Calf venous compliance measured with head-up tilt equals supine calf compliance

Elevated calf compliance may contribute to orthostatic intolerance following space flight and bed rest. Calf venous compliance is measured conventionally with venous occulusion plethysmography in supine subjects. With this well-established technique, subjects undergo inflation of a pressure cuff around the thigh just above the knee, which increases calf venous pressure. A plethysmograph simultaneously measures calf volume elevation. Compliance equals calf volume elevation per mm Hg thigh occlusion (calf venous) pressure in relaxed legs of the supine subjects. Compliance may also be measured during stepwise head-up tilt (HUT) as calf volume elevation per mm Hg gravitational venous pressure elevation produced by HUT. However, during HUT on a tilt table with a footplate, calf muscles activate to counteract gravity: this is an obvious and natural response to gravitational force. Such muscle activation conceivably could reduce calf compliance, yet relatively little calf muscle activation occurs during HUT and orthostasis (<10% of maximal voluntary levels). Also, this activation produces minimal calf volume change (<0.3%). Therefore, we hypothesized that calf compliance measured with HUT equals that measured with supine venous occlusion.     

Venous occlusion plethysmography reduces arterial diameter and flow velocity

The measurement of peripheral blood flow by plethysmography assumes that the cuff pressure required for venous occlusion does not decrease arterial inflow. However, studies in five normal subjects suggested that calf blood flow measured with a plethysmograph was less than arterial inflow calculated from Doppler velocity measurements. We hypothesized that the pressure required for venous occlusion may have decreased arterial velocity. Further studies revealed that systolic diameter of the superficial femoral artery under a thigh cuff decreased from 7.7 +/- 0.4 to 5.6 +/- 0.7 mm (P less than 0.05) when the inflation pressure was increased from 0 to 40 mmHg. Cuff inflation to 40 mmHg also reduced mean velocity 38% in the common femoral artery and 47% in the popliteal artery. Inflation of a cuff on the arm reduced mean velocity in the radial artery 22% at 20 mmHg, 26% at 40 mmHg, and 33% at 60 mmHg. We conclude that inflation of a cuff on an extremity to low pressures for venous occlusion also caused a reduction in arterial diameter and flow velocity.     

Criteria for analysis of arterial and venous occlusion

To provide a better understanding of analysis of arterial (AO) and venous occlusion (VO) tracings, using a constant and nonpulsatile perfusion pressure system, we set up an isolated in situ dog lobe preparation perfused with autologous blood. Four signals were recorded: arterial pressure, arterial inflow rate, venous pressure, and venous outflow rate. The four signals were recorded into the memory of a computer. When flow into the lobe was abruptly stopped (AO), flow out of the lung continued unchanged for approximately 150 ms and then decreased slowly to zero. Likewise, when flow out of the lung was abruptly stopped (VO), the flow into the lung continued unchanged for approximately 130 ms and then decreased slowly to zero. A monoexponential curve was fitted to different stretches of data between 0.1 and 5 s postocclusion and extrapolated to the instant of occlusion (defined here as the instant when flow at the site of occlusion becomes zero). The results indicate that 1) the first 150 ms postocclusion should be avoided because of the oscillatory artifacts generated by the occlusion maneuver, 2) use of a long segment of postocclusion data (5 s) tends to underestimate the middle pressure gradient and overestimate the arterial and venous pressure gradients, and 3) the changes in segmental vascular resistance under different experimental conditions were found to be unaffected by the criteria of analysis. Analysis of the postocclusion (AO and VO) tracings was found to be most compatible with the double-occlusion capillary pressure by fitting a stretch of data between 0.2 and 2.5 s postocclusion and extrapolating back to the instant when flow becomes zero at the site of occlusion but no earlier.     

Systemic venous circulation. Waves propagating on a windkessel: relation of arterial and venous windkessels to systemic vascular resistance

Compared with arterial hemodynamics, there has been relatively little study of venous hemodynamics. We propose that the venous system behaves just like the arterial system: waves propagate on a time-varying reservoir, the windkessel, which functions as the reverse of the arterial windkessel. During later diastole, pressure increases exponentially to approach an asymptotic value as inflow continues in the absence of outflow. Our study in eight open-chest dogs showed that windkessel-related arterial resistance was approximately 62% of total systemic vascular resistance, whereas windkessel-related venous resistance was only approximately 7%. Total venous compliance was found to be 21 times larger than arterial compliance (n = 3). Inferior vena caval compliance (0.32 +/- 0.015 ml x mmHg(-1) x kg(-1); mean +/- SE) was approximately 14 times the aortic compliance (0.023 +/- 0.002 ml x mmHg(-1) x kg(-1); n = 8). Despite greater venous compliance, the variation in venous windkessel volume (i.e., compliance x windkessel pulse pressure; 7.8 +/- 1.1 ml) was only approximately 32% of the variation in aortic windkessel volume (24.3 +/- 2.9 ml) because of the larger arterial pressure variation. In addition, and contrary to previous understanding, waves generated by the right heart propagated upstream as far as the femoral vein, but excellent proportionality between the excess pressure and venous outflow suggests that no reflected waves returned to the right atrium. Thus the venous windkessel model not only successfully accounts for variations in the venous pressure and flow waveforms but also, in combination with the arterial windkessel, provides a coherent view of the systemic circulation.     

Comparative effects of vasodilator drugs on flow distribution and venous return

Systemic vascular effects of hydralazine, prazosin, captopril, and nifedipine were studied in 115 anesthetized dogs. Blood flow (Q) and right atrial pressure (Pra) were independently controlled by a right heart bypass. Transient changes in central blood volume after an acute reduction in Pra at a constant Q showed that blood was draining from two vascular compartments with different time constants, one fast and the other slow. At three dose levels producing comparable reductions in systemic arterial pressure (30-40% at the highest dose), these drugs had different effects on flow distribution and venous return. Hydralazine and prazosin had parallel and balanced effects on arterial resistance of the two vascular compartments, and flow distribution was unaltered. Captopril preferentially reduced arterial resistance of the compartment with a slow time constant for venous return (-26 +/- 6%, -30 +/- 6%, -50 +/- 5% at 0.02, 0.10, and 0.50 mg X kg-1 X h-1, respectively; means +/- SEM) without altering arterial resistance of the fast time-constant compartment. Blood flow to the slow time-constant compartment was increased 43 +/- 14% at the highest dose, and central blood volume was reduced 108 +/- 15 mL. In contrast, nifedipine had a balanced effect on arterial resistance with the lowest dose (0.025 mg/kg) but caused a preferential reduction in arterial resistance of the fast time-constant compartment at higher doses (-38 +/- 4% and -55 +/- 2% at 0.05 and 0.10 mg/kg, respectively). Blood flow to the slow time-constant compartment was reduced 36 +/- 5% at the highest dose of nifedipine, and central blood volume was increased 66 +/- 12 mL. Total systemic venous compliance was unaltered or slightly reduced by each of the four drugs. These results add further evidence to the hypothesis that peripheral blood flow distribution is a major determinant of venous return to the heart.     

Localization of the sites of pulmonary vasomotion by use of arterial and venous occlusion

In this study, we present a new approach for using the pressure vs. time data obtained after various vascular occlusion maneuvers in pump-perfused lungs to gain insight into the longitudinal distribution of vascular resistance with respect to vascular compliance. Occlusion data were obtained from isolated dog lung lobes under normal control conditions, during hypoxia, and during histamine or serotonin infusion. The data used in the analysis include the slope of the arterial pressure curve and the zero time intercept of the extrapolated venous pressure curve after venous occlusion, the equilibrium pressure after simultaneous occlusion of both the arterial inflow and venous outflow, and the area bounded by equilibrium pressure and the arterial pressure curve after arterial occlusion. We analyzed these data by use of a compartmental model in which the vascular bed is represented by three parallel compliances separated by two series resistances, and each of the three compliances and the two resistances can be identified. To interpret the model parameters, we view the large arteries and veins as mainly compliance vessels and the small arteries and veins as mainly resistance vessels. The capillary bed is viewed as having a high compliance, and any capillary resistance is included in the two series resistances. With this view in mind, the results are consistent with the major response to serotonin infusion being constriction of large and small arteries (a decrease in arterial compliance and an increase in arterial resistance), the major response to histamine infusion being constriction of small and large veins (an increase in venous resistance and a decrease in venous compliance), and the major response to hypoxia being constriction of the small arteries (an increase in arterial resistance). The results suggest that this approach may have utility for evaluation of the sites of action of pulmonary vasomotor stimuli.     

Effects of spaceflight on human calf hemodynamics.

Chronic microgravity may modify adaptations of the leg circulation to gravitational pressures. We measured resting calf compliance and blood flow with venous occlusion plethysmography, and arterial blood pressure with sphygmomanometry, in seven subjects before, during, and after spaceflight. Calf vascular resistance equaled mean arterial pressure divided by calf flow. Compliance equaled the slope of the calf volume change and venous occlusion pressure relationship for thigh cuff pressures of 20, 40, 60, and 80 mmHg held for 1, 2, 3, and 4 min, respectively, with 1-min breaks between occlusions. Calf blood flow decreased 41% in microgravity (to 1.15 +/- 0.16 ml x 100 ml(-1) x min(-1)) relative to 1-G supine conditions (1.94 +/- 0.19 ml x 100 ml(-1) x min(-1), P = 0.01), and arterial pressure tended to increase (P = 0.05), such that calf vascular resistance doubled in microgravity (preflight: 43 +/- 4 units; in-flight: 83 +/- 13 units; P < 0.001) yet returned to preflight levels after flight. Calf compliance remained unchanged in microgravity but tended to increase during the first week postflight (P > 0.2). Calf vasoconstriction in microgravity qualitatively agrees with the "upright set-point" hypothesis: the circulation seeks conditions approximating upright posture on Earth. No calf hemodynamic result exhibited obvious mechanistic implications for postflight orthostatic intolerance.     

Reference cardiopulmonary values in normal dogs

The purpose of this project was to collate canine cardiopulmonary measurements from published and unpublished studies in our laboratory in 97 instrumented, unsedated, normovolemic dogs. Body weight; arterial and mixed-venous pH and blood gases; mean arterial, pulmonary arterial, pulmonary artery occlusion, and central venous blood pressures; cardiac output; heart rate; hemoglobin; and core temperature were measured. Body surface area; bicarbonate concentration; base deficit; cardiac index; stroke volume index, systemic and pulmonary vascular resistance indices; left and right cardiac work indices; alveolar partial pressure of oxygen (pO2) ; alveolar-arterial pO2 gradient (A-apO2); arterial, mixed-venous, and pulmonary capillary oxygen content; oxygen delivery; oxygen consumption; oxygen extraction; venous admixture; arterial and mixed-venous blood CO2 contents; and CO2 production were calculated. In the 97 normal, resting dogs, mean arterial and mixed-venous pH were 7.38 and 7.36, respectively; partial pressure of carbon dioxide (pCO2), 40.2 and 44.1 mm Hg, respectively; base-deficit, -2.1 and -1.9 mEq/liter, respectively; pO2, 99.5 and 49.3 mm Hg, respectively; oxygen content, 17.8 and 14.2 ml/dl, respectively; A-a pO2 was 6.3 mm Hg; and venous admixture was 3.6%. The mean arterial blood pressure (ABPm), mean pulmonary arterial blood pressure (PAPm), pulmonary artery occlusion pressure (PAOP) were 103, 14, and 5.5 mm Hg, respectively; heart rate was 87 beats/min; cardiac index (CI) was 4.42 liters/min/m2; systemic and pulmonary vascular resistances were 1931 and 194 dynes.sec.cm-5, respectively; oxygen delivery, consumption and extraction were 790 and 164 ml/min/m2 and 20.5%, respectively. This study represents a collation of cardiopulmonary values obtained from a large number of dogs (97) from a single laboratory using the same measurement techniques.     

Pulmonary vascular compliance and viscoelasticity

When dog lung lobes were perfused at constant arterial inflow rate, occlusion of the venous outflow (VO) produced a rapid jump in venous pressure (Pv) followed by a slower rise in both arterial pressure (Pa) and Pv. During the slow rise Pa(t) and Pv(t) tended to converge and become concave upward as the volume of blood in the lungs increased. We compared the dynamic vascular volume vs. pressure curves obtained after VO with the static volume vs. pressure curves obtained by dye dilution. The slope of the static curve (the static compliance, Cst) was always larger than the slope of the dynamic curve (the dynamic compliance, Cdyn). In addition, the Cdyn decreased with increasing blood flow rate. When venous occlusion (VO) was followed after a short time interval by arterial occlusion (AO) such that the lobe was isovolumic, both Pa and Pv fell with time to a level that was below either pressure at the instant of AO. In an attempt to explain these observations a compartmental model was constructed in which the hemodynamic resistance and vascular compliance were volume dependent and the vessel walls were viscoelastic. These features of the model could account for the convergence and upward concavity of the Pa and Pv curves after VO and the pressure relaxation in the isovolumic state after AO, respectively. According to the model analysis, the difference between Cst and Cdyn and the flow dependence of Cdyn are due to wall viscosity and volume dependence of compliance, respectively. Model analysis also suggested ways of evaluating changes in the viscoelasticity of the lobar vascular bed. Hypoxic vasoconstriction that increased total vascular resistance also decreased Cst and Cdyn and appeared to increase the vessel wall viscosity.     

Arterial blood ketone body ratio as an indicator of the no-return point in hepatic inflow occlusion without venous shunt in dogs

The effects of hepatic inflow occlusion without venous shunt on the viability of the liver were investigated with respect to liver energy metabolism in dogs, subjected to portal triad cross-clamping (Pringle's maneuver) for 10, 30 and 60 min. The concentrations of ketone bodies and the arterial blood ketone body ratio (KBR) were decreased markedly by hepatic inflow occlusion, but recovered upon recirculation. The initial velocity of KBR recovery was 0.150/min after 10-min clamping, 0.140/min after 30-min clamping and 0.032/min after 60-min clamping. KBR recovery was delayed when hepatic inflow occlusion exceeded 30 min, which indicates that hepatic inflow occlusion for 60 min causes severe inhibition of energy generation in liver mitochondria. These findings indicate that the safety period for hepatic inflow occlusion without venous shunt is between 30 and 60 min in dogs, and that mortality can be predicted by measuring the initial velocity of KBR recovery upon recirculation.     

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.     

Effective vascular compliance of dogs in acute heart failure.

Effective vascular compliance was measured repeatedly in dogs without circulatory arrest utilizing a closed-circuit venous bypass system and constant cardiac output. Compliance, determined by the delta V/delta P relationship at the end of a 1-min infusion of 5% of the circulating volume into the inferior vena cava, was independent of the initial venous pressure, total circulating volume and systemic arterial pressure. It remained constant over a 3 h experimental period at 1.55 plus or minus 0.05 ml (mm Hg)-1-kb-1 body weight. Elevation of mean left atrial pressure and mean pulmonary arterial pressure by gradual aortic constriction was associated with a large and significant reduction in vascular compliance to a value of 1.14 plus or minus 0.06 ml (mm Hg)-1-kg-1 after 2 h. This reduction was independent of the initial venous pressure and total circulating volume but was associated with the changes in left atrial and pulmonary artery pressures and an increase in plasma catecholamine concentrations. The mechanism responsible for the reduction in effective compliance is not clear from the present experiments. Increased circulating catecholamines and sympathetic nerve traffic resulting from baro- and volume receptor stimulation in the vascular tree may be the causative mechanism.     

Venous cuff pressures from 30 mmHg to diastolic pressure are recommended to measure arterial inflow by plethysmography.

Venous occlusion strain gauge plethysmography (VOP) is based on the assumption that the veins are occluded and arterial inflow is undisturbed by the venous cuff pressure. Literature is not clear concerning the pressure that should be used. The purpose of this study was to determine the optimal venous occlusion pressure at which the highest arterial inflow is achieved in the forearm, calf, and leg by using VOP. We hypothesized that, for each limb segment, an optimal (range of) venous cuff pressure can be determined. Arterial inflow in each limb segment was measured in nine healthy individuals by VOP by using pressures ranging from 10 mmHg up to diastolic blood pressure. Arterial inflows were similar at cuff pressures between 30 and 60 mmHg for the forearm, leg, and calf. Arterial inflow in the forearm was significantly lower at 10 mmHg compared with the other cuff pressures. In addition, arterial inflows at 20 mmHg tended to be lower in each limb segment than flow at higher cuff pressures. In conclusion, no single optimum venous cuff pressure, at which a highest arterial inflow is achieved, exists, but rather a range of optimum cuff pressures leading to a similar arterial inflow. Venous cuff pressures ranging from 30 mmHg up to diastolic blood pressure are recommended to measure arterial inflow by VOP.     

Central transmural venous pressure and plasma arginine vasopressin during negative pressure breathing in man

After overnight food and fluid restriction, 8 normal healthy males were examined in the upright sitting position before (prestudy), during and after (recovery) negative pressure breathing (NPB) with a pressure (P = difference between airway pressure and barometric pressure) of -9.6 +/- 0.5 to -10.4 +/- 0.4 mm Hg for 30 min. Plasma arginine vasopressin (pAVP) did not change significantly comparing prestudy with 10 and 30 min of NPB or comparing recovery with NPB at 10, 20 or 30 min. However, at 20 min of NBP, pAVP was slightly lower than at prestudy (p less than 0.05). Central venous pressure (CVP) decreased significantly during NPB, and central transmural venous pressure (CVP-P) increased significantly from -0.9 +/- 0.8 mm Hg to 3.8 +/- 0.7, 4.3 +/- 0.7 and 4.5 +/- 0.6 mm Hg (p less than 0.001) after 10, 20 and 30 min, respectively. Systolic, diastolic and mean arterial pressure and heart rate did not change significantly during NPB. Diuresis, natriuresis, kaliuresis, osmotic excretion and clearance were slightly increased during the recovery hour after NPB compared to prestudy, while urine osmolality decreased during NPB (n = 6). However, none of these changes were significant. There was no significant correlation between CVP-P and pAVP. In conclusion, -10 mm Hg NPB for 30 min in upright sitting subjects did not change pAVP consistently, while CVP-P was significantly increased and HR and arterial pressures were unchanged. This lends support to the concept that arterial baroreceptors and not cardiopulmonary mechanoreceptors are of importance in regulating AVP secretion in man.     

Effects of hemorrhage and hepatic nerve stimulation on venous compliance and unstressed volume in cat liver

Intrahepatic blood volume-pressure relationships were studied using plethysmography to measure hepatic blood volume and a hepatic venous long-circuit to control intrahepatic pressure. In cats anesthetized with pentobarbital or with ketamine-chloralose, hemorrhage (to reduce hepatic blood flow to 60% of control) caused marked reductions in hepatic blood volume and intrahepatic pressure but did not significantly change hepatic blood volume-pressure relationships. We were unable to demonstrate an active reflex venous response to hemorrhage in these preparations, although a large passive response occurred. The volume-pressure relationships in innervated livers were different from those in denervated livers: apparent venous compliance was much greater and apparent unstressed volume was zero or negative. Hepatic nerve stimulation in denervated livers caused a marked decrease in hepatic blood volume at low intrahepatic pressures but failed to alter hepatic blood volumes at high intrahepatic pressures (15 mmHg) (1 mmHg = 133.3 Pa). This resulted in large apparent compliances and apparently negative unstressed volumes, as seen in the innervated livers. Thus blood volume-pressure relationships in innervated livers may not give valid measurements of compliance and unstressed volume. A remarkable feature in all these experiments was the linearity of the relationship between hepatic blood volume and intrahepatic pressure. Exudation of fluid begins at higher intrahepatic pressures in innervated compared with denervated livers.     

Blood flow measurement from plethysmographic pulse waves without venous occlusion

An air plethysmograph with a sensitive phototransducer was constructed so that plethysmographic volume-change pulsations could be displayed in detail without using venous occlusion. Software was developed to allow analysis of the pulses using a modification of the backward extrapolation technique. This allowed calculation of the forward arterial blood flow and noninvasive derivation of the resting arterial flow waveform. There is good reproducibility of the technique, with 8% variability between pairs of measurements at rest and 4% variability after hand exercise. Direct comparison made with blood flows measured by venous occlusion plethysmography showed good average agreement. The mean blood flow for venous occlusion (rest and exercise) was 0.76 +/- 0.07 mL/beat (mean +/- SEM), and the mean blood flow for backward extrapolation (rest and exercise) was 0.74 +/- 0.09 mL/beat (mean +/- SEM). This corresponds to 3.86 +/- 0.36 mL/min/100 mL and 3.76 +/- 0.46 mL/min/100 mL, respectively. Important assumptions when using this method are that venous return is constant and that forward arterial flow is over before the end of the cardiac cycle.     

Central venous pressure and plasma arginine vasopressin during water immersion in man

The influence of increased central venous pressure (CVP) on the plasma concentration of arginine vasopressin (pAVP) was examined in 7 healthy males subjected to water immersion (WI) up to the neck following overnight food- and fluid restriction. During WI the subject sat upright in a pool (water temperature = 35.0 degrees C) for 6 h. In control experiments the subject assumed the same position outside the pool wearing a water perfused garment (water temperature = 34.6 degrees C). CVP increased markedly during WI and after 20 min of immersion it attained a level which was significantly higher than the control value (10.9 +/- 1.5 (mean +/- SE) vs. 2.2 +/- 1.3 mm Hg, p less than 0.01). This increase was sustained throughout the 6 h WI period. Simultaneously, after 20 min pAVP during WI was significantly lower than control values (1.8 +/- 0.3 vs. 2.2 +/- 0.3 pg X ml-1, p less than 0.05) and sustained throughout WI. Systolic arterial pressure increased significantly by 7-10 mm Hg (p less than 0.05) after 2 h of WI, while diastolic arterial pressure was unchanged. Heart rate was decreased by 10 bpm throughout immersion. There was no change in plasma osmolality when comparing control with immersion. A pronounced osmotic diuresis, natriuresis and kaliuresis occurred during WI, counteracting an acute significant increase in plasma volume of 6.5 +/- 1.9% (P less than 0.01 within 20 min of immersion). We conclude that an increase in CVP due to WI is accompanied by suppressed pAVP.     

Muscle blood flow response to contraction: influence of venous pressure.

The skeletal muscle pump is thought to be at least partially responsible for the immediate muscle hyperemia seen with exercise. We hypothesized that increases in venous pressure within the muscle would enhance the effectiveness of the muscle pump and yield greater postcontraction hyperemia. In nine anesthetized beagle dogs, arterial inflow and venous outflow of a single hindlimb were measured with ultrasonic transit-time flow probes in response to 1-s tetanic contractions evoked by electrical stimulation of the sciatic nerve. Venous pressure in the hindlimb was manipulated by tilting the upright dogs to a 30 degrees angle in the head-up or head-down positions. The volume of venous blood expelled during contractions was 2.2 +/- 0.2, 1.6 +/- 0.2, and 1.4 +/- 0.2 ml with the head-up, horizontal, and head-down positions, respectively. Although altering hindlimb venous pressure influenced venous expulsion during contraction, the increase in arterial inflow was similar regardless of position. Moreover, the volume of blood expelled was a small fraction of the cumulative arterial volume after the contraction. These results suggest that the muscle pump is not a major contributor to the hyperemic response to skeletal muscle contraction.     

Repeated pregnancies (multiparity) increases venous tone and reduces compliance

In humans, multiparity (repeated pregnancy) is associated with increased risk of cardiovascular disease. In rats, multiparity increases the pressor response to phenylephrine and to acute stress, due in part to changes in tone of the splanchnic arterial vasculature. Given that the venous system also changes during pregnancy, we studied the effects of multiparity on venous tone and compliance. Cardiovascular responses to volume loading (2 ml/100 g body wt), and mean circulatory filling pressure (MCFP, an index of venomotor tone) were measured in conscious, repeatedly bred (RB), and age-matched virgin rats. In addition, passive compliance and venous reactivity of isolated mesenteric veins were measured by pressure myography. There was a greater increase in mean arterial pressure after volume loading in RB rats (+7.2 +/- 2.5 mmHg, n = 8) than virgin rats (-1.4 +/- 1.7 mmHg, n = 7) (P < 0.05). The increase in MCFP in response to norepinephrine (NE) was also greater in RB rats [half maximal effective dose (ED(50)) 3.1 +/- 0.5 nmol.kg(-1).min(-1), n = 6] than virgins (ED(50): 12.1 +/- 2.7 nmol.kg(-1).min(-1), n = 6) (P < 0.05). Pressure-induced changes in passive diameter were lower in isolated mesenteric veins from RB rats (29.3 +/- 1.8 microm/mmHg, n = 6) than from virgins (36.9 +/- 1.3 microm/mmHg, n = 6) (P < 0.05). Venous reactivity to NE in isolated veins was also greater in RB rats (EC(50): 2.68 +/- 0.37x10(-8) M, n = 5) than virgins (EC(50): 4.67 +/- 0.93 x 10(-8) M, n = 8). We conclude that repeated pregnancy induces a long-term reduction in splanchnic venous compliance and augments splanchnic venous reactivity and sympathetic tonic control of total body venous tone. This compromises the ability of the capacitance (venous) system to accommodate volume overloads and to buffer changes in cardiac preload.     

Effect of portal hypertension on splenic blood flow,intrasplenic extravasation and systemic blood pressure

We have previously shown that intrasplenic fluid extravasation is important in controlling blood volume. We proposed that, because the splenic vein flows in the portal vein, portal hypertension would increase splenic venous pressure and thus increase intrasplenic microvascular pressure and fluid extravasation. Given that the rat spleen has no capacity to store/release blood, intrasplenic fluid extravasation can be estimated by measuring the difference between splenic arterial inflow and venous outflow. In anesthetized rats, partial ligation of the portal vein rostral to the junction with the splenic vein caused portal venous pressure to rise from 4.5 +/- 0.5 to 12.0 +/- 0.9 mmHg (n = 6); there was no change in portal venous pressure downstream of the ligation, although blood flow in the liver fell. Splenic arterial flow did not change, but the arteriovenous flow differential increased from 0.8 +/- 0.3 to 1.2 +/- 0.1 ml/min (n = 6), and splenic venous hematocrit rose. Mean arterial pressure fell (101 +/- 5.5 to 95 +/- 4 mmHg). Splenic afferent nerve activity increased (5.6 +/- 0.9 to 16.2 +/- 0.7 spikes/s, n = 5). Contrary to our hypothesis, partial ligation of the portal vein caudal to the junction with the splenic vein (same increase in portal venous pressure but no increase in splenic venous pressure) also caused the splenic arteriovenous flow differential to increase (0.6 +/- 0.1 to 1.0 +/- 0.2 ml/min; n = 8). The increase in intrasplenic fluid efflux and the fall in mean arterial pressure after rostral portal vein ligation were abolished by splenic denervation. We propose there to be an intestinal/hepatic/splenic reflex pathway, through which is mediated the changes in intrasplenic extravasation and systemic blood pressure observed during portal hypertension.