Endothelial and neural factors functionally involved in the modulation of noradrenergic vasoconstriction in healthy pig internal mammary artery.

The role of endothelial and neural factors as modulators of neurogenic- and noradrenaline-induced vasoconstriction was examined in healthy pig internal mammary artery (IMA). Tetrodotoxin-, guanethidine-sensitive electrical field stimulation (EFS)-, and noradrenaline-elicited contractions were significantly diminished by prazosin (n=8, P<0.001) and less so by rauwolscine, indicating functional α1- and α2-adrenoceptor-mediated noradrenergic innervation of the IMA. Endothelium removal reduced neurogenic (n=8, P<0.01) but augmented noradrenaline responses (n=8, P<0.01), suggesting the release of two endothelium-dependent factors with opposite effects. In the presence of endothelium, neurogenic and exogenous noradrenaline vasoconstrictions were enhanced by L-NOArg (n=7, P<0.05 and P<0.01 respectively) and ODQ (n=7, both P<0.05); in denuded arteries, nNOS inhibition with N(ω)-propyl-L-arginine increased neurogenic contraction (n=7, P<0.05). Western blotting indicated the presence of neural and endothelial origin NO (n=6, P<0.001). Tetraethylammonium (n=9, P<0.001), iberiotoxin (n=7, P<0.001) and 4-aminopyridine (n=8, P<0.01) enhanced vasoconstrictions revealing a modulatory role of big conductance Ca²âº-activated K⁺ (BK(Ca)) and voltage-dependent K⁺ (K(v)) channels in noradrenergic responses. Bosentan pretreatment (n=8, P<0.05) suggested endothelin-1 as the inferred contractile neurogenic endothelial-dependent factor. Indomethacin-induced inhibition involved a muscular prostanoid (n=9, P<0.05), functionally and immunologically localized, and derived from cyclooxygenase (COX)-1 and COX-2, as revealed by Western blots (n=5, P=0.1267). Thus, noradrenergic IMA contractions are controlled by contractile prostanoid activation and endothelin-1 release, and offset by BK(Ca) and K(v) channels and neural and endothelial NO. These results help clarify the mechanisms of vasospasm in IMA, as the preferred vessel for coronary bypass.

Histomorphometric and sympathetic innervation of the human internal thoracic artery.

INTRODUCTION: Internal thoracic artery (ITA) is an established arterial graft for the coronary artery by-pass surgery. Special micro-anatomical features of the ITA wall may protect it from age related pathological changes. One of the complications seen after coronary artery bypass grafting is vasospasm. Sympathetic nerves may be involved in vasospasm. OBJECTIVE: To ascertain the sympathetic innervation of the internal thoracic artery and to assess the effect of aging on this artery by histomorphometry. METHOD: Fifty-four human internal thoracic artery samples were collected from 27 cadavers (19 male and 8 female) with ages of 19 to 83 years. Samples were divided into three age groups: G1, 19-40 years; G2, 41-60 years; G3, >61 years. Sections (thickness 5 mm) of each sample were taken and stained with hematoxylin-eosin and Verhoeff-Van Gieson stains. Five of fifty-four samples were processed for tyrosine hydroxylase immunostaining. RESULTS: The thickness of the tunica intima was found to be constant in all age groups, whereas the thickness of the tunica media decreased in proportion to age. Verhoeff-Van Gieson staining showed numerous elastic laminae in the tunica media. Significant differences (p < 0.0001) in the number of elastic laminae were found between G1 with G2 cadavers, between G2 and G3 cadavers and between G3 and G1 cadavers. Tyrosine hydroxylase immunostaining demonstrated sympathetic fibers, located mainly in the tunica adventitia and the adventitia-media border. The sympathetic nerve fiber area and sympathetic index were found to be 0.0016 mm² and 0.012, respectively. DISCUSSION: Histology of the ITA showed features of the elastic artery. This may be associated with lower incidence of Atherosclerosis or intimal hyperplasia in ITA samples even in elderly cases. Low sympathetic index (0.012) of ITA may be associated with fewer incidences of sympathetic nervous systems problems (vasospasm) of the ITA. CONCLUSION: Sympathetic nerve fibers are present in the adventitia of the internal thoracic artery. This is an elastic artery, although anatomically it is considered to be medium-sized. The sympathetic index may be used for analysis of sympathetic nerve fiber-related problems of the internal thoracic artery.

Histomorphometric and sympathetic innervation of the human internal thoracic artery

INTRODUCTION: Internal thoracic artery (ITA) is an established arterial graft for the coronary artery by-pass surgery. Special micro-anatomical features of the ITA wall may protect it from age related pathological changes. One of the complications seen after coronary artery bypass grafting is vasospasm. Sympathetic nerves may be involved in vasospasm. OBJECTIVE: To ascertain the sympathetic innervation of the internal thoracic artery and to assess the effect of aging on this artery by histomorphometry. METHOD: Fifty-four human internal thoracic artery samples were collected from 27 cadavers (19 male and 8 female) with ages of 19 to 83 years. Samples were divided into three age groups: G1, 19-40 years; G2, 41-60 years; G3, >61 years. Sections (thickness 5 mm) of each sample were taken and stained with hematoxylin-eosin and Verhoeff-Van Gieson stains. Five of fifty-four samples were processed for tyrosine hydroxylase immunostaining. RESULTS: The thickness of the tunica intima was found to be constant in all age groups, whereas the thickness of the tunica media decreased in proportion to age. Verhoeff-Van Gieson staining showed numerous elastic laminae in the tunica media. Significant differences (p<0.0001) in the number of elastic laminae were found between G1 with G2 cadavers, between G2 and G3 cadavers and between G3 and G1 cadavers. Tyrosine hydroxylase immunostaining demonstrated sympathetic fibers, located mainly in the tunica adventitia and the adventitia-media border. The sympathetic nerve fiber area and sympathetic index were found to be 0.0016 mm² and 0.012, respectively. DISCUSSION: Histology of the ITA showed features of the elastic artery. This may be associated with lower incidence of Atherosclerosis or intimal hyperplasia in ITA samples even in elderly cases. Low sympathetic index (0.012) of ITA may be associated with fewer incidences of sympathetic nervous systems problems (vasospasm) of the ITA. CONCLUSION: Sympathetic ...

Both skeletonized and pedicled internal thoracic arteries supply adequate graft flow after coronary artery bypass grafting even during intense sympathoexcitation.

The internal thoracic artery (ITA) is harvested by either the pedicled or the skeletonized technique in coronary artery bypass grafting (CABG), with no clear advantage of one technique over the other. We compared graft flow between the pedicled and skeletonized ITA grafts while varying myocardial oxygen demand. CABG was performed to the left anterior descending artery in five anesthetized dogs using a pedicled ITA graft and the graft was subsequently skeletonized. Graft flow was measured during stepwise electrical stimulation of the stellate ganglion. The baseline graft flow before sympathetic stimulation was higher in skeletonized (27.8 ± 1.9 ml/min) than that in pedicled ITA grafts (22.6 ± 2.7 ml/min) (P < 0.05). In both ITA grafts, however, graft flow increased to a similar level during sympathetic stimulation that doubled the double product, correlating with the double product. Based on these results, we conclude that metabolic demand can override the potential difference in sympathetic vasoconstriction in both pedicled and skeletonized ITA grafts.

Colgajo de perforantes de arteria epigrástica superior para cobertura de defecto cutáneo preesternal / Covergae of a presternal skin defect with a superior epigastric perforator Flap

Los colgajos basados en arterias perforantes representan hoy en día una muy buena alternativa para la reconstrucción y cobertura de defectos cutáneos. Sus numerosas ventajas tales como la mínima morbilidad de la zona donante, su fácil recuperación postquirúrgica, su gran versatilidad y la simplicidad que presentan tanto en su planteamiento prequirúrgico como en la técnica misma, han sido algunos de los motivos por los que durante la última década su uso ha tenido un desarrollo notable, siendo quizás el colgajo DIEP el mayor representante de este grupo. Recientemente se ha descrito un tipo de colgajo de similares características basado en arterias perforantes de la arteria epigástrica superior para la cobertura de defectos de la región preesternal baja. En el trabajo actual presentamos un caso clínico en el que una lesión en dicha zona previamente sometida a radioterapia es tratada con este colgajo, obteniendo una cobertura completa de la herida y un resultado estético aceptable (AU)

Perforator flaps nowadays represent a very good therapeutic alternative for reconstruction and coverage of skin defects. Their advantages such as the minimal morbidity of the donor site, their good and easy postsurgical recovery, great versatility and rather simple surgical approach and technique are some of the reasons why these flaps have been rapidly developed over the last decade, being the flap based on perforator from de deep inferior epigastric artery, DIEP flap, probably their main model. A flap of similar characteristics based on perforators coming from the superior epigastric artery has been recently described for the coverage of the lowers ternum region. In this article we present a clinical case in which a wound in this area that had been previously exposed to radiotherapy is treated with a superior epigastric perforator flap, achieving complete coverage of the defect and an acceptable a esthetic result (AU)

Evolution of anterior chest wall blood supply in female adolescents with progressive right-convex thoracic idiopathic scoliosis.

Breast asymmetry was believed to be related to the asymmetry of anterior chest wall blood supply and subsequently to etiology of idiopathic thoracic scoliosis in female adolescents. Recent investigations on the anterior chest wall blood supply with colour Doppler ultrasonography in such individuals did not show anatomic and hemodynamic abnormalities. The present study investigated the evolution of anterior chest wall blood supply in these individuals over a 2-year period. Twenty female adolescents with progressive right-convex idiopathic thoracic scoliosis (scoliotics), who were during the study in therapy with thoracolumbosacral orthosis and 20 age-matched girls, without spine deformity (controls) were studied with colour Doppler ultrasonography [internal mammary artery (IMA)] twice within the 2-year period. IMA-anatomic parameters [lumen diameter (D) and cross sectional area (AR)] and also hemodynamic flow parameters [time average mean flow velocity (TAM) and flow volume per minute (FV)] were measured. In the 2-year period of observation, thoracolumbosacral orthosis prevented scoliosis progression (P=0.004), whereas IMA-AR decreased bilaterally in the individuals of both groups (P<0.03). In the last evaluation: in scoliotics right IMA FV decreased (P<0.04), whereas in controls IMA FV decreased bilaterally (P<0.03); left IMA FV was significantly higher (P<0.05) in scoliotics than in controls. The significant, within the 2-year period, decrease of IMA-diameter, cross-sectional area, and flow volume seems to be a physiologic ageing process because it was observed in all individuals (scoliotics and controls) and thus these anatomic and hemodynamic changes seem not to have been affected by bracing. The maintenance of left flow volume of IMA in the prebrace levels in scoliotics was the most significant finding of this investigation. In conclusion, this study provided evidences for abnormalities in the evolution of anterior chest wall blood supply in female adolescents with progressive right-convex female thoracic scoliosis. Further studies are needed to investigate if this asymmetric blood evolution contributes to the development of this pattern of scoliosis in girls.

Neuropeptide Y is released from human mammary and radial vascular biopsies and is a functional modulator of sympathetic cotransmission.

The role of neuropeptide Y (NPY) as a modulator of the vasomotor responses mediated by sympathetic cotransmitters was examined by electrically evoking its release from the perivascular nerve terminals of second- to third-order human blood vessel biopsies and by studying the peptide-induced potentiation of the vasomotor responses evoked by exogenous adenosine 5' triphosphate (ATP) and noradrenaline (NA). Electrical depolarization of nerve terminals in mammary vessels and radial artery biopsies elicited a rise in superfusate immunoreactive NPY (ir-NPY), which was chromatographically identical to a standard of human NPY (hNPY); a second peak was identified as oxidized hNPY. The amount released corresponds to 4-6% of the total NPY content in these vessels. Tissue extracts also revealed two peaks; hNPY accounted for 68-85% of the ir-NPY, while oxidized hNPY corresponded to 7-15%. The release process depended on extracellular calcium and on the frequency and duration of the electrical stimuli; guanethidine blocked the release, confirming the peptide's sympathetic origin. Assessment of the functional activity of the oxidized product demonstrated that while it did not change basal tension, the NA-evoked contractions were potentiated to the same extent as with native hNPY. Moreover, NPY potentiated both the vasomotor action of ATP or NA alone and the vasoconstriction elicited by the simultaneous application of both cotransmitters. RT-PCR detected the mRNA coding for the NPY Y(1) receptor. In summary, the release of hNPY or its oxidized species, elicited by nerve terminal depolarization, coupled to the potentiation of the sympathetic cotransmitter vasomotor responses, highlights the modulator role of NPY in both arteries and veins, strongly suggesting its involvement in human vascular sympathetic reflexes.

Skeletonization does not influence internal thoracic artery innervation.

BACKGROUND: This study was designed to compare the effect of surgical harvesting on internal thoracic artery innervation and to assess the eventual presence of denervation supersensitivity in skeletonized grafts. METHODS: Nineteen patients who underwent primary isolated coronary artery bypass grafting were randomly assigned to receive a skeletonized (n = 9) or pedicled (n = 10) internal thoracic artery graft. Immunohistochemical nerve localization using anti-S-100 protein, anti-160-kd neurofilament polypeptide and anti-tyrosine hydroxylase antibodies was performed on distal specimens of arteries to study vascular innervation. Moreover, endovascular vasoactive challenges using serotonin and methylergometrine were performed at early angiographic control to evaluate the eventual presence of denervation supersensitivity. RESULTS: Quantitative analysis of immunohistochemical specimens revealed lack of difference in the number of positive cells between skeletonized and pedicled arteries for all the antibodies used. No difference in the reaction to serotonin and methylergometrine was found between skeletonized and pedicled arteries. CONCLUSIONS: Skeletonization does not influence internal thoracic artery innervation.

Lateral costal artery: accessory thoracic vessel of clinical interest.

The lateral costal artery (LCA), a supernumerary branch of the internal thoracic artery (ITA), occurs in several ethnic groups on one side of the thorax or on both, in 15-30% of cases. It has been considered responsible for the "steal-syndrome" of the coronary blood after coronary artery bypass grafting and it used occasionally for myocardial revascularization. To clarify its functional significance, an interpretation based on our findings and human and comparative anatomy and embryology has been attempted. We report on a case where a right LCA of about 2 mm in caliber, rising from the ITA 2.5 cm below the subclavian, coursed as far as the 4th intercostal space for a distance of 13 cm after the anterior axillary line. Anastomosing with the intercostal arteries, it can act as a blood derivative circuit of the thoracic wall. Embryologically, this artery, like the normal parietal arteries of the trunk, might form a longitudinal channel connecting the intersegmental arteries. In mammals having a thoracic cage transversely restricted (quadrupeds), the ITA is more lateral than in primates having a circular thorax, and gives off a ventral branch toward the sternum. It might be hypothesized that the sternal branch occurring in quadrupeds, undergoing adaptation to the thoracic shape of primates, may become the main trunk of the ITA, whereas the LCA may be the remnant of the ITA of quadrupeds. Because the LCA ran partly along the "milk line" of humans, it might be regarded as a supernumerary mammary artery.

Effects of CGS-15943A on the relaxations produced by adenosine analogs in human blood vessels.

The antagonistic effects of CGS-15943A on the relaxations produced by adenosine and its analogs in human blood vessels were investigated in vitro. Donor hearts were the source of coronary arteries, whereas the internal mammary arteries and saphenous veins were obtained from patients undergoing coronary bypass surgery. Adenosine and its analogs, 5'-N-ethylcarboxamidoadenosine (NECA) and 2-chloroadenosine (CAD), produced concentration-dependent relaxations in KCl-contracted coronary rings. CGS-15943A antagonized, significantly, the relaxations produced by adenosine, NECA and CAD in coronary arteries. Similarly, the adenosine receptor antagonist, 8-phenyltheophylline (8PT, 10-mumol/l), caused a significant attenuation of the relaxing responses to adenosine, NECA and CAD in coronary arteries. In rings obtained from internal mammary arteries and saphenous veins, adenosine, NECA and CAD all produced concentration-dependent relaxations. These relaxations were smaller in magnitude than those obtained in coronary arteries, and were slightly greater in rings contracted with 10 mumol/l prostaglandin F2 alpha (PGF2 alpha) as compared to 35 mmol/l KCl. However, the mammary arteries and saphenous veins relaxed completely in response to 100 mumol/l papaverine. CGS-15943A (10 mumol/l) did not antagonize the relaxing effects of adenosine and its analogs in these vessels. The results show that coronary arteries are more responsive than mammary arteries or saphenous veins to the relaxing effects of adenosine analogs and that these relaxing responses are dependent on the contracting agent. Furthermore, CGS-15943A demonstrated antagonism of the adenosine response in coronary arteries.

Differences in alpha-adrenergic responsiveness between human internal mammary arteries and saphenous veins.

Little is known regarding specific biologic and pharmacologic differences between human internal mammary arteries and saphenous veins. To better define the role of alpha-adrenoceptor-mediated vasoconstriction in human internal mammary arteries and saphenous veins, we obtained fresh specimens of both vessels from 32 patients undergoing coronary artery bypass surgery. Dose-response curves were generated for the relatively selective alpha 1-receptor agonist phenylephrine, the alpha 2-receptor agonist BHT-920, and the alpha 1- and alpha 2-receptor agonist norepinephrine. Phenylephrine elicited similar contractile responses in internal mammary arteries and saphenous veins, with a mean EC50 (the effective concentration necessary to produce 50% of the maximal contraction) of 1.4 X 10(-6) M for internal mammary arteries and 1.8 X 10(-6) M for saphenous veins (p = NS). Selective stimulation of alpha 2-receptors with BHT-920 elicited a marked contractile response only in saphenous veins. Dose-response curves for phenylephrine and BHT-920 were shifted to the right for both vessels in the presence of the alpha 1-receptor antagonist prazosin and the alpha 2-receptor antagonist yohimbine, respectively. Norepinephrine elicited contraction at a lower concentration in saphenous veins than in internal mammary arteries with a mean EC50 of 7.8 X 10(-8) M for saphenous veins and a mean EC50 of 3.4 X 10(-7) M for internal mammary arteries (p less than 0.05). The results suggest that alpha-adrenoceptor-mediated vasoconstriction is caused primarily by alpha 1-receptors in human internal mammary arteries and by alpha 1- and alpha 2-receptors in human saphenous veins.