Distention promotes platelet and leukocyte adhesion and reduces short-term patency in pig arteriovenous bypass grafts.

A pig model of autologous saphenous vein to common carotid artery bypass grafting was developed. An end-to-end anastomotic technique led to lower middle graft and distal turbulence. Saphenous veins were surgically prepared with or without distention at 600 mm Hg, implanted into the arterial circulation, and removed 2 hours later. Medial integrity was then assessed by adenosine triphosphate/adenosine diphosphate concentration ratio, and endothelial integrity, leukocyte and platelet adhesion by scanning electron microscopy. In grafts made with undistended vein adenosine triphosphate/adenosine diphosphate concentration ratio was not significantly lower (3.0 +/- 0.1, n = 32) than in freshly isolated vein (3.3 +/- 0.1, n = 26), endothelial cover was 98% +/- 1%, n = 6, and there was little platelet or leukocyte adhesion. In distended grafts adenosine triphosphate/adenosine diphosphate concentration ratio was reduced to 2.2 +/- 0.2 (n = 7, p less than 0.005), endothelial cover was reduced to 38% +/- 14% (n = 6, p less than 0.001), and there was extensive platelet and leukocyte adhesion to exposed subendothelium. In separate experiments graft patency measured at 1 to 5 weeks was significantly greater (96%, n = 25) when undistended vein was used than when distended vein was used (64%, n = 25, p less than 0.005). The data show that distention leads to medial and endothelial damage and that this is associated with increased platelet and leukocyte adhesion and with reduced early patency.

Quantitation and localization of apolipoproteins [a] and B in coronary artery bypass vein grafts resected at re-operation.

Lp[a] is a lipoprotein whose plasma concentration is highly correlated with cardiovascular disease. Its protein moiety, apoLp[a], consists of two large polypeptides, apo[a] and apo B. The possible contribution of Lp[a] to atherosclerosis in saphenous vein aortocoronary bypass grafts was studied in a population of patients undergoing coronary re-bypass surgery. The vein graft tissue levels of apoLp[a] were compared with graft duration, gross and light microscopic pathology, as well as plasma levels of apoLp[a]. The localization pattern of apo[a] and apo B in vein graft tissue was determined. In addition, the plasma levels of cholesterol, triglycerides, apoproteins (apo) A-I, A-II, and E were measured. In a representative subpopulation of 17 patients with a mean age of 63 years from whom grafts with a mean duration of 112 months were resected, the mean total plasma cholesterol level was 221 mg/dl, the mean high density lipoprotein cholesterol level was 31 mg/dl, and the mean plasma triglyceride level was 228 mg/dl. In normal saphenous veins, the level of apoLp[a] was below measurable limits (less than 2 ng/mg), and the level of apo B was very low (3.3 ng/mg). In resected grafts, the mean tissue level of apoLp[a] was 32 ng/mg, and that of apo B was 70 ng/mg, demonstrating the net accumulation of these apoproteins in veins from the time of their grafting into the arterial bed. The apoLp[a]/apo B ratio was determined in 77 tissue segments from 59 grafts (28 patients) and was found to be 0.313. This tissue ratio was significantly higher (p = 0.02) than the plasma apoLp[a]/apo B ratio from these patients, which was 0.132. Immunostaining showed co-localization of apo[a] and apo B in the neointima of grafts. The most abundant pathologic features observed in resected grafts were proliferated intima (43/52), thrombus (28/52), and atherosclerotic core regions (21/52). The level of tissue apo B correlated well with the abundance of core regions (r = 0.501), whereas the level of tissue apoLp[a] did not correlate as well with this feature (r = 0.233). Although apo[a] and apo B are almost absent from normal saphenous vein, these apoproteins (and presumably the lipoproteins Lp[a] and low density lipoprotein) accumulate in bypass vein grafts. The data support the view that these lipoproteins play a significant role in vein graft atherosclerosis.

Viscoelastic properties and collagen content of the long saphenous vein in normal and varicose veins.

Veins taken from patients undergoing surgery for varicose veins were compared with those obtained from patients undergoing other surgical procedures ('normals'). Varicose veins had a lower breaking strength and breaking energy than normal veins. Elastic stiffness was less in normals (tan theta = 41 (24] than in varicose veins (tan theta = 55 (18); P less than 0.01). There was no difference in viscoelastic behaviour between samples taken above, at, or below the valve leaflet insertion. In normals, perivalvular vein wall exhibited a 50 per cent lower breaking strength and elastic stiffness than vein from other sites. Collagen content was significantly higher in normal vein specimens in all sites examined (mean collagen content = 70 (21) micrograms/mg, versus 51 (20) micrograms/mg for varicose veins; P less than 0.001). We conclude that significant structural changes are seen in varicose veins. In normal veins, the perivalvular vein wall has distinct viscoelastic features when compared with vein wall from other sites. This difference was not found in veins which became varicose.

[Quantitative determination of tissue-type plasminogen activator in varicose soleus veins]. / Détermination quantitative de l'activateur du plasminogène tissulaire dans les veines soléaires variqueuses.

Any thrombotic affection can involve the deep veins as well as the superficial veins of the calf. It is considered that venous thrombosis may be a result of low concentrations of the activator of plasminogen levels in the vein wall, which produces a mediocre fibrinolytic response. The concentrations of the activator of plasminogen in these veins are little knows. Immediately after amputation, for pain in the decubitus position, samples of the soleus vein (N = 9) and long saphenous vein (LSV; N = 9) were removed and frozen in liquid nitrogen. In 6 limbs operated for varicose veins, samples of the vein in the calf (VC; N = 6) were removed and frozen. As a control, we examined samples of normal veins removed from the groin of patients undergoing hernia repairs. The quantitative determination of the activator of plasminogen was achieved thanks to a homogenate technique, and the results were expressed in taps by the minute by a tissue microgram. The median activity and the range of results were: LSV 1675 (777-8119); soleus vein 6795 (2232-21 570); CV 2356 (676-4099); inguinal veins 11 221 (6717-13 410). The low concentration of activator of plasminogen in the calf veins may contribute to a mediocre fibrinolytic response in these veins. This is not likely to be the case in the soleus veins. The results may indicate a different thrombotic mechanism in the two types of veins.

Adaptation of canine saphenous veins to grafting. Correlation of contractility and contractile protein content.

Saphenous veins are used extensively to replace stenotic coronary arteries. However, the contractile and biochemical adaptations of grafted veins are unknown. The three purposes of this work were to characterize the contractile properties of grafted veins, to determine whether altered contractile characteristics were associated with quantitative changes in actin, myosin and collagen, and to determine which changes were associated with the surgical procedure and which with placement in the arterial circulation. Canine saphenous veins were removed and returned to their original location (venous autograft), while others were used to replace a segment of femoral artery (arterial graft). The grafts were removed 1, 4, and 8 weeks later and compared with the contralateral saphenous vein. Both graft types exhibited an increase in sensitivity to norepinephrine but not to potassium chloride. The venous autograft exhibited a reversible reduction in myosin content and in maximum contractile response (force/cross-sectional area) to potassium chloride and norepinephrine. In contrast, the arterial graft exhibited increased wall thickness and content of all measured proteins and decreased maximum contractile response. The latter occurred even though there was an increase in the net production of actin and myosin. Expressing the maximum contractile response in terms of the myosin content did not normalize the contractile response. These results suggest that, except for the elevated sensitivity to norepinephrine, the vein is capable of recovering from the effects of surgery within 8 weeks; however, placement of the vein in the arterial circulation delays this recovery and initiates a hypertrophic response that includes an attenuation of contractile function.

Factor VIII-related antigen in occluded human arteries and grafts.

Direct immunofluorescence was used to determine the disposition of factor VIII-related antigen (VIIIR:Ag) in occluded arteries and grafts from patients undergoing reconstructive operation. The presence of VIIIR:Ag on the luminal surface of these vessels was equated with their endothelialization according to the work of others. In 12 of the 20 arteries examined, stain for VIIIR:Ag was absent or markedly reduced from the luminal surfaces, and in six more it was only present focally. The adventitial capillaries were brightly stained in most of these specimens. Both of two saphenous vein grafts and all of six Dacron grafts stained for VIIIR:Ag along their luminal surfaces and in the adventitial capillaries as brightly as normal arteries. However, all of eight Gore-tex grafts had little or no stain for VIIIR:Ag along their luminal surfaces, and the capillaries of the adventitia were not as plentiful as those in the normal arteries and Dacron grafts. With one exception, the Gore-tex grafts had become occluded less than 1 year after implantation, while the Dacron grafts had remained patent for 2 to 8 years. Thus many of the diseased arteries and the short-lived Gore-tex grafts were characterized by relative absence of VIIIR:Ag from their luminal surfaces, presumably reflecting the loss or absence of endothelialization.

Abnormalities of vascular wall sodium content in dogs with benign and malignant renal hypertension.

The water and sodium content of the saphenous vein was measured in 26 dogs with one-kidney, one wrapped hypertension. For comparison, the same measurements were performed on the contralateral saphenous vein which was removed prior to the induction of hypertension. Malignant hypertension characterized by blindness and a rise in plasma renin activity, developed in 10 dogs. The course of hypertension in the remaining 16 dogs was benign. In benign hypertension, the water and sodium content of the saphenous vein was increased. In contrast, the water content of the saphenous vein was unchanged and its sodium content fell in dogs with malignant hypertension. The dogs with malignant hypertension had a greater sodium content of the saphenous vein prior to the induction of hypertension than the dogs with benign hypertension. The findings indicate that the loss of body water and sodium that has been described in malignant hypertension also affects the composition of blood vessels. The sodium content of blood vessels may be a predictor of the dog's response to a hypertension-producing stimulus.

Adrenergic transmitter release.

Presynaptic release-modulating receptors on sympathetic nerve fibres have been found not only in a great number of animal tissues but also in various human blood vessels. Although basically the same types of receptors are present in animals and man (e.g., inhibitory muscarinic receptors and alpha 2-adrenoceptors; facilitatory beta-adrenoceptors), there may be considerable species differences if a certain blood vessel or the effect of a certain agonist or antagonist is considered. Hormones may also influence noradrenergic transmission by acting presynaptically. Thus, ACTH increases the impulse-evoked noradrenaline (NA) release in the rabbit pulmonary artery by activating presynaptic ACTH receptors, and an adenylate cyclase may be involved in this effect. Results obtained with new pharmacological tools (forskolin and selective inhibitors of cAMP phosphodiesterase) support the suggestion that the sympathetic nerves of the rabbit pulmonary arteries are endowed with an adenylate cyclase activation of which increases evoked NA release.

Functional postsynaptic alpha 2- but not alpha 1-adrenoceptors in dog saphenous vein exposed to phenoxybenzamine.

Phenoxybenzamine greatly attenuated phenylephrine-induced contractions of dog saphenous vein in vitro, but had less effect on contractions induced by clonidine. The phenoxybenzamine-resistant responses to clonidine were not affected by prazosin or by corynanthine but were competitively antagonized by yohimbine (pA2 8.2). It is concluded that exposure of saphenous vein to phenoxybenzamine resulted in blockade of alpha 1-adrenoceptors to the extent that there remained a virtually homogeneous population of postsynaptic alpha 2-adrenoceptors. The effects of agents at postsynaptic alpha 2-adrenoceptors can be studied on this preparation without the complications caused by the presence of functional alpha 1-adrenoceptors.

Uptake and metabolism of noradrenaline by blood vessels of perinephritic hypertensive dogs.

Tissue noradrenaline content as well as uptake and metabolism of tritiated exogenous noradrenaline were studied comparatively, in vitro in mesenteric arteries, and in saphenous veins of normotensive and perinephritic hypertensive dogs. The influence of cocaine, iproniazid and 3'-4'-dihydroxy-2-methyl-propiophenone (U-0521) on these variables was also investigated. The concentration of (-)-7-3H-noradrenaline used was 1.08 microM. No changes were observed in noradrenaline content, uptake and metabolism in saphenous vein strips obtained from normotensive or hypertensive animals. However, in mesenteric artery strips obtained from hypertensive dogs, a marked reduction in endogenous noradrenaline content was observed as well as a reduction in noradrenaline accumulation (20 weeks after surgery). The deamination pattern was also modified in these strips: the formation of DOPEG was markedly diminished and the formation of DOMA was increased. These results agree well with the degeneration of the sympathetic innervation of the mesenteric arteries of hypertensive dogs described by Azevedo et al. (1981).

Connective tissue in varicose veins.

The collagen, elastin, total sugar, and nonscleroprotein content was evaluated in 32 samples of saphenous varicose vein and in 34 controls. A significantly lower collagen and elastin content was found in the varicose samples without correlation with the degree of pathologic broadening. Otherwise the total sugars and the soluble nonscleroproteins were found to be increased in varicose samples. The results are more significant when expressed as milligrams per surface unit of endothelium. Our data support the hypothesis that the decrease in collagen and elastin content is a primary rather than secondary change.

[The mineral composition of veins and arteries as a function of age]. / Die mineralische Zusammensetzung von Venen und Arterien als Funktion des Alters.

In the present investigation the contents of sodium, potassium, calcium, magnesium, iron, copper, and zinc were determined in ashes of cadaver material from great saphenous veins and arteries.

Collagen, elastin and sugar content in primary varicose veins.

The collagen, elastin and total sugar content was evaluated in 32 samples of saphenous varicose veins and in 34 controls. A significantly lower collagen and elastin content was found in the varicose samples. In addition, the total sugars and the soluble non-scleroproteins were found to be increased in varicose samples. The results are more significant when expressed as mg per unit surface of endothelium. Our findings support the hypothesis that the decrease in collagen and elastin content is a primary rather than a secondary change.

Norepinephrine metabolism in canine saphenous vein: prevalence of glycol metabolites.

To examine the disposition of [3H]norepinephrine ([3H]NE) in adrenergically innervated veins, helical strips of canine saphenous veins were incubated in Krebs-Ringer solution containing D,L[3H]NE (2 X 10(-7) M) for 2 h. [3H]NE and its metabolites were measured in extracts of veins and in superfusate (Krebs-Ringer) collected during basal conditions and during release of [3H]NE evoked by electrical stimulation (1-8 Hz), tyramine (5 X 10(-6) to 5 X 10(-4) M), or high concentrations of potassium (35-100 meq/liter). During basal conditions, the efflux from veins comprised mainly metabolits of [3H]NE, especially 3,4-dihydroxphenylglycol (DOPEG) and 3-methoxy-4-hydroxyphenylglycol (MOPEG); this pattern was unchanged by cocaine treatment, and monoamine oxidase inhibition reduced the formation of DOPEG. During evoked release of NE, the major metabolites in the perfusate were DOPEG, MOPEG, and normetanephrine, and their proportions differed with the stimulus used: O-methylated metabolites in the perfusate always increased more than did the deaminated catechol compounds; DOPEG and MOPEG were released in greater amounts than the corresponding acids; and cocaine treatment caused a higher content of all metabolites except DOPEG. 3-Methoxy-4-hydroxymandelic acid was also formed by the vein but was retained in the tissue.

[Studies on investigation of primary pathologic deterioration of the lower limbs. The contents of calcium, magnesium, sodium and potassium in the walls of veins (author's transl)]. / Studien zur Abklärung der primär krankhaften Veränderungen der unteren Extremitäten. Untersuchungen des Calcium-, Magnesium-, Natrium- und Kaliumgehaltes der Venenwand

The content of calcium, magnesium, potassium and sodium in the walls of v.femoralis, v.saphena and v.brachialis was measured with atomic-absorption spectrometry. Calcium showed distinct differences among the veins with increasing age. There is a remarkably high increase and more inhomogenous distribution for calcium in the v.femoralis of older people.

Further study of the adrenoceptors of the saphenous vein of the dog: influence of factors which interfere with the concentrations of agonists at the receptor level.

In the present study the affinities of some sympathomimetic amines for alpha- and beta-adrenoceptors of the dog saphenous vein tissue were determined after all known factors interfering with the concentration of these agonists at the receptor level had been assessed and excluded. It was observed that in control experiments the relative potencies of sympathomimetic agonists for inducing contractions were: adrenaline (1.6) greater than noradrenaline (1.0) greater than phenylephrine (0.38) greater than isoprenaline (0.009). The elimination of neuronal uptake by cocaine, 4 X 10(-6) M, enhanced predominantly the effects of noradrenaline (by a factor of 7.5), whereas block of catechol-O-methyl transferase (COMT) by U-0521, 10(-4) M, only enhanced those of adrenaline (by a factor of 2.6) and block of beta-adrenoceptors by propranolol, 5 X 10(-7) M, enhanced those of isoprenaline (by a factor of 3) and adrenaline (by a factor of 1.8). Block of COMT enhanced the effects of adrenaline approximately as much as did the blockade of neuronal uptake; this seems to indicate that the affinity of adrenaline for extraneuronal and neuronal uptake processes is approximately the same. Regarding the relaxation-inducing capacity of sympathomimetic agents it was observed that isoprenaline, adrenaline and noradrenaline are full agonists, whereas phenylephrine was not able to produce relaxation amounting to more than 5% of the maximum. Denervation did not modify the relaxant effects of isoprenaline. After elimination of all known factors interfering with the concentration of the sympathomimetic agonists in the biophase, the ratios between the ED50's of each amine for alpha- and beta-adrenoceptors were: adrenaline = 34, noradrenaline = 109 and isoprenaline = 0.0041.

Free amino acids in normal and varicose human saphenous veins.

An increase in the activity of lysosomal enzymes in varicose veins has been suggested in the literature, as well as an alteration of collagen fibrils situated near muscle cells. In view of these results, we have compared the free amino acid contents of varicose veins with those of healthy veins removed few hours after death. The amino acid analyses of extracts have shown that the varicose vein appears to contain about 2.7 times more free amino acids than normal one, except in the case of phosphoethanolamine. Controls have shown that this discrepancy can be ascribed to a rapid liakage of the amino acids after death. The absence of hydroxyproline suggests that collagen does not seem liable to degradation in the varicose vein. On the other hand, the constant phosphoethanolamine content found can be attributed to a much higher concentration of this compound in the varicose vein or alternatively, to a postmortem process of degradation, compensating for the losses due to diffusion.