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BACKGROUND: The existence of intratissular lymphaticovenous anastomoses has often been suggested, but it has never been demonstrated. This study aims at demonstrating the presence of such anastomoses. METHODS AND RESULTS: The free flap model was used to investigate the drainage of radiolabeled colloid particles whose size prevents direct passage to the blood vessels. The tracer was injected into the muscle or the skin during the surgical procedure. Blood samples were sequentially drawn from the venous pedicle over the 30 minutes that followed the tracer injection. The blood samples were counted using a gamma well-counter. In all 14 patients, the venous blood radioactivity steadily increased over time. Radiochemical analyses performed on the blood samples demonstrated that the radioactivity is related to the labeled colloids and not to free pertechnetate. Planar imaging performed 24 hours after the surgical procedure showed a significant liver uptake, and no accumulation in the area of normal lymphatic relays. CONCLUSIONS: As, in the free flap model, there is no lymphatic drainage through the classical pathways whatsoever, and since the size of the radiolabeled particles prevents them from directly entering the blood stream, the results strongly suggest the presence of functional intratissular lymphovenous anastomoses.

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OBJECTIVE: Investigation of the transport of viral-size particles after intravenous versus intralymphatic injection and the functional validity of lymphatico-venous communications. METHODS: In the canine model, [99mTc] sulfur colloid particles (100-200 nm) were injected into either the principal vein or into the main lymphatic channel exposed at the paw. Samples of blood and lymph were collected at the groin from the cannulated femoral vein and from a major lymphatic vessel. Parameters including particle arrival time, concentration, flux, and accumulation were determined for a 45-minute period using gamma counting. RESULTS: After intralymphatic injection, particles arrived in the venous blood in an average of 4 seconds. The mean arrival time of particles in the lymph after intravenous injection was 25.4 +/- 6.44 minutes. Intralymphatic injection increased lymph flow and enhanced particle transport. Concentration values in the venous blood after intralymphatic injection and in lymph after intravenous injection were comparable. Flux values depended primarily on flow conditions. Particle accumulation in the lymph after intravenous injection was delayed, but continued to increase throughout the experiment. CONCLUSIONS: There are functional lymphatico-venous communications at the very peripheral level under physiological conditions, which allow rapid transport of viral-size particulate matter between the two pathways and may contribute to the spread of viral infection.

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OBJECTIVE: We investigated the propagation of viral-size particles by lymph and blood after subcutaneous injection. METHODS: In the canine model, transport of [99mTc] sulfur colloid particles of different sizes was studied in different settings in venous blood and lymph for 45 minutes after inoculation. RESULTS: The mean arrival time of particles in the blood was 2.10+/-0.46 minutes and 8.87+/-1.72 minutes in the lymph. Lymph flow in the canine leg was 28.79 +/-2.09) microl/min and was increased by leg massage. The particle concentration was 1000 times higher in the lymph fluid than in blood. Particle flux values were comparable in blood and lymph. The accumulation of particles in blood initially rose faster than in lymph. Accumulation in lymph rises slower but continues longer and reaches higher values. Ninety percent of the inoculum remains at the injection site for at least 45 minutes. Particle size matters more in blood distribution. Leg massage enhances particle transport by lymph. CONCLUSIONS: After subcutaneous injection, viral-size particles initially arrive in the blood and later in the lymph. Accumulation in lymph and blood increases for a prolonged time after inoculation. Results suggest possibilities for limiting the spread of infectious matter by early local antiviral treatment.

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Technetium-99m sulfur colloid scintigraphy was used to study alterations of reticuloendothelial function in 7 dogs with experimentally induced biliary cirrhosis and portosystemic shunting. Scintigraphic studies were performed before and 6 weeks after common bile duct ligation. Radiocolloid plasma clearance rate was determined by measuring activity in plasma samples and by analyzing the rate of liver uptake on dynamic scintigraphic image sequences. Percentage of uptake in the liver, spleen, and lungs, as well as the ratio of hepatic-to-extrahepatic uptake, was determined from static equilibrium images. Relative to preoperative values, there were significant decreases in plasma clearance rate, percentage of liver uptake, and ratio of hepatic-to-extrahepatic uptake and significant increases in percentage of spleen and lung uptake on postoperative studies. The mechanism of technetium-99m-labeled sulfur colloid extraction by the liver is different from that of other radiocolloids; it does not require active phagocytosis or pinocytosis. Thus, liver uptake of this tracer principally reflects effective liver blood flow. Portosystemic shunting was documented in these dogs at the time of the postoperative radiocolloid scans, and we believed was responsible for the decrease in liver reticuloendothelial activity. Possible mechanisms for the increased splenic and pulmonary reticuloendothelial activities are discussed.

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The percentage binding of 99Tcm sulphur colloid to blood components (formed elements and plasma proteins) was studied within 1 min of the intravenous injection of the radiopharmaceutical in humans as well as rats. In humans, 68% of the total blood counts were bound to the formed elements (erythrocytes, leucocytes and platelets). The binding pattern (as percentage of plasma counts) among the plasma protein fractions in humans was as follows: albumin, 9.85 +/- 2.06; fibrinogen, 56.70 +/- 7.96; and total proteins, 66.55 +/- 7.32. Activity bound to fibrinogen represented 82.3 +/- 9.1% of the total protein-bound activity in humans. In rats as well fibrinogen was the predominant binding protein (73.8 +/- 5.6). The significant binding of the 99Tcm sulphur colloid to plasma fibrinogen and formed elements of blood may be one of the reasons for the uptake of this radiocolloid in renal transplants before rejection.

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