Vascular sclerosing effects of bleomycin on cutaneous veins: a pharmacopathologic study on experimental animals

Abstract: Background: Varicose veins and the complications of venous disease are common disorders in humans. Objective: To study the effects of bleomycin as a potential new sclerosing agent and its adverse events in treating varicose veins. Methods: Bleomycin-loaded liposomes 0.1ml was injected in the dorsal ear veins of white New Zealand rabbits. Sodium tetradecyl sulfate was used as a positive control. Normal saline was used as negative control. The blood vessels of the treated ears were photographed before and at one hour and two, eight and 45 days after treatment. Biopsies from the treated areas were obtained for histological examination. Blood samples were collected to determine any possible toxicity. Results: Bleomycin by itself was ineffective; therefore, liposomes were used as a vector to deliver bleomycin to the vein lumen. Subsequently, bleomycin started showing its sclerosing effects. Toxicity monitoring showed no apparent hematologic, pulmonary, hepatic or renal toxicities. This study revealed that bleomycin induced vasculitis, which led to vascular occlusion, which was observed on day 1 and day 8. No bleomycin-related injury was noted by histopathological examination of lung sections. The calculation of the lung/body weight coefficient indicated that edema was present in the experimental groups compared with the negative and positive controls. Study limitations: Relatively small number of experimental animals used. Conclusions: This study showed that bleomycin-loaded liposomes were able to induce vasculitis and vascular occlusion without any toxicity or complications. It might be useful, hence, to treat patients suffering from Varicose veins and other ectatic vascular diseases with this agent.

Effects of different frequencies of transcutaneous electrical nerve stimulation on venous vascular reactivity

Transcutaneous electrical nerve stimulation (TENS) is a type of therapy used primarily for analgesia, but also presents changes in the cardiovascular system responses; its effects are dependent upon application parameters. Alterations to the cardiovascular system suggest that TENS may modify venous vascular response. The objective of this study was to evaluate the effects of TENS at different frequencies (10 and 100 Hz) on venous vascular reactivity in healthy subjects. Twenty-nine healthy male volunteers were randomized into three groups: placebo (n=10), low-frequency TENS (10 Hz, n=9) and high-frequency TENS (100 Hz, n=10). TENS was applied for 30 min in the nervous plexus trajectory from the superior member (from cervical to dorsal region of the fist) at low (10 Hz/200 μs) and high frequency (100 Hz/200 μs) with its intensity adjusted below the motor threshold and intensified every 5 min, intending to avoid accommodation. Venous vascular reactivity in response to phenylephrine, acetylcholine (endothelium-dependent) and sodium nitroprusside (endothelium-independent) was assessed by the dorsal hand vein technique. The phenylephrine effective dose to achieve 70% vasoconstriction was reduced 53% (P<0.01) using low-frequency TENS (10 Hz), while in high-frequency stimulation (100 Hz), a 47% increased dose was needed (P<0.01). The endothelium-dependent (acetylcholine) and independent (sodium nitroprusside) responses were not modified by TENS, which modifies venous responsiveness, and increases the low-frequency sensitivity of α1-adrenergic receptors and shows high-frequency opposite effects. These changes represent an important vascular effect caused by TENS with implications for hemodynamics, inflammation and analgesia.

Bradykinin or acetylcholine as vasodilators to test endothelial venous function in healthy subjects

INTRODUCTION: The evaluation of endothelial function has been performed in the arterial bed, but recently evaluation within the venous system has also been explored. Endothelial function studies employ different drugs that act as endothelium-dependent vasodilatory response inductors. OBJECTIVES: The aim of this study is to compare the endothelium-dependent venous vasodilator response mediated by either acetylcholine or bradykinin in healthy volunteers. METHODS AND RESULTS: Changes in vein diameter after phenylephrine-induced venoconstriction were measured to compare venodilation induced by acetylcholine or bradykinin (linear variable differential transformer dorsal hand vein technique). We studied 23 healthy volunteers; 31 percent were male, and the subject had a mean age of 33 ± 8 years and a mean body mass index of 23 ± 2 kg/m². The maximum endothelium-dependent venodilation was similar for both drugs (p = 0.13), as well as the mean responses for each dose of both drugs (r = 0.96). The maximum responses to acetylcholine and bradykinin also had good agreement. CONCLUSION: There were no differences between acetylcholine and bradykinin as venodilators in this endothelial venous function investigation.

Estudo morfométrico do efeito do Tenoxicam e do seu diluente no endotélio venoso, em coelhos / Morphometric study on the effect of tenoxicam and its diluent in the venous endothelium, in rabbits

Com o objetivo de avaliar pela morfometria o efeito do tenoxicam e do seu diluente no endotélio venoso, foram utilizados 48 coelhos (Oryctolagus cuniculus), brancos, da linhagem Nova Zelândia, machos, com idade acima de 10 semanas, com peso variando entre 2.350 e 3.500 gramas, divididos em dois grupos, denominados Experimento e Controle, que foram observados nos tempos de 6, 12 e 24 horas. Administrou-se nas venae auriculares dextra e sinistra, diluente ou tenoxicam/diluente no Grupo Experimento e cloreto de sódio a 0,9 por cento no Grupo Controle. Näo se constatou diferença estatisticamente significante entre o peso dos animais do Grupo Experimento e do Grupo Controle, antes da realizaçäo do procedimento. Pode-se observar que após a administraçäo do tenoxicam com o seu diluente ou do diluente isolado, os diâmetros dos núcleos das células endoteliais apresentaram significativamente menor dimensäo, quando comparados aos do grupo Controle, em que foi injetado cloreto de sódio a 0,9 por cento. Os resultados encontrados permitem concluir que o tenoxicam com o seu diluente comercial ou o diluente isolado reduzem o diâmetro dos núcleos das células endoteliais das venae em que foram injetados os fármacos.

Effect of glomerulo pressin on several isolated veins and arteries of different species

Se estudió el efecto de la glomerulopresina en varias venas aisladas de perro, conejo, hamster y rata y en arterias de perro. La glomerulopresina produjo contractión en las venas de perro: yugular, porta femoral, cava, ilíaca, esplénica y no tuvo efecto en las venas: pulmonar, mesentérica y renal. La glomerulopresina también produjo una contractión en algunas arterias de perro: ilíaca, femoral, renal y no tuvo efecto en la aorta, hepática, esplénica y pulmonar. En la rata aumentó la frecuencia del ritmo de las contracciones espontáneas de la vena porta. No se observó ningún efecto en las venas de conejo estudiadas: cava, yugular, ilíaca y porta. Tampoco tuvo efecto en la porta de hamster. En un grupo de experimentos se ensayó clorpromazina y mepacrina, in hibidores de la fosfolipasa A2. Estos inhibidores bloquearon la acción de la glomerulopresina en los tres vasos ensayados: yugular, porta y arteria ilíaca de perro. Estos resultados muestran que la glomerulopresina produce una contracción en varios, pero no en todos los vasos estudiados y sugieren que este efecto es mediado por la liberación de ácido araquidónico