Lower limb venous diameters and haemodynamics during pregnancy and postpartum period in healthy primigravidae.

Objective Analyse venous haemodynamics in healthy primigravidae during pregnancy and in the postpartum. Methods Cohort with primigravidae evaluated in the three trimesters of pregnancy and postpartum. Duplex evaluated venous diameters and reflux; air plethysmography evaluated venous filling index, ejection fraction, residual volume fraction and outflow fraction in both limbs. Results During pregnancy, diameters increased in bilateral common femoral and right infravalvar great saphenous, but returned to first trimester values after delivery. Reflux developed in one woman (5%) in the second trimester and in two more women (15%) in the third trimester. No reflux was detected in postpartum. Bilateral venous filling index was higher during pregnancy. Bilateral ejection fraction and residual volume fraction did not change. Bilateral outflow fraction increased progressively. The right limb outflow fraction in left lateral decubitus was similar. All changes returned to first trimester values after delivery. Conclusions Healthy primigravidae presented changes in lower limbs' veins during pregnancy: diameters in bilateral common femoral and infravalvar great saphenous veins increased; new reflux was developed in 15% of women, but there was no venous hypertension. Calf muscular pump function did not change. All changes returned to first trimester values after delivery.

Intraoperative Analysis of Flow Dynamics in Arteriovenous Composite Y Grafts.

Objective: Composite graft of left internal thoracic artery and great saphenous vein in revascularization of the left coronary system is a technique well described in literature. The aim of this study is to analyze blood flow dynamics in this configuration of composite graft especially in what concerns left internal thoracic artery's adaptability and influence of great saphenous vein segment on left internal thoracic artery's flow. Methods: Revascularization of left coronary system with composite graft, with left internal thoracic artery revascularizing the anterior interventricular artery and a great saphenous vein segment, anastomosed to the left internal thoracic artery, revascularizing another branch of the left coronary system, was performed in 23 patients. Blood flow was evaluated by transit time flowmetry in all segments of the composite graft (left internal thoracic artery proximal segment, left internal thoracic artery distal segment and great saphenous vein segment). Measures were performed in baseline condition and after dobutamine-induced stress, without and with non-traumatic temporary clamping of the distal segments of the composite graft. Results: Pharmacological stress resulted in increase of blood flow values in the analyzed segments (P<0.05). Non-traumatic temporary clamping of great saphenous vein segment did not result in statistically significant changes in the flow of left internal thoracic artery distal segment, both in baseline condition and under pharmacological stress. Similarly, non-traumatic temporary clamping of left internal thoracic artery distal segment did not result in statistically significant changes in great saphenous vein segment flow. Conclusion: Composite grafts with left internal thoracic artery and great saphenous vein for revascularization of left coronary system, resulted in blood flow dynamics with physiological adaptability, both at rest and after pharmacological stress, according to demand. Presence of great saphenous vein segment did not alter physiological blood flow dynamics in distal segment of left internal thoracic artery.

Intraoperative analysis of flow dynamics in arteriovenous composite y grafts

Abstract Objective: Composite graft of left internal thoracic artery and great saphenous vein in revascularization of the left coronary system is a technique well described in literature. The aim of this study is to analyze blood flow dynamics in this configuration of composite graft especially in what concerns left internal thoracic artery's adaptability and influence of great saphenous vein segment on left internal thoracic artery's flow. Methods: Revascularization of left coronary system with composite graft, with left internal thoracic artery revascularizing the anterior interventricular artery and a great saphenous vein segment, anastomosed to the left internal thoracic artery, revascularizing another branch of the left coronary system, was performed in 23 patients. Blood flow was evaluated by transit time flowmetry in all segments of the composite graft (left internal thoracic artery proximal segment, left internal thoracic artery distal segment and great saphenous vein segment). Measures were performed in baseline condition and after dobutamine-induced stress, without and with non-traumatic temporary clamping of the distal segments of the composite graft. Results: Pharmacological stress resulted in increase of blood flow values in the analyzed segments (P<0.05). Non-traumatic temporary clamping of great saphenous vein segment did not result in statistically significant changes in the flow of left internal thoracic artery distal segment, both in baseline condition and under pharmacological stress. Similarly, non-traumatic temporary clamping of left internal thoracic artery distal segment did not result in statistically significant changes in great saphenous vein segment flow. Conclusion: Composite grafts with left internal thoracic artery and great saphenous vein for revascularization of left coronary system, resulted in blood flow dynamics with physiological adaptability, both at rest and after pharmacological stress, according to demand. Presence of great saphenous vein segment did not alter physiological blood flow dynamics in distal segment of left internal thoracic artery.

The flavonoid dioclein is a selective inhibitor of cyclic nucleotide phosphodiesterase type 1 (PDE1) and a cGMP-dependent protein kinase (PKG) vasorelaxant in human vascular tissue.

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.

Resistência tensional do pericárdio bovino fixado em glutaraldeído comparada com a da veia safena magna / Comparative analysis of rupture resistance between glutaraldehyde-treated bovine pericardium and great saphenous vein

CONTEXTO: O uso do pericárdio bovino como remendo na endarterectomia de carótida é uma alternativa à veia safena magna. As vantagens do pericárdio incluem facilidade de obtenção, menor tempo operatório e principalmente menor índice de ruptura. OBJETIVO: Avaliar a resistência tensional do pericárdio bovino tratado com glutaraldeído e compará-la com a da veia safena magna. MÉTODOS: Os remendos de pericárdio bovino (grupo I, n = 20) e de veia safena magna (grupo II, n = 20) foram recortados em dimensões iguais (50 x 5 mm) e preparados de modo habitual a sua utilização. Os grupos foram submetidos a ensaio de tração e comparados em relação a força de ruptura, força máxima e tensão de ruptura utilizando-se o teste t de Student. A correlação da espessura do remendo com a força de ruptura também foi analisada utilizando-se o coeficiente de correlação linear de Pearson. RESULTADOS: Os parâmetros força de ruptura e força máxima foram significativamente maiores no grupo dos remendos de pericárdio bovino: 1,97 versus 1,36 kgf (p = 0,001230) e 2,27 versus 1,51 kgf (p = 0,0001087), respectivamente. A tensão de ruptura média para o material pericárdio bovino também foi maior (193,99±43,05 versus 49,19±22,96 kgf/cm², p = 7,603e-16) do que na veia safena. A correlação entre a espessura e a força de ruptura foi considerada moderada (r = 0,5032993) para o pericárdio bovino e baixa (r = 0,3062166) para o grupo da veia safena. CONCLUSÃO: Os autores concluem que a resistência do pericárdio bovino à ruptura foi considerada adequada neste estudo, e é significativamente maior que a da veia safena magna, retirada da região da coxa. Além disso, a espessura do remendo em ambos os grupos não apresenta boa correlação com sua resistência a ruptura.

BACKGROUND: Carotid endarterectomy using bovine pericardium is an acceptable alternative to great saphenous vein patch. Bovine pericardium is easily obtained and provides a shorter operative time and lower rupture rate. OBJECTIVE: To evaluate rupture resistance of glutaraldehyde-treated bovine pericardium patch in comparison with great saphenous vein patch. METHODS: The sample was divided into two groups: bovine pericardium patch (group I, n = 20) and great saphenous vein patch (group II, n = 20). Both bovine pericardium and saphenous vein patches were prepared in the same dimensions (50 mm x 5 mm) and tested using standard procedures. The patches were tested in the longitudinal axis until the point of material failure. The following parameters were addressed: failure force, ultimate force and failure stress. Statistical analysis was conducted using the Student t test and Pearson's linear correlation. RESULTS: Failure force and ultimate force parameters were significantly higher in the bovine pericardium patch group: 1.97 vs. 1.36 kgf (p = 0.001230) and 2.27 vs. 1.51 kgf (p = 0.0001087), respectively. Mean failure stress in the bovine pericardium patch group was also significantly higher than that in the great saphenous vein group (193.99±43.05 vs. 49.19±22.96 kgf/cm², p = 7.603e-16). The correlation between thickness and failure force was considered moderate (r = 0.5032993) for the bovine pericardium group and low (r = 0.3062166) for the great saphenous vein group. CONCLUSION: The failure stress related to the bovine pericardium group was considered appropriate in this study, and was significantly higher than that observed in the great saphenous vein group. In addition, patch thickness in both groups did not show a good correlation with rupture resistance.

A quantitative chemiluminescent method for studying replicative and stress-induced premature senescence in cell cultures.

beta-Galactosidase (beta-Gal) activity is a widely accepted biomarker to detect senescence both in situ and in vitro. A cytochemical assay based on production of a blue-dyed precipitate that results from the cleavage of the chromogenic substrate X-Gal is commonly used. Blue and nonblue cells are counted under the microscope and a semiquantitative percentage of senescent cells can be obtained. Here, we present a quantitative, fast, and easy to use chemiluminescent assay to detect senescence. The Galacton chemiluminescent method used to detect the prokaryotic beta-Gal reporter enzyme in transfection studies was adapted to assay mammalian beta-Gal. The assay showed linear production of luminescence in a time- and cell-number-dependent manner. The chemiluminescent assay showed significant correlation with the cytochemical assay in detecting replicative senescence (Pearson r=0.8486, p<0.005). Moreover, the chemiluminescent method (Galacton) also detected stress-induced senescence in cells treated with H2O2 similar to the cytochemical assay (X-Gal) (Galacton: control 25,207.3+/-6548.6, H2O2 52,487.4+/-16,284.9, p<0.05; X-Gal: control 41.31+/-7.0%, H2O2 92.97+/-2.8%, p<0.01). Thus, our method is well suited to the detection of replicative and stress-induced senescence in cell culture.

Mechanical forces and human saphenous veins: coronary artery bypass graft implications.

Vascular endothelial cells are exposed to a variety of in vivo mechanical forces, specifically, shear stress for the blood flow, tensile stress from the compliance of the vessel wall and the hydrostatic pressure from containment of blood within inside the vasculature. Many authors studied hemodynamic, functional and morphological human saphenous veins alterations caused by these different forces with conflictant results. This review text was motivated with the specific aim of analyze literature data and some experimental data carried out in our laboratory. The adopted review subjects were: 1) Endothelial responses and gene regulation to shear stress; 2) Effects of the hydrostatic pressure in the endothelial cell morphology, gene expression of the endothelial cellular surface and proliferation of endothelial cells; 3) Effects of the traction on the human saphenous vein endothelium.

Endothelium dysfunction caused by acute pressure distension of human saphenous vein used for myocardial revascularization.

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.

New insights in endothelial and smooth muscle cell communication.

Based on immunohistochemical techniques against connexins and the intercellular flux of staining molecules, it has previously been shown that electrotonic communication occurs among endothelial and vascular smooth muscle cells, this due to the presence of myoendothelial gap junctions. The aim of this study was to evaluate the density of myoendothelial contacts in the left coronary and internal mammary arteries as well as in the left saphenous vein by means of electron microscopy, the distance between both cells participating in an myoendothelial contact with a semi-automatic image analysis system and the presence of homocellular and heterocellular gap junctions between endothelial and smooth muscle cells by using the immunohistochemical technique and confocal microscopy in thoracic aorta were also analyzed. The results are that all blood vessels studied present myoendothelial contacts, while density studies show that they are more abundant in the saphenous vein. The myoendothelial contact distance is constant and in no case the cytoplasmic processes reach the plasma membrane of the partner cell toward which they are advanced. Homocellular gap junctions were found between smooth muscle cells and between endothelial cells. Heterocellular gap junctions were absent, evidencing the possibility that signaling molecules between endothelial and smooth muscle cells may be transferred through plasma membranes as was once thought and not necessarily by electrotonic communication.

Efecto agudo de las estatinas sobre la relajación vascular in vitro mediada por acetilcolina y nitroprusiato en vasos usados en la revascularización coronaria / Acute effect of statins on acetylcholine and nitroprusside induced vascular relaxation of vessels used for revascularization purposes

Antecedentes: Uno de los efectos pleiotrópicos de las estatinas es su capacidad de inducir relajación vascular tanto in Vitro como in Vivo cuando son administradas crónicamente, pero el efecto agudo en los vasos no ha sido estudiado en detalle. Objetivos: Evaluar los efectos agudos de las estatinas en la relajación vascular in vitro mediada por acetilcolina (ACh) y nitroprusiato en vasos usados en revascularización coronaria. Método: Se analizaron segmentos de vasos obtenidos de pacientes programados para cirugía de revascularización coronaria. Cada segmento de arteria radial, mamaria y vena safena fue dividido en dos, uno de ellos incubado durante dos horas con estatinas y el otro con solución buffer. Luego, se contrajo cada vaso con 80 mM de KCl y posteriormente con 10-4 M de noradrenalina seguido de administración de dosis acumulativas de ACh para inducir la relajación del vaso. Después de lavados repetidos, se contrae con la misma dosis de noradrenalina y se relaja con dosis creciente de nitroprusiato (NP). Resultados: La administración de KCl produjo una mayor contracción, aunque no significativa, en arterias radiales en relacióna los otros vasos, tanto en los incubados con estatinas como el grupo control. La noradrenalina produjo una mayor contracción no significativa en venas safenas; sin embargo no hubo diferencias entre los segmentos incubados con y sin estatinas. La vasodilatación por acetilcolina no se vio afectada por estatinas. La vasodilatación inducida por nitroprusiato no se modificó en presencia de estatinas en arterias radiales o mamaria. Sin embargo el tratamiento con estatina disminuyó significativamente la relajación inducida por nitroprusiato en la vena safena (p<0,05). Conclusión: Los resultados de este trabajo demuestran una respuesta diferencial de los vasos usados en revascularización coronaria frente al efecto agudo de estatina.

Relationship between the diameter of great saphenous vein and body mass index

OBJECTIVE: This study has been designed to correlate the diameter of the greater saphenous vein in different levels of the lower limbs with the body mass index of each individual to determine a possible relation between them. METHODS: Fifty-two lower limbs in 26 volunteers (six males and 20 females) without a chronic venous disease record, aged 21-68 were evaluated. Prior to color-flow duplex scanning the body mass index was defined. The deep and superficial venous systems and perforator veins were assessed as described in the literature. The diameter of the greater saphenous vein was measured with ultrasound longitudinal imaging in seven different levels. For the statistical analysis, Student t test for paired data and Spearman test were used. RESULTS: The difference observed in saphenous venous in the second and third levels when compared to the lower right and left limbs was not considered significant and a single group was formed to correlate with body mass index. The correlation was considered statistically irrelevant. CONCLUSION: By correlating the diameters of the greater saphenous vein with the body mass index of each individual it was noted that the relation between them is not significant, therefore it can be assumed that tall thin individuals can have greater saphenous vein with similar diameter as short fat individuals.

OBJETIVO: Este estudo teve o objetivo de comparar o diâmetro da veia safena magna em diferentes níveis dos membros inferiores e o índice de massa corporal dos sujeitos para determinar uma possível relação entre esses fatores. MÉTODOS: Cinqüenta e dois membros inferiores de 26 voluntários (seis homens e 20 mulheres) sem registro de doença venosa crônica, com idades entre 21 e 68 anos, foram avaliados. O índice de massa corporal foi definido antes do eco-Doppler colorido. Os sistemas venosos superficial e profundo e as veias perfurantes foram avaliados de acordo com a literatura. O diâmetro da veia safena magna foi medido através de imagem ultra-sonográfica longitudinal em sete níveis diferentes. Para a análise estatística, foram utilizados o teste t de Student para dados pareados e o teste de Spearman. RESULTADOS: A diferença observada na veia safena no segundo e terceiro níveis, quando comparada aos membros inferiores direito e esquerdo, não foi considerada significativa, e somente um grupo foi formado para a comparação com o índice de massa corporal. A correlação foi considerada estatisticamente irrelevante. CONCLUSÃO: Através da comparação dos diâmetros da veia safena magna com o índice de massa corporal dos sujeitos, percebeu-se que a relação entre esses dois fatores não é significativa e, portanto, pode-se concluir que indivíduos altos e magros podem ter veias safenas magnas com diâmetros similares aos de indivíduos baixos e gordos.

O eco-Doppler colorido na avaliação das varizes recidivadas / Color-flow duplex scanning in assessment of recurent varicose veins

Objetivo: O objetivo do presente trabalho é avaliar a aprevalência de refluxo no coto da veia safena magna em pacientes com recidiva de varizes pós-safenectomia, de forma isolada e associada a outras causas de recidiva. Método: Durante 3 anos, foram avaliados prospectivamente, com o eco-Doppler colorido, 469 pacientes com varizes recidivadas previamente submetidos à cirurgia de varizes com safenectomia. A maioria dos pacientes era do sexo feminino (424 mulheres e 45 homens), com média de idade de 53,5 anos (25 a 82 anos). Foram analisados, ao todo, 683 membros inferiores. em cada membro, foram avaliados os cotos da veia safena magna, bem como todos os possíveis pontos de refluxo do sistema superficial, profundo e veias perfurantes que pudessem estar relacionados à recidiva, de forma isolada ou associada...

Cardiac and vascular effects of diltiazem, dobutamine and amrinone, drugs used after myocardial revascularization.

Hemodynamic care during postoperative management of myocardial revascularization should include vasorelaxing drugs to insure adequate graft and coronary flow, and stimulation of stroke volume to maintain vascular perfusion pressure. We tested the cardiac (inotropic and lusitropic) and vascular (relaxant) effects of diltiazem (0.1 nM to 0.1 mM), dobutamine (10 microM to 10 mM) and amrinone (10 microM to 1 mM) on isolated rat atria and thoracic aorta, and also on isolated human saphenous vein (HSV) and human mammary artery (HMA). Dobutamine produced a maximal positive inotropic effect (+dF/dt max = 29 +/- 7%) at its ED50 for aortic relaxation (88 +/- 7 microM). Conversely, at their ED50 for aortic relaxation diltiazem depressed myocardial contractility and amrinone did not exhibit myocardial effects. In HSV and HMA contracted with 80 mM potassium, diltiazem and dobutamine (but not amrinone) had a vasorelaxant activity similar to that in rat aorta. Norepinephrine-contracted human vessels were significantly more sensitive than potassium-contracted vessels to the relaxant effect of amrinone (ED50 HMA = 15 +/- 5 microM, ED50 HSV = 72 +/- 31 microM, P < 0.05). We conclude that at concentrations still devoid of myocardial effects dobutamine and amrinone are effective dilators in graft segment vessels and rat aorta contracted by membrane depolarization. If the difference between aortic and myocardial tissue still holds in human tissues, at the appropriate concentrations these drugs should be expected to improve cardiac performance while still contributing to the maintenance of graft patency.

[Structural and functional aspects of the human saphenous vein used as aorto-coronary graft in myocardial revascularization]. / Aspectos estructurales y funcionales de la vena safena humana utilizada como puente aorto-coronario en la cirugia de revascularización miocárdica.

The human saphenous vein (HSV) is currently used as a graft in coronary revascularization as well as in some other vascular beds, namely those of the inferior limbs. Since a significant proportion of HSV grafts develop stenosis, many studies have focused on the factors that could promote graft failure. This article reviews the results on structural and functional features that might be concurrent in the production of saphenous vein graft stenosis. The reactivity of HSV to several physiological agonists is analyzed, including those derived from the endothelium with contractile or relaxing properties, since these are relevant inducers of graft spasm and/or modifiers of the expression of graft factors involved in either tissue growth or thrombotic-atherosclerotic processes. Mechanisms that regulate vascular smooth muscle contractile state, in particular the activity of K+ channels of the plasma membrane, are described.

Aspectos estructurales y funcionales de la vena safena humana utilizada como puente aorto-coronario en la cirugia de revascularización miocárdica / Structural and functional aspects of the human saphenous vein used as aorto-coronary graft in myocardial revascularization

La vena safena humana (VSH) se utiliza como puente en la cirugía de revascularización coronaria y de otros lechos arteriales, especialmente de miembros inferiores. Dado que los puentes de VSH presentan un porcentaje considerable de obliteración, numerosos estudios han investigado los factores que promoverían la producción de la estenosis en los mismos. Este artículo describe resultados sobre las condiciones estructurales y funcionales que confluyen para producir la obstrucción de los puentes de VSH. Se analiza la reactividad de la VSH a agonistas fisiológicos, incluídos los factores contrayentes y relajantes derivados del endotelio, por su importancia en determinar el vasoespasmo y en modificar la expresión de factores de crecimiento tisular y/o promotores de procesos trombóticos y ateromatosos. Se describen mecanismos involucrados en la regulación del estado contráctil de los miocitos lisos, en particular la actividad de canales de K+ de la membrana

Aspectos estructurales y funcionales de la vena safena humana utilizada como puente aorto-coronario en la cirugia de revascularización miocárdica / Structural and functional aspects of the human saphenous vein used as aorto-coronary graft in myocardial revascularization

La vena safena humana (VSH) se utiliza como puente en la cirugía de revascularización coronaria y de otros lechos arteriales, especialmente de miembros inferiores. Dado que los puentes de VSH presentan un porcentaje considerable de obliteración, numerosos estudios han investigado los factores que promoverían la producción de la estenosis en los mismos. Este artículo describe resultados sobre las condiciones estructurales y funcionales que confluyen para producir la obstrucción de los puentes de VSH. Se analiza la reactividad de la VSH a agonistas fisiológicos, incluídos los factores contrayentes y relajantes derivados del endotelio, por su importancia en determinar el vasoespasmo y en modificar la expresión de factores de crecimiento tisular y/o promotores de procesos trombóticos y ateromatosos. Se describen mecanismos involucrados en la regulación del estado contráctil de los miocitos lisos, en particular la actividad de canales de K+ de la membrana

Vasorelaxant effects of the potassium channel opener SR 47063 on the isolated human saphenous vein and rat aorta.

The vasorelaxant effects of SR 47063 (4-(2-cyanimino-1, 2-dihydropyrid-1-yl)-2,2-dimethyl-6-nitr ochromene), a new K(+)-channel opener structurally related to levcromakalim, were examined in isolated human saphenous vein (HSV) and rat aorta (RA). HSV or RA rings were precontracted with either KCl or noradrenaline and cumulative relaxant concentration-response curves were obtained for SR 47063 (0.1 nM to 1 microM) in the presence or absence of 3 microM glibenclamide. SR 47063 potently relaxed HSV and RA precontracted with 20 mM (but not 60 mM) KCl or 10 microM noradrenaline in a concentration-dependent manner, showing slightly greater activity in the aorta. The potency of the effect of SR 47063 on HSV and RA was 12- and 58-fold greater, respectively, than that reported for the structurally related K(+)-channel opener levcromakalim. The vasorelaxant action of SR 47063 in both blood vessels was strongly inhibited by 3 microM glibenclamide, consistent with a mechanism of action involving ATP-dependent K(+)-channels.

The antineoplastic agent paclitaxel (Taxol) increases contractile activity in human saphenous veins and human mammary arteries.

Effects of the antineoplastic agent paclitaxel (Taxol) were studied on contractions of isolated human saphenous vein (HSV) and mammary artery (HMA). Peak force developed by vascular segments with cumulative concentrations of physiologic agonists was enhanced by paclitaxel, producing a shift to the left of dose-response curves. Paclitaxel 1 microM decreased ED50 (in microM) for norepinephrine from 1.01 +/- 0.24 to 0.20 +/- 0.06 (n = 16, p < 0.05) in HSV and from 1.30 +/- 0.30 to 0.51 +/- 0.21 (n = 15, p < 0.05) in HMA and for 5-hydroxytriptamine from 0.64 +/- 0.19 to 0.21 +/- 0.07 (n = 20, p < 0.05) in HSV. Paclitaxel 1 microM also significantly increased the peak force of contractions elicited by endothelin-1 0.01 microM in HSV. In contrast, it did not affect contractions evoked by KCl 80 mM. These results show that paclitaxel produces a hyperreactivity in human vessels challenged by physiologic agonists, which suggests that administration of paclitaxel to patients could augment peripheral resistance and increase blood pressure.

Differential vasorelaxant effects of levcromakalim and P1060 in the isolated KCl- and RbCl-precontracted human saphenous vein: possible involvement of intracellular Ca2+ stores.

The influence of rubidium-substituted physiological salt solution (Rb-PSS) on the relaxant effects of K+ channel openers was investigated in the human saphenous vein. In tissues precontracted with 20 mM KCl (in K-PSS) levcromakalim and P1060 produced complete, sustained relaxations. However, in Rb-PSS (containing 20 mM RbCl) these effects were inhibited and, although complete relaxations still occurred, were transient. When caffeine was applied at the beginning of this fade of levcromakalim-induced relaxation in Rb-PSS its contractile effect was potentiated. Similarly, the contraction to noradrenaline was potentiated when applied at the beginning of this fade of levcromakalim-induced relaxation, whereas this response was attenuated in control tissues bathed in 20 mM KCl (in K-PSS). Our results show that the relaxant effects of K+ channel openers in human saphenous vein are inhibited in Rb-PSS, in agreement with previous studies in animal tissue, and suggest that an increased Ca2+ uptake into intracellular stores may be contributory to vasorelaxation.

[Reactivity of internal mammary artery and saphenous vein used in human myocardial revascularization: studies with endogenous vasoconstrictors and vasodilators]. / Reactividad de la arteria mamaria interna y vena safena utilizadas en revascularización miocárdica humana: estudios con vasoconstrictores y vasodilatadores endógenos.

Biopsies of human internal mammary artery and saphenous vein were examined to ascertain the functional integrity of these vessels employed in myocardial revascularization. Studies were performed in vascular rings derived from 28 patients without previous consideration of age, sex, underlying additional pathology or drug treatments previous to and during surgery. Isometric muscle contraction of the circular muscle layer was monitored. Endothelin-1 (ET) is equipotent as a vasoconstrictor in arteries and veins, with a potency at least 10 to 100-fold that of noradrenaline (NA) or serotonin (5-HT). The potency of ET, NA or 5-HT is unaltered by mechanical removal of the endothelial cell layer. Arterial rings precontracted with NA relaxed in a concentration-dependent fashion in the presence of acetylcholine and sodium nitroprusside. Whereas the potency of nitroprusside was unaltered by removal of the endothelium, the efficacy of acetylcholine was greatly reduced. Saphenous vein rings were refractory to acetylcholine but not nitroprusside. Results open new perspectives to explain the larger patency of internal mammary artery grafts as compared to that of saphenous vein grafts in human myocardial revascularization.