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The role of the hepatic transudation barrier in determining ascites volume and protein content in chronic liver disease is poorly understood. Therefore, the purpose of the present study was to characterize how chronic sinusoidal hypertension impacts hepatic transudation barrier properties and the transudation rate. The suprahepatic inferior vena cava was surgically constricted, and animals were exposed to either short-term (SVH; 2–3 wk) or long-term venous hypertension (LVH; 5–6 wk). Compared with SVH, LVH resulted in lower peritoneal fluid pressure, ascites volume, and ascites protein concentration. The transudation barrier protein reflection coefficient was significantly higher, and the transudation barrier hydraulic conductivity, transudation rate, and transudate-to-lymph protein concentration ratio were significantly lower in LVH animals compared with SVH animals. The sensitivity of transudation rates to acute changes in interstitial fluid pressures was also significantly lower in LVH animals compared with SVH animals. In contrast, there was no detectable difference in hepatic lymph flow rate or sensitivity of lymph flow to acute changes in interstitial fluid pressures between SVH and LVH animals. Taken together, these data suggest that decreased hepatic transudation barrier permeability to fluid and protein and increased reflection coefficient led to a decrease in the hepatic contribution to ascites volume. The present work, to the best of our knowledge, is the first to quantify an anti-ascites adaptation of the hepatic transudation barrier in response to chronic hepatic sinusoidal hypertension.

Lymphangions, the segments of lymphatic vessels between two adjacent lymphatic valves, actively pump lymph. Acute changes in transmural pressure and lymph flow have profound effects on lymphatic pump function in vitro. Chronic changes in pressure and flow in vivo have also been reported to lead to significant changes in lymphangion function. Because changes in pressure and flow are both cause and effect of adaptive processes, characterizing adaptation requires a more fundamental analysis of lymphatic muscle properties. Therefore, the purpose of the present work was to use an intact lymphangion isovolumetric preparation to evaluate changes in mesenteric lymphatic muscle mechanical properties and the intracellular Ca2+ in response to sustained mesenteric venous hypertension. Bovine mesenteric veins were surgically occluded to create mesenteric venous hypertension. Postnodal mesenteric lymphatic vessels from mesenteric venous hypertension (MVH; n = 6) and sham surgery (Sham; n = 6) animals were isolated and evaluated 3 days after the surgery. Spontaneously contracting MVH vessels generated end-systolic active tension and end-diastolic active tension lower than the Sham vessels. Furthermore, steady-state active tension and intracellular Ca2+ concentration levels in response to KCl stimulation were also significantly lower in MVH vessels compared with those of the Sham vessels. There was no significant difference in passive tension in lymphatic vessels from the two groups. Taken together, these results suggest that following 3 days of mesenteric venous hypertension, postnodal mesenteric lymphatic vessels adapt to become weaker pumps with decreased cytosolic Ca2+ concentration.

Lymph flow is the primary mechanism for returning interstitial fluid to the blood circulation. Currently, the adaptive response of lymphatic vessels to mesenteric venous hypertension is not known. This study sought to determine the functional responses of postnodal mesenteric lymphatic vessels. We surgically occluded bovine mesenteric veins to create mesenteric venous hypertension to elevate mesenteric lymph flow. Three days after surgery, postnodal mesenteric lymphatic vessels from mesenteric venous hypertension (MVH; n = 7) and sham surgery (Sham; n = 6) group animals were evaluated and compared. Contraction frequency (MVH: 2.98 ± 0.75 min−1; Sham: 5.42 ± 0.81 min−1) and fractional pump flow (MVH: 1.14 ± 0.30 min−1; Sham: 2.39 ± 0.32 min−1) were significantly lower in the venous occlusion group. These results indicate that postnodal mesenteric lymphatic vessels adapt to mesenteric venous hypertension by reducing intrinsic contractile activity.

The individual processes involved in interstitial fluid volume and protein regulation (microvascular filtration, lymphatic return, and interstitial storage) are relatively simple, yet their interaction is exceedingly complex. There is a notable lack of a first-order, algebraic formula that relates interstitial fluid pressure and protein to critical parameters commonly used to characterize the movement of interstitial fluid and protein. Therefore, the purpose of the present study is to develop a simple, transparent, and general algebraic approach that predicts interstitial fluid pressure ( P i) and protein concentrations ( C i) that takes into consideration all three processes. Eight standard equations characterizing fluid and protein flux were solved simultaneously to yield algebraic equations for P i and C i as functions of parameters characterizing microvascular, interstitial, and lymphatic function. Equilibrium values of P i and C i arise as balance points from the graphical intersection of transmicrovascular and lymph flows (analogous to Guyton's classical cardiac output-venous return curves). This approach goes beyond describing interstitial fluid balance in terms of conservation of mass by introducing the concept of inflow and outflow resistances. Algebraic solutions demonstrate that P i and C i result from a ratio of the microvascular filtration coefficient (1/inflow resistance) and effective lymphatic resistance (outflow resistance), and P i is unaffected by interstitial compliance. These simple algebraic solutions predict P i and C i that are consistent with reported measurements. The present work therefore presents a simple, transparent, and general balance point characterization of interstitial fluid balance resulting from the interaction of microvascular, interstitial, and lymphatic function.

The lymphatic system acts to return lower-pressured interstitial fluid to the higher-pressured veins by a complex network of vessels spanning more than three orders of magnitude in size. Lymphatic vessels consist of lymphangions, segments of vessels between two unidirectional valves, which contain smooth muscle that cyclically pumps lymph against a pressure gradient. Whereas the principles governing the optimal structure of arterial networks have been identified by variations of Murray's law, the principles governing the optimal structure of the lymphatic system have yet to be elucidated, although lymph flow can be identified as a critical parameter. The reason for this deficiency can be identified. Until recently, there has been no algebraic formula, such as Poiseuille's law, that relates lymphangion structure to its function. We therefore employed a recently developed mathematical model, based on the time-varying elastance model conventionally used to describe ventricular function, that was validated by data collected from postnodal bovine mesenteric lymphangions. From this lymphangion model, we developed a model to determine the structure of a lymphatic network that optimizes lymph flow. The model predicted that there is a lymphangion length that optimizes lymph flow and that symmetrical networks optimize lymph flow when the lymphangions downstream of a bifurcation are 1.26 times the length of the lymphangions immediately upstream. Measured lymphangion lengths (1.14 ± 0.5 cm, n = 74) were consistent with the range of predicted optimal lengths (0.1–2.1 cm). This modeling approach was possible, because it allowed a structural parameter, such as length, to be treated as a variable.

Coronary arterioles from hypercholesterolemic swine display attenuated adenosine-mediated vasodilatation that is attributable to the elimination of voltage-dependent K+ (Kv) channel stimulation. For the present study, we tested the hypotheses that exercise training would correct impaired adenosine-induced dilatation in coronary arterioles from hypercholesterolemic pigs through restoration of adenosine activation of Kv channels and that vasodilatation to the receptor-independent adenylyl cyclase activator, forskolin, would also be attenuated in arterioles from hypercholesterolemic pigs. Pigs were randomly assigned to a control (NC) or high-fat, high-cholesterol (HC) diet for 20 wk. Four weeks after the diet was initiated, pigs from both groups were assigned to exercise training (Ex; 5 days/wk for 16 wk) or sedentary (Sed) protocols, resulting in four groups of pigs: NC-Sed, NC-Ex, HC-Sed, and HC-Ex. Arterioles (∼150 μm) from both HC-Sed and HC-Ex pigs displayed impaired adenosine-mediated dilatation that was attributable to the elimination of 4-aminopyridine (4-AP; 1 mM)-sensitive Kv channel activation compared with NC counterparts. Arteriolar smooth muscle whole cell Kv currents were significantly reduced in HC-Sed compared with NC-Sed, although HC-Ex and NC-Ex did not differ. Forskolin-mediated dilatation was attenuated by 4-AP (1 mM) and in a concentration-dependent manner by tetraethylammonium (TEA; 0.1–1 mM) in NC-Sed but not HC-Sed. Further, TEA-sensitive Kv currents were diminished in cells of HC-Sed compared with NC-Sed pigs. Quantitative RT-PCR revealed similar expression levels of Kv3.1 and 3.3 in arterioles of NC-Sed and HC-Sed swine with undetectable expression of Kv1.1, 3.2, and 3.4. Taken together, these results suggest that hypercholesterolemia-mediated attenuation of adenosine-induced vasodilatation in coronary arterioles is not corrected by exercise training and is likely attributable to an impairment in the pathway coupling adenylyl cyclase with a highly TEA-sensitive Kv channel isoform(s).

Although the Boyer Commission (1998) lamented the lack of research opportunities for all undergraduates at research-extensive universities, it did not provide a feasible solution consistent with the mandate for faculty to maintain sustainable physiology research programs. The costs associated with one-on-one mentoring, and the lack of a sufficient number of faculty members to give intensive attention to undergraduate researchers, make one-on-one mentoring impractical. We therefore developed and implemented the “research-intensive community” model with the aim of aligning diverse goals of participants while simultaneously optimizing research productivity. The fundamental organizational unit is a team consisting of one graduate student and three undergraduates from different majors, supervised by a faculty member. Undergraduate workshops, Graduate Leadership Forums, and computer-mediated communication provide an infrastructure to optimize programmatic efficiency and sustain a multilevel, interdisciplinary community of scholars dedicated to research. While the model radically increases the number of undergraduates that can be supported by a single faculty member, the inherent resilience and scalability of the resulting complex adaptive system enables a research-intensive community program to evolve and grow.

To return lymph to the great veins of the neck, it must be actively pumped against a pressure gradient. Mean lymph flow in a portion of a lymphatic network has been characterized by an empirical relationship (Pin − Pout = −Pp + RLQL), where Pin − Pout is the axial pressure gradient and QL is mean lymph flow. RL and Pp are empirical parameters characterizing the effective lymphatic resistance and pump pressure, respectively. The relation of these global empirical parameters to the properties of lymphangions, the segments of a lymphatic vessel bounded by valves, has been problematic. Lymphangions have a structure like blood vessels but cyclically contract like cardiac ventricles; they are characterized by a contraction frequency ( f) and the slopes of the end-diastolic pressure-volume relationship [minimum value of resulting elastance ( Emin)] and end-systolic pressure-volume relationship [maximum value of resulting elastance ( Emax)]. Poiseuille's law provides a first-order approximation relating the pressure-flow relationship to the fundamental properties of a blood vessel. No analogous formula exists for a pumping lymphangion. We therefore derived an algebraic formula predicting lymphangion flow from fundamental physical principles and known lymphangion properties. Quantitative analysis revealed that lymph inertia and resistance to lymph flow are negligible and that lymphangions act like a series of interconnected ventricles. For a single lymphangion, Pp = Pin ( Emax − Emin)/ Emin and RL = Emax/ f. The formula was tested against a validated, realistic mathematical model of a lymphangion and found to be accurate. Predicted flows were within the range of flows measured in vitro. The present work therefore provides a general solution that makes it possible to relate fundamental lymphangion properties to lymphatic system function.

Skin blood flow increases in response to local heat due to sensorineural and nitric oxide (NO)-mediated dilation. It has been previously demonstrated that arteriolar dilation is inhibited with NO synthase (NOS) blockade. Flow, nonetheless, increases with local heat. This implies that the previously unexamined nonarteriolar responses play a significant role in modulating flow. We thus hypothesized that local heating induces capillary recruitment. We heated a portion (3 cm2) of the Pallid bat wing from 25°C to 37°C for 20 min, and measured changes in terminal feed arteriole (∼25 μm) diameter and blood velocity to calculate blood flow ( n = 8). Arteriolar dilation was reduced with NOS and sensorineural blockade using a 1% (wt/vol) NG-nitro-l-arginine methyl ester (l-NAME) and 2% (wt/vol) lidocaine solution ( n = 8). We also measured changes in the number of perfused capillaries, and the time precapillary sphincters were open with ( n = 8) and without ( n = 8) NOS plus sensorineural blockade. With heat, the total number of perfused capillaries increased 92.7 ± 17.9% ( P = 0.011), and a similar increase occurred despite NOS plus sensorineural blockade 114.4 ± 30.0% ( P = 0.014). Blockade eliminated arteriolar dilation (−4.5 ± 2.1%). With heat, the percent time precapillary sphincters remained open increased 32.3 ± 6.0% ( P = 0.0006), and this increase occurred despite NOS plus sensorineural blockade (34.1 ± 5.8%, P = 0.0004). With heat, arteriolar blood flow increased (187.2 ± 28.5%, P = 0.00003), which was significantly attenuated with NOS plus sensorineural blockade (88.6 ± 37.2%, P = 0.04). Thus, capillary recruitment is a fundamental microvascular response to local heat, independent of arteriolar dilation and the well-documented sensorineural and NOS mechanisms mediating the response to local heat.

Myocardial ischemia-reperfusion, including cardioplegic arrest (CA), has been associated with cardiac apoptosis induction. However, the time course of apoptosis activation and the trigger mechanisms are still unclear. Because apoptosis inhibition may represent a novel therapeutic strategy for long-term myocardial preservation, we sought to investigate the time course of apoptosis signal-pathway induction during CA. As to method, Sprague-Dawley rats (300–350 g) were anesthetized, intubated, and mechanically ventilated. CA was initiated by infusion of ice-cold crystalloid solution (Custodiol, 10 ml/kg) into the aortic root, and hearts were rapidly excised and stored for 0, 30, 60, and 120 min in 0.9% sodium chloride solution (28°C). In controls, no CA was initiated before removal and storage at 28°C. In another group, calcium-rich cardioplegia was used, and an additional group received a caspase-8 inhibitor before CA induction. Left ventricular cytosolic extracts were isolated and investigated for the activity of caspase-3 and -6 (effector caspases) and caspase-8 and -9 (involved in extrinsic and intrinsic pathways of apoptosis induction). Fluorometric activity assays were performed by using specific substrates. As a result, activities of all tested caspases were significantly increased immediately after CA induction compared with controls. Administration of the caspase-8 inhibitor significantly reduced activities of all caspases. With calcium-rich cardioplegia, caspase activities were significantly lower compared with low-calcium CA. Control hearts also showed an increase of caspase activities during cold-storage ischemia without CA but had significantly different time courses compared with hearts with CA. In conclusion, our data show rapid apoptosis signal-pathway induction immediately following CA exposure. Thus apoptosis signal-pathway inhibition as a potential strategy for improved myocardial preservation would have the greatest effect when applied before CA exposure.

Investigators report that local heat causes an increase in skin blood flow consisting of two phases. The first is solely sensory neural, and the second is nitric oxide mediated. We hypothesize that mechanisms behind these two phases are causally linked by shear stress. Because microvascular blood flow, endothelial shear stress, and vessel diameters cannot be measured in humans, bat wing arterioles (26.6 ± 0.3, 42.0 ± 0.4, and 58.7 ± 2.2 μm) were visualized noninvasively on a transparent heat plate via intravital microscopy. Increasing plate temperature from 25 to 37°C increased flow in all three arterial sizes (137.1 ± 0.3, 251.9 ± 0.5, and 184.3 ± 0.6%) in a biphasic manner. With heat, diameter increased in large arterioles ( n = 6) by 8.7 ± 0.03% within 6 min, medium arterioles ( n = 8) by 19.7 ± 0.5% within 4 min, and small arterioles ( n = 8) by 31.6 ± 2.2% in the first minute. Lidocaine (0.2 ml, 2% wt/vol) and NG-nitro-l-arginine methyl ester (0.2 ml, 1% wt/vol) were applied topically to arterioles (∼40 μm) to block sensory nerves, modulate shear stress, and block nitric oxide generation. Local heat caused only a 10.4 ± 5.5% increase in diameter with neural blockade ( n = 8) and only a 7.5 ± 4.1% increase in diameter when flow was reduced ( n = 8), both significantly lower than control ( P < 0.001). Diameter and flow increases were significantly reduced with NG-nitro-l-arginine methyl ester application ( P < 0.05). Our novel thermoregulatory animal model illustrates 1) regulation of shear stress, 2) a nonneural component of the first phase, and 3) a shear-mediated second phase. The time course of dilation suggests that early dilation of small arterioles increases flow and enhances second-phase dilation of the large arterioles.

Cannulation of the canine major prenodal cardiac lymphatic (MPCL) is the most common approach for the investigation of myocardial lymphatic function. However, the assumption that the MPCL drains pure cardiac lymph has been questioned. We studied variations of MPCL anatomy and investigated whether noncardiac lymph is drained by this lymphatic. After dye was injected into the lungs and left ventricular myocardium in 21 dogs, dissection of the cardiac lymphatic system yielded 3 anatomic variations. In variations 1 and 2 (81% of dogs), a mixture of cardiac and pulmonary lymph was drained via the MPCL. In variation 3 (19% of dogs) no connection was found between MPCL and pulmonary lymphatics. In variations 1 and 2, alteration of tidal volume resulted in significant changes of lymph flow rate. The pulmonary contribution to MPCL lymph flow was estimated as 34% in variation 2. We conclude that MPCL lymph may contain not only cardiac lymph but also significant pulmonary contamination. This finding should be considered in the interpretation of lymph data from cannulation of the canine MPCL.

Venomotion, spontaneous cyclic contractions of venules, was first observed in the bat wing 160 years ago. Of all the functional roles proposed since then, propulsion of blood by venomotion remains the most controversial. Common animal models that require anesthesia and surgery have failed to provide evidence for venular pumping of blood. To determine whether venomotion actively pumps blood in a minimally invasive, unanesthetized animal model, we reintroduced the batwing model. We evaluated the temporal and functional relationship between the venous contraction cycle and blood flow and luminal pressure. Furthermore, we determined the effect of inhibiting venomotion on blood flow. We found that the active venous contractions produced an increase in the blood flow and exhibited temporal vessel diameter-blood velocity and pressure relationships characteristic of a peristaltic pump. The presence of valves, a characteristic of reciprocating pumps, enhances the efficiency of the venular peristaltic pump by preventing retrograde flow. Instead of increasing blood flow by decreasing passive resistance, venular dilation with locally applied sodium nitroprusside decreased blood flow. Taken together, these observations provide evidence for active venular pumping of blood. Although strong venomotion may be unique to bats, venomotion has also been inferred from venous pressure oscillations in other animal models. The conventional paradigm of microvascular pressure and flow regulation assumes venules only act as passive resistors, a proposition that must be reevaluated in the presence of significant venomotion.

Lymphangions, the segments of lymphatic vessel between two valves, contract cyclically and actively pump, analogous to cardiac ventricles. Besides having a discernable systole and diastole, lymphangions have a relatively linear end-systolic pressure-volume relationship (with slope Emax) and a nonlinear end-diastolic pressure-volume relationship (with slope Emin). To counter increased microvascular filtration (causing increased lymphatic inlet pressure), lymphangions must respond to modest increases in transmural pressure by increasing pumping. To counter venous hypertension (causing increased lymphatic inlet and outlet pressures), lymphangions must respond to potentially large increases in transmural pressure by maintaining lymph flow. We therefore hypothesized that the nonlinear lymphangion pressure-volume relationship allows transition from a transmural pressure-dependent stroke volume to a transmural pressure-independent stroke volume as transmural pressure increases. To test this hypothesis, we applied a mathematical model based on the time-varying elastance concept typically applied to ventricles (the ratio of pressure to volume cycles periodically from a minimum, Emin, to a maximum, Emax). This model predicted that lymphangions increase stroke volume and stroke work with transmural pressure if Emin < Emax at low transmural pressures, but maintain stroke volume and stroke work if Emin= Emax at higher transmural pressures. Furthermore, at higher transmural pressures, stroke work is evenly distributed among a chain of lymphangions. Model predictions were tested by comparison to previously reported data. Model predictions were consistent with reported lymphangion properties and pressure-flow relationships of entire lymphatic systems. The nonlinear lymphangion pressure-volume relationship therefore minimizes edema resulting from both increased microvascular filtration and venous hypertension.

Estimates of the pulmonary microvascular membrane reflection coefficient (sigma) and permeability-surface area product (PS) are frequently made with the assumption that a percent change in transmicrovascular fluid flux (Jv) will be represented by an equal percent change in the lymph flow rate (QL) from a single cannulated lung lymph vessel. To test this, we measured QL in seven anesthetized dogs with the outflow end of the lymph cannula set at several heights (H) above and below the lung hilus. The left atrial pressure was then elevated to increase Jv, and QL was again measured at several H's. The percent increase in QL at elevated left atrial pressure depended on H. We used the QL data and lymph and plasma protein concentrations to estimate sigma and PS with a modified form of the Kedem and Katchalsky equations. The calculated values varied considerably with H. Our results indicate that changes in Jv are not represented by equal changes in QL. Therefore, techniques for estimating permeability that depend upon QL as an estimate of Jv may lead to erroneous estimates of sigma and PS.

The preparation for collecting lung lymph from sheep caudal mediastinal lymph node (CMN) efferent vessels is widely used to study the effects of endotoxin on lung microvascular permeability. However, there are nonpulmonary lymph vessels that drain into the CMN along with the afferent lymph vessels from the lung. Thus CMN lymph is a mixture of lymph from the lung and diaphragm lymph vessels as well as from other nonpulmonary lymph vessels. We studied the effect of 0.5–1.0 microgram/kg Escherichia coli endotoxin on the flow rates in diaphragm and CMN efferent lymph vessels (Qdi and QCMN, respectively) in unanesthetized sheep. For the time period between 2 and 5.5 h after endotoxin QCMN was increased from its base line of 7.2 +/- 4.4 (SD) to 17.3 +/- 10.6 ml/h and the lymph-to-plasma protein concentration ratio (L/PCMN) had increased from 0.68 +/- 0.11 to 0.81 +/- 0.06. During the same time period, Qdi was 4.5 +/- 3.1 ml/h compared with 1.0 +/- 0.8 ml/h at base line and the diaphragm lymph-to-plasma protein concentration ratio (L/Pdi) was 0.92 +/- 0.07 (base line = 0.74 +/- 0.15). The increases in flow rate and protein concentration were significant for each type of vessel (P less than 0.05). We conclude that the period of increased QCMN and L/PCMN after endotoxin is associated with an increase in Qdi and L/Pdi. Thus, it is difficult to determine how much of the CMN lymph response comes from the lungs and how much comes from diaphragm lymph vessels.

Control of transmicrovascular fluid exchange in the heart is of critical importance in the prevention of myocardial edema formation. To quantify the absolute values for, and the interrelationships between, the forces and flows governing fluid balance within the normal heart, the following variables were measured: arterial pressure (Pa), coronary sinus pressure (Pcs), myocardial interstitial fluid pressure (Pint), plasma protein concentration (Cp), and oncotic pressure (tau cap) along with interstitial protein concentration (CL), interstitial oncotic pressure (tau int), and left ventricular lymph flow rate (Jv). All parameters were recorded under control conditions and during graded venous pressure elevations. Control values were Pa, 125 +/- 21 mmHg; Pcs, 7.3 +/- 1.3 mmHg; Pint, 14.9 +/- 3.1 mmHg; CL/Cp, 0.82 +/- 0.12; and Jv, 7.0 +/- 2.7 ml/h. As Pcs was elevated to eight times control, Pint increased from 15 to 50 mmHg and lymph flow rose sixfold. A filtration-independent value for CL/Cp could not be obtained for total plasma protein, although a washdown CL/Cp value for beta-lipoprotein of 0.04 was obtained. Our data indicate that a large surface area of myocardial exchange vessels coupled with lymphatics of relatively low sensitivity to extravascular volume expansion produce a system that relies on a large increase in interstitial hydrostatic pressure to limit edema formation.

The liver lymphatic system plays an important role in removing excess fluid from the hepatic tissue. A complete analysis of the liver lymphatic system would be difficult. However, we used a simple circuit-analysis technique to represent the intrahepatic portion of the lymph system as a single pressure source (PL) pushing lymph through a single resistance (RL). Liver lymphatic vessels were cannulated in nine halothane-anesthetized dogs. The lymphatic vessel outflow pressure (PO) was varied by raising the outflow end of the cannula. Lymph flow from the cannula (QL) decreased linearly with PO, and we calculated RL as -delta PO/delta QL and PL as the extrapolated PO at which QL = 0. At base line, PL = 8.5 +/- 2.9 cmH2O, and RL = 0.05 +/- 0.03 cmH2O.min/microliter. After we increased inferior vena caval pressure from 5.8 +/- 2.7 to 15.2 +/- 2.5 cmH2O, PL increased significantly to 13.7 +/- 3.4 cmH2O, and RL decreased to 0.02 +/- 0.02 cmH2O.min/microliter (P less than 0.05). The results indicate that increases in QL occur because the effective pressure pushing lymph from the liver (PL) increases, and the effective resistance of the intrahepatic lymph vessels (RL) decreases.

Fluid accumulation within the lungs is a potentially fatal complication in critically ill patients. Sepsis and increased microvascular permeability are often implicated as the cause. This article shows that edema can be prevented by lowering systemic venous pressure (to permit pulmonary lymph to drain), by lowering pulmonary arterial pressure, and by maintaining plasma colloid osmotic pressure. It points out the importance of understanding the basic physiology behind pulmonary edema and therapeutic measures.

Pulmonary lymph drains into the thoracic duct and then into the systemic venous circulation. Since systemic venous pressure (SVP) must be overcome before pulmonary lymph can flow, variations in SVP may affect lymph flow rate and therefore the rate of fluid accumulation within the lung. The importance of this issue is evident when one considers the variety of clinical interventions that increase SVP and promote pulmonary edema formation, such as volume infusion, positive-pressure ventilation, and various vasoactive drug therapies. We recorded pulmonary arterial pressure (PAP), left atrial pressure (LAP), and SVP in chronic unanesthetized sheep. Occlusion balloons were placed in the left atrium and superior vena cava to control their respective pressures. The superior vena caval occluder was placed above the azygos vein so that bronchial venous pressure would not be elevated when the balloon was inflated. Three-hour experiments were carried out at various LAP levels with and without SVP being elevated to 20 mmHg. The amount of fluid present in the lung was determined by the wet-to-dry weight ratio method. At control LAP levels, no significant difference in lung fluid accumulation could be shown between animals with control and elevated SVP levels. When LAP was elevated above control a significantly greater amount of pulmonary fluid accumulated in animals with elevated SVP levels compared with those with control SVP levels. We conclude that significant excess pulmonary edema formation will occur when SVP is elevated at pulmonary microvascular pressures not normally associated with rapid fluid accumulation.