Early acute rejection of renal homografts: a characteristic clinical syndrome

Seven of 74 patients with early functioning cadaveric renal homografts developed acute oliguric renal failure after the second but before the ninth day post-transplantation. The syndrome characteristically begins with an abrupt and simultaneous decrease in creatinine clearance, urine volume and urine sodium concentration. After a variable period and despite a reduction in immunosuppressive therapy, a diuretic phase ensues and renal function is restored. Complications associated with the syndrome include groin hematoma, pulmonary edema and renal rupture with shock. Renal rupture does not require nephrectomy: if the hemorrhage is controlled, the transplanted organ will resume function. Angiographic studies show normal nephrograms, stretched arterial vasculature and filling defects in the veins. Percutaneous renal biopsy shows interstitial edema and hemorrhage, venous congestion and tubular necrosis. Evidence is presented to support the hypothesis that this is a form of rejection occurring as the result of injury to the renal venous system.     

Dynamics of the glycemic profile in women in long-term antiorthostatic hypokinesia

The dynamics of the glycemic curve profile was investigated in 8 healthy women during performance of the glucose tolerance test (GТТ) in 120-day antiorthostatic hypokinesia (–6°) (АNОH) simulating the effects of weightlessness. Glycemic profiles were characterized by more marked hyperglycemic response at 30 min of GТТ in the first month of stay under ANOH conditions and had a flattened appearance three months later. Glycemic profiles characteristic of delayed restoration of the blood glucose concentration appeared in the fourth month, which persisted over the first week after the end of АNОH. The glycemic profile changes developed against the background of the signs of progressive congestion of blood in the venous system of the abdominal cavity. The expansion of diameters of the main veins of the abdominal cavity was noted at the beginning of АNОH; an increase in the size of the organs and the signs of expansion of venous plexuses at the site of portocaval anastomoses, after three months; the occurrence of the signs of transudation and free fluid in the abdominal cavity was revealed at the end of hypokinesia. The countermeasures against hypodynamia did not prevent transformation of the glycemic profile nor did they influence the progression of blood flow congestion in the venous system of the abdominal cavity whose features determined the character changes in the glycemic profile in different periods of ANOH.     

Effects of hypohydration on thermoregulation during exercise before and after 5-day aerobic training in a warm environment in young men

We examined whether enhanced cardiovascular and thermoregulatory responses during exercise after short-term aerobic training in a warm environment were reversed when plasma volume (PV) expansion was reversed by acute isotonic hypohydration. Seven young men performed aerobic training at the 70% peak oxygen consumption rate (Vo(?peak)) at 30°C atmospheric temperature and 50% relative humidity, 30 min/day for 5 days. Before and after training, we performed the thermoregulatory response test while measuring esophageal temperature (T(es)), forearm skin vascular conductance, sweat rate (SR), and PV during 30 min exercise at the metabolic rate equivalent to pretraining 65% Vo(?peak) in euhydration under the same environment as during training in four trials (euhydration and hypohydration, respectively). Hypohydration targeting 3% body mass was attained by combined treatment with low-salt meals to subjects from ~48 h before the test and administration of a diuretic ~4 h before the test. After training, the T(es) thresholds for cutaneous vasodilation and sweating decreased by 0.3 and 0.2°C (P = 0.008 and 0.012, respectively) when PV increased by ~10%. When PV before and after training was reduced to a similar level, ~10% reduction from that in euhydration before training, the training-induced reduction in the threshold for cutaneous vasodilation increased to a level similar to hypohydration before training (P = 0.093) while that for sweating remained significantly lower than that before training (P = 0.004). Thus the enhanced cutaneous vasodilation response after aerobic training in a warm environment was reversed when PV expansion was reversed while the enhanced SR response remained partially.     

Status of the circulatory bed of the vascular membrane of the eyeball and retrobulbar structures during experimental venous stasis

In 43 test animals the state of the blood bed in the retrobulbar formations and the eyeball vasular tunic has been studied under venous congestion produced by ligation of the anterior vena cava (in dogs) and both external jugular veins (in rabbits). A complex of histological, histotopographic, morphometric and variation-statistical techniques has been used. The results obtained demonstrate that disturbances in the venous outflow in the anterior vena cava system produce certain responses in all parts of the retrotubular adipose tissue, of the eyeball muscles, of the optic nerve tunics, of the vascular tunic. Certain stageness is noted in the course of venous congestion. Places of the greatest morphological changes in the eyeball vascular tunic are determined. They are zones of vorticose veins formation and the area corresponding to the posterior pole of the eyeball. The analysis of the specific areas of the intermuscular arteries and veins cross sections demonstrates that in the reaction of these vessels to the different venous outflow in the anterior vena cava system these is certain unevenness in different ofthalmic muscles.     

Splanchnic vascular capacitance and positive end-expiratory pressure in dogs

We have investigated the effect of positive end-expiratory pressure ventilation (PEEP) on regional splanchnic vascular capacitance. In 12 anesthetized dogs hepatic and splenic blood volumes were assessed by sonomicrometry. Vascular pressure-diameter curves were defined by obstructing hepatic outflow. With 10 and 15 cmH2O PEEP portal venous pressure increased 3.1 +/- 0.3 and 5.1 +/- 0.4 mmHg (P less than 0.001) while hepatic venous pressure increased 4.9 +/- 0.4 and 7.3 +/- 0.4 mmHg (P less than 0.001), respectively. Hepatic blood volume increased (P less than 0.01) 3.8 +/- 0.9 and 6.3 +/- 1.4 ml/kg body wt while splenic volume decreased (P less than 0.01) 0.8 +/- 0.2 and 1.3 +/- 0.2 ml/kg body wt. The changes were similar with closed abdomen. The slope of the hepatic vascular pressure-diameter curves decreased with PEEP (P less than 0.01), possibly reflecting reduced vascular compliance. There was an increase (P less than 0.01) in unstressed hepatic vascular volume. The slope of the splenic pressure-diameter curves was unchanged, but there was a significant (P less than 0.05) decrease in unstressed diameter during PEEP. In conclusion, hepatic blood volume increased during PEEP. This was mainly a reflection of passive distension due to elevated venous pressures. The spleen expelled blood and thus prevented a further reduction in central blood volume.     

Functional state of the liver during simulation of the hemodynamic effects of microgravity on the human body

Radioisotope studies of the choleresis function of the liver, ultrasonic studies of the liver and contractile function of the gallbladder and gastroduodenoscopy were carried out in eight subjects after a 24-h stay in a 12° antiorthostatic position (AOP) simulating the hemodynamic changes in the abdominal cavity caused by microgravity. The dynamically hindered venous blood outflow from the liver induced in the AOP model caused activation of choleresis on an empty stomach. This activation manifested itself as an increase in the central perfusion zone of the liver parenchyma, dilation of the biliary ductules, and contraction of the gall-bladder, as well as choleresis into the duodenum. Activation of choleresis in the liver took place against the background of a reduction of the area of radioactive marker distribution in the liver and a decrease in the hepatocyte metabolic activity and the concentration function of the biliary excretion system. The functional characteristics of the liver in the AOP model reflected the reaction caused by changes in its blood content due to the changes in the body position negative to the gravity vector. The mechanism of the changes includes the occurrence of a dynamic venous plethora in the liver; centralization of hepatic blood flow, and activation of choleresis activity against the background of peripheral blood flow depletion, as well as the reduction of metabolic activity of hepatocytes and the concentration function of the biliary excretion system.     

Hepatic venous resistance site in the dog: localization and validation of intrahepatic pressure measurements

Intrahepatic pressure (9.4 +/- 0.3 mmHg; 1 mmHg = 133.32 Pa), measured proximal to a hepatic venous resistance site, was insignificantly different from portal venous pressure (9.6 +/- 0.4 mmHg). This lobar venous pressure is not wedged hepatic venous pressure as it is measured from side holes in a catheter with a sealed tip. Validation of the lobar venous pressure measurement was done in a variety of ways and using different sizes and configurations of catheters. The site of hepatic venous resistance in the dog is localized to a narrow sphincterlike region about 0.5 cm in length and within 1-2 cm (usually within 1 cm) of the junction of the vena cava and hepatic veins. Sinusoidal and portal venous resistance appears insignificant in the basal state and large increases in liver blood volume (histamine infusion or passive vena caval occlusion) or large decreases in liver blood volume (passive vascular occlusion) do not alter the insignificant pressure gradient between portal and lobar venous pressures. Norepinephrine infusion (1.25 microgram X kg-1 X min-1 intraportal) and hepatic sympathetic nerve stimulation (10 Hz) led to a significantly greater rise in portal venous pressure than in lobar venous pressure, indicating some presinusoidal (and (or) sinusoidal) constriction and this indicates that lobar venous pressure cannot be assumed under all conditions to accurately reflect portal pressure. However, most of the rise in portal venous pressure induced by intraportal infusion of norepinephrine or nerve stimulation and virtually all of the pressure rise induced by histamine could be attributed to the postsinusoidal resistance site.(ABSTRACT TRUNCATED AT 250 WORDS)     

Redistribution of bodily fluids under conditions of microgravity and in microgravity models

This review is focused on the redistribution of blood and other bodily fluids along the body axis in the cranial direction under conditions of microgravity or during simulation of the physiological effects of microgravity. This redistribution of bodily fluids in the direction of the thorax or head results in respective physiological responses and induces a whole cascade of secondary adaptation mechanisms. Changes in central venous pressure, heart cavity volume, kidney functioning, and hormonal volume regulation lead to adaptive modifications in bodily fluid sectors. Modification of the hemodynamic in the splanchnic vascular system influences the organs of the abdominal cavity. Pharmacological correction accelerates the adaptation of the human body to unusual living conditions.     

The blood-brain barrier: an alternative hypothesis

Brain blood vessels, unlike most vessels elsewhere in the body, exhibit a blood-brain barrier (BBB) to certain substances, e.g. trypan blue. Under some circumstances this barrier is no longer effective and the permeability of the vessels increases. Although capillarization is much less in the brain than in many other organs, e.g. heart muscle, total cerebral blood flow per minute is enormous. Consequently, to accommodate a large blood volume with a limited capillary bed, the velocity of blood through brain vessels must be extremely fast. The hypothesis presented in this paper is that this rapid flow results in a low or negative pressure on the endothelium, and plasma and trypan blue are prevented from passing through the wall. The tight junctions of cerebral endothelial cells may be able to withstand only a limited amount of pressure on their luminal surface. If the velocity of blood in brain capillaries decreases, pressure on the endothelium should increase, and brain vessels, like blood vessels elsewhere in the body, become permeable to vital dyes. Other conditions also increase capillary permeability, e.g. acute arterial hypertension or venous congestion. Although brain vessels can adapt to a moderate, gradual change in systemic pressure, when a significant rise in cerebral arterial pressure is abrupt, the compensatory changes in the postcapillary venous bed may be inadequate and consequently intracapillary pressure and vascular permeability are increased. Venous congestion increases intracapillary pressure by restricting capillary outflow as well as by reducing velocity through capillary beds. Under such conditions increased capillary permeability may be indicated by cerebral edema, and even, on occasion, by petechial hemorrhages. In short, if the flow is fast and unimpeded the BBB will be effective; if the velocity decreases, or intracapillary pressure increases for whatever reason, the permeability of the brain endothelium will be abnormally increased.     

Mechanism for negative water balance during weightlessness: an hypothesis

The mechanism for the apparent decrease in body fluid volume in astronauts during spaceflight remains obscure. The widespread postulate that the hypohydration is the result of the Henry-Gauer reflex, a diuresis caused by inhibition of vasopressin secretion resulting from increased left and perhaps right atrial (central) venous pressure, has not been established with direct measurements on astronauts. An hypothesis is proposed to account for fluid-electrolyte shifts during weightlessness. A moderate but transient increase in central venous pressure occurs when orbit is entered that is insufficient to activate the Henry-Gauer reflex but sufficient to stimulate the release of atrial natriuretic peptides. Increased sodium excretion would facilitate some increased urinary water loss. The resulting relatively dilute plasma and interstitial fluids would cause fluid to shift into the cellular space, resulting in edema in the head and trunk and inhibition of thirst and drinking. Thus the negative water balance in astronauts would be caused by a gradual natriuresis and diuresis coupled with reduced fluid intake.     

Mechanism of salutary effects of estradiol on organ function after trauma-hemorrhage: upregulation of heme oxygenase

A growing body of evidence indicates that heme degradation products may counteract the deleterious consequences of hypoxia and/or ischemia-reperfusion injury. Because heme oxygenase (HO)-1 induction after adverse circulatory conditions is known to be protective, and because females in the proestrus cycle (with high estrogen) have better hepatic function and less hepatic damage than males after trauma-hemorrhage, we hypothesized that estrogen administration in males after trauma-hemorrhage will upregulate HO activity and protect the organs against dysfunction and injury. To test this hypothesis, male Sprague-Dawley rats underwent 5-cm laparotomy and hemorrhagic shock (35-40 mmHg for 93 +/- 2 min), followed by resuscitation with four times the shed blood volume in the form of Ringer lactate. 17beta-Estradiol and/or the specific HO enzyme inhibitor chromium mesoporphyrin (CrMP) were administered at the end of resuscitation, and the animals were killed 24 h thereafter. Trauma-hemorrhage reduced cardiac output, myocardial contractility, and serum albumin levels. Portal pressure and serum alanine aminotransferase levels were markedly increased under those conditions. These parameters were significantly improved in the 17beta-estradiol-treated rats. Estradiol treatment also induced increased HO-1 mRNA expression, HO-1 protein levels, and HO enzymatic activity in cardiac and hepatic tissue compared with vehicle-treated trauma-hemorrhage rats. Administration of the HO inhibitor CrMP prevented the estradiol-induced attenuation of shock-induced organ dysfunction and damage. Thus the salutary effects of estradiol administration on organ function after trauma-hemorrhage are mediated in part via upregulation of HO-1 expression and activity.     

Changes in plasma volume during hypohydration and rehydration in subjects from the tropics

Plasma volume (PV) at different levels of hypohydration was determined using radio-iodinated serum albumin-125 in 28 heat acclimated male volunteers in hot dry condition in a climatic chamber. The heat acclimated subjects were hypohydrated to varying degrees i.e. 1%, 2%, 3% and 4% body mass deficit by moderate work in hot conditions in a climatic chamber maintained at 45 degrees C dry bulb temperature and 30% relative humidity. A rehydration study was carried out in only those subjects who were hypohydrated to 3% and 4% body mass and they were brought back to a 2% level of hypohydration by giving a calculated amount of water. A significant decrease in PV was observed at 3% and 4% hypohydration only. The magnitude of the decrease was the same in both the groups and not related to the level of hypohydration. With partial rehydration in the 3% hypohydrated group PV was restored fully, while in the 4% hypohydrated group restoration was incomplete, indicating that at this hypohydration level some of the replenished water that entered in plasma may have moved to the intracellular compartment which may have contributed more at 4% hypohydration. It is suggested that with higher levels of thermal hypohydration significant reduction in the intracellular compartment may result in accentuated physiological strain during work in the heat.     

Influence of Desmopressin on water-salt homeostasis and the orthostatic tolerance during head-down tilting

Influence of Desmopressin, a synthetic analog of antidiuretic hormone (ADH), on the water-salt metabolism and orthostatic tolerance in humans during head-down tilting (HDT 15°) for 24 h has been studied. Smaller decrease in the total body water and extracellular fluid content, suppression of diuresis, and positive water balance were observed after Desmopressin administration as compared to the control group (without ADH). At the same time, the tolerance of the standard orthostatic test is increased. Thus, Desmopressin has been shown to prevent hypohydration of the body under the HDT conditions and, hence, an increase of orthostatic tolerance.     

Thermoregulatory activity in the rat: effects of hypohydration, hypovolemia and hypertonicity and their interaction with short-term heat acclimation

Hypothalamic temperature thresholds to heat-induced (40 degrees C ambient temperature) tail vasodilation (Vth) and salivation (Sth) as well as salivary flow rate and volume were studied in conscious rats, hypohydrated (24 hr water deprivation), hypovolemic (20% dextran sc), hypertonic (1M NaCL po), hypertonic and hypovolemic and heat-acclimated (5 days at 34 degrees C) before and after hypohydration. Sth was elevated in hypohydrated, hypovolemic, hypertonic and heat-acclimated hypohydrated rats concomitantly with a remarkable decrease in saliva volume, flow rate and heat tolerance. Heat acclimation alone resulted in a reduction in Vth, Sth, salivary flow and volume. Vth was not affected by hypohydration, but was elevated following hypovolemia and combined hypovolemia and hypertonicity. It is concluded that alterations in both plasma volume and osmolarity, which may occur during hypohydration, play a major role in the alteration in thermoregulatory responses during hypohydration. Heat acclimation does not improve tolerance during hypohydration. Thus, during hypohydration, the control of body fluids overrides thermoregulation.     

Prolonged exercise following diuretic-induced hypohydration effects on fluid and electrolyte hormones.

To investigate the hypothesis that a reduction in plasma volume (PV) induced by diuretic administration would result in an increase in the fluid and electrolyte hormonal response to exercise, ten untrained males (VO(2) peak = 3.96 +/- 0.14 l/min) performed 60 min of cycle ergometry at 61 % VO(2) peak twice. The test was carried out once under control conditions (CON) (placebo) and once after 4 days of diuretic administration (DIU) (Novotriamazide; 100 mg triamterene and 50 mg hydrochlorothiazide). Calculated resting PV decreased by 14.6 +/- 3.3 % (p < 0.05) with DIU. No difference in plasma osmolality was observed between conditions. For the hormones measured, differences (p < 0.05) between conditions at rest were noted for plasma renin activity (PRA) (0.62 +/- 0.09 vs. 5.61 +/- 0.94 ng/ml/h), angiotensin I (ANG 1) (0.26 +/- 0.03 vs. 0.56 +/- 0.08 ng/ml), aldosterone (ALD) (143 +/- 14 vs. 1603 +/- 302 pg/ml), arginine vasopressin (AVP) (4.13 +/- 1.1 vs. 9.58 +/- 1.6 pg/ml) and atrial natriuretic peptide (alpha-ANP) (11.5 +/- 2.8 vs. 6.33 +/- 1.0 pg/ml). The exercise resulted in increases (p < 0.05) in PRA, ANG I, ALD, AVP, alpha-ANP. DIU led to higher levels of PRA, ANG I, and ALD (p < 0.05) and lower levels of alpha-ANP (p < 0.05) compared to CON. Arginine vasopressin was not affected by the loss of PV. For the catecholamines--norepinephrine (NE) and epinephrine (EPI)--only NE was higher during exercise with DIU compared to CON (p < 0.05). For PRA and ALD, the higher levels observed during exercise with DIU could be explained both by higher resting levels and a greater increase during exercise itself. For ANG I and NE, the effect of DIU only manifested itself during exercise. In contrast, the lower alpha-ANP observed during exercise with DIU was due to the lower resting levels. These results support the hypotheses that hypohydration leads to alterations in the secretion of all of the fluid and electrolyte hormones with the exception of AVP. The specific mechanisms of these alterations remain unclear, but appear to be related directly to the decrease in PV.     

Acute effects on the lung and the liver of oral administration of cerium chloride on adult, neonatal and fetal mice

We evaluated tissue changes associated with cerium chloride administration via gavage to adult mice, via milk to neonatal mice and transplacentally to fetal mice. Change in adults consisted of extensive pulmonary hemorrhage, pulmonary venous congestion, thickened alveolar septae, hepatic necrosis and neutrophil infiltrations. Those in fetal mice consisted of pulmonary and hepatic congestion. These results indicate that gavage cerium administration elicited subtle tissue changes, though oral toxicity is rather low. These changes were less severe in neonatal and fetal mice. When cerium was injected into adult mice through the tail vein, cerium was distributed mainly to the liver, spleen and lung dose-dependently with the cerium concentration gradually decreasing after 3 days. A study of cerium anticoagulation in mouse plasma showed that clotting time was significantly prolonged when cerium was added to plasma. These results suggest that cerium may disturb blood coagulation and cause pulmonary and hepatic vascular congestion.     

Extrajugular pathways of human cerebral venous blood drainage assessed by duplex ultrasound.

Cerebral venous drainage in humans is thought to be ensured mainly via the internal jugular veins (IJVs). However, anatomic, angiographic, and ultrasound studies suggest that the vertebral venous system serves as an important alternative drainage route. We assessed venous blood volume flow in vertebral veins (VVs) and IJVs of 12 healthy volunteers using duplex ultrasound. Measurements were performed at rest and during a transient bilateral IJV and a circular neck compression. Total venous blood volume flow at rest was 766 +/- 226 ml/min (IJVs: 720 +/- 232, VVs: 47 +/- 33 ml/min). During bilateral IJV compression, VV flow increased to 128 +/- 64 ml/min. Circular neck compression, causing an additional deep cervical vein obstruction, led to a further rise in VV volume flow (186 +/- 70 ml/min). As the observed flow increase did not compensate for IJV flow cessation, other parts of the vertebral venous system, like the intraspinal epidural veins and the deep cervical veins, have to be considered as additional alternative drainage pathways.     

Thermoregulatory and blood responses during exercise at graded hypohydration levels

We studied the effects of graded hypohydration levels on thermoregulatory and blood responses during exercise in the heat. Eight heat-acclimated male subjects attempted four heat-stress tests (HSTs). One HST was attempted during euhydration, and three HSTs were attempted while the subjects were hypohydrated by 3, 5, and 7% of their body weight. Hypohydration was achieved by an exercise-heat regimen on the day prior to each HST. After 30 min of rest in a 20 degrees C antechamber the HST consisted of a 140-min exposure (4 repeats of 10 min rest and 25 min treadmill walking) in a hot-dry (49 degrees C, 20% relative humidity) environment. The following observations were made: 1) a low-to-moderate hypohydration level primarily reduced plasma volume with little effect on plasma osmolality, whereas a more severe hypohydration level resulted in no further plasma volume reduction but a large increment in plasma osmolality; 2) core temperature and heart rate responses increased with severity of hypohydration; 3) sweating rate responses for a given rectal temperature were systematically decreased with severity of hypohydration; and 4) the reduction in sweating rate was more strongly associated with plasma hyperosmolality than hypovolemia. In conclusion, an individual's thermal strain increases linearly with the severity of hypohydration during exercise in the heat, and plasma hyperosmolality influences the reduction in sweating more profoundly than hypovolemia.     

Insulin stimulates triacylglycerol secretion by perfused livers from fed rats but inhibits it in livers from fasted or insulin-deficient rats implications for the relationship between hyperinsulinaemia and hypertriglyceridaemia.

We determined whether the direction of the acute effect of insulin on hepatic triacylglycerol secretion is dependent on the prior physiological state or on the in vitro experimental system used. The effect of insulin on triacylglycerol secretion was studied using perfused livers isolated from rats under three metabolic conditions: fed normo-insulinaemic, 24-h fasted and fed, streptozotocin-diabetic (insulin-deficient). Insulin acutely activated triacylglycerol secretion (by 43%) in organs from fed, normo-insulinaemic animals, whereas it inhibited triacylglycerol secretion in livers isolated from fasted or insulin-deficient rats (by 30 and 33%, respectively). By contrast, in 24-h-cultured hepatocytes insulin invariably acutely inhibited triacylglycerol secretion irrespective of the metabolic state of the donor animals. It is concluded that the use of perfused livers enables the observation of a switch in the direction of insulin action on hepatic triacylglycerol secretion from stimulatory, in the normo-insulinaemic state, to inhibitory in the fasting or insulin-deficient state. The possible implications of this switch for the relationship between hyperinsulinaemia, increased hepatic very-low-density lipoprotein-triacylglycerol secretion and hypertriglyceridaemia observed in vivo are discussed.     

Dynamics of human cardiovascular responses in different periods of long-term exposure to weightlessness

The purpose of this work was to determine the dynamics of changes in the state of the human cardiovascular system at rest and upon exposure to lower body negative pressure (LBNP) in different periods of short-term (8?C25 days) and long-term (126?C438 days) space flights (SFs) using the data of ultrasonic examinations and leg occlusive plethysmography. It was established that the changes caused by blood redistribution and hypovolemia development??a decreased left-ventricular filling and stroke volume without an impairment of myocardial contractility, a decreased renal artery resistance, and an increased maximal capacity of leg veins??occurred in the first week of an SF. Over 30?C40 days of SF, these changes increased and were followed by the relative stabilization of hemodynamics at rest. Arterial cerebral blood flow was stable; however, the phenomena of venous congestion in this region increased with the SF??s duration. The most dramatic changes were observed in leg vessels, both in arteries (decreased resistance) and veins (increase in maximum capacity). Changes in the venous part of the cardiovascular system were more marked than in the arterial one. Despite the relative stabilization of the hemodynamics at rest, exposure to LBNP revealed a deterioration of gravity-dependent reactions, which changed as a function of the SF duration. In the first month of FS, the downward trend of the femoral artery vasoconstriction was not detrimental to cerebral blood flow. SF extension impaired the regulation of the vascular tone and caused increased blood flow deficiency on exposure to LBNP. In some cases, the hemodynamic response was affected to the extent that could be regarded as a failure to adapt to orthostatic effects.