Relationship between pericardial pressure and lymphatic pericardial fluid transport in sheep

We investigated the relationship between pericardial pressure and the volumetric lymphatic clearance rate of pericardial fluid in sheep. A single catheter perfusion system was established to deliver tracer to the pericardial cavity and control pericardial pressure. In addition, catheters were placed into the thoracic duct and into the jugular vein at the base of the neck. (125)I-human serum albumin (HSA) was administered into the pericardial perfusate to serve as the lymph flow marker and its concentration monitored in the effluent from the outflow end of the perfusion system. (131)I-HSA was injected intravenously to permit calculation of plasma tracer loss and tracer recirculation into lymphatics. From mass balance equations, estimates of total pericardial clearance into lymphatics increased significantly as pericardial pressures were elevated in 2. 5 cm H(2)O increments from 2.5 to 12.5 cm H(2)O (P = 0.018). Pericardial lymph transport ranged from 0.89 +/- 0.10 to 3.09 +/- 0. 66 ml/h at 2.5 and 12.5 cm H(2)O pericardial pressure, respectively. The majority of transport occurred through mediastinal vessels with a small proportion (10.3 to 23.9%) being cleared into lymphatics leading to the thoracic duct. We conclude that lymphatic pericardial fluid transport increases approximately 3.5-fold over a pericardial pressure range that encompasses the transition between the shallow and steep portions of the pericardial pressure-volume relationship.     

Lymphatic transport pathways during volume expansion

Morphological evidence on lymphatic transport was derived qualitatively and quantitatively in control and volume-expanded rats in order to identify any changes in transendothelial pathways which accompany enhanced lymph formation. Volume expansion was induced by intravenous mannitol and by intraperitoneal hypertonic or hypotonic saline (10% of body wt). Horseradish peroxidase and ferritin were used as macromolecular tracers. Volume expansion had little effect upon intraendothelial cytoplasmic components. Intracytoplasmic vesicles contained tracer molecules in control and experimental groups and quantitative analysis revealed only one significant difference between the groups—a reduction in vesicular volume and numerical densities in animals receiving mannitol. The major changes between control and experimental animals were in the presence of attenuated areas of cytoplasm, widening of intercellular pathways, and the presence of open regions in the expanded group. In these respects there was little qualitative difference among the three experimental groups, although some quantitative differences were recorded. It was concluded that vesicular transport plays a significant role in translymphatic protein movement and that when the interstitial fluid load to lymphatics is increased the excess fluid preferentially enters between adjacent endothelial cells or diffuses across areas of extreme attenuation. Open regions or junctions were considered to play little if any role in lymph formation under control conditions, but to achieve increasing importance with increases in fluid movement.     

淋巴管参与胆固醇逆向转运

细胞需要胆固醇才能生存,但过量的胆固醇对细胞具有毒性,因此细胞需要调节胆固醇的稳态。细胞内胆固醇被转运到高密度脂蛋白载脂蛋白AI,会以胆固醇逆向转运的方式返回肝脏代谢。胆固醇逆向转运不仅是维持细胞胆固醇稳态所需的生理过程,而且对动脉粥样硬化发展起到潜在的抑制作用。目前的研究主要集中在细胞胆固醇流出的最初途径和最终代谢上,但关于胆固醇是如何离开血液却知之甚少。越来越多的研究表明,在胆固醇逆向转运过程中高密度脂蛋白需要通过淋巴管转运以返回到肝脏代谢。因此,研究高密度脂蛋白从血液流入外周组织的过程,以及它是怎样通过淋巴管转运对治疗动脉粥样硬化具有重要意义。本综述主要介绍淋巴管与胆固醇逆向转运之间的联系,为治疗动脉粥样硬化性心血管疾病提供新的策略。     

Cellular expression of PCNA and procollagen in vital and ethanol-treated autologous pericardial implants in sheep

BACKGROUND AND AIMS OF THE STUDY: Cardiovascular surgeries involving repair or reconstruction of heart valve leaflets with vital autologous pericardium have shown detrimental healing outcomes, mainly fibrosis with retraction. It is proposed that cells intrinsic to the pericardial implants may contribute to this fibrosis by becoming activated to proliferate and synthesize type I collagen. METHODS: Vital and ethanol-treated autologous pericardium were implanted as rectangular flaps bisecting the lumen in the descending aorta of sheep to simulate a heart valve leaflet. Implants recovered at 5, 10, 15, and 30 days were evaluated immunohistologically for expression of PCNA and procollagen. RESULTS: In ethanol-treated pericardium, concentrations of activated cells shifted from the fibrin layers on the periphery of implants at days 5 and 10 to cells internal to the implant at days 15 and 30. In contrast, concentrations of activated cells in vital pericardium shifted from cells within the implants at days 5 and 10 to the fibrin deposits overlaying the implants at days 15 and 30. CONCLUSION: Different distributional patterns of activated cells were observed between vital and ethanol-treated pericardial flap implants. These different patterns may be important in understanding the cause of the detrimental healing outcome observed with vital autologous pericardial flap implants.     

Placental transport of low molecular weight heparin in the pregnant sheep

Standard heparin, an effective treatment for antepartum thromboembolic disease, is thought to be safe for the fetus since it does not cross the placenta. Recently, a number of low molecular weight heparins have been prepared which have been shown to produce less bleeding than standard heparin for an equivalent antithrombotic effect in experimental animals. These observations suggest that the low molecular weight heparins may also provide superior antithrombotic therapy in antepartum thromboembolic disease. However, it is not known whether the low molecular weight heparins cross the placenta. To determine this, we examined the pharmacokinetics of 125I-labelled standard heparin and a low molecular weight heparin, and their anticoagulant effects in mother and fetus, using a pregnant sheep model. Catheters were inserted into maternal and fetal femoral arteries at 108-119 d gestation (term: 147 d). 1-3 days later the mothers were given a bolus i.v. injection of 5000 anti-Xa units of 125I-labelled standard heparin or low molecular weight heparin, CY 222. Nine serial blood samples were collected over 4 h from both mother and fetus for measurements of radioactivity, anti-Xa activity (chromogenic) and activated partial thromboplastin times. When therapeutic levels of standard and CY 222 heparins were achieved in the mother, there was no detectable radioactivity or anticoagulant effect in the fetus. We conclude that standard heparin and the low molecular weight CY 222 do not cross the placenta in the pregnant sheep.     

Lymphatic transport of cholesterol from exogenous and biliary origins in nonfasting rats after intraduodenal infusions of triolein

Labelled thoracic-duct lymph was collected from nonfasting rats with a bile fistula after simultaneous intraduodenal infusions of bile labelled with [1-2 3H] cholesterol and a nutritive mixture containing [4-14C] cholesterol. The gastrointestinal tract, feces, chylomicrons and infranatants were analysed. Both biliary and exogenous cholesterol were absorbed by lymphatic way but the recovery of 3H labelling in total lymph was markedly higher than that of 14C activity. This fact might be due to different rates of cholesterol exchanges from the two origins with the nonlabelled cholesterol present in the enterocytes and further exchanges of the enterocytes cholesterol with plasma cholesterol. Most of radioactivity was detected in chylomicrons. The relative [3H] and [14C] cholesterol specific activities were always low; thus when a little exogenous cholesterol is brought the major part of lymph cholesterol had an endogenous--other than biliary--source.     

Lung vascular transport at controlled pressures with reduced coronary flow in sheep

This study was performed to measure the effects of sustained coronary flow reduction on lung lymph flow and protein clearance at normal and elevated lung microvascular pressures. Eleven halothane-anesthetized sheep were provided with lung lymph and carotid-to-left-anterior-descending coronary artery cannulas. Six sheep (ischemic group) were observed in a protocol of five periods, each of 2 hr duration: baseline, left atrial pressure (PLA) increased by mitral valve obstruction, return to baseline, reduced coronary flow, and reduced coronary flow plus increased PLA. Five sheep (control group) were studied in an identical protocol except that coronary flow was not reduced. PLAS were equal in the second and fifth periods. Lung lymph flow QL and protein clearance (QL times the lymph-to-plasma protein concentration ratio) normalized to second baseline were greater during ischemia than in the comparable control period, and clearance was also greater during the second increased-pressure period. We conclude that reduced coronary flow is related to sustained, significant increases in lung vascular transport at elevated as well as at normal vascular pressures.     

Lymphatic Microcirculation

Objective : The importance of the lymphatic system during inflammatory response is underscored by the discovery that numerous inflammatory mediators alter the lymph pump. Inhibition of the lymph pump will reduce the lymphatic outflow from the interstitial space and thus initiate the lymphatic generation of edema. We evaluated the effect that reactive oxygen metabolites have on the contractile activity of lymphatic vessels. Methods : Reactive oxygen metabolites are produced during inflammation and have been implicated in a number of pathologies. Exposure to reactive oxygen metabolites inhibited the lymph pump flow in a time- and concentration-dependent fashion by decreasing contraction frequency, strength, and propagation. Results : Substance P (SP) (1.0 μM) produced the following changes (% control): reductions in diastolic diameter (56%), systolic diameter (47%), and stroke volume of the lymph pump (62%); a large increase in lymphatic contraction frequency (640%); and a modest increase in lymph pump flow (43%). SP also stimulated quiescent vessels to develop typical contraction-relaxation patterns. These effects may serve to minimize the formation of edema in the face of inflammatory edemagenic conditions that are produced by SP. Conclusions : We concluded that reactive oxygen metabolites significantly inhibit the active lymph pump and that this inhibition could be an important contributing factor in the formation of interstitial edema during inflammation. We have also determined the effects of a putative mediator of inflammation (SP) on the lymphatic pumping function.     

Closed pericardial drainage for relief of pericardial tamponade

The method of continuous catheter drainage for pericardial tamponade as used in 108 patients is described. The efficacy of this procedure in relieving tamponade resulting from a variety of diseases is demonstrated. Blood clot in the pericardium probably constitutes a contraindication to catheter drainage.     

Hemorrhagic pericardial effusion causing pericardial tamponade in hereditary hemorrhagic telangiectasia

Osler-Weber-Rendu disease, or Hereditary Hemorrhagic Telangiectasia (HHT), is a rare, inherited autosomal dominant disorder characterized by telangiectasia and arteriovenous malformations in various organs. We report a unique case of HHT-associated hemorrhagic pericardial effusion presenting with pericardial tamponade.     

Physiological features of pericardial constriction in the absence of pericardial disease.

To sustain a clinical diagnosis of constriction it is classically held that the fibrous pericardium must be thickened and adherent to the surface of the heart. A case is presented in which leukaemic infiltration of the fat overlying the myocardium resulted in the physiological features of constriction, although all layers of the pericardium itself were normal. Constriction is thus a physiological diagnosis; it may develop in the absence of the classical anatomical findings.