RESUMO
OBJECTIVE: In this study, we aimed to examine the effects of amitriptyline, fluoxetine, tranylcypromine and venlafaxine on saphenous vein grafts in coronary artery bypass graft surgeries. METHODS: 59 patients (40 males and 19 females; mean age 65.1 years, distribution: 45-84 years) who had coronary artery bypass graft surgery between February 2014 and May 2016 were included in the study. After the saphenous vein grafts with intact and denuded endothelium were precontracted with 3×10-6M phenylephrine, amitriptyline, fluoxetine and tranylcypromine were cumulatively added to isolated organ baths in the range of 10-11-3x10-5M, while venlafaxine was added in the range of 10-9-3×10-5M. Then, the antidepressant-induced relaxation responses were recorded isometrically. RESULTS: While the relaxation response of amitriptyline at -6.42 (Log M) was 74.6%, the response at -6.32 (Log M) was 75.5%. While the relaxation response at -6.46 (Log M) of fluoxetine was 68.02%, the response at -6.02 (Log M) was 72.12%. While the relaxation response of tranylcypromine at -7.53 (Log M) was 61.13%, the response at -7.23 (Log M) was 65.53%. While the relaxation response of venlafaxine at -6.21 (Log M) was 29.98%, the response at -5.90 (Log M) was 32.96%. CONCLUSION: The maximum relaxation at minimum and maximum therapeutic concentrations was obtained with amitriptyline, fluoxetine and tranylcypromine, and the minimum relaxation was obtained with venlafaxine. The relaxation responses were independent of the endothelium.
Assuntos
Amitriptilina/farmacologia , Antidepressivos/farmacologia , Fluoxetina/farmacologia , Veia Safena/efeitos dos fármacos , Veia Safena/transplante , Tranilcipromina/farmacologia , Cloridrato de Venlafaxina/farmacologia , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Ponte de Artéria Coronária/métodos , Endotélio Vascular/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Liso Vascular/efeitos dos fármacos , Valores de Referência , Transplantes/efeitos dos fármacos , Vasodilatação/efeitos dos fármacosRESUMO
Abstract Objective: In this study, we aimed to examine the effects of amitriptyline, fluoxetine, tranylcypromine and venlafaxine on saphenous vein grafts in coronary artery bypass graft surgeries. Methods: 59 patients (40 males and 19 females; mean age 65.1 years, distribution: 45-84 years) who had coronary artery bypass graft surgery between February 2014 and May 2016 were included in the study. After the saphenous vein grafts with intact and denuded endothelium were precontracted with 3×10-6M phenylephrine, amitriptyline, fluoxetine and tranylcypromine were cumulatively added to isolated organ baths in the range of 10-11-3x10-5M, while venlafaxine was added in the range of 10-9-3×10-5M. Then, the antidepressant-induced relaxation responses were recorded isometrically. Results: While the relaxation response of amitriptyline at -6.42 (Log M) was 74.6%, the response at -6.32 (Log M) was 75.5%. While the relaxation response at -6.46 (Log M) of fluoxetine was 68.02%, the response at -6.02 (Log M) was 72.12%. While the relaxation response of tranylcypromine at -7.53 (Log M) was 61.13%, the response at -7.23 (Log M) was 65.53%. While the relaxation response of venlafaxine at -6.21 (Log M) was 29.98%, the response at -5.90 (Log M) was 32.96%. Conclusion: The maximum relaxation at minimum and maximum therapeutic concentrations was obtained with amitriptyline, fluoxetine and tranylcypromine, and the minimum relaxation was obtained with venlafaxine. The relaxation responses were independent of the endothelium.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Veia Safena/efeitos dos fármacos , Veia Safena/transplante , Tranilcipromina/farmacologia , Fluoxetina/farmacologia , Amitriptilina/farmacologia , Antidepressivos/farmacologia , Valores de Referência , Vasodilatação/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Ponte de Artéria Coronária/métodos , Análise de Variância , Transplantes/efeitos dos fármacos , Cloridrato de Venlafaxina/farmacologia , Músculo Liso Vascular/efeitos dos fármacosRESUMO
Resumen Introducción: Prolongar la permeabilidad de los injertos utilizados en bypass coronario es un desafío constante. Objetivo: Comparar anatomofuncionalmente venas safenas humanas (VSH) extraídas con técnica convencional (TC) vs técnica "no-touch" (NT). Material y Método: Estudio experimental. Se diseccionó VSH con TC y NT en el pabellón de cirugía cardiaca del Hospital Regional de Antofagasta. Las muestras de VSH fueron seccionadas en anillos de 3 mm y conservados en cámaras de órganos aislados con solución Ringer-Krebs. Para evaluar la vasomotilidad se administró norepinefrina (10-6M), papaverina (10-4M), acetilcolina (10-6M) y nitroprusiato de sodio (10-5M). Un segmento de las muestras fue fijado en formalina al 10%, procesado con técnica histológica y analizado bajo microscopía óptica. Las muestras fueron teñidas con hematoxilina-eosina, Verhoeff y orceína. El análisis estadístico fue realizado mediante el software Prism Graphad. Resultados: Reactividad vascular: La vasoconstricción inducida por noradrenalina fue significativamente superior en anillos del grupo NT vs TC (p < 0,0001). La vasodilatación producida por papaverina y acetilcolina fue superior en el grupo NT (p < 0,004) y (p < 0,0003), respectivamente. Estudio morfométrico: El grupo NT presentó túnica muscular (0,755 vs 0,680 mm), adventicia (0,5600 vs 0,4663 mm) y pared total (1,344 vs 0,962 mm) más gruesa que el grupo TC. No hubo diferencias significativas respecto el número de vasa vasorum. Conclusión: El grupo NT responde significativamente mejor a estímulos vasoconstrictores y vasodilatadores. Los resultados se asocian con las diferencias morfométricas.
Introduction: Prolonging of the grafts permeability used in coronary bypass is a constant challenge. Objective: To compare anatomical and functional human saphenous veins (VSH) extracted "No touch" (NT) technique vs conventional technique (TC). Materials and Methods: Experimental study. VSH dissected with CT and NT in the Regional Hospital of Antofagasta cardiac surgery ward. VSH samples were sectioned into 3 mm rings and preserved in isolated organs chambers with Krebs-Ringer solution. To evaluate the vasomotor activity, norepinephrine (10-6M), papaverine (10-4M), acetylcholine (10-6M) and sodium nitroprusside (10-5M) was administered. A segment of samples was fixed in 10% formalin, processed and histological analyzed under light microscopy technique with hematoxylin-eosin, Verhoeff and orceína. Statistical analysis was performed using the Prism software Graphad. Results: Vascular Reactivity: norepinephrine-induced vasoconstriction was significantly higher in the group rings NT vs TC (p < 0.0001). Vasodilation was higher with papaverine and acetylcholine in the NT group (p < 0.004) and (p < 0.0003), respectively. Morphometric study: The NT group presented muscularis (0.755 vs 0.680 mm), adventitious (0.5600 vs 0.4663 mm), and total wall (1.344 vs 0.962 mm) thicker than the TC group. No significant differences in vasa vasorum number identified. Conclusion: The NT group vasoconstrictor and vasodilator responds significantly better. Results correlate with morphometric differences.
Assuntos
Humanos , Veia Safena/efeitos dos fármacos , Veia Safena/transplante , Coleta de Tecidos e Órgãos/métodos , Vasoconstrição/efeitos dos fármacos , Vasoconstritores/farmacologia , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Técnicas In Vitro , Ponte de Artéria CoronáriaRESUMO
Although the vasorelaxing effects of testosterone (T) and various androgen metabolites have been observed in a variety of blood vessels and species, previous studies have not systematically compared the vasorelaxing effects of androgen metabolites in different vascular beds within the same species. Therefore, we studied the vasorelaxing effects of T and its 5-reduced metabolites (5α- and 5ß-DHT) on KCl-induced contractions of the canine left coronary artery, femoral artery and saphenous vein, using standard isometric recordings. KCl contractions were inhibited by each androgen in a concentration-dependent manner from 1.8 to 310µM. Vascular sensitivity and efficacy were expressed as inhibitory concentration 50 (IC50) and maximal relaxation (R(max)), respectively. The coronary artery was significantly more sensitive to androgen-induced vasorelaxation than the saphenous vein or femoral artery. These vasorelaxing responses were unaffected by an antiandrogen (Flutamide) or the sulfhydryl reagent, N-ethylmaleimide, suggesting a nongenomic mechanism independent of signaling mediated by the androgen receptor or G proteins. Concentration-response curves were unchanged in endothelium-denuded preparations; thus, the endothelium appears to have no role in androgen-induced vasorelaxation. 5ß-DHT was the most potent androgen in both coronary and femoral artery, but all three androgens were equipotent in the saphenous vein. It is concluded that: 1) significant regional differences exist in vasorelaxing effects of androgen metabolites in the canine vasculature; 2) structural differences in these androgens determine their vasorelaxing efficacy; and 3) regional differences in androgen-induced vasorelaxation may account for some of the conflicting findings reported on the vasorelaxing effects of the androgens.
Assuntos
Androgênios/metabolismo , Vasos Sanguíneos/metabolismo , Di-Hidrotestosterona/metabolismo , Testosterona/metabolismo , Vasodilatação , Vasodilatadores/metabolismo , Antagonistas de Androgênios/farmacologia , Androgênios/química , Animais , Vasos Sanguíneos/efeitos dos fármacos , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/metabolismo , Di-Hidrotestosterona/antagonistas & inibidores , Di-Hidrotestosterona/química , Cães , Etilmaleimida/farmacologia , Artéria Femoral/efeitos dos fármacos , Artéria Femoral/metabolismo , Flutamida/farmacologia , Técnicas In Vitro , Masculino , Concentração Osmolar , Reprodutibilidade dos Testes , Veia Safena/efeitos dos fármacos , Veia Safena/metabolismo , Estereoisomerismo , Reagentes de Sulfidrila/farmacologia , Testosterona/antagonistas & inibidores , Vasodilatação/efeitos dos fármacos , Vasodilatadores/antagonistas & inibidores , Vasodilatadores/químicaRESUMO
Nowadays, the great saphenous vein is the vascular conduit that is most frequently employed in coronary and peripheral revascularization surgery. It is known that saphenous vein bypass grafts have shorter patency than arterial ones, partly because the wall of the normal saphenous vein has different structural and functional characteristics. The features of this vein can be affected by the large distention pressures it is submitted to during its preparation and insertion into the arterial system. Indeed, a vein graft is subjected to considerable changes in hemodynamic forces upon implantation into the arterial circulation, since it is transplanted from a non-pulsatile, low-pressure, low-flow environment with minimal shear stress to a highpressure system with pulsatile flow, where it undergoes cyclic strain and elevated shear. These changes can be responsible for functional and morphological alterations in the vessel wall, culminating in intima hyperproliferation and atherosclerotic degeneration, which contribute to early graft thrombosis. This review has followed a predetermined strategy for updating information on the human saphenous vein (HSV). Besides presenting the aspects relative to the basic pharmacology, this text also includes surgical aspects concerning HSV harvesting, the possible effects of the major groups of cardiovascular drugs on the HSV, and finally the interference of major cardiovascular diseases in the vascular reactivity of the HSV.
Assuntos
Fármacos Cardiovasculares/farmacologia , Doenças Cardiovasculares/fisiopatologia , Veia Safena/transplante , Animais , Implante de Prótese Vascular/métodos , Doenças Cardiovasculares/cirurgia , Ponte de Artéria Coronária/métodos , Humanos , Veia Safena/efeitos dos fármacos , Veia Safena/metabolismo , Coleta de Tecidos e Órgãos/métodosRESUMO
The inhibitory effect of the flavonoid dioclein was assessed on purified vascular cyclic nucleotide phosphodiesterase isoforms (EC 3.1.4.17, PDE1-5) in comparison with 8-methoxymethyl-isobutylmethylxanthine (8-MM-IBMX) and vinpocetine which are currently used as PDE1 inhibitors. The mechanism underlying the vasorelaxant effect of dioclein was investigated in human saphenous vein. Dioclein inhibited PDE1 more selectively than vinpocetine and 8-MM-IBMX, with IC(50) values of 2.47+/-0.26 and 1.44+/-0.35 microM, respectively in basal- and calmodulin-activated states. Dioclein behaved as a competitive inhibitor for cGMP hydrolysis by PDE1 in basal- and calmodulin-activated states (K(i)=0.62+/-0.14 and 0.55+/-0.07 microM, respectively), indicating this inhibitory effect to be independent of calmodulin interactions. In addition, dioclein induced a concentration-dependent relaxation of human saphenous vein which was independent on the presence of functional endothelium (EC(50) values of 7.3+/-3.1 and 11+/-2.7 microM, respectively with and without endothelium). 8-MM-IBMX relaxed human saphenous vein with an EC(50)=31+/-16 microM, whereas vinpocetine did not cause any vasorelaxation at concentrations up to 100 microM. Rp-8-pCPT-cGMPS, which inhibits cGMP-dependent protein kinase (PKG), blocked the vasodilator effect of dioclein, whereas H-89, which is a cAMP-dependent protein kinase (PKA) inhibitor, had a minor inhibitory effect. Our data show that dioclein is a potent calmodulin-independent selective inhibitor of PDE1 and that inhibition of PDE1 is involved in the PKG-mediated vasorelaxant effect of dioclein in human saphenous vein. Furthermore, dioclein may represent a new archetype to develop more specific PDE1 inhibitors.
Assuntos
Proteínas Quinases Dependentes de GMP Cíclico/antagonistas & inibidores , Nucleotídeo Cíclico Fosfodiesterase do Tipo 1/antagonistas & inibidores , Flavanonas/farmacologia , Inibidores de Fosfodiesterase/farmacologia , Veia Safena/citologia , Veia Safena/fisiologia , Vasodilatação/efeitos dos fármacos , Animais , Bovinos , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Humanos , Isoenzimas/antagonistas & inibidores , Isoenzimas/isolamento & purificação , Veia Safena/efeitos dos fármacosRESUMO
In segments of human varicose veins, endothelial function was assessed by measuring relaxation induced by acetylcholine in noradrenaline-precontracted preparations. In addition, concentration-response curves to acetylcholine were obtained before and after incubation with the arterial endothelium protectant agents captopril, losartan, troglitazone, pravastatin, or simvastatin. The antivaricose agent escin was also tested. Mean acetylcholine-induced relaxation of varicose venous rings was about 13%, approximately one third of that reported for control saphenous veins. Concentration-response curves to acetylcholine were ''u'' shaped, the result of endothelium-mediated relaxation at low concentrations, superseded by subsequent smooth muscle contractile responses. Relaxation was enhanced by the endothelium-protecting agents and by escin, troglitazone being the least, and simvastatin the most effective. It was concluded that endothelial dysfunction is present in varicose veins, that this anomaly can be reverted by cardiovascular protecting agents, and that it can play a role in the pathogenesis and treatment of chronic venous insufficiency.
Assuntos
Fármacos Cardiovasculares/uso terapêutico , Endotélio Vascular/fisiopatologia , Veia Safena/fisiopatologia , Vasodilatação/fisiologia , Insuficiência Venosa/fisiopatologia , Adulto , Idoso , Doença Crônica , Endotélio Vascular/efeitos dos fármacos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Veia Safena/diagnóstico por imagem , Veia Safena/efeitos dos fármacos , Ultrassonografia Doppler Dupla , Vasodilatação/efeitos dos fármacos , Insuficiência Venosa/diagnóstico por imagem , Insuficiência Venosa/prevenção & controleRESUMO
OBJECTIVE: To study morphofunctional alterations induced by brief pressure increases in human saphenous veins utilized in coronary artery bypass grafting. METHOD: Saphenous veins of 20 patients undergoing coronary artery bypass grafting, were distributed into four experimental groups, control, 100 mmHg, 200 mmHg and 300 mmHg, and submitted to pressure distention over 15 seconds using Krebs solution. The evaluation included CD34 immunohistochemistry and an In vitro vascular reactivity study in organ chambers. RESULTS: The main experimental findings were 1) From pressures of 200 mmHg there was a tendency to reduce the CD34 expression which became statistically significant at 300 mmHg; 2) There was no impairment of the contraction and relaxation as evidenced by in vitro vascular reactivity tests. CONCLUSION: Although vascular reactivity impairment was not demonstrated in vitro, the CD34 expression, measured by immunohistochemistry, shows there is endothelium dysfunction at pressures of 300 mmHg.
Assuntos
Antígenos CD34/análise , Ponte de Artéria Coronária , Endotélio Vascular/fisiopatologia , Veia Safena/fisiologia , Resistência Vascular/fisiologia , Vasoconstrição/fisiologia , Difosfato de Adenosina/farmacologia , Análise de Variância , Antígenos CD34/metabolismo , Pressão Sanguínea , Estudos de Casos e Controles , Ponte de Artéria Coronária/métodos , Ponte de Artéria Coronária/normas , Doença das Coronárias/cirurgia , Endotélio Vascular/efeitos dos fármacos , Feminino , Humanos , Pressão Hidrostática , Imuno-Histoquímica , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/fisiologia , Veia Safena/efeitos dos fármacos , Veia Safena/transplante , Estresse Mecânico , Resistência à Tração/fisiologia , Coleta de Tecidos e Órgãos , Resistência Vascular/efeitos dos fármacos , Vasoconstrição/efeitos dos fármacos , Vasodilatadores/farmacologiaRESUMO
Background: Endothelial dysfunction is associated to a lower production of nitric oxide and a reduction of endothelium mediated vasodilation. Aim: To study the effects of pharmacological agents that modify nitric oxide synthetase (NOS) activity on tension changes induced by phenylephrine in rings of internal mammary and radial arteries and saphenous vein. Material and methods: Vessel rings of 7 to 10 mm length were obtained from 32 patients subjected to coronary vascular surgery Fourteen samples of radial artery, 12 samples of internal mammary artery and 15 samples of saphenous vein were obtained. A maximal contraction was induced with KC1 and dose response curves for phenylephrine (FE) in the absence or presence of L-arginine and L-arginine methyl ester (L-NAME), were constructed. Results: The tension induced by FE in internal mammary artery and saphenous vein reached a maximum, near 90 percent of 80 mM KCl-induced contraction, but in the radial artery, it reached a maximum of 63 percent (p <0.05). In all vessels, the dose response curves were significantly shifted to the right by L-arginine and to the íeft by L-NAME. Conclusions: Pre-incubation of human rings with L-ARG or L-NAME, changed the response to FE induced contraction, which may be related to different degrees of endothelial nitric oxide production or NO sensitivity. The basal NO production in radial artery seems to be larger than the other vessels.
Assuntos
Humanos , Arginina/farmacologia , Inibidores Enzimáticos/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Fenilefrina/farmacologia , Vasoconstritores/farmacologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/enzimologia , Artéria Torácica Interna/efeitos dos fármacos , Músculo Liso Vascular/enzimologia , Artéria Radial/efeitos dos fármacos , Veia Safena/efeitos dos fármacos , VasoconstriçãoRESUMO
BACKGROUND: Endothelial dysfunction is associated to a lower production of nitric oxide and a reduction of endothelium mediated vasodilation. AIM: To study the effects of pharmacological agents that modify nitric oxide synthetase (NOS) activity on tension changes induced by phenylephrine in rings of internal mammary and radial arteries and saphenous vein. MATERIAL AND METHODS: Vessel rings of 7 to 10 mm length were obtained from 32 patients subjected to coronary vascular surgery Fourteen samples of radial artery, 12 samples of internal mammary artery and 15 samples of saphenous vein were obtained. A maximal contraction was induced with KC1 and dose response curves for phenylephrine (FE) in the absence or presence of L-arginine and L-arginine methyl ester (L-NAME), were constructed. RESULTS: The tension induced by FE in internal mammary artery and saphenous vein reached a maximum, near 90% of 80 mM KCl-induced contraction, but in the radial artery, it reached a maximum of 63% (p <0.05). In all vessels, the dose response curves were significantly shifted to the right by L-arginine and to the left by L-NAME. CONCLUSIONS: Pre-incubation of human rings with L-ARG or L-NAME, changed the response to FE induced contraction, which may be related to different degrees of endothelial nitric oxide production or NO sensitivity. The basal NO production in radial artery seems to be larger than the other vessels.