Maintained geometry, elasticity and contractility of human saphenous vein segments stored in a complex tissue culture medium.

OBJECTIVE: Improved maintenance of endothelial function and higher viability of saphenous vein grafts stored in a complex tissue culture medium (TCM) have been demonstrated. This article studies the biomechanical properties of saphenous vein segments. DESIGN: Biomechanical properties of 72 saphenous vein segments remaining from coronary bypass grafting of 32 patients have been studied after different storage procedures. MATERIALS: The materials studied included fresh segments, segments stored in a cooled conventional physiological salt solution (normal Krebs-Ringer (nKR)) for 1-2 weeks, segments stored in a cooled chemically defined TCM (X-Vivo) for 1,2,3 and 4 weeks and segments cryopreserved for a few weeks. METHODS: Specimens were cannulated at both ends and pressure-diameter curves were recorded in the 0-85-mmHg range in nKR with 10 microM norepinephrine added to induce maximum smooth muscle contraction, as well as in Ca(2+)-free medium to induce full relaxation. Tensile strength was checked at 300 mmHg. Distensibility, elastic modulus and active strain were computed. RESULTS: Segments stored in nKR dilated morphologically, their distensibility decreased and they lost their ability to contract (1.5+/-0.7% from 10.1+/-1.5% of control) in 1 week. The TCM-stored segments preserved their contractility until 1 week, and this parameter only slowly decreased afterwards (first week, 11.5+/-7.3%; fourth week, 3.9+/-0.6%). There was a slight decrease in wall thickness but the lumen diameter was not affected. The elastic parameters of these segments were practically identical to those of fresh segments. Cryopreserved segments narrowed morphologically, their wall thickened and contractility diminished. CONCLUSIONS: Storage in TCM helps preserve the passive and active biomechanical properties of human saphenous vein segments. Such properties can be expected to improve graft tissue viability.

Generalized alterations in the biomechanical properties of large veins in non-thrombotic thrombophilic young patients.

AIM: In young, post-thrombotic patients, venous distensibility is decreased not only in the affected lower limb, but also in the contralateral limb and in the jugular vein when compared to age-matched control subjects. In the present study, we investigated venous wall mechanical properties in young, asymptomatic thrombophilic patients. METHODS: Eleven young (24+/-0.4 years) control subjects and 9 age-matched patients (21.1+/-1.8 years) with proven thrombophilic molecular defects, but without any signs or history of previous deep vein thrombosis, were compared. Anterolateral and mediolateral diameters of the common femoral, axillary and internal jugular veins were measured by ultrasonography in situ. Pressure alterations were induced by altering body positions and by pressure-controlled Valsalva tests. Distensibility was calculated from diameter and pressure changes. RESULTS: In thrombophilic patients, resting diameter of both the common femoral and of internal jugular veins at low transmural pressure was larger than those for the control subjects. Distensibility, however, was significantly less when high pressures were applied. Alterations in diameter of the axillary vein were minimal. CONCLUSION: Our measurements suggest that there are generalized changes in venous mechanical properties in thrombophilic patients even before the appearance of thrombotic processes. These biomechanical alterations of the venous wall and/or surrounding connective tissue are similar to those found in connection with aging and in post-thrombotic patients. The pathological mechanisms behind these processes are unknown.

Chronic administration of quercetin induces biomechanical and pharmacological remodeling in the rat coronary arteries.

Acute dilation brought about by the dietary flavonoid quercetin in coronary arterioles has been described earlier, but no information is available on its chronic effects. Male Wistar rats (body weight about 190 g) were divided to two groups: the quercetin-treated group (n=22) had quercetin supplementation of approximately 30 mg/kg/day, whereas the control group (n=20) had none. After eight weeks of treatment, intramural coronary arterioles with identical passive diameters (178+/-14 microm and 171+/-9 microm) were prepared and their biomechanics and pharmacological reactivities were tested using pressure arteriography ex vivo. The spontaneous tone of quercetin-treated arteries was higher (16.5+/-1.9 % vs. 12.9+/-0.9 %), which resulted in a reduced lumen size (144+/-9 microm vs. 167+/-12 microm), thicker vascular wall (22.6+/-1.8 microm vs. 17.4+/-1.6 microm) and decreased tangential wall stress (16.8+/-1.1 kPa vs. 20.5+/-1.6 kPa) in supplemented animals (in spontaneous tone at 50 mm Hg, p<0.01 in all these comparisons). Elevated basal NO release resulted in increased endothelial dilation in quercetin-treated animals, especially at higher intraluminal pressures (10.8+/-2.5 % vs. 5.7+/-1.3 % at 70 mm Hg, p<0.01). We found remodeling of the geometry of coronary arterioles to ensure higher dilatory reserve and nitrogen monoxide production, as well as lowered elastic stress of the vessel wall.

A simple standard technique for labyrinthectomy in the rat: A methodical communication with a detailed description of the surgical process.

Aims Labyrinthectomized rats are suitable models to test consequences of vestibular lesion and are widely used to study neural plasticity. We describe a combined microsurgical-chemical technique that can be routinely performed with minimum damage. Methods Caudal leaflet of the parotis is elevated. The tendinous fascia covering the bulla is opened frontally from the sternomastoid muscle's tendon while sparing facial nerve branches. A 4 mm diameter hole is drilled into the bulla's hind lower lateral wall to open the common (in rodents) mastoid-tympanic cavity. The cochlear crista (promontory) at the lower posterior part of its medial wall is identified as a bony prominence. A 1 mm diameter hole is drilled into its lower part. The perilymphatic/endolymphatic fluids with tissue debris of the Corti organ are suctioned. Ethanol is injected into the hole. Finally, 10 µL of sodium arsenite solution (50 µM/mL) is pumped into the labyrinth and left in place for 15 min. Simple closure in two layers (fascia and skin) is sufficient. Results and conclusion All rats had neurological symptoms specific for labyrinthectomy (muscle tone, body position, rotatory movements, nystagmus, central deafness). Otherwise, their behavior was unaffected, drinking and eating normally. After a few days, they learned to balance relying on visual and somatic stimuli (neuroplasticity).

Regional differences in statistical geometry of endothelial dense granules in human extremity veins.

OBJECTIVES: Leg and arm human veins are exposed to different gravitational stresses. We investigated if there is difference in the amount and geometry of secretory vesicles in their endothelium. METHODS: Superficial small vein segments were removed during vascular operations for electromicroscopic analysis. Vesicular area/total endothelial cross-sectional area was determined by computer-based morphometry. Long and short axes of granule cross sections were measured by image analyzing software. RESULTS: Vesicular density in all samples was 2.26 ± 0.34%. There was no significant difference between the vesicular densities of upper extremity and leg. The shape of the vesicles was more frequently elongated in leg than in arm sections (p < 0.01). CONCLUSIONS: The density of the vesicles does not depend on vascular region or orthostatic load. Ellipticity of these granules is significantly different in areas exposed to different gravitational stresses. This might contribute to the differences of thrombotic and hemodynamic properties of leg and upper body veins.

Effect of two week lymphatic occlusion on the mechanical properties of dog femoral arteries.

In order to study the long-term effect of impaired lymphatic drainage on the mechanical properties of the arterial wall, cylindrical femoral artery segments from 10 mongrel dogs after 2 weeks of hindlimb lymphatic occlusion were subjected to in vitro mechanical test and compared with the contralateral, sham-operated segments. Smooth muscle contraction was induced by norepinephrine (7.4 X 10(-6) M) and smooth muscle relaxation by papaverine (1.6 X 10(-4) M). As a result of 2 weeks of lymphatic occlusion, wall thickness increased from 243 +/- 18 to 343 +/- 35 microns (P less than 0.02), inner radius decreased from 1.69 +/- 0.11 to 1.42 +/- 0.12 mm (P less than 0.01) and elastic modulus decreased from 1.23 X 10(6) to 0.55 X 10(6) N/m2 (P less than 0.01), when determined at 100 mm Hg (13.3 kPa) intraluminal pressure and with relaxed smooth muscle. The contractile apparatus was able to produce active strain in the vessels with lymphostasis and at physiological pressures not significantly different from the controls (0.89 +/- 0.02 vs. 0.91 +/- 0.02), but at significantly lower levels of tangential stress. Active stress decreased significantly. This study shows that a reorganization of the vessel wall mechanical force-bearing elements occurs in lymphostasis, which, in some respects, resembles the mechanical alterations found in different forms of atherosclerosis.

Effect of ovariectomy and hormone replacement therapy on small artery biomechanics in angiotensin-induced hypertension in rats.

OBJECTIVES: To test the effects of chronic angiotensin II administration on blood pressure and small artery biomechanics in the female sex hormone-depleted state (proposed to increase cardiovascular vulnerability) and with hormone replacement. DESIGN: Biomechanical properties of saphenous artery segments from ovariectomized (n = 10), ovariectomized + chronically angiotensin II infused-(n = 10), and ovariectomized + chronically angiotensin II-infused + sex hormone-replaced (n = 10) rats were studied. METHODS: Surgical ovariectomy was performed. Osmotic minipumps were used for chronic angiotensin II infusion (100 ng/min per kg). For hormone replacement therapy, oestradiol-propionate, 450 microg/kg for 7 days + medroxyprogesterone-acetate, 15 mg/kg for 14 days were given, intramuscularly. After 4 weeks, cylindrical segments of the saphenous artery were prepared and subjected to in-vitro microarteriographic measurements. Pressure-diameter curves (0-200 mmHg) were recorded in Krebs-Ringer solution, with smooth muscle contracted (norepinephrine, 16 micromol/l) and with relaxed (papaverine, 28 micromol/l). RESULTS: Chronic angiotensin II infusion significantly reduced the inner radius (at 100 mmHg: 298 +/- 17 microm versus 347 +/- 7 microm, P< 0.001), while wall-thickness did not change. Hormone replacement restored the morphological radius (333 +/- 7 microm). Angiotensin II infusion slightly increased the full contraction range of the segments (defined as the percentage difference between fully contracted and fully relaxed diameters), which was further significantly increased by hormone replacement (39 +/- 4%, 46 +/- 8%, 62 +/- 7% at 100 mmHg, in the three groups, respectively; P < 0.05). Despite unaltered stiffness in relaxed state, elastic moduli computed for the contracted segments decreased after hormone replacement. CONCLUSIONS: These observations give further experimental support to the hypothesis that sex hormone replacement might be useful in preventing the development and/or stabilization of postmenopausal hypertension, as well as in treating existing disease.

Sex hormone replacement therapy reverses decreased venous distensibility in pharmacologically ovariectomized rats.

OBJECTIVE: To test the effect of female sex hormone depletion and replacement on the distensibility and geometry of the saphenous vein in female rats. DESIGN: Twenty Sprague-Dawley rats were pharmacologically ovariectomized by triptorelin. Ten of these animals received combined hormone replacement with estradiol and medroxyprogesterone acetate. The rest were given vehicle. Ten animals kept parallel without pharmacological ovariectomy served as controls. After 3 months of treatment, a segment of the saphenous vein was dissected. Pressure-diameter curves were recorded in relaxed, contracted, and control states using a microangiograph. RESULTS: Pharmacological ovariectomy lowered venous wall distensibility measured in contraction (at P=8 mm Hg: 4.41+/-1.21*10(-3) m2/N vs. control: 0.79+/-0.14*10(-3) m2/N; p < 0.05). Hormone replacement partially restored this value (1.8+/-0.49*10(-3) m2/N). No alterations in distensibility were found in the relaxed state. After adjusting for body weight, we found that pharmacological ovariectomy lowered venous inner radius significantly compared with control (p < 0.05), whereas hormone replacement increased it compared with pharmacological ovariectomy (p < 0.05) and more significantly compared with control (p < 0.01). CONCLUSION: Sex hormone depletion induces significant alterations in venous distensibility, presumably by inducing initial remodeling of the venous wall. Hormone dependency of distensibility differed in relaxed and contracted states of the vein, so some alterations of contractile elements of the wall may be hypothesized. Lower distensibility of the venous wall found after pharmacological ovariectomy could be part of the mechanism of predisposition for postmenopausal hypertension. This can be reversed by female sex hormone replacement.

Acute, nongenomic vasodilatory action of estradiol is attenuated by chronic estradiol treatment.

Deficiency of estradiol or chronic estrogen treatment may alter the responses to this hormone in many tissues. A possible interaction between the acute nongenomic and the chronic effects of estradiol on microvessels have not been investigated yet. In the present study we have investigated whether acute in vitro vasodilatory action of estradiol on a small artery is altered by chronic estradiol pretreatment. Female rats were surgically ovariectomized and subjected to either estradiol replacement therapy (estradiol propionate, 450 micrograms/kg/week) or vehicle administration for 5 weeks. Cylindrical segments of the saphenous artery were studied using videocomputerized microarteriography in vitro. Estradiol, in concentrations of 10(-6) to 10(-4) M relaxed norepinephrine precontracted vessel segments in a dose-dependent manner. Magnitude of relaxation observed in arteries of estradiol replaced animals was significantly smaller at all concentrations than that of nonreplaced ovariectomized rats; maximal relaxation in the control ovariectomized group was 64.5% +/- 3.6%, while it was 34.3% +/- 4.2% only in the ovariectomized and estradiol replaced group (P < 0.001). Comparison of acute relaxations in response to papaverine and nifedipine failed to prove a reduced activity of the general relaxation machinery in estradiol replaced animals. We conclude that chronic estradiol replacement can downregulate the acute nongenomic vasorelaxation effect of this hormone in small arteries of ovariectomized rats.

Hormone replacement reduces elevated in vivo venous tone in hypertensive ovariectomized rats.

OBJECTIVE: The venous system may play a role in the development and progression of postmenopausal hypertension. In the present study, we investigated the effect of chronic angiotensin II-induced hypertension on the geometric, elastic, and contractile properties of the saphenous vein in sex hormone deficient and replaced female rats. METHODS: Thirty Sprague-Dawley rats were ovariectomized (n = 10), ovariectomized and angiotensin-infused (n = 10), or ovariectomized plus angiotensin-infused and hormone replaced with estradiol and medroxyprogesterone (n= 10). After 4 weeks, the saphenous veins were removed and cylindrical segments of the vessels were placed into a microangiograph and cannulated at both ends. Intraluminal pressure versus outer diameter curves were registered in Krebs-Ringer solution, in maximal norepinephrine contraction, and in full papaverine relaxation. RESULTS: In vivo venous tone of the saphenous vein in ovariectomized plus angiotensin-infused animals was significantly higher than in ovariectomized animals without angiotensin treatment (27.2 +/- 3.7% versus 5.3 +/- 2.1%, respectively; P <.05). Hormone replacement restored venous tone (9.6 +/- 3.4%; P <.01). In vitro pressure-induced myogenic tone was markedly reduced by chronic angiotensin infusion, which was partially reversed by hormone replacement. Passive incremental distensibility was lowered after angiotensin infusion independently of the sex hormone state. CONCLUSION: Hormone replacement improved venous contractility (rapid adaptation response), which was seen as decreased in vivo venous tone, but venous distensibility (chronic adaptation) was not improved by hormone replacement in our short-term study. We demonstrate beneficial short-term effects of hormone replacement on the venous system in our model of postmenopausal hypertension. Further studies might be warranted to see whether long-term benefits can be achieved.

Effects of combined sex hormone replacement therapy on small artery biomechanics in pharmacologically ovariectomized rats.

OBJECTIVES: The purpose of this study was to determine the effects of long-term combined sexual hormone replacement therapy on the biomechanical properties of the small artery wall in castrated female rats. METHODS: 30 non-pregnant mature female Sprague-Dawley rats were pharmacologically ovariectomized with 750 microg/kg triptorelin im. every 4th week. Ten of them received combined hormone replacement in form of 15 mg/kg medroxyprogesterone acetate (MPA) im. every 2 weeks and 450 microg/kg estradiol propionate im. once a week. Ten castrated animals received MPA only. Ten control, castrated animals were given the vehicles of these steroids. Ten other animals were kept parallelly, receiving the vehicles of all drugs (control animals). After 12 weeks of treatment cylindrical segments of the saphenous artery were isolated and cannulated at both ends and subjected to in vitro microarteriographic test. Pressure diameter curves, in the range of 0-200 mmHg, were recorded from segments in normal Krebs-Ringer (nKR) solution, in contraction with norepinephrine (1.6 x 10(-5) M), and then in relaxation with papaverine (2.8 x 10(-5) M). Biomechanical parameters were calculated based on the pressure diameter curves. RESULTS: Combined hormone replacement therapy significantly increased the passive diameter of small arteries, as compared to those from ovariectomized animals without hormone replacement. MPA monotherapy did not alter the vessel diameter, the inner radii at 100 mmHg intraluminal pressure were, 300+/-9 microm in the control castrated, 340+/-7 microm in the estradiol + MPA replaced and 306+/-8 microm in the MPA treated groups (P < 0.05 between the control castrated and the combined treatment groups). The vascular reactivity to norepinephrine or papaverine was not changed significantly either by combined hormone replacement or by MPA monotherapy when compared with ovariectomized controls. No significant alterations were found in wall thickness and distensibility. CONCLUSIONS: These results suggest that chronic medroxyprogesterone pretreatment does not influence the geometric, elastic and contractile properties of small arteries in castrated female rats. The combination of MPA + estradiol increased the morphological lumen: the morphological vasodilatation induced by estrogen, described earlier, was not affected by the addition of this progestin to the regimen.

Remodeling of the rat saphenous vein network in response to long-term gravitational load.

Our main objective was to test whether chronic orthostatic body position induces network changes in the saphenous vein superficial tributary system of the rat. Fourteen male Sprague-Dawley rats were kept in tilted tube cages (45-degree head-up position) for two weeks to induce chronic gravitational load to their leg veins. Ten animals housed in normal cages and four animals kept in horizontally positioned tube cages served as controls. The whole superficial network of the left saphenous vein was microprepared surgically under anesthesia, superfused with saline and observed under a videomicroscope, while normal flow and pressure were maintained in the lumen. Branching angles, lengths of venous segments and their diameters were measured offline from digitized images using special image-analyzing software. Several branching angles at the popliteal confluence were significantly reduced by 12.5-15.8 %. The in vivo diameter of the main branch (936+/-34 vs. 805+/-44 microm) and of one of the popliteal tributaries (776+/-38 vs. 635+/-36 microm) increased (p<0.05), comparing vessels from tilted animals with those from normal controls. Maintaining the animals in horizontal tube cages did not induce the above alterations. The increased diameters and reduced branching angles of the saphenous vein network observed are adaptive responses of the venous network to a long-term gravitational load.

Determination of venous blood flow velocity using digital videomicroscopy (A short methodical communication).

BACKGROUND/AIM: There is a limited number of methods to measure blood flow velocity in small veins. A cheap and simple new videomicroscopic method developed in our laboratories is described in the paper. METHODS: A stretch of the saphenous vein of the rat was exposed by careful micropreparation on the thigh of anesthetized animals. Bolus amount (approx. 5 µl) of saline was infused into a small side branch through a microcannula to dilute flowing blood. Videomicroscopic picture of the vein was then taken of the exposed upstream stretch of the vein. Serial pictures were digitized and analyzed using macro functions of the Image J software. Sensitive areas of serial pictures were selected and fitted. Consecutive pictures were subtracted from each other to better characterize their alteration in-between frames. Greyscale intensity values measured at different points of the inner diameter were averaged for each point of the vessel axis. Cross-correlations along the axis were then computed for consecutive frames with delays of 40, 80, 120 and 160 msec. Pixel offsets producing cross-correlation maxima were determined and used to compute mean flow velocity. RESULTS: Combination of digital subtraction and cross-correlation computations yielded easily identifiable maximums. Mean flow velocities could be determined with limited uncertainty. CONCLUSION: The described technique gives a cheap, simple and reproducible mean to determine mean blood flow velocities in small veins in anesthetized animals, where other current techniques (ultrasonography, laser-Doppler, fluorescently labelled red cell movement) are either expensive or can be applied with difficulty only.

Biomechanics and vasoreactivity of female intramural coronaries in angiotensin II induced hypertension.

Hypertension causes small vessel remodeling, vasomotor alterations. We investigated diameter, tone and mechanics of intramural small coronaries of female rats that received chronic angiotensin treatment to induce hypertension.Angiotensin II infusion (AII, 100 ng/bwkg/min, sc.) was used to establish hypertension in 10 female rats. Other 10 rats served as controls. Following 4 weeks of treatment, side branches of the left anterior descendant coronary (diameter approximately 200 microm) were isolated, cannulated and pressure-diameter curves were registered between 2-90 mmHg. Changes in vessel diameter were measured in Krebs solution, in the presence of thromboxane A2 receptor agonist (U46619, 10(-6) M), bradykinin (BK, 10(-6) M), and finally at complete relaxation (in Ca2+-free solution). Chronic AII treatment raised the mean arterial pressure (130+/-5 mmHg vs. 96+/-2 mmHg, average +/-SEM) significantly. Wall thickness of the AII group was significantly greater (40.2+/-4.2 microm vs. 31.4+/-2.7 microm at 50 mmHg in Ca2+ -free solution), but cross-section of the vessel wall did not differ. Tangentional wall stress and elastic modulus decreased significantly in hypertensive animals. Constrictions in the presence of U46619 were greater in the AII group (24.4+/- 5.6% vs. 14.5+/-3.3% at 50 mmHg). In hypertension, intramural small coronaries showed inward eutrophic remodeling, as a morphological adaptation following AII treatment enhanced thromboxane A2-induced tone.

Nitric oxide modulates the interaction of pressure-induced wall mechanics and myogenic response of rat intramural coronary arterioles.

Interactions between the biomechanical characteristics and pressure-induced active response of coronary microvessels are still not well known. We tested the hypothesis that pressure-dependent biomechanical characteristics of the coronary vascular wall are modulated by the active myogenic response and local vasodilators. We have utilized data obtained previously in isolated rat intramural coronary arterioles (approximately 100 microm in diameter), in which the diameter was investigated as a function of intraluminal pressure (Szekeres et al.: J. Cardiovasc. Pharmacol., 43, 242-249, 2004). To characterize the magnitude of myogenic response, diameter was expressed as percent of passive diameter as a function of pressure (normalized diameter; ND). In addition, circumferential wall stress (WS) and incremental distensibility (ID) were calculated. In control conditions, after an initial increase between 0-30 mm Hg, ND decreased substantially as pressure increased from 30 to 150 mm Hg. Correspondingly, WS gradually increased as a function of pressure (from 0.3 +/- 0.03 to 34.7 +/- 4.4 kPa) exhibiting a plateau phase between 40-80 mm Hg. In contrast, ID decreased and reached negative values (min: -104.9 +/- 21.9 10(-6) m2/N at 50 mm Hg). Inhibition of nitric oxide (NO) synthase by L-NNA decreased basal diameter (approximately 35% at 2 mm Hg), eliminated pressure-induced changes in ND, reduced the slope of pressure-WS curve, and decreased ID at lower pressures. Simultaneous administration of L-NNA and adenosine (which restored initial diameter, i.e. length of smooth muscle) restored--in part--the pressure-induced reduction in ND, reversed the pressure-induced behavior of WS to control, but not that of ID. These results not only confirm that in coronary arterioles wall stress is regulated by the myogenic response, but also suggest that there is interplay between the mechanical behavior of the wall and the myogenic response. Furthermore, the presence of NO seems to be necessary for maintaining a higher distensibility of intramural coronary arterioles allowing increases in diameter to lower pressures, which then activate the myogenic mechanism resulting in constrictions and full development of myogenic tone, as indicated by the presence of negative slope of pressure-diameter curve in the presence of NO.

Pharmacological modulation of prostacyclin and thromboxane production of rat and cat venous tissue slices.

To reveal a potential modulating effect of vasoactive pharmacological agents on the prostanoid production of the venous wall, prostacyclin and thromboxane release from venous tissue slices was studied. Aortic and caval vein samples from 20 rats as well as from 21 cats were studied. Prostacyclin and thromboxane productions were determined by radioimmunoassay as 6-keto-PGF1 alpha and TxB2 released into the incubation medium. Venous tissue produced significantly less prostacyclin per unit weight than arterial tissue in rats (30.7 +/- 4.6 vs. 52.1 +/- 8.2 pg/mg/min), while in cats an opposite situation was found (16.6 +/- 3.2 vs. 7.06 +/- 1.9 pg/mg/min). Thromboxane production of venous tissue was consequently higher than corresponding values for aortic tissue (3.72 +/- 0.46 vs. 1.54 +/- 0.14 in rats and 3.4 +/- 0.6 vs. 1.33 +/- 0.19 in cats, all values in pg/mg/min). Norepinephrine and dopamine significantly increased both the prostacyclin and the thromboxane release from venous tissue, while isoproterenol had no effect. Vasopressin significantly increased thromboxane release and decreased the ratio of prostacyclin vs. thromboxane production (from 10.4 +/- 1.6 to 7.5 +/- 1.6, in acetylsalicylic acid pretreated cats). Angiotensin and thrombin had no significant effects. Bradykinin (0.5 microgram/ml) significantly augmented prostacyclin release from venous tissue (14.4 +/- 2.6 from 10.9 +/- 2.4 pg/mg/min) and decreased thromboxane release (0.65 +/- 0.18 from 1.35 +/- 0.22 pg/mg/min). Methionine-enkephalin (5 micrograms/ml) significantly reduced the thromboxane release from venous tissue slices. The presented material demonstrates that several vasoactive agents modulate the vasoactive prostanoid release of the venous wall. In some cases, the prostacyclin and the thromboxane productions are influenced separately, which in turn will have its impact on smooth muscle activity and thrombocyte aggregation.

In vivo dose-response characteristics of endothelin-1: studies on rat saphenous vein.

Microangiometric studies were made in vivo on rat saphenous vein to obtain dose-response contraction curves with endothelin-1. During superfusion of the drug, threshold concentrations were found to be in the range of 4 x 10(-11) -4 x 10(-10) moles/lit, maximal concentrations were about 4 x 10(-8) moles/lit. These values are close to published in vitro threshold values. During intravascular administration of the drug contraction could be observed in response to a dose as small as 4.37 femtomoles/s. The data presented show that characteristic dose response curves resembling those found in vitro can be recorded in vivo with endothelin on appropriate vascular preparata. The rat in situ saphenous vein microangiometric technic can be used for delicate pharmacologic examination of venoactive substances in vivo.

Spontaneous periodic contraction of the ampullar segment of the human fallopian tube in vitro.

Spontaneous mechanical activity of 36 segments from the ampullar part of human Fallopian tubes was studied in vitro. The age of the patients varied between 37-64 years. Outer diameter and axial tension were continuously measured at an intraluminal pressure of 5 mmHg (0.67 kPa) and at 10% axial extension. All segments have shown periodic contractions both in diameter and axial tension. The amplitude of the outer diameter contractions was 0.03-0.64 mm, the frequencies were between 1.5 and 7.3 min-1. The amplitude of the axial tension contractions was 1.87-33.2 mN, the frequencies varied between 1.8 and 7.6 min-1. The diameter and axial tension contractions were mostly synchronized. The frequency of the basal rhythm increased with age. Increase of the intraluminal pressure up to 15 mmHg (2.0 kPa) significantly increased the diameter and decreased the amplitude of diameter contractions. Increase in the axial length significantly decreased the outer diameter and the amplitude of diameter contractions; it also increased axial tension, and caused a transitory increase in frequency.

Effect of pharmacological agents on the activity of the circular and longitudinal smooth muscle layers of human fallopian tube ampullar segments.

The in vitro determination of the effects of some pharmacological agents on the outer diameter and axial tension of human Fallopian tube ampullar segments showed that some drugs may act on the circular and longitudinal smooth muscle layers relatively separately. PGF2 alpha elicited an excitatory response in both muscle layers while norepinephrine and isoproterenol decreased the activity. Oxytocin and indomethacin had relatively limited effects on the spontaneous motility of the ampullar segments. The calcium antagonist verapamil inhibited the spontaneous periodic activity.

Are there systemic changes in the arterial biomechanics of intracranial aneurysm patients?

Current theories on the development of intracranial aneurysm suggest that there is a general weakness of vascular connective tissue. Potential systemic alterations in arterial wall biomechanics were tested in the present study. A three-dimensional in vitro stress-strain analysis was made in the 0-200-0 mmHg pressure range on cylindrical segments excised from the anterior cerebral artery, the radial artery and from the arteria dorsalis pedis of aneurysm patients and of control cadavers. In the anterior cerebral artery from aneurysm patients (intracranial artery segments directly not affected by the aneurysm or by the subarachnoid bleeding), we found the wall thickness to be larger (0.1480+/-.019 versus 0.091+/-0.004 mm), the radius/wall thickness ratio smaller (9.7+/-1.4 versus 14.1+/-1.2), and the tangential wall stress lower [(0.122+/-0.019)x10(6) versus (0.181+/-0.016)x10(6) N/m2 at 100 mmHg] than in control subjects. Reduced radius was found in the extremity arteries studied. Elastic parameters, as incremental distensibility and elastic modulus, were remarkable similar. Our study demonstrates changes in the geometry of walls of arteries not directly affected by aneurysm formation, and it thus confirms systemic vascular pathology in this disease. At the same time, these data show that the molecular and morphological defects of arterial connective tissue formation generally thought to induce intracranial aneurysms will probably not affect the components responsible for the passive elastic properties of the vascular wall.