[en] The technique of vascular labeling was developed to mark sites of increased microvascular permeability. We used the vascular labeling technique in anesthetized sheep and found that hemodynamics and airway pressure were adversely affected by intraarterial infusions of two vascular tracers. Monastral blue (nine sheep) immediately caused systemic arterial hypotension, pulmonary arterial hypertension, and bronchoconstriction. All three physiological responses were partially blocked by a cyclooxygenase inhibitor (indomethacin) but not by an H1-antihistamine (chlorpheniramine). Colloidal gold (nine sheep) caused immediate, but less dramatic, pulmonary arterial hypertension which was not attenuated by the blocking agents. We conclude that these two vascular tracers caused detrimental physiological side effects in sheep at the usual doses used to label injured microvessels in other species

[en] Capillary permeability of ¹³¹I-albumin in skeletal muscle was determined by applying the ''single injection, residue detection'' method to the autoperfused cat gastrocnemius muscle preparation. Experiments at zero venous pressure gave an average capillary extraction fraction, E, of 0.028 at a plasma flow of about 3 ml X (100 g)-1 X min-1. The permeability-surface area product, PS, was on average 0.075 ml X (100 g)-1 X min-1. Experiments at a venous pressure of 10 mm Hg gave essentially the same PS product (0.070 ml X (100 g)-1 X min-1. Further experiments demonstrated that stagnant intravascular pools of ¹³¹I-albumin were not present. The free diffusion coefficient in water at 37 degrees of the purified ¹³¹I-albumin was 0.0631 X 10-5 cm2 X sec-1). The distribution volume for ¹³¹I-albumin in the interstitial space was 3.5 ml X (100 g)-1 X sec-1. Assuming a capillary surface area of 70 cm2 X g-1 the permeability coefficient was calculated to be 18 X 10(-8) cm X sec-1 which is about 3 to 10 times higher than values obtained by lymph sampling methods. The results indicate that the predominant transcapillary transport mechanism for ¹³¹I-albumin is diffusion. When analyzed according to the theory of restricted diffusion the results are compatible with transcapillary diffusion through pores with an effective equivalent pore radius of 145 A

[en] Regional differences in plasma extravasation during endotoxin shock in rats and a possible relationship with changes in regional blood flow were studied with radioactive isotopes (¹²⁵I-HSA, 51Cr-labeled red blood cells, microspheres) in anesthetized rats (pentobarbital). Shock was induced by intravenous infusion of endotoxin (Eschericia coli; 10 mg X kg-1) for 60 min (starting at t = 0); at t = 120 min, the experiments were terminated. These rats (n = 8) were compared with time-matched control rats (n = 8). A third group (rats killed 7.5 min after injection of ¹²⁵I-HSA, i.e., no extravasation; n = 8) served as baseline. The amount of plasma extravasated in 2 hr of endotoxin shock was significantly increased over control values in skin (by 67%), colon (88%), skeletal muscle (105%), stomach (230%), pancreas (300%), and diaphragm (1300%). Losses of ¹²⁵I-HSA into intestinal lumen and peritoneal cavity had also increased over control values by 146 and 380%, respectively. Blood flow was compromised in most organs except heart and diaphragm. Extravasation when normalized for total plasma supply was correlated with total blood supply; the more the blood supply decreased, the higher the normalized extravasation. In the diaphragm, however, blood supply and plasma leakage increased together. Decreased blood supply and plasma extravasation may be related but they could also be simultaneously occurring independent phenomena with a common origin

[en] A perfused, in situ rabbit lung preparation was used to study the diffusion of tritiated water and labeled lipophilic solutes from the airways into the pulmonary vasculature. Following instillation into the airways, initial concentrations of labeled ethanol and butanol in the left atrial outflow usually exceeded those of ³H₂O when the lungs were perfused at 37 degrees. In contrast, initial concentrations of [¹⁴C]acetone equaled ³H₂O concentrations, and those of [¹⁴C]antipyrine were below ³H₂O concentrations. Increasing the rate of perfusion increased concentrations of the labeled butanol and acetone but decreased that of antipyrine relative to ³H₂O. This suggests that the tissues separating the gaseous and vascular compartments of the lung are more permeable to ³H₂O than to antipyrine but less permeable to ³H₂O than to the alcohols and acetone. Cooling slowed permeation of ethanol and antipyrine relative to ³H₂O but seemed to slow diffusion of butanol less than that of ³H₂O. These differences cannot be related to movement in the aqueous phase and suggest that cooling slows solute diffusion through lipid membranes. This phenomenon appears to be related to the activation energy of each molecule between the aqueous and lipid phases rather than a phase change in the membrane. ³H₂O seems to diffuse through aqueous regions of the air-perfusate barrier

[en] We studied isolated bovine mesenteric lymphatics to elucidate the pharmacological characteristics of pre- and postjunctional alpha-adrenoceptors at the sympathetic neuroeffector junction. Cylindrical strips were incubated with [³H]-noradrenaline and mounted for superfusion. Electrical stimulation (2 Hz, 0.5 msec, 50 V) augmented the fractional release of labeled noradrenaline. Exogenous noradrenaline and clonidine caused a depression of the evoked tracer release. Phenoxybenzamine and yohimbine markedly enhanced the evoked overflow of adrenergic transmitter. Rings of lymphatic vessels were mounted for isometric tension recording in organ chambers filled with Krebs-Ringer bicarbonate solution. The vessels contracted when exposed to phenylephrine and clonidine. The ED50 of clonidine was significantly lower than that of phenylephrine. Prazosin caused a parallel shift to the right of the dose-response curve to phenylephrine. The antagonist, however, suppressed the magnitude of the maximum response to clonidine. Yohimbine caused parallel shift to the right of the dose-response curves to phenylephrine and clonidine, respectively. The Schild plots for yohimbine demonstrated that the drug was a competitive antagonist to phenylephrine and clonidine. The pA2 value of yohimbine to clonidine (7.6 +/- 0.4) was larger than that to phenylephrine (6.2 +/- 0.4). The pA2 value of prazosin to phenylephrine was 7.2 +/- 0.3. These results suggest that prejunctional alpha-adrenoceptors are involved in the negative feedback mechanism for autoregulation of noradrenaline release during postganglionic sympathetic nerve stimulation, and that both alpha 1- and alpha 2-like adrenoceptors do exist on lymphatic smooth muscle cells

[en] Endotoxemia in rats increases plasma extravasation but does not result in continuously rising hematocrit. These contradictory observations led us to design a study in anesthetized rats (C, control rats, n = 10; E, endotoxin rats, n = 10) in which we continuously measured in blood hematocrit (conductivity cell) and changes in concentration of 125I-HSA (human serum albumin) and 51Cr-labeled red cell (51Cr-RBC; multichannel analyzer) in an extracorporeal circuit. In two additional series of experiments we measured in blood samples changes in protein concentration (series II, C: n = 7, E: n = 7) and uptake of intraperitoneally injected 125I-HSA and 51Cr-RBC (reflecting lymph flow rate; series III, C: n = 6, E: n = 7). Endotoxemia was induced by infusion (iv, 0.2 ml/100 g.hr) of Escherichia coli endotoxin (20 mg/kg) from t = 0 to t = 60 min; controls received saline. Experiments ended at t = 120 (series I and II) or 150 min (series III). The endotoxemia resulted in a marked rise of serum lactate (by ca 500% at t = 120); heart rate increased and central venous pressure decreased (by ca 20 and -95% at t = 120, respectively). All rats showed characteristic changes in hematocrit during endotoxemia: an increase from t = 20 to t = 45 (by ca 9%) followed by a decrease to preshock values or less at t = 120. The 51Cr activity per microliter blood cells did not change, indicating that there was no red cell mobilization. Protein concentration and 125I-HSA activity also showed a temporary increase during endotoxemia, but 125I-HSA activity per gram protein was decreased. Peritoneal uptake of 125I-HSA and 51Cr-RBC was significantly increased during endotoxemia (by 200%)

[en] The simultaneous plasma disappearance curves of 131I-albumin and 125I-fibrinogen were recorded in normal rabbits for 1 hr. Using fibrinogen as a plasma reference, the disappearance curves of albumin were shown to contain two separate phases of efflux: one fast from zero to 10 min. comprising 8% of the total tracer; and one slow appearing in the interval of 10 to 60 min. containing another 9% of the tracer. Total albumin escape was analyzed to yield an initial slope of 0.024 ± 0.004 min-1, corresponding to a wholebody unidirectional albumin clearance (Cl(0)) of 0.090 ± 0.009 ml(min*100 g)-1. The distribution of efflux was assessed by biopsy uptakes using the same tracers in spleen, kidney, heart, lung, liver, intestine, skin, muscle, and brain. The disappearance curve generally reflects a biphasic pattern of uptake in peripheral tissue, predominantly by muscle and lung. The rapid phase has contributions from the fast near equilibration of liver, and intestine and skin are significant codeterminants of the slow phase. Due to their low body masses highly perfused organs such as kidney, spleen, and heart have little influence on the plasma disappearance. In accordance, the Cl(0) determined for the wholebody was higher than initial clearances found in skin (0.053 ml(min*100 g)-1) and muscle (0.054 ml(min*100 g)-1), but much lower than those found in the highly perfused organs. The initial (unidirectional) rates of peripheral albumin transfer demonstrated, ranged from 10 to 30 times higher than estimates of lymphatic return, suggesting that transcapillary albumin exchange is mediated by high-rate bidirectional diffusion. The rapid decrease of net albumin exchange rates suggests a second, highly significant barrier located within the interstitial matrix, which restricts plasma escape and reduces plasma to lymph albumin transport

[en] Short communication

[en] A study was designed to compare three independent measures of cutaneous blood flow in normal healthy volunteers: xenon-133 washout, helium flux, and laser velocimetry. All measurements were confined to the volar aspect of the forearm. In a large group of subjects we found that helium flux through intact skin changes nonlinearly with the controlled local skin temperature whereas helium flux through stripped skin, which is directly proportional to skin blood flow, changes linearly with cutaneous temperature over the range 33 degrees to 42 degrees. In a second group of six volunteers we compared helium flux through stripped skin to xenon-133 washout (intact skin) at a skin temperature of 33 degrees, and we found an essentially linear relationship between helium flux and xenon measured blood flow. In a third group of subjects we compared helium flux blood flow (stripped skin) to laser doppler velocimetric (LDV) measurements (intact skin) at adjacent skin sites and found a nonlinear increase in the LDV skin blood flow compared to that determined by helium over the same temperature range. A possible explanation for the nonlinear increases of helium flux through intact skin and of LDV output with increasing local skin temperature is that they reflect more than a change in blood flow. They may also reflect physical changes in the stratum corneum, which alters its diffusional resistance to gas flux and its optical characteristics

[en] The tissue to plasma transfer of ¹³¹I-albumin was recorded in perfused rabbit ears (n = 6) following equilibration for 24 hr. 125I-fibrinogen served as the plasma marker, and was introduced intravenously 15 min before clamping. The ears were rollerpump perfused with isotonic diluted plasma at a constant rate of (mean ± SD) 5.1 ± 1.5 ml (min.100 g)-1. The mean extravascular albumin distribution volume was 12.4 ± 1.1 ml.100 g-1, and the fibrinogen volume (plasma volume in tissue) was 3.1 ± 0.4 ml.100 g-1 as determined from biopsies of the contralateral ear. The initial transfer of albumin was marked, and occurred at rates corresponding to a unidirectional clearance (Cl(0)) of 0.068 ± 0.012 ml (min.100 g)-1. However, with a reduction of mean interstitial albumin tracer content of no more than 4%, net transport decreased to reach slowly declining levels 5 to 10 times lower within 10 min of continued perfusion. The decrease was considered due to rapid exhaustion of a small interstitial pool of tracer immediately adjacent to the exchange vessel membrane, followed by an increasingly retarded outwash from more distant areas. The results suggest a bimodal structural resistance to albumin movement: a relatively low resistance in the capillary membrane, and a considerable restriction to albumin transport located within the interstitial space