Lymphatic transport of pericardial effusate in sheep

In this report, we quantified fluid loss from the pericardial cavity during simulated saline effusions and determined what proportion of this loss occurred through lymphatics. Fifty or 100 ml of Ringers lactate solution [containing 0.5% sheep albumin and (131)I-human serum albumin (HSA)] was injected into the pericardial cavity of sheep. Pericardial pressures, systemic arterial pressures, and plasma/pericardial fluid concentrations of the radioactive tracer were measured. Lymph transport of pericardial fluid was estimated from the plasma recovery of tracer using a mass balance equation. Plasma recoveries were corrected for tracer loss using a coefficient of elimination calculated from the plasma disappearance curve of intravenously administered (125)I-HSA. Over 4 h, 27.6 +/- 4.9 (+/-SE) and 36.7 +/- 4.2 ml were lost from the pericardial cavity in the 50- and 100-ml effusion series, respectively, of which 5.2 +/- 0.8 (20.2 +/- 3.8% of volume lost) and 7.7 +/- 1.6 ml (21.5 +/- 3.3% of volume lost) could be attributed to lymphatic transport. We conclude that lymphatic transport is one of the factors that contribute to pericardial "reserve" function by helping to restore pericardial fluid volume to resting levels.     

Pericardial fluid absorption into lymphatic vessels in sheep

We estimated the volumetric lymphatic clearance rate of pericardial fluid in sheep. In the first group of studies, 125I-human serum albumin (HSA) was injected into the pericardial cavity and after 4 h, various lymph nodes and tissues were excised and counted for radioactivity. Several lymphatic drainage pathways existed defined by elevated 125I-HSA in the middle and caudal mediastinal, intercostal, and the cardiac nodes located near the root of the aorta. In a second group of experiments, the plasma recovery of intrapericardially administered tracer was compared in sheep with intact lymphatics and in animals in which thoracic duct lymph was diverted and other relevant lymphatics ligated. The 4-h plasma recoveries were reduced significantly from an average of 12.2 +/- 3. 4% injected dose in the lymph-intact group to 3.0 +/- 1.1% injected dose in the diverted/ligated group (an inhibition of approximately 75%). In order to estimate the volumetric clearance of pericardial fluid through lymphatics in conscious sheep, 125I-HSA was administered into the pericardial cavity to serve as the lymph flow marker. 131I-HSA was injected intravenously to permit calculation of plasma tracer loss and tracer recirculation into lymphatics. From mass balance equations, total pericardial clearance into lymphatics averaged 1.50 +/- 0.43 ml/h or approximately 1.13 ml/h if one was to assume that the average 25% recovered plasma tracer in lymph diverted/ligated animals was due to nonlymphatic transport. In conclusion, mediastinal lymphatic pathways remove a volume equivalent to the pericardial volume (8.1 +/- 1.1 ml) every 5.4 to 7. 2 h.     

Comparison between pore model predictions and sheep lung fluid and protein transport

The multiple pore model of T. R. Harris and R. J. Roselli (1981, J. Appl. Physiol: Respir. Environ. Exercise Physiol. 50, 1-14), was used to simulate lung lymph flow and protein transport at various levels of microvascular pressure. Response of the three-pore structure determined in that study was found to be in excellent agreement with the experimental sheep lung lymph measurements of R. E. Parker, R. J. Roselli, T. R. Harris, and K. L. Brigham (1981, Circ. Res. 49, 1164-1172). Optimal one- and two-pore model structures were also determined and their responses compared with the experimental data. The two-pore model behavior was found to be very similar to that of the three-pore model but a homoporous model which reproduced the experimental findings could not be found. All simulations required interstitial fluid pressure to increase as microvascular pressure was elevated. True filtration-independent conditions could only be simulated when lung vascular pressures were raised to physiologically unrealistic values.     

Properties of the lymphatic cerebrospinal fluid transport system in the rat: impact of elevated intracranial pressure

Previous studies suggested that a major portion of cerebrospinal fluid (CSF) is absorbed by extracranial lymphatics located in the olfactory turbinates. The objective of this study was to determine the impact of elevated intracranial pressure (ICP) on downstream cervical lymphatic pressures in the rat. Pressures were measured in the deep cervical lymph nodes using a servo-null micropressure system. A catheter was placed in a lateral ventricle and fluid was infused from a reservoir at defined ICPs. When Ringer's solution was infused, elevations of ICP from 10 to 50 cm H2O resulted on average in a reduction of diastolic cervical node pressures. In contrast, when a diluted plasma solution (80% plasma in Ringer's) was infused, downstream diastolic lymphatic pressures increased as ICP was elevated to 50 cm H2O. These data are consistent with the view that much of the CSF-derived water that convects into the lymphatics is absorbed into the ethmoidal or nodal blood vessels. This study supports the concept of fluid continuity between the subarachnoid space and extracranial lymphatics and suggests that this loss of CSF-derived water may act as a safety mechanism to reduce the volume load to the downstream lymphatic vessels.     

Tissue fluid pressure, lymph pressure, and fluid transport in rat intestinal villi

Tissue fluid pressure (Pt) and lymph pressure (Pl) as well as fluid transport between initial lymphatics and tissue matrix were determined in the villi of the jejunum in vivo and in vitro. When the intestine was absorbing fluid, free tissue fluid as a micro pool appeared in the villi. Pt and Pl were 2.4 +/- 0.7 and 2.9 +/- 0.8 mm Hg (mean +/- SE), respectively, in the villi in vivo (26 villi of 5 rats) or 0.8 +/- 0.4 and 1.2 +/- 0.5 mm Hg, respectively, in the villi in vitro (30 villi of 5 rats). Pl was significantly (P less than 0.01) higher than Pt. When Evans blue in saline was continuously infused into an initial lymphatic, dye rapidly leaked out into the tissue matrix, but when it was infused into the free tissue fluid, dye did not enter the lymphatics but leaked out of the epithelial layer, apparently due to low hydraulic conductance of the tissue matrix to fluid transport in this direction. Furthermore, in the villi with fat absorption, a retrograde flow of chylous lymph out of the villous tips always occurred, indicating that there are large pores at the villous tips to allow free passage of fluid and chylomicrons. From these findings and other evidences, it is inferred that during fluid absorption a fraction of the lymph may be formed by the transport of the luminal fluid directly into the terminal end of the initial lymphatics via large pores at the villous tips presumably by inhibition of the tissue matrix or by lymphatic suction or both.     

Assessment of pericardial constraint: the relation between right ventricular filling pressure and pericardial pressure measured after pericardiocentesis

Experimental studies have shown that right ventricular filling pressure (that is, intracavitary diastolic pressure) approximates pericardial surface pressure but, in many patients after removal of pericardial effusion, right ventricular filling pressure has been found to markedly exceed pericardial pressure recorded by an open catheter. The aim of this study was to determine whether this apparent contradiction was related to the technique of pericardial pressure measurement. Nine patients with chronic pericardial effusion were studied and, although these pressures diverged to varying degrees in individual patients, the previous observation was confirmed in that, although initially similar, right ventricular filling pressure and pericardial pressure (measured by means of an open catheter) tended to diverge during removal of the effusate; when the evacuation was as complete as possible pericardial pressure was 2.1 +/- 1.0 (mean +/- SE), while right ventricular filling pressure was 8.7 +/- 1.7 mm Hg (p less than 0.01). In six open chest, anesthetized, volume-loaded dogs with pericardial effusion (50 ml), right ventricular filling pressure and pericardial pressures measured with both open catheter and flat balloon were all equal. With decreasing volume of pericardial fluid, right ventricular filling pressure and pericardial pressure (by catheter) diverged as had been observed in patients. However, pericardial pressure (balloon) continued to be equal to right ventricular filling pressure. (With 0 ml in the pericardium, right ventricular filling pressure = 12.9 +/- 0.9 mm Hg, pericardial pressure [catheter] = 1.4 +/- 1.9 mm Hg and pericardial pressure [balloon] = 12.4 +/- 1.5 mm Hg.) Thus, these observations support the use of right ventricular filling pressure as an estimate of pericardial constraint in patients.     

Mechanical forces and lymphatic transport

This review examines the current understanding of how the lymphatic vessel network can optimize lymph flow in response to various mechanical forces. Lymphatics are organized as a vascular tree, with blind-ended initial lymphatics, precollectors, prenodal collecting lymphatics, lymph nodes, postnodal collecting lymphatics and the larger trunks (thoracic duct and right lymph duct) that connect to the subclavian veins. The formation of lymph from interstitial fluid depends heavily on oscillating pressure gradients to drive fluid into initial lymphatics. Collecting lymphatics are segmented vessels with unidirectional valves, with each segment, called a lymphangion, possessing an intrinsic pumping mechanism. The lymphangions propel lymph forward against a hydrostatic pressure gradient. Fluid is returned to the central circulation both at lymph nodes and via the larger lymphatic trunks. Several recent developments are discussed, including evidence for the active role of endothelial cells in lymph formation; recent developments on how inflow pressure, outflow pressure, and shear stress affect the pump function of the lymphangion; lymphatic valve gating mechanisms; collecting lymphatic permeability; and current interpretations of the molecular mechanisms within lymphatic endothelial cells and smooth muscle. An improved understanding of the physiological mechanisms by which lymphatic vessels sense mechanical stimuli, integrate the information, and generate the appropriate response is key for determining the pathogenesis of lymphatic insufficiency and developing treatments for lymphedema.     

Relationship between red cell sodium transport, blood pressure, and family history of hypertension

Numerous studies have demonstrated that Na+/Li+ countertransport is increased in erythrocytes from hypertensive patients. Since Na+/Li+ countertransport is conducted through the physiologically occurring Na+/Na+ exchange, we studied the latter pathway in 20 subjects with essential hypertension and 20 normotensive subjects matched for age and sex. Ten hypertensives and six normotensives had a positive family history of hypertension. Ouabain (0.1 mM) and furosemide (0.1 mM) were used to assess the active Na+ efflux and Na+-K+-Cl- pathway. There was no significant difference between hypertensive and normotensive subjects in any of the three pathways studied. Among the 16 subjects with a positive family history of hypertension, the mean value for external Na+-dependent Na+/Na+ exchange was significantly higher than in 24 subjects with no family history of hypertension (0.0457 +/- 0.0337 versus 0.0283 +/- 0.0202; P less than 0.05). This study suggests that an inherited membrane transport defect may exist for Na+/Na+ exchange in families of hypertensive subjects.     

The lymphatic drainage of the pericardial space in the dog

The purpose of this study was to characterize definitively the lymphatic drainage system of the pericardial space in the dog. The reports on this subject, based on dissection experiments and acute dye injections, remain controversial, and our own previous studies have been incomplete. Seventeen dogs were studied using a radiographic technique. Micropulverized barium sulfate instilled into the pericardial sac was followed with serial chest x-rays in seven dogs with intact cardiac lymphatics, in seven dogs after section of the cardiac lymphatic drainage node (the cardiac lymph node) in the right upper mediastinum, and in three dogs after resection of cardiac drainage lymphatic nodes in the left upper mediastinum. These studies revealed that the lymphatic drainage of the pericardial space is via (a) the principal coronary lymphatic which drains from the left ventricular muscle and passes to the right upper mediastinum via the cardiac lymph node, (b) the lesser coronary lymphatic which drains the right ventricular muscle and passes to the left upper mediastinum, and (c) bilateral internal mammary (parasternal) lymphatic chains. These observations are important in planning experimental approaches to the effects of impairment of lymph drainage from the pericardial space. An understanding of the lymph drainage from the pericardial space may prove significant to understanding fibrotic reactions within it and the pathologic mechanisms of such entities as constrictive pericarditis.     

Reflex modulation of lymphatic pumping in sheep

Lymphatic pumping activity was examined in halothane-anesthetized sheep. A doubly cannulated preparation of the mesenteric lymph duct was "isolated" from lymph input, other than that from a constant pressure reservoir of artificial lymph attached to its inflow cannula, but had its blood supply and innervation intact. A cerebral ischemic response, evoked by injection of 2 ml air into the common carotid artery, increased both mean arterial pressure and fluid propulsion by the lymphatic. The latter rose from a control value of 45 microliters/min to a peak of 74 microliters/min. When 10(-4) M phentolamine was introduced into the lymphatic lumen, there was a transient increase followed by a sustained fall in lymph pumping. Repetition of the air injection while phentolamine was present in the duct lumen produced no increase in lymph pumping. In adrenalectomized animals, resting lymph propulsion by the mesenteric duct was depressed, and the response to air injection was attenuated but remained significantly greater than control. These results suggest that reflex activation of the sympathetic nervous system can increase lymph propulsion and that this may be augmented by the release of circulating catecholamines.     

Effects of alveolar hypoxia on lung fluid and protein transport in unanesthetized sheep.

To determine whether hypoxia directly affects pulmonary microvascular filtration of fluid or permeability to plasma proteins, we measured steady state lung lymph flow and protein transport in eight unanesthetized sheep breathing 10% O2 in N2 for 4 hours. We also studied three sheep breathing the same gas mixture for 48 hours. We surgically prepared the sheep to isolate and collect lung lymph and to measure average pulmonary arterial (Ppa) and left atrial (Pla) pressures. We placed a balloon catheter in the left atrium to elevate Pla. After recovery, the sheep breathed air through a tracheostomy for 2-4 hours, followed by 4 or 48 hours of hypoxia. In 13 4-hour studies, the average arterial PO2 fell from 97 to 38 torr; Ppa rose from 20 to 33 cm H2O; and lung lymph flow and lymph protein flow were unchanged. We also found that during 48-hour hypoxia, with a sustained elevation in Ppa and a decline in Pla, lymph flow and protein flow did not increase. In four sheep, we also raised Pla for 4 hours, followed by 4 hours of hypoxia with elevated Pla. Again, despite the added stress of elevated Pla, we found that lymph flow and lymph protein flow remained constant during hypoxia. We conclude that severe alveolar hypoxia, for 4 or 48 hours, alone or with increased pulmonary microvascular pressure, produced no change in lung fluid filtration or protein permeability, a finding supported by normal postmortem histology and extravascular lung water content.     

原发性甲状腺功能减退性心包积液与甲状腺功能、心肌酶、胆固醇的关系

目的探讨原发性甲状腺功能减退性心包积液与甲状腺功能、心肌酶、总胆固醇的关系。方法回顾性分析90例原发性甲状腺功能减退症合并心包积液患者,进行甲状腺功能、心肌酶、总胆固醇的调查,并按有无心包积液分为2组进行比较。结果 (1)两组患者在年龄、性别构成、病程、病因上差异无统计学意义。(2)甲状腺功能减退伴心包积液组患者TT3、TT4、FT3、FT4均较无心包积液组低[(0.66±0.48)nmol/L比(1.20±0.57)nmol/L,(14.64±24.46)nmol/L比(62.22±50.67)nmol/L,(2.11±0.74)pmol/L比(3.66±2.02)pmol/L,(3.12±4.49)pmol/L比(6.37±4.78)pmol/L],而TSH较无心包积液组高[(68.85±32.05)mU/L比(46.47±39.44)mU/L,均为P<0.05]。(3)心包积液组心肌酶谱、胆固醇均较无心包积液组高(P<0.05)。(4)偏相关分析提示心包积液与TT3、TT4、FT3、FT4、TSH相关(r=-0.400,-0.467,-0.368,-0.340,0.284;均为P<0.05)。结论原发性甲状腺功能减退性心包积液与甲状腺功能严重程度有关,与年龄、病程、病因无关,同时多伴有胆固醇及心肌酶谱升高。     

Fluconazole concentrations in pulmonary tissue and pericardial fluid

Summary In order to investigate the clinical efficacy of the triazole antifungal agent fluconazole (FCA) in the treatment of pulmonary mycosis, in the present study the concentrations of fluconazole in human pulmonary tissue, pericardial fluid and serum were determined at 1, 2, 12 and 13 h after intravenous administration of fluconazole 200 mg. The mean FCA concentrations in the serum were 4.04 mg/l (1 h), 3.82 mg/l (2 h), 2.35 mg/l (12 h) and 2.13 mg/l (13 h). The respective FCA levels in the pulmonary tissue were 4.64 mg/kg, 4.54 mg/kg; 3.50 mg/kg and 3.40 mg/kg and the concentrations in the pericardial fluid were 3.86 mg/l, 3.57 mg/l, 2.35 mg/l and 2.13 mg/l. The FCA concentrations in the pulmonary tissue that were statistically significant higher than the serum concentrations were found at 2 h, 12 h and 13 h after intravenous administration (p<0.05).     

Renal lymphatic ultrastructure and translymphatic transport

Information on the mechanisms of transport across renal lymphatic endothelium in the dog was derived by qualitative and quantitative ultrastructural analyses. Interlobular and intralobular renal lymphatics were studied in dogs with ureteric obstruction and lymphatic ligation, in dogs with lymphatic ligation only, and in dogs with unimpeded lymph and urine flow. Minor differences were detected in the ultrastructural features of lymphatic endothelium among the three groups of animals and between the two types of lymphatics studied within each group. Approximately 5% of the endothelial intracytoplasmic volume was occupied by vesicles, the majority of which were of the small uncoated variety. On an average 65% of these vesicles lay within the cytoplasm, and of the remainder, most were associated with the luminal border. Interendothelial contacts were of three varieties—end-to-end, overlapping, and complexly interdigitating. One-third of these lacked any specialized junctional complexes, whereas about 60% of the identifiable complexes revealed a fascia occludens. The remainder (approximately 10%) possessed fascia adhaerentes. Only 2 examples, out of 240 contacts studied, could be described as open junctions (greater than 50 nm). The conclusions drawn from this study were that (1) interlobular and intralobular renal lymphatics subserve similar functions in lymph formation, (2) at least in the absence of local irritation or trauma, open junctions do not play a significant role in translymphatic transport of fluid and protein, and (3) for poorly diffusible substances the primary pathways into the lymphatic lumen are intravesicular transport and the normal intercellular channels between contiguous cells.     

Effects of increased pericardial pressure on the coupling between the ventricles

STUDY OBJECTIVE--The mechanical coupling between the ventricles occurs directly through the myocardium (ventricular-ventricular coupling) and indirectly through the pericardium (ventricular-pericardial-ventricular coupling). We postulated that the magnitude of ventricular-pericardial-ventricular coupling would increase at high pericardial pressures, while ventricular-ventricular coupling would be unaltered. DESIGN--Canine hearts were removed and placed in cold cardioplegic solution. Balloons were inserted into each ventricle and the left and right ventricular pressure (dP1, dPr) and volume (dV1, dVr) changes caused by increasing the pressure and volume of the other ventricle and by increasing pericardial pressure (dPp) were measured. EXPERIMENTAL MATERIALS--Hearts from 10 random source dogs, weight 12.5-18 kg, were used. MEASUREMENT AND MAIN RESULTS--At control pericardial pressure levels, the magnitude of the pericardial-ventricular interactions was greater than the ventricular-ventricular interactions: dP1/dPp was significantly greater than dP1/dPr, at 0.71 (SEM 0.04), n = 6, v 0.18 (0.03), p less than 0.01, and dV1/dPp was significantly greater than dV1/dPr, at -0.83 (0.09) v -0.24 (0.06), p less than 0.05. Raising the pericardial pressure increased the mechanical coupling between the ventricles: dP1/dPr approximately, dV1/dPr approximately, dPr/dP1 approximately, and dVr/dP1 approximately increased significantly (p less than 0.05) by 0.48 (0.03), 0.67 (0.13), 0.38 (0.05), and 0.61 (0.09) respectively. This increased coupling occurred through pericardial pressure changes. If pericardial pressure was maintained constant, the coupling between the ventricles was unaltered. This same pattern was observed in four in situ experiments. For these experiments, at the raised pericardial pressure levels, dP1/dPr increased, from 0.51 (0.03) to 0.79 (0.01), p less than 0.05, if pericardial pressure was allowed to vary, but was unaltered with a constant pericardial pressure, at 0.42 (0.03) v 0.44 (0.04), p greater than 0.5. CONCLUSIONS--Ventricular interdependence was increased with raised pericardial pressure and this increased coupling was due primarily to an increased ventricular-pericardial-ventricular coupling. This increased coupling may help to explain the paradoxical pulse observed in cardiac tamponade.     

Effect of increased vascular pressure on lung fluid balance in unanesthetized sheep.

In 20 unanesthetized sheep, we measured lung lymph flow and lymph and plasma protein concentrations during steady-state base-line conditions and during steady-state elevations of pulmonary microvascular hydrostatic pressure (range 3 to 23 cm H2O). In every sheep there was a base-line lung lymph flow (average 5.7 +/- 2.5 (SD) ml/hour), demonstrating that net fluid filtration occurred. The base-line lymph-plasma total protein ratio averaged 0.69 +/- 0.05, indicating a high protein osmotic pressure in the interstitial fluid at the filtration site. Lymph flow increased and lymph protein concentration decreased approximately linearly whenever hydrostatic pressure rose. A new steady-state condition was reached in 1-2 hours. The difference in plasma-to-lymph protein osmotic pressure increased by half the hydrostatic pressure increment (50% negative feedback regulation). Extravascular lung water content, measured post-mortem, did not change significantly until microvascular hydrostatic pressure more than doubled, indicating a large safety factor that protects the lungs against fluid accumulation normally. The major contributions to the safety factor appeared to be a sensitive and efficient lymph pump coupled to a washout of interstitial protein. The fluid filtration coefficient, whose calculation required many assumptions, averaged 1.64 +/- 2.65 ml/(cm H2O times hour) in the base-line condition and did not change significantly over the pressure range studied.     

Relationship between glucose and 20 alpha-hydroxysteroid dehydrogenase in fetal sheep erythrocytes

We have examined whether glucose supply to fetal sheep erythrocytes limits the rate of 20 alpha-reduction of progesterone in blood and as such is associated with the progressive loss of 20 alpha-hydroxysteroid dehydrogenase activity which has been observed from 30 days before term. Enzyme activity in erythrocytes depleted of glucose by washing was regained in the presence of at least 0.167 mmol glucose/1. The cofactor NADPH was necessary to support the reaction in lysed cells. Addition of glucose to whole blood diluted 20-fold for assay of 20 alpha-hydroxysteroid dehydrogenase did not increase the rate of reaction. Infusion of dextrose to increase fetal plasma glucose concentrations had no effect on 20 alpha-hydroxysteroid dehydrogenase activity. Over the period from 114 to 137 days of gestation, both dextrose- and saline-infused fetuses showed a decline in enzyme activity from a combined mean of 1.45 +/- 0.21 (S.E.M.) to a mean of 0.78 +/- 0.18 mumol/ml erythrocytes per h. Fetal leucocytes did not contribute significantly to the activity of 20 alpha-hydroxysteroid dehydrogenase in whole blood. The rate of 20 alpha-reduction of progesterone in the blood of eight fetuses with indwelling carotid catheters declined from 2.31 +/- 0.09 mumol/ml erythrocytes per h at 90-95 days of gestation to 0.73 +/- 0.04 mumol/ml per h at 141-145 days. However, a consistent decline was only observed after 116-120 days. The apparent equilibrium position for progesterone reduction to 20 alpha-dihydroprogesterone varied between 83.9 +/- 1.8 and 65.7 +/- 4.2%.(ABSTRACT TRUNCATED AT 250 WORDS)