Rabbit Ear Vein Research Articles

Endothelial cell compatibility of clarithromycin for intravenous use

Objectives: Tolerance of intravenously applied clarithromycin has been tested on marginal ear veins of rabbits. Use of human umbilical venous endothelial cells (HUVEC) for testing antibiotic solutions for intravenous compatibility provides a valuable alternate model. Design and methods: In order to evaluate the effect of clarithromycin on intracellular purines, reflecting cell viability, energy production, signal transduction and DNA/RNA synthesis, intracellular adenosine 5’ triphosphate (ATP), adenosine 5’ diphosphate (ADP), guanosine 5’ triphosphate (GTP), and guanosine 5’ diphosphate (GDP) levels were measured by means of high performance liquid chromatography (HPLC). Results: Incubation of cells with 2 mg/mL clarithromycin resulted in a rapid decrease of the intracellular ATP from 12.6 ± 1.1 to 8.87 ± 0.82 nmol/million cells or 1.5 ± 0.6 nmol/million cells, after 20 or 60 min, respectively. In addition, ADP was extensively depleted. Purine nucleotide profiles were markedly different following exposure to 1 mg/mL clarithromycin. There was no significant decline of intracellular high energy phosphate levels after 20 min. Conclusion: These results show that clarithromycin has a better endothelial compatibility if diluted to a final concentration of 1 mg/mL. These data are in line with our clinical observations that the occurrence of phlebitis could be minimized by diluting the manufacturers’ preparation of clarithromycin to 1 mg/mL.

Experimental infusion phlebitis: tolerance osmolality of peripheral venous endothelial cells.

This study aimed to determine the osmolality that peripheral venous endothelial cells can tolerate and to clarify the relationship between tolerance osmolality and duration of infusion. Nutrient solutions of 539-917 mOsm/kg, prepared to have no acidic effect, were infused into rabbit ear veins, and the veins were examined histopathologically. In each experiment of 8-, 12-, or 24-h infusion, the higher osmolality solutions caused some phlebitic changes, such as loss of venous endothelial cells, inflammatory cell infiltration, and edema; however, the lowest osmolality solution caused few changes. Infusion of 120 mL/kg of 814 mOsm/kg solution caused phlebitis at 5 or 10 mL.kg-1.h-1, however, the same volume of the same solution scarcely caused phlebitis at 15 mL.kg-1.h-1 because of the shortened infusion duration. These results suggest that the tolerance osmolality of peripheral venous endothelial cells with poor blood flow is about 820 mOsm/kg for 8 h, 690 mOsm/kg for 12 h, and 550 mOsm/kg for 24 h, and that the tolerance osmolality falls as the duration of infusion increases. In conclusion, hypertonic solutions should be infused at as high a rate as is clinically acceptable and compatible with nutrient bioavailability because increasing the infusion rate reduces the duration of infusion and phlebitis.

Dilution is effective in reducing infusion phlebitis in peripheral parenteral nutrition: An experimental study in rabbits

To clarify conflicting clinical results that had been reported as to whether dilution is effective or not in reducing infusion phlebitis, this study was undertaken. We undertook two experiments with the different infusion conditions in rabbits to confirm the generality and the reproducibility of the results. To test the effect of dilution, 120 mL/kg of solution A (784 mOsm/kg) was infused into rabbit ear veins at 10 mL.kg-1.h-1 for 12 h, and 144 mL/kg of 1.2-fold-diluted solution A (648 mOsm/kg) was infused at 12 mL.kg-1.h-1 for 12 h. Similarly, 120 mL/kg of solution B (718 mOsm/kg) was infused at 5 mL.kg-1.h-1 for 24 h, and 168 mL/kg of 1.4-fold-diluted solution B (514 mOsm/kg) was infused at 7 mL.kg-1.h-1 for 24 h. The infused veins were sampled 24 h after the end of the infusion and examined histopathologically. After the 12-h infusion, phlebitic changes were observed in six of eight rabbits given solution A but in only one of eight rabbits given diluted solution A, although the same quantities of the same nutrients were infused. Also, after the 24-h infusion, phlebitic changes were observed in six of eight rabbits given solution B but in no animals given diluted solution B. The same result that dilution reduced or eliminated phlebitic changes was confirmed in the different conditions. These results suggest that osmolality of the infusion solution is an important factor in the development of phlebitis regardless of infusion volume or infusion rate and that dilution is effective in reducing the phlebitic potential of infusion solutions.

Effects of pH and osmolality on phlebitic potential of infusion solutions for peripheral parenteral nutrition.

In this study, we investigated the phlebitic potentials of several infusion solutions for peripheral parenteral nutrition to clarify the effects of pH and osmolality on the development of infusion phlebitis. A 10% glucose solution with electrolytes (GE, pH 4.93, 727 mOsm/kg), a 10% amino acid solution (AA, pH 6.95, 929 mOsm/kg), or a 5:2 admixture of GE and AA (GEAA, pH 6.46, 779 mOsm/kg) was infused into the rabbit ear vein for 6 hr at 10 mL/kg/hr, and the infused veins were examined histopathologically. Both GE and AA caused phlebitic changes, such as loss of venous endothelial cells, inflammatory cell infiltration, and perivascular edema. However, their admixture, GEAA, caused scant phlebitic changes. These results were as follows: 1) rabbit peripheral veins could tolerate the pH (6.46) and the osmolality (779 mOsm/kg) of GEAA under the conditions of this study; 2) GE caused phlebitis due to its acidity (pH 4.93); 3) AA caused phlebitis due to its hyperosmolality (929 mOsm/kg); and 4) mixing GE and AA eliminated the factors causing phlebitis in each solution. The admixture of GE and another 10% amino acid solution (AB, pH 6.04) at the ratio of 5:2 (GEAB, pH 5.76, 758 mOsm/kg) caused phlebitic changes. Since its osmolality was lower than that of GEAA, it was considered that GEAB caused phlebitic changes due to its acidity (pH 5.76), which was attributed to the acidic amino acid solution used as a component.

Clinical and histologic evaluation of polyiodinated iodine with and without hypertonic saline/dextrose in the rabbit ear vein model.

Certain types of varicose veins can be successfully sclerosed with polyiodinated iodine (PII). Although this sclerosant is widely used in Canada and in Europe, it is not marketed in the United States. The following study was undertaken to determine whether an American polyiodinated iodine (APII) formula, compounded in a hospital pharmacy, is as effective as a commercially available brand of PII in the rabbit ear vein model. The two sclerosants were identical in composition. After being mixed with either normal saline (NS), Sclerodex, or an American dextrose-hypertonic solution (ADHS) compounded in a hospital pharmacy, each sclerosant was injected in concentrations of 0.1% and 0.5%. The veins were examined clinically and histologically 1 hour, and 2, 8, and 28 days after injection. They were examined with electron microscopy at 8 and 28 days. When diluted with NS, Sclerodex, or ADHS and injected in a 0.1% concentration, each sclerosant produced a hyperplastic regenerating endothelium without evidence of mixed cellular infiltrates at 2 days. By 28 days, the endothelium was regenerated. When diluted with NS, Sclerodex, or ADHS and injected in a 0.5% concentration, each sclerosant produced more thrombosis, yielding a mild perivascular mixed cellular infiltrate and fibrin coagulum at 8 days and thrombus cord formation at 28 days. When mixed with NS, Sclerodex, or ADHS, APII has the same efficacy as PII.

Visualization of retinal and choroidal blood flow with fluorescein leukocyte angiography in rabbits.

To visualize the retinal and choroidal leukocytes in rabbits with a new technique, fluorescein leukocyte angiography using a scanning laser ophthalmoscope. Blood was withdrawn from an ear vein of a rabbit (New Zealand White), mixed with fluorescein dye in a test tube and centrifuged. The yellow-brown coat layer containing fluorescein-stained leukocytes was collected and injected into the ear vein of the same rabbit while performing fluorescein angiography with a scanning laser ophthalmoscope. The angiographic image displaying circulating fluorescent leukocytes in retinal and choroidal vessels was recorded on a videotape. Fluorescent leukocytes were clearly visible in the retinal arteries, capillaries, veins and choroidal vessels for more than 1 h. Plugging of leukocytes was seen throughout this period of time in choroidal vessels, while plugging was rare in retinal vessels. Fluorescein leukocyte angiography is a new technique which can be used for visualization of the leukocytes in retinal and choroidal vessels non-invasively and in vivo.

Comparison of the Proarrhythmic Effect of GLG‐V‐13, a Novel Class III Antiarrhythmic Compound, in Two Rabbit Models of Torsades de Pointes Ventricular Tachycardia

Objective: The proarrhythmic potential of a new IKr‐blocking Class III antiarrhythmic agent, GLG‐V‐13 was studied and compared in two rabbit models of torsades de pointes (TdP) ventricular tachycardia (TdP).Methods: Chloralose‐anesthetized rabbits (n = 8) were given a concomitant infusion of GLG‐V13 (84 nmol/kg per min) and the α1‐agonist methoxamine (70 nmol/kg per min); in another set of experiments, GLG‐V‐13 was administered solely into the ear vein of electrode catheter instrumented conscious rabbits (n = 6). The doses of GLG‐V‐13, to produce maximum prolongation of the QTUc interval or the right ventricular effective refractory period (VERP), and that inducing ventricular ectopic beats (EBs) and TdP, respectively, were determined.Results: In anesthetized rabbits, GLG‐V‐13 increased QTUc from 125 ± 3 to 161 ± 6 ms after a cumulative dose of 0.84 μmol/kg (P < 0.001) and caused EBs at a mean cumulative dose of 3.9 ± 1.1 μmol/kg. In five of the rabbits, the EBs turned into TdP at a dose of 5.2 ± 3.2 μmol/kg. In conscious rabbits, maximum prolongation of the VERP (27%± 4.3%; P < 0.01) by GLG‐V‐13 was seen at a dose of 1.2 ± 0.54 μmol/kg, whereas EBs and TdP were induced after 6.3 ± 1.4 (6/6) and 8.1 ± 1.4 μmol/kg (6/6), respectively.Conclusion: (1) The dose‐dependent “torsadogenic” potential of IKr‐blockers can be evaluated in conscious rabbits without concomitant methoxamine administration; (2) in the conscious state, the EB‐ and TdP‐inducing dose of GLG‐V‐13 is about 50% higher than in the chloralose‐anesthetized animal; and (3) irrespective of the chemical nature of the compound applied, blockade of the cardiac IKr potassium channel is associated with proarrhythmic effect.

食道静脈瘤に対するICG併用半導体レーザー治療の基礎的検討

We developed ICG dye enhanced diode laser therapy as prophylactic therapy for esophageal varices. Low dose irradiation of the diode laser after submucosal injection of wavelength-specific dye (ICG: indocyanine green) could provide selective eradication of esophageal mucosa and submucosa including varices without bleeding during the irradiation. We demonstrated efficacy and safety of this new moderlity using animal experiment.In the dose-response study with the use of pig esophagus. Thermal injury limited up to deep submucosal layer without any deffect on surface nor any injury of muscle layer was easily achieved with the power at 6 and 12W. Based on these findings, the procedure was carried endoscopically on dog esophagus. After the submucosal injection of the ICG solution, the diode laser irradiation was applied with 12W laser power and 1.0 second pulse mode. We were not able to found defect on the surface immidiately after irradiation. After 7 days, we found selective erai cation of mucasa and submucosa pathologically.Effect on thrombus formation was studied with the use of ear veins of rabbits. The diode laser was applied after the submucosal injection of the ICG solution around ear veins. Post operative 7 days specimen revieled white thrombus in the veins.We conclude that the ICG dye enhanced diode laser therapy may provide a simple, safe and effective altenative to the prophylactic therapy of esophageal varices.

Photodynamic treatment for atherosclerotic plaques of the rabbit abdominal aorta by the laparoscopical approach using a pheophorbide derivative

A new photosensitizer, PH-1126, was administered intravenously into the ear veins of cholesterol-fed atherosclerotic rabbits at a dose of 1 mg/kg of body weight. At 24 hr after PH-1126 administration, the atherosclerotic abdominal aorta was irradiated with a krypton ion laser with a wavelength of 647 nm by 100 J/cm2 by the laparoscopical approach. Twenty-four hours later, the abdominal aorta irradiated by the laser beam was excised for histological analysis. In the atherosclerotic plaques with photodynamic treatment, damaged foam cells were observed by scanning electron microscopy and transmission electron microscopy. Some of these cells were exposed to the aortic lumen. No significant changes were shown in the abdominal aorta either with plaques not injected with PH-1126 or without plaques after photodynamic treatment. These findings suggest that atherosclerotic plaques of the abdominal aorta could be selectively degraded by laparoscopical photodynamic treatment.

Measurement of retinal blood flow with fluorescein leucocyte angiography using a scanning laser ophthalmoscope in rabbits.

To measure blood flow in the rabbit retinal circulation with fluorescein leucocyte angiography using a scanning laser ophthalmoscope. Blood was withdrawn from the ear vein of a rabbit (New Zealand White), mixed with fluorescent dye in a test tube and centrifuged. The yellow-brown layer containing fluorescein stained leucocytes was collected and injected into the ear vein of the same rabbit while performing fluorescein angiography with a scanning laser ophthalmoscope. The image of retinal angiography displaying circulating fluorescent leucocytes was recorded on video tape. From each frame of the video tape, the consecutive positions of fluorescein stained leucocytes were digitised using an image analysis system and the velocity of blood flow was calculated. Fluorescent leucocytes were clearly visualised in the retinal arteries, capillaries, and veins which allowed measurement of blood flow. The mean capillary velocity was 0.69 (SD 0.21) mm/s. The mean velocities of leucocytes measured in different sized vessels were as follows: 5.83 (2.42) mm/s in arteries over 50 microns, 3.33 (0.62) mm/s in those 35-50 microns, and 2.42 (1.08) mm/s in arteries under 35 microns, 3.08 (1.56) mm/s in veins over 50 microns, 2.79 (1.49) mm/s in those 35-50 microns, and 1.21 (0.50) mm/s in veins under 35 microns. Blood flow pulsation occurs in arteries, arterioles, veins, and venules but not capillaries. Fluorescein leucocyte angiography can be used for simultaneous measurement of the blood flow in retinal arteries, veins, and capillaries.

Denopamine as an α1H-adrenoceptor antagonist in isolated blood vessels

The effects of denopamine, clinically used as a cardiotonic β 1-adrenoceptor agonist, were investigated on α-adrenoceptor-mediated contraction in vascular preparations of rats, guinea-pigs and rabbits. Norepinephrine, phenylephrine ( α 1-adrenoceptor agonist) and clonidine [and 5-bromo-6-(2-imidazolin-2-ylamino)quinoxaline (UK 14,304, α 2-adrenoceptor agonists)] concentration dependently contracted the vascular preparations. Phenylephrine was more potent than the α 2-adrenoceptor agonists in the rat aorta and carotid artery. The reverse was true in the rabbit ear vein. pA 2 values for prazosin (rat tissues, 9.7–10; guinea-pig aorta, 9.1–9.3) and for yohimbine (rat tissues, 6.6–6.9; guinea-pig aorta, 6.2–6.3; rabbit ear vein, 7.9) suggested that α 1H (high affinity for prazosin)-, α 1L (lower affinity for prazosin)-, and α 2-adrenoceptors were predominantly distributed in the rat tissues, the guinea-pig aorta, and in the rabbit ear vein, respectively. Vasoconstrictions mediated by α 1H-adrenoceptor subtypes were more susceptible to inhibition by denopamine than those mediated by α 1L and α 2 subtypes. These results suggested that in addition to activity as a β 1-adrenoceptor agonist, denopamine also possessed activity as an α 1H-adrenoceptor-selective antagonist. These actions may contribute to the denopamine-induced decrease in total peripheral resistance in vivo.

Notes on the early history of infective endocarditis and the development of an experimental model.

Experimental models of infective endocarditis antedate Garrison and Freedman's work in 1970. The hypothesis of the role of parasites (microorganisms) microscopically observed in vegetations and cardiac valves of patients with endocarditis was first put forth by Winge in Sweden in 1869. Winge's work led Klebs and Rosenbach in Germany to establish, between 1878 and 1881, an animal model of experimental endocarditis in which the aortic valves of rabbits were perforated with a metallic probe (loaded with septic material) introduced through the carotid artery. Ten years after Winge's work, Pasteur emphasized the importance of bacteriologic "blood cultures." During the period 1881-1886, Netter and Grancher (Pasteur's associates) introduced a method for drawing aseptic blood samples from patients with clinical endocarditis and performing bacteriologic blood cultures. In Vienna in 1885-1886, Orth, Weichselbaum, and Wyssokowitsch further developed Rosenbach's procedure of inducing experimental endocarditis by injecting material from a bacterial culture into a rabbit's ear vein. The development of an experimental model of endocarditis by investigators in the latter part of the nineteenth century provided anatomopathological and bacteriologic data that in turn led to a better understanding of infective endocarditis.

Irritability study of paclitaxel in rabbit ear vein

The vascular irritability of paclitaxel at concentrations of 0.6 and 1.2 mg/ml was examined using the rabbit ear vein by a single intravenous drip in comparison with its vehicle consisting of ethanol and Cremophor, and physiological saline. The results were as follows: 1. Slight to moderate congestion was macroscopically observed around some injection sites of the retroauricular veins infused by paclitaxel, the vehicle and saline. Its incidence and severity caused by paclitaxel was not so much different from that caused by the vehicle or saline. 2. Histopathological findings at the injection sites of the rabbits treated with paclitaxel consisted of vascular and perivascular changes, as well as alterations of the dermis and epidermis. These changes were severer than those brought by saline, and dose-dependent in their incidence and severity. Moreover, the lesions caused by paclitaxel at a concentration of 1.2 mg/ml were correspondent to those caused by the vehicle. Based on these results, the microscopic examinations suggested that the vascular irritability of paclitaxel might be attributable to administration of the vehicle.

In vivo microdialysis for pharmacokinetic investigations: a plasma protein binding study of valproate in rabbits.

The use of microdialysis to study the binding of valproate (VPA) to plasma proteins was evaluated in rabbits. Prior to an in vivo microdialysis, in vitro relative recovery of VPA respectively from Ringer's solution, 5% (w/v) of albumin solution and plasma sample via a microdialysis probe was examined. The in vitro relative recovery was defined as a ratio of the VPA concentration determined in the dialysate to the free VPA concentration in the sample solution surrounding the membrane of the microdialysis probe. When the sample solution was well stirred at 700 rpm and maintained at 37 degrees C, the in vitro relative recovery of VPA was significantly different among them. It increased in the order of Ringer's solution (34.3 +/- 2.6%) > 5% (w/v) of albumin solution (25.7 +/- 4.6%) > rabbit plasma sample (15.8 +/- 1.2%). Thereafter, pharmacokinetics of VPA was determined using both microdialysis sampling via the rabbit femoral vein and collection of whole blood via the rabbit ear vein after intravenous administration of VPA at a dose of 43 mg/kg. Free concentrations of VPA in plasma were determined by ultrafiltration method as opposed to microdialysis method. There was no difference in the elimination half-life of VPA determined by microdialysis, 1.09 +/- 0.22 h, or ultrafiltration, 1.22 +/- 0.21 h. The AUC of VPA in dialysate was 15 +/- 4 micrograms.h/ml, which corresponded to 15% of that in ultrafiltrate (103 +/- 17 micrograms.h/ml). The value was in good agreement with the in vitro relative recovery of VPA from plasma sample (15.8 +/- 1.2%).(ABSTRACT TRUNCATED AT 250 WORDS)

Human Saphenous Vein In Vitro Model for Studying the Action of Sclerosing Solutions

Previous studies detailing the clinical and histologic effects of sclerosing solutions in rabbit ear and other animal vein models have provided information comparing the effects of various concentrations of hypertonic saline with and without dextrose (Sclerodex), polidocanol, scleremo (chromated glycerin), and sodium tetradecyl sulfate. To observe short-term histologic changes of sclerosing solutions in vitro in large diameter human vein. Human saphenous vein segments were obtained following cardiac bypass procedures. Several types of sclerosing solutions, including 23.4% hypertonic saline, 1% polidocanol, and 3% sodium tetradecyl sulfate, were allowed continuous contact with the vessel wall for 10 minutes. Test vein segments were immediately fixed and observed for histologic changes compared with normal saline controls. Endothelium was rapidly destroyed by all tested sclerosing solutions. Vessel wall necrosis occurred quickly with the extent determined by the sclerosing solution. Destructive potential of 3% sodium tetradecyl sulfate greatly exceeded that of 23.4% hypertonic saline or 1% polidocanol, in agreement with previous animal studies. Direct toxic effects of sclerosing agents may be compared in a constant, reproducible environment with this in vitro model.

Pyrogenic action of endothelin in conscious rabbit

Injection of 0.3 nmol/kg endothelin(ET)-1 into the ear vein of conscious rabbits induced a significant increase in body temperature. ETB receptor specific agonist, namely 4-Ala-ET-1, also caused an elevation of the body temperature in a dose-dependent manner by injection into the ear vein of rabbit. These results suggest that ET play important roles in regulation of body temperature through selective stimulation of ETB receptor.

Intravenous infusion of n-3 polyunsaturated fatty acids.

Dietary supplementation with n-3 polyunsaturated fatty acids (PUFA) is regarded as beneficial for the prevention and treatment of atherosclerosis and thrombosis and chronic inflammatory diseases like rheumatoid arthritis and psoriasis. It may be possible to treat some acute diseases like acute myocardial infarction or acute rejection of grafted organs if it is possible to make n-3 PUFA take effect quickly (in hours instead of days). Three sets of experiments were done. In Experiment 1, emulsion of trieicosapentaenoyl-glycerol (EPA-TG) and tridocosahexaenoyl-glycerol was infused through rabbit ear veins, and the leukotriene B4/B5 production from polymorphonuclear leukocytes was measured at different time points by high-performance liquid chromatography. In Experiment 2, delayed type hypersensitivity (DTH) of mice was measured with sheep red blood cells as an antigen. Pure n-3 PUFA emulsions or a control solution were infused through tail veins just before the second challenge of the antigen. DTH was measured 24 hr after the second challenge. In Experiment 3, human natural killer cell activity was measured using K562 target cells before and after the infusion of pure EPA-TG emulsion to an antecubital vein. Leukotriene B4 production by rabbit polymorphonuclear leukocytes was depressed by 40% by EPA-TG infusion. DTH was suppressed almost completely by n-3 PUFA infusion. Natural killer cell activity was suppressed almost completely by EPA-TG infusion in 8 hr. DTH, natural killer cell activity, and leukotriene B4 production are probably related to acute rejection of grafted organs.(ABSTRACT TRUNCATED AT 250 WORDS)

α2‐Adrenoceptor blocking profile of SK&F 104078: further evidence for receptor subtypes

1. The ability of the putative, selective post-junctional alpha 2-adrenoceptor antagonist, SK&F 104078 to antagonize the effects of structurally-diverse agonists at pre-junctional alpha 2-adrenoceptors in the guinea-pig ileum and rat vas deferens in vitro and in the rat heart in vivo, and at post-junctional alpha 2-adrenoceptors in the rabbit ear vein in vitro, was examined. Results obtained with SK&F 104078 were compared with those obtained with yohimbine. 2. Xylazine and B-HT933 each caused a concentration-dependent inhibition of the field-stimulation-evoked twitch responses of the guinea-pig ileum and rat vas deferens. SK&F 104078 did not antagonize either agonist in the guinea-pig ileum and exerted only minimal blocking activity against xylazine in the rat vas deferens. In contrast, SK&F 104078 competitively antagonized B-HT933 in the rat vas deferens (pA2 = 6.45). Yohimbine competitively antagonized both agonists in each tissue (pA2 values ranged between 7.46 and 7.88). 3. In the pithed rat xylazine and B-HT933, injected intravenously, caused a dose-dependent reduction in the tachycardia elicited by stimulation of the cardiac preganglionic sympathetic nerves. SK&F 104078 (10 mg kg-1, i.v.) caused a 20-30 fold rightward displacement of the dose-response curve to xylazine, but did not affect responses to B-HT933. Yohimbine (1 mg kg-1, i.v.) antagonized both agonists to a similar degree. 4. In the rabbit ear vein xylazine, B-HT933, noradrenaline and UK 14304 elicted vasoconstrictor responses. Prazosin was without effect, but in contrast, SK&F 104078 was a competitive antagonist of each of the agonists (pA2 values ranged between 6.63 and 6.72). Yohimbine also competitively antagonized each of the agonists in this preparation (pA2 values ranged between 7.81 and 8.07). 5. SK&F 104078 was also a competitive antagonist (pA2 = 6.20) against noradrenaline at post-junctional alpha 1-adrenoceptors in the rabbit aorta. 6. These data show that SK&F 104078 is a competitive antagonist at post-junctional alpha l- and alpha 2-adrenoceptors. Its antagonist potency at pre-junctional alpha 2-adrenoceptors is agonist- and tissuedependent. Yohimbine does not discriminate between pre- and post-junctional alpha 2-adrenoceptors. The findings are discussed in terms of the possible existence of subclasses of OC2-adrenoceptors.

A Comparison of Sclerosing Agents: Clinical and Histologic Effects of Intravascular Sodium Morrhuate, Ethanolamine Oleate, Hypertonic Saline (11.7%), and Sclerodex in the Dorsal Rabbit Ear Vein

The dorsal marginal rabbit ear vein was injected with 0.25 mL of 2.5, 1, or 0.5% sodium morrhuate, 2.5, 1, or 0.5% ethanolamine oleate, hypertonic saline 11.7%, or Sclerodex. Only the vessel injected with 2.5% sodium morrhuate demonstrated clinical and histologic evidence of endosclerosis with microangiopathic recanalization; 2.5% ethanolamine oleate demonstrated partial clinical sclerosis and luminal recanalization histologically. All other evaluated solutions except 0.5% ethanolamine oleate produced immediate clinical and histologic endothelial damage and thrombosis. However, these latter solutions did not produce sufficient endothelial damage to cause endosclerosis. Extravasated red blood cells occurred in vessels injected with 1 and 2.5% ethanolamine oleate and 1 and 2.5% sodium morrhuate at 1 hour and 2 days, but not in vessels injected with sodium morrhuate 0.5%, ethanolamine oleate 0.5%, Sclerodex, or hypertonic saline 11.7%. Hemosiderin discoloration was not apparent clinically. Cutaneous necrosis was not observed with any of the evaluated solutions.

Enhanced clearance from plasma of low density lipoproteins containing a truncated apolipoprotein, apoB-89.

Previously we have reported on a kindred with hypobetalipoproteinemia in which three sisters were found to be compound heterozygotes for two newly described truncated forms of apoB. apoB-40 and apoB-89. ApoB-89-containing low density lipoproteins (LDL) bound with increased affinity to cultured normal human fibroblasts and were internalized and degraded at increased rates, suggesting that the low plasma concentrations of apoB-89-LDL of the patients could be due to enhanced rates of clearance through LDL-receptors. To examine this hypothesis, apoB-89-LDL was isolated from the three study subjects and apoB-100-LDL from two control subjects. LDL was conjugated to the radioiodinated residualizing label, dilactitol tyramine (*I-DLT, containing either 125I or 131I). *I-DLT-apoB-89-LDL and *I-DLT-apoB-100-LDL were simultaneously injected into ear veins of rabbits. The clearance from plasma and hepatic accumulations of both radiolabeled LDL fractions were followed over 24 h. Fractional catabolic rates (FCR) of apoB-89-LDL were 0.105 +/- 0.012 h-1 compared to 0.054 +/- 0.007 h-1 for apoB-100-LDL. In agreement with the enhanced clearance from plasma, 1.72 to 1.87 times more *I-DLT-apoB-89-LDL than *I-DLT-apoB-100-LDL accumulated in the livers 24 h after injection. There was no significant difference in splenic accumulation, suggesting that LDL-receptors rather than scavenger receptors mediated the enhanced clearance of apoB-89-LDL. To assess further the importance of LDL-receptors, *I-DLT-apoB-89-LDL and *I-DLT-apoB-100-LDL were reductively methylated to inhibit their interactions with LDL-receptors.(ABSTRACT TRUNCATED AT 250 WORDS)