial blood shortly before it enters the brain. The survival advantage of this anatomy traditionally is believed to be a protection of brain tissue from heat injury, especially during exercise. Perissodactyls such as horses do not possess a carotid rete, and it has been proposed that their guttural pouches serve the heat-exchange function of the carotid rete by cooling the blood that traverses them, thus protecting the brain from heat injury. We have tested this proposal by measuring brain and carotid artery temperature simultaneously in free-living horses. We found that despite evidence of cranial cooling, brain temperature increased by about 2.5 degrees C during exercise, and consistently exceeded carotid temperature by 0.2-0.5 degrees C. We conclude that cerebral blood flow removes heat from the brain by convection, but since SBC does not occur in horses, the guttural pouches are not surrogate carotid retes.     

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.     

Arterio-venous heat exchange systems in the Jackass penguin Spheniscus demersus

Extensive arterio-venous associations occur in the head, axillae and legs of the Jackass penguin Spheniscus demersus. These vascular arrangements appear to facilitate counter-current heat exchange. The major heat exchange system in the head is the post orbital rete mirabile formed by the superior orbital artery. Blood from this rete supplies the eye, nasal passages and superficial jaw muscles. Other blood vessels supplying the superficial areas of the head and mouth associate closely with their corresponding veins.
In the axilla the brachial artery divides to form a humeral plexus of parallel running arteries each associating with up to three interlinking veins. Only the marginal vein does not associate with an artery. It appears that a shunt mechanism, which bypasses the veins in the humeral plexus, functions to permit heat loss when required; for instance in a heat-stressed bird breeding or moulting on land.
In both the upper and lower leg all the major arteries and their branches associate closely with corresponding veins.
The development of these arterio-venous associations indicates that Spheniscus demersus is adapted to a cool aquatic environment in which heat retention is of prime importance.     

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.     

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.     

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.     

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.     

Arterialization of the venous system of the brain

The possibility of reverse perfusion of the brain (in which arterial blood flows to brain tissues through venous vessels, and venous blood is drained by the arteries) was studied in acute and chronic experiments on dogs. Blood pressure in cerebral veins could reach 90--120 mm Hg, in Willisii arteries it was 5--35 mm Hg. Liquor pressure reached 20--35 mmHg. After temporary arterialization of the brain venous system (10, 30 and 60 min) the animals survived without impairment of the brain function and behaviour. In the future reverse perfusion of the brain (in which blood pressure in the arteries falls to the level of venous pressure) could be used as a means of urgent surgical intervention in cases of threatened or beginning intracranial arterial hemorrhage.     

An inquiry into the role of cardiac filling pressure in acclimatization to heat

During the first exposure of exercising subjects to hot environments (30-50 degrees C), cardiac output, heart rate, and body temperature increase over that seen in cool environments, while stroke volume decreases. If daily heat exposures occur, during the second heat exposure, heart rates and rectal temperatures are decreased from day 1 while cardiac output is maintained. This decrease in physiological strain occurs with little or no increase in evaporative heat loss. The alleviating agent appears to be an expansion of plasma volume. Several brief studies have indicated decreases in cardiac filling pressure during exercise in heat, and though inferential, it appears that the progressive increase in plasma volume during the first five to six days of heat exposure assists in maintaining cardiac filling pressure. Later, with increased evaporative heat loss due to increased sweat secretion, the mechanism of supplying increased volume to maintain cardiac filling is changed; fluid is transferred from extravascular to intravascular compartment, thus protecting venous return and cardiac filling pressure. These statements are based on limited data, and there is need of experiments designed to confirm or deny certain conclusions as to the role of cardiac filling pressure in acclimatization to heat.     

Orbital rete and red muscle vein anatomy indicate a high degree of endothermy in the brain and eye of the salmon shark

The salmon shark has been ranked as the most endothermic lamnid shark based upon geographical range, extent of slow twitch muscle, supra-hepatic rete size, and limited temperature measurements, yet its anatomy has remained largely undescribed, and measurements of brain or eye temperatures have not been reported. In this study, four specimens are examined to determine if the morphological requirements for warming the brain and eyes are present. A well-developed arterial orbital rete lies within a venous sinus on both sides of the cranium. Cool, oxygenated blood from the gills can pass through the vessels of this exchanger before reaching the brain or eyes. Since venous blood in the sinus flows opposite the arterial blood, counter-current heat exchange can occur. A vein originating in the red swimming muscle likely contributes to the warmth of the venous sinus by supplying blood directly from the warmest region of the shark. Before collecting in the orbital sinus, this red muscle vein bathes the brain in warm blood. These morphological data suggest the salmon shark has a significant capacity to warm the brain and eyes.     

Local vascular pathway for progesterone transfer to the brain after nasal administration in gilts

In the present study we examined whether local transfer of intranasally administrated tritiated progesterone (3H-P4) would increase its concentration in blood supplying the brain and hypophysis in comparison with other organs. Additionally, the effect of estrous cycle on the P4 transfer was evaluated on isolated gilts' heads. In the first experiment 3H-P4 was instilled into the nasal cavities of anaesthetized, immature pigs (n=10). Simultaneous blood samples were collected for radioactivity measurement every minute from the same occluded carotid artery through two catheters; one catheter was pointed towards the head, the other one towards the heart. In eight animals the ratio calculated between the 'head' and 'heart' samples was significantly (p<0.05) higher than 1 and reached a mean (+/- SEM) level of 3.23 +/- 0.81. In two animals a much higher ratio was observed. A head/heart ratio>1 indicates an existence of local transfer of 3H-P4 from venous blood to the carotid blood. In the second experiment, heads of 26 mature, cycling gilts were perfused through the right carotid artery with autologous blood. The outflow from the left carotid artery was collected as 1 min samples. 3H-P4 was infused into the angularis oculi veins. Transfer of 3H-P4 from the venous blood into the arterial blood reached the mean (+/- SEM) level of 4.11 +/- 1.08 pg/ml on days 2-4, 3.2 +/- 0.70 on days 17-21 and 0.94 +/- 0.22 pg/ml on days 15-16 of the estrous cycle. No 3H-P4 transfer was observed on days 9-11. These findings demonstrate that nasally administered progesterone can reach the brain in locally higher concentration through the vascular pathway. Moreover, the between-vessel transfer of P4 is significantly affected by the stage of the estrous cycle.     

The study of cerebral venous blood flow disturbance peculiarity in the norm and under the extravasal compression of brachiocephalic veins with the use of magnetic resonance venography and ultrasound duplex scanning

The MR-venography of the veins and brain venous sinuses, brachiocephalic veins an internal jugular veins duplex scanning have been performed in order to study the distinctions of cerebral venous hemodynamics of healthy people and the patients with venous encephalopathy caused by the extravasal compression of the brachiocephalic veins at the neck level and the superior sections of mediastinum. It has been revealed that the blood flow reducing in transverse brain sinuses occurs not only in the case of outflow disorder in the distal sections of the venous system, but also in norm. This reducing depends on anatomic constitution of confluens sinuum and the venous angle type of brachiocephalic veins. The three venous angle types of brachiocephalic veins have been distinguished: y-type, mu-type and Y-type. It has been registered that in case of the mu-type angle the blood flow can be reduced in norm due to peripheral resistance increase at the physiological bends of nearly a right angle type. The distinctions of hemodynamics in case of venous obstruction in contrast to arterial obstruction have been described. It has been registered that in case of outflow trouble in one of the internal jugular veins the speed and the volume of the blood flow in it are progressively reduced depending on the duration and the manifestation of compression. All this results in narrowing of the vein diameter from the affected side, and in compensatory distention of the diameter and increase of blood flow volume in the contralateral internal jugular vein, vertebral and external jugular veins, in succession.     

Histological studies of the dorsal nasal,Angularis Oculi,and facial veins of sheep (Ovis aries)

Selective brain cooling (SBC) requires vasoactivity in the superficial veins of the face of the animal. This vasoactivity is possible because of an adequate amount of smooth muscle in the tunica media of each of these superficial vessels, enabling it to act as a “muscle sphincter.” In this study, the angularis oculi, dorsal nasal, distal, and proximal parts of the facial veins in sheep were examined histologically to describe an anatomical basis for SBC. Measurements of the tunica media thickness, the lumen diameter, and the ratio of these measurements showed that the relative tunica media thicknesses in the angularis oculi vein and the dorsal nasal vein are statistically smaller (P < 0.001) than in the distal or the proximal parts of the facial vein. In the angularis oculi, dorsal nasal, and distal part of the facial vein, the tunicae mediae were composed of five to seven circularly arranged smooth muscle layers, suggesting their ability to vasoconstrict. The proximal part of the facial vein possesses both circularly and longitudinally arranged smooth muscle layers. The circular smooth muscle layers suggest a vasoconstrictory function, whereas the longitudinal smooth muscle layers imply a vasodilatory function in this part of the facial vein. Both the dorsal nasal and the proximal part of the facial vein, but not the angularis oculi or the distal part of the facial vein, possess endothelial valves near their confluences with other veins. It was concluded from this study that the angularis oculi and the distal part of the facial vein vasoconstrict, whereas the proximal part of the facial vein vasodilates, enabling the necessary changes in blood flow in SBC. J. Morphol. 237:275–281, 1998. © 1998 Wiley-Liss, Inc.     

Anatomy of the crocodilian spinal vein

The crocodilian spinal vein is remarkably robust yet historically overlooked. Using corrosion casting, we describe the anatomy of this vessel and its connections with the caval and hepatic venous systems in representatives from four crocodilian genera. The spinal vein arises from an enlarged occipital sinus over the medulla and extends the entire length of the vertebral column. Unlike in squamate reptiles, the spinal vein is single (nonplexiform), voluminous, and situated dorsal to the spinal cord, and plexi lateral to the cord span between emerging intercostal veins. The connections with the other venous systems are otherwise similar to those in other tetrapods. The overall anatomy of this vessel and its abundant connections with the other venous systems indicate it likely plays a primary role in returning blood to the heart from all parts of the body. Preliminary studies of function suggest that this vessel could also play an adaptive role during basking and diving.     

Training Rats to Voluntarily Dive Underwater: Investigations of the Mammalian Diving Response

Underwater submergence produces autonomic changes that are observed in virtually all diving animals. This reflexly-induced response consists of apnea, a parasympathetically-induced bradycardia and a sympathetically-induced alteration of vascular resistance that maintains blood flow to the heart, brain and exercising muscles. While many of the metabolic and cardiorespiratory aspects of the diving response have been studied in marine animals, investigations of the central integrative aspects of this brainstem reflex have been relatively lacking. Because the physiology and neuroanatomy of the rat are well characterized, the rat can be used to help ascertain the central pathways of the mammalian diving response. Detailed instructions are provided on how to train rats to swim and voluntarily dive underwater through a 5 m long Plexiglas maze. Considerations regarding tank design and procedure room requirements are also given. The behavioral training is conducted in such a way as to reduce the stressfulness that could otherwise be associated with forced underwater submergence, thus minimizing activation of central stress pathways. The training procedures are not technically difficult, but they can be time-consuming. Since behavioral training of animals can only provide a model to be used with other experimental techniques, examples of how voluntarily diving rats have been used in conjunction with other physiological and neuroanatomical research techniques, and how the basic training procedures may need to be modified to accommodate these techniques, are also provided. These experiments show that voluntarily diving rats exhibit the same cardiorespiratory changes typically seen in other diving animals. The ease with which rats can be trained to voluntarily dive underwater, and the already available data from rats collected in other neurophysiological studies, makes voluntarily diving rats a good behavioral model to be used in studies investigating the central aspects of the mammalian diving response.     

Cardiovascular changes during deep breath-hold dives in a pressure chamber

Ferrigno, Massimo, Guido Ferretti, Avery Ellis, DanWarkander, Mario Costa, Paolo Cerretelli, and Claes E. G. Lundgren. Cardiovascular changes during deep breath-hold dives ina pressure chamber. J. Appl. Physiol.83(4): 1282-1290, 1997.Electrocardiogram, cardiac output, andblood lactate accumulation were recorded in three elite breath-holddivers diving to 40-55 m in a pressure chamber in thermoneutral(35°C) or cool (25°C) water. In two of the divers, invasiverecordings of arterial blood pressure were also obtained during divesto 50 m in cool water. Bradycardia during the dives was more pronouncedand developed more rapidly in the cool water, with heart rates droppingto 20-30 beats/min. Arrhythmias occurred, particularly during thedives in cool water, when they were often more frequent than sinusbeats. Because of bradycardia, cardiac output decreased during thedives, especially in cool water (to <3 l/min in 2 of the divers).Arterial blood pressure increased dramatically, reaching values as highas 280/200 and 290/150 mmHg in the two divers, respectively. Thishypertension was secondary to peripheral vasoconstriction, which alsoled to anaerobic metabolism, reflected in increased blood lactateconcentration. The diving response of these divers resembles the onedescribed for diving animals, although the presence of arrhythmias andlarge increases in blood pressure indicate a less perfect adaptation inhumans.

     

A mathematical model for human brain cooling during cold-water near-drowning

A two-dimensionalmathematical model was developed to estimate the contributions ofdifferent mechanisms of brain cooling during cold-water near-drowning.Mechanisms include 1) conductive heat loss through tissue to the water at the head surface and in theupper airway and 2) circulatorycooling to aspirated water via the lung and via venous return from thescalp. The model accounts for changes in boundary conditions, bloodcirculation, respiratory ventilation of water, and head size. Resultsindicate that conductive heat loss through the skull surface or theupper airways is minimal, although a small child-sized head willconductively cool faster than a large adult-sized head. However,ventilation of cold water may provide substantial brain cooling throughcirculatory cooling. Although it seems that water breathing is requiredfor rapid "whole" brain cooling, it is possible that conductivecooling may provide some advantage by cooling the brain cortexperipherally and the brain stem centrally via the upper airway.

     

Limitations on arteriovenous cooling of the blood supply to the human brain

Arteriovenous heat transfer (AVHT) is a thermoregulatory phenomenon which enhances tolerance to thermal stress in a variety of animals. Several authors have speculated that human responses to thermal stress reflect AVHT in the head and neck, even though primates lack the specialized vascular arrangements which characterize AVHT in other animals. We modeled heat transfer based on the anatonmical relationships and blood flows for the carotid artery and associated venous channels in the human neck and cavernous sinus. Heat transfer rate was predicted using the effectiveness-number of transfer units method for heat exchanger analysis. Modeling showed that AVHT is critically dependent upon (1) heat exchanger effectiveness and (2) arteriovenous inlet temperature difference. Predicted heat exchanger effectiveness is less than 5.5% for the neck and 0.3% for the cavernous sinus. These very low values reflect both the small arteriovenous interface for heat exchange and the high flow rate in the carotid artery. In addition, humans lack the strong venous temperature depression required to drive heat exchange; both the cavernous sinus and the internal jugular vein carry a large proportion of venous blood warmed by its passage through the brain as well as a small contribution from the face and scalp, whose temperature varies with environmental conditions. Under the most optimistic set of assumptions, carotid artery temperature would be lowered by less than 0.1° C during its passage from the aorta to the base of the brain. Physiologically significant cooling of the blood supply to the brain cannot occur in the absence of a suitably scaled site specialized for heat exchange.     

Structure of the endotheliocytes of cerebral vessels of aquatic mammals

By means of scanning microscopy the relief of luminal surface of endotheliocytes, lining microvessels of various parts of the brain in the Pusa sibirica, Phoca vitulina and Delphinapterus leucas have been studied. Specialized formations of the cellular surface--various processes, projections, toruli have been revealed; their character in various parts of the brain in diving animals is determined by the blood stream conditions and their different sensitivity to oxygen deficiency during diving. The peculiarities, revealed in the structure of the cerebral vessels intima, are considered as one manifestations of the adaptive properties in the organism of diving animals, which had been developed in them during the process of a long evolution, while they adapted to the aquatic environment.