Normal physiological values for conscious pigs used in biomedical research

Although the domestic pig is rapidly becoming an animal of choice in certain areas of biomedical research requiring a large animal model, effective utilization of the species is often encumbered by a lack of reference values for common functional variables. To address this problem, normal data for over 100 physiologic or related variables were collected from conscious chronically instrumented animals that were maintained under near basal conditions. Included were measurements of body composition, fluid volumes, blood physical and biochemical characteristics, blood gas and acid-base status, plasma hormone levels, energy metabolism, renal function, hemodynamics and pulmonary function. Most porcine values were similar to those collected under comparable conditions from humans. Compared to adult man, however, pigs had higher values for extracellular space, plasma volume, arterial pH, plasma bicarbonate, cardiac output, arterial pressure, expired ventilation, heat production, and core temperature, and lower values for red cell volume, hemoglobin level, plasma osmotic and oncotic pressure, arterial O2 content, renal blood flow and glomerular filtration rate. Many of these deviations were due to immaturity. Nevertheless, we have found pigs to be an excellent large animal model for a variety of functional studies.     

Intravascular infusions of plasma into fetal sheep cause arterial and venous hypertension.

Fetal volume control is driven by an equilibrium between fetal and maternal hydrostatic and oncotic pressures in the placenta. Renal contributions to blood volume regulation are minor because the fetal kidneys cannot excrete fluid from the fetal compartment. We hypothesized that an increase in fetal plasma protein would lead to an increase in plasma oncotic pressure, resulting in an increase in fetal arterial and venous pressures and decreased angiotensin levels. Plasma or lactated Ringer solution was infused into each of five twin fetuses. After 7 days, fetal protein concentration was 71.2 +/- 4.2 g/l in the plasma-infused fetuses compared with 35.7 +/- 6.3 g/l in the lactated Ringer-solution-infused fetuses. Arterial pressure was 68.0 +/- 3.6 compared with 43.4 +/- 1.9 mmHg in the lactated Ringer solution-infused fetuses (P < 0.0003), whereas venous pressure was 4.8 +/- 0.3 mmHg in the plasma-infused fetuses compared with 3.3 +/- 0.4 mmHg in the lactated Ringer solution-infused fetuses (P < 0.036). Six fetuses were studied on days 0, 7, and 14 of plasma protein infusion. Fetal protein concentration increased from 31.1 +/- 1.5 to 84.8 +/- 3.8 g/l after 14 days (P < 0.01), and arterial pressure increased from 43.1 +/- 1.8 to 69.1 +/- 4.1 mmHg (P < 0.01). Venous pressure increased from 3.0 +/- 0.4 to 6.2 +/- 1.3 mmHg (P < 0.05). Fetal heart rate did not change. Angiotensin II concentration decreased, from 24.6 +/- 5.6 to 2.9 +/- 1.3 pg/l, after 14 days (P < 0.01). Fetal plasma infusions resulted in fetal arterial and venous hypertensions that could not be corrected by reductions in angiotensin II levels.     

Role of atrial natriuretic peptide in systemic responses to acute isotonic volume expansion.

Atrial natriuretic peptide (ANP) may activate multiple mechanisms that protect against circulatory volume overload. We hypothesized that a temporal relationship exists between increases in cardiac filling pressure and plasma ANP concentration and also between ANP elevation and vasodilation, fluid movement from plasma to interstitium, and increased urine volume (UV). We infused 30 ml/kg isotonic saline at 100 ml/min in seven supine male subjects and monitored responses for 3 h postinfusion. Right atrial pressure (RAP) was measured via a central catheter. ANP (pmol/l) was measured by radioimmunoassay. Transcapillary fluid transport (TFT) equaled infused volume minus UV, insensible fluid loss, and change in plasma volume (PV, measured with Evan's blue). Systemic vascular resistance (SVR) was calculated as (mean arterial pressure-RAP)/cardiac output (determined by acetylene rebreathing). Plasma oncotic pressure (OP) was measured directly. During infusion, mean TFT (+/- SE) increased from net reabsorption during control of 111 +/- 27 ml/h to net filtration of 1,219 +/- 143 ml/h (P < 0.01). At end infusion, mean RAP, heart rate, and PV exhibited peak increases of 146, 23, and 27%, respectively. Concurrently, SVR and OP achieved nadirs 29 and 31% below control, respectively. Mean plasma ANP and UV peaked (45 and 390%, respectively) at 30 min postinfusion. Systemic vasodilation and capillary filtration resulted from and compensated for infusion-induced circulatory pressure increases and hemodilution. By 1 h postinfusion, most cardiovascular variables had returned toward control levels, and net reabsorption of extravascular fluid ensued.(ABSTRACT TRUNCATED AT 250 WORDS)     

Starling forces that oppose filtration after tissue oncotic pressure is increased

We tested the hypothesis that the effective oncotic force that opposes fluid filtration across the microvessel wall is the local oncotic pressure difference across the endothelial surface glycocalyx and not the global difference between the plasma and tissue. In single frog mesenteric microvessels perfused and superfused with solutions containing 50 mg/ml albumin, the effective oncotic pressure exerted across the microvessel wall was not significantly different from that measured when the perfusate alone contained albumin at 50 mg/ml. Measurements were made during transient and steady-state filtration at capillary pressures between 10 and 35 cmH(2)O. A cellular-level model of coupled water and solute flows in the interendothelial cleft showed water flux through small breaks in the junctional strand limited back diffusion of albumin into the protected space on the tissue side of the glycocalyx. Thus oncotic forces opposing filtration are larger than those estimated from blood-to-tissue protein concentration differences, and transcapillary fluid flux is smaller than estimated from global differences in oncotic and hydrostatic pressures.     

Protective effect of prenatal water restriction on offspring cardiovascular homeostasis in response to hemorrhage

We determined the cardiovascular and AVP responses of prenatally dehydrated (PreDehy) neonates to intravascular hemorrhage. Ewes with singleton fetuses were subjected to water restriction from 110 days of gestation to full term to achieve hypernatremia of 8-10 meq/l. Water and food were provided ad libitum to control ewes. After delivery, water and food were provided ad libitum to ewes from both groups, and newborns were allowed to nurse ad libitum. At 15 +/- 2 days of age, PreDehy and control lambs were prepared with bladder and femoral catheters and studied at 25 +/- 2 days of age. After a 2-h basal period, lambs were hemorrhaged to 30% of blood volume over 1 h (0.5% of blood volume/min) and monitored 1 h after hemorrhage. Neonatal arterial blood pressure was measured, and blood samples were collected. Basal plasma sodium levels, plasma osmolality, hematocrit, and mean arterial pressure were increased in PreDehy lambs compared with controls. Both groups had similar basal AVP levels and heart rate. In response to hemorrhage, all parameters remained significantly elevated in PreDehy lambs. Blood pressure decreased less in PreDehy lambs than in controls. The hemorrhage-AVP threshold (percent blood volume withdrawal at which plasma AVP values significantly increased) was markedly elevated (20 vs. 15%) and peak hemorrhage-induced AVP plasma levels were lower (5.6 +/- 1.5 vs. 10.1 +/- 1.5 pg/ml, P < 0.01) in PreDehy lambs than in controls. Thus offspring of dehydrated ewes demonstrate enhanced AVP secretory responses to hypotension. Despite potential long-term adverse effects of systemic hypertension, these results suggest a protective effect of prenatal water restriction on offspring cardiovascular homeostasis during blood volume reduction.     

Does gravitational pressure of blood hinder flow to the brain of the giraffe?

Vascular pressure consists of the sum of two pressures: (a) pressure developed by the pumping of the ventricles against the resistance of vessels, designated as viscous flow pressure, and (b) pressure caused by gravity, traditionally called hydrostatic, better described as gravitational pressure. In a conduit, both of these pressures must be overcome when a liquid is discharged to a higher level of gravitational potential energy. If a liquid is returned to its original level, gravity neither helps nor hinders flow because of the siphon effect. This circumstance prevails in the circulatory system. Hence, P1-P2 in the Poiseuille equation excludes gravitational pressure between those points. The long neck of the giraffe, therefore, poses no impediment to blood flow in the erect posture. The giraffe has a high aortic pressure. This is not for driving the blood to its head but is for minimizing the gravitational drop of intravascular pressure and collapse of the vessels. The cerebral circulation is protected by the cerebrospinal fluid which undergoes parallel changes in pressure with posture. Other vessels in the head are less protected by connective tissue, surrounding muscles and other structures. The high aortic pressure in the giraffe is probably caused by the high total peripheral resistance of the systemic circuit due to vascular adaptations related to the overall height of the animal.     

Effects of leg venous hemodynamics on cardiovascular responses to lower body negative pressure and aging

In aged people, decreases in stroke volume and cardiac output during orthostatic challenge are less. It is suggested that the stiffness of blood vessels is greater in the elderly, blunting leg venous pooling and drop in central blood volume in an upright position. Leg venous hemodynamics plays an important role in human cardiovascular homeostasis against gravitational stress. This study aimed to clarify how aging influences the leg venous hemodynamics and its contribution to cardiovascular homeostasis during lower body negative pressure (LBNP) in humans.     

Effects of hypoproteinemia on lung microvascular protein sieving and lung lymph flow

Experiments were conducted on five chronically instrumented unanesthetized sheep to determine the effects of sustained hypoproteinemia on lung fluid balance. Plasma total protein concentration was decreased from a control value of 6.17 +/- 0.019 to 3.97 +/- 0.17 g/dl (mean +/- SE) by acute plasmapheresis and maintained at this level by chronic thoracic lymph duct drainage. We measured pulmonary arterial pressure, left atrial pressure, aortic pressure, central venous pressure, cardiac output, oncotic pressures of both plasma and lung lymph, lung lymph flow rate, and lung lymph-to-plasma ratio of total proteins and six protein fractions for both control base-line conditions and hypoproteinemia base-line conditions. Moreover, we estimated the average osmotic reflection coefficient for total proteins and the solvent drag reflection coefficients for the six protein fractions during hypoproteinemia. Hypoproteinemia caused significant decreases in lung lymph total protein concentration, lung lymph-to-plasma total protein concentration ratio, and oncotic pressures of plasma and lung lymph. There were no significant alterations in the vascular pressures, lung lymph flow rate, cardiac output, or oncotic pressure gradient. The osmotic reflection coefficient for total proteins was found to be 0.900 +/- 0.004 for hypoproteinemia conditions, which is equal to that found in a previous investigation for sheep with a normal plasma protein concentration. Our results suggest that hypoproteinemia does not alter the lung filtration coefficient nor the reflection coefficients for plasma proteins. Possible explanations for the reported increase in the lung filtration coefficient during hypoproteinemia by other investigators are also made.     

Changes in myocardial contractility and contractile proteins after four weeks of simulated [correction of simulate] weightlessness in rats

The interaction between the gravitational field, the position of the body, and the functional characteristics of the blood vessels determines the distribution of intravascular volume. In turn, this distribution determines cardiac pump function. One of the most profound circulatory changes that occurs in man during exposure to weightlessness is a cephalad redistribution of fluid caused by the lack of hydrostatic pressure in this microgravitative environment. The cephalad redistribution of fluid results in a loss of blood volume and then induces a decrease in preload. Recently, a decrease in sensitivity of arteriole to catecholamine has reported in rats of simulated weightlessness. This change in arteriole may reduce afterload. As a result, cardiovascular system may be shifted to a hypokinetic state during weightlessness condition for long-term. Echocardiographic data from astronauts during space flight showed an increase in heart rate, a 12 % decrease in stroke volume, and a 16 % decrease in left end diastolic volume. Electron-microscopic studies have shown changes in cardiac morphology in rats after exposure to microgravity for 7-12.5 days. After the COSMOS 2044 flight for 14 days, the light-microscopic studies have shown an atrophy of papillary muscles in rats left cardiac ventricle. It is not clear whether the function of atrophic myocardium is impaired. The data in three aspects as mentioned above suggest that weightlessness or simulated weightlessness may decrease the myocardial function. However, definite changes in cardiac performance have been hard to prove due to many limits. This studies were to answer two questions: Is the myocardial contractility depressed in rats subjected to simulated weightlessness for four weeks? What are the underlying mechanisms of the changing contractility?     

Noninvasive beat-to-beat stroke volume computation during acute hydrostatic pressure changes in parabolic flight

A three-element model of the cardiovascular system was used to monitor stroke volume (SV) changes during parabolic flight. Aortic blood flow was estimated from continuous arterial finger pressure and SV computed by integrating simulated aortic flow during each systole. SV was significantly higher in microgravity (microgravity) compared to 1 G whereas in hypergravity (hG), SV was significantly lower. Exponential SV transients were observed after the transitions to and from microgravity and the succeeding or preceeding hG phases. These SV transients present different time constants, which reflect two different mechanisms of cardiovascular adaptation to sudden gravitational changes. These results show that beat-to-beat computation of SV provides noninvasive information on circulatory adaptation to acute hydrostatic pressure changes.     

Effects of changes in intravascular oncotic pressure on renal responses to volume loading in the saltwater-acclimated Pekin duck (Anas platyrhynchos)

Summary The relative contributions of the intra-and extravascular compartments of the extracellular fluid (ECF) to the control of osmoregulatory renal functions were examined in saltwater-acclimated Pekin ducks. Having established steady-state diuresis and salt gland secretion by continuous infusion of 1 ml·min^-1 isotonic Krebs-Ringer-Bicarbonate (KRB) solution, 5% dextran-70 was added to the infusate for 30 min thereby confining volume expansion to the intravascular compartment. General volume expansion by isotonic KRB caused a drop in plasma osmolality by 23 mOsm·kg^-1, due to NaCl elimination by the salt glands, and decreases in hematocrit (het) and radioimmunologically measured plasma levels of Arg⁸-vasotocin (AVT) and Val⁵-angiotensin II (ANG II), whereas immunoreactivity associated with atrial natriuretic factor (ir-ANF) was increased. Adding 5% dextran-70 to the infusate left plasma osmolality and electrolytes unchanged but was followed by a further decrease in hct and a 36% increase in the plasma colloidosmotic pressure (COP) facilitating fluid shifts from the extra-to the intravascular compartment of the ECF. Plasma levels of AVT and ANG II remained unchanged, but ir-ANF rose three-fold, its increase being three times as great relative to the decrease in hct, as during general volume expansion by isotonic KRB solution. Arterial and central venous pressure measurements did not indicate changes in cardiovascular function. Hyperoncotic infusion initially induced marked antidiuresis with decreased osmolal excretion, despite a slightly elevated urine osmolality. This effects, however, was trasient and not proportional to the rise in COP, but rather seemed to be related to fluid shifts resulting from hyperoncotic loading. With tracer dilution techniques, reductions in both renal plasma flow and glomerular filtration rate were found to contribute to antidiuresis which was associated with reduced fractional water excretion. Salt gland secretion rate did not increase during hyperoncotic intravascular volume expansion but rather tended to decrease. The results of this study are in line with the idea that contributions of the interstitial fluid compartment (IFC) to volume-dependent control of osmoregulatory functions have to be considered. In the present study on saltwater-acclimated ducks, AVT, ANG II, and ir-ANF could be excluded as mediators of the adjustments in renal water and salt handling following fluid shifts due to hyperoncotic intravascular volume expansion.Abbreviations ANF atrial natriuretic factor - ir-ANF ANF-like immunoreactivity - ANG II angiotensin II - AVT arginine vasotocin - BF breathing frequency - b. w. body weight - COP colloid osmotic pressure - CVP central venous pressure - ECF extracellular fluid - ERPF effective renal plasma flow - FF filtration fraction - GFR glomerular filtration rate - IFC interstitial fluid compartment - i.v. intravenous(ly) - hct hematocrit - HR heart rate - KRB Krebs-Ringer Bicarbonate solution - MABP mean arterial blood pressure - PAH paraaminohippuric acid - SEM standard error of mean     

Evaluation of Starling forces in the equine digit

A pump-perfused extracorporeal digital preparation was used to evaluate blood flow, arterial pressure, venous pressure, isogravimetric capillary filtration coefficient, capillary pressure, and vascular compliance in six normal horses. From these data, pre- and postcapillary resistances and pre- and postcapillary resistance ratios were determined. Vascular and tissue oncotic pressures were estimated from plasma and lymph protein concentrations, respectively. By use of the collected and calculated data, tissue pressure in the digit was calculated using the Starling equation. In the isolated equine digit, isogravimetric capillary pressure averaged 36.7 mmHg, plasma and lymph oncotic pressures averaged aged 19.12 and 6.6 mmHg, respectively, interstitial fluid pressure averaged 25.6 mmHg, and the capillary filtration coefficient averaged 0.0013 ml.min-1.mm-1.100 g-1. Our results indicate that digital capillary pressure in the laterally recumbent horse is much higher than in analogous tissues in other species such as dog and human. However, the potential edemagenic effects of this high digital capillary pressure are opposed by at least two mechanisms: 1) a high tissue pressure and 2) a low microvascular surface area for fluid exchange and/or a low microvascular permeability to filtered fluid.     

Acute volume loading, atrial natriuretic peptide release and cardiac function in healthy men. Effects of beta-blockade

Release of ANP is dependent on right atrial distension and pressure, which in turn are dependent on both venous return and left ventricular function. These two latter parameters are both modulated by beta-receptors. In the present study, the effects of selective beta-blockade vs non-selective beta-blockade on hypertonic volume expansion induced changes in ANP release and systemic hemodynamics were assessed in 8 healthy normotensive male volunteers. On placebo, infusion of hypertonic saline (1200 ml of 2.5% NaCl) caused an intravascular volume expansion of 10-11%, and small non-significant increases in cardiac performance (LVEDV, SV, or CI), but it provoked a 2-fold increase in plasma ANP. Beta-blockade by either atenolol or propranolol blunted the increase in cardiac volume load (reflected by LVEDV) as compared to placebo, but did not affect the ANP response to volume expansion. The increase in ANP correlated closely with the intravascular volume expansion on placebo and to a lesser extent on beta-blockade. In healthy men, therefore, intravascular volume expansion that caused only small changes in cardiac activity, resulted in clear increases in release of ANP. Inhibition of the increase in cardiac volume load by beta-blockade did not interfere with ANP increase, suggesting a role for extra-cardiac receptors in the release of ANP or a change in the pressure/volume relationship.     

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.     

Dissociation between right atrial pressure and plasma atrial natriuretic factor following prolonged high salt intake

The influence of prolonged high salt intake on intravascular volume, right atrial pressure, plasma atrial natriuretic factor, and extra-atrial tissue (lung, kidney, and liver) COOH- and NH2-terminal atrial natriuretic factor content was investigated in normotensive rats. Despite prolonged high salt (8% NaCl) intake for 5 weeks, total intravascular volume was not impaired. However, right atrial pressure was increased by 54% (p less than 0.01) after salt loading. Although this increment in right atrial pressure should favor atrial natriuretic factor release after NaCl intake, plasma atrial natriuretic factor (COOH-terminal) concentrations markedly decreased from 97.8 +/- 27 to 38.9 +/- 8 pg/mL. Sodium and circulatory homeostasis was, however, well preserved. The lungs contained the highest levels of COOH- and NH2-terminal atrial natriuretic factor. Salt loading resulted in increased concentrations of low as well as high molecular weight atrial natriuretic factor in the lung but not in the kidney or the liver. Our study indicates a limited role of atrial natriuretic factor in adaptation to prolonged salt consumption in rats. Dissociation between right atrial pressure and plasma atrial natriuretic factor after salt intake implicates other factors regulating circulating peptide levels. Prolonged salt intake increases lung generation of atrial natriuretic factor.     

Body fluids and their distribution in experimental hypertension

The relation between blood pressure level and extracellular fluid volume and its distribution was studied in rats subjected to the following hypertensive stimuli--1K1C and 2K1C renal artery constriction, subtotal nephrectomy-salt and DOCA-salt. In all experimental groups the blood pressure increase was accompanied by increased extracellular fluid volume which was not always distributed proportionally between intravascular (PV) and interstitial (IFV) compartments. The blood pressure rise was further potentiated by plasma volume expansion so that the increased PV/IFV ratio was associated with a more pronounced hypertensive response (1K1C vs 2K1C, DOCA-salt vs subtotal nephrectomy-salt). However, adequate expansion of interstitial fluid is a necessary prerequisite for the hypertensive response. In DOCA-salt treated DI Brattleboro rats (lacking antidiuretic vasopressin action) plasma volume expansion per se was not accompanied by severe DOCA-salt hypertension. It is concluded that the expansion of both compartments of extracellular space, i.e. plasma volume and interstitial fluid volume, was necessary for a full development of severe hypertension. The expansion of only one of these compartments was accompanied by a mild blood pressure increase or blood pressure did not change significantly.     

Assessment of fluid balance in isolated sheep lungs

In this study we demonstrate the validity and utility of an isolated lung preparation developed for the study of pulmonary fluid balance. Lungs of 2- to 3-mo-old sheep were perfused in situ with autologous blood treated with indomethacin (20 micrograms/ml). Lung lymph flow (QL), uncontaminated by systemic lymph, was measured from either the efferent duct of the caudomediastinal lymph node or the thoracic duct in the superior mediastinum. Lung weight change (delta W) was measured as the opposite of the change in weight of the extracorporeal blood reservoir. A unique feature of this experimental model is the ability to assess lung fluid balance from simultaneous measurements of delta W and QL. In addition, hemodynamic and blood gas variables can be tightly controlled. Our results show that changes in QL and the lymph-to-plasma oncotic pressure ratio caused by an increase in microvascular pressure were comparable with those seen previously in intact sheep. When microvascular pressure was returned to control levels, QL fell despite a sustained increase in the amount of extravascular lung water, suggesting compartmentalization of the filtrate and/or effects of intravascular volume on lymph-driving pressure or resistance. Lymph flow was directly proportional to respiratory frequency over the range of 0-30 min-1 when the change in frequency was maintained for periods as long as 30 min. This preparation should prove useful in the study of lung fluid balance, particularly when it is desired to use interventions which are precluded or difficult in intact animals.     

The role of the blood-brain barrier in perfusion fixation of the brain for electron microscopy

Synopsis Regions of the brain vascularized by capillaries of the blood-brain barrier (BBB) type require a different fixative from regions which have capillaries of the endocrine type. Fixative with isotonic buffer gives excellent ultrastructural preservation in the BBB regions, but causes severe shrinkage of cells in the endocrine regions. This is evidently due to the difference in the permeability of the capillary walls to solutes in the fixative. In the BBB regions the less perimeable capillaries do not allow outflow of osmotically active particles to a harmful extent, whereas in the endocrine regions osmotic imbalances are created between the intra-and extracellular compartments.The diffusion rate of the fixative and the final volume of the fixed brain depend on the balance between the intravascular and interstitial hydrostatic and oncotic pressures across the capillary wall during the perfusion fixation, as those pressures regulate the amount of perfusate that will enter the parenchyma. Generally, as high a perfusion pressure as possible is recommended to obtain effective wash-out of blood and rapid diffusion of dixative into the tissue. Addition of macromolecules (2% PVP, mol. wt. 40000) into the fixative slightly improved the ultrastructural preservation in the BBB regions of the centrel nervous system.     

Body height and blood pressure regulation in humans during anti-orthostatic tilting

The hypothesis was tested that the cardiovascular changes during an upper body anti-orthostatic maneuver in humans are more pronounced in tall than in short individuals, because of the larger intravascular hydrostatic pressure gradients. In 34 males and 41 females [20-30 yr, body height (BH) = 147-206 cm], inter-individual multiple linear regression analyses adjusted for gender and body weight were conducted between changes in cardiovascular variables versus BH during tilting of the upper body from vertical to horizontal while keeping the legs horizontal. In all the subjects, tilting induced increases in stroke volume and arterial pulse pressure and a decrease in heart rate, which each correlated significantly with BH. In males (n = 51, BH = 163-206 cm), 24-h ambulatory mean arterial pressure increased significantly with BH (P = 0.004, r = 0.40, α = 0.15 mmHg/cm) so that systolic/diastolic blood pressure increased by 2/2 mmHg per 15 cm increase in BH. There was no significant correlation between mean arterial pressure and BH in females (n = 53, BH = 147-193 cm). In conclusion, a larger BH induces larger cardiovascular changes during anti-orthostatic tilting, and in males 24-h ambulatory mean arterial pressure increases with BH. The lack of a mean arterial pressure to BH correlation in females is probably because of their lower BH and greater variability in blood pressure.     

Cardiovascular, metabolic and endocrine effects of chemical sympathectomy and of adrenal demedullation in fetal sheep

A procedure in fetal sheep for causing peripheral sympathectomy by regular intravascular guanethidine sulphate administration and for causing adrenal demedullation by intragland injection of acid formalin is reported. Demedullation substantially removed adrenaline from the fetal circulation, but has a small effect only on noradrenaline. Plasma noradrenaline levels were depressed by 50% when demedullated fetuses were also subject to peripheral sympathectomy by guanethidine sulphate treatment. This provides some evidence that the paraganglia in the sheep fetus contributes to resting plasma catecholamines. Furthermore the ability of adrenal demedullation to increase markedly this pool of extra-adrenal chromaffin tissue indicates that in the fetus adrenal activity regulates the growth of these para-aortic bodies. In response to sympathectomy plasma vasopressin concentrations rose substantially, whilst adrenal demedullation caused a small rise. Demedullation and sympathectomy depressed fetal plasma glucose and elevated plasma cortisol. In both sympathectomised and adrenal demedullated fetuses resting heart rate and blood pressure was not depressed. However in those with a depleted peripheral nervous system periods of cardiovascular instability were apparent after 2-3 days of treatment with guanethidine sulphate. Hence there were regular episodes where fetal blood pressure and heart rate fell sharply followed 60-90s later by very large increases in blood pressure sustained for up to 10 min and associated with substantial production of plasma vasopressin and catecholamines. These results show that fine cardiovascular control in the fetus requires an intact sympathetic system as the endocrine system is too slow responding to effectively maintain reflex vascular control.