Posterior tibial perforators relationship with superficial nerves and veins: A cadaver study.

BACKGROUND: Most authors have evaluated the location of lower leg arterial perforators, but little is still known about the relationship between the arterial network and great saphenous vein (GSV) and saphenous nerve (SN). The aim of this study is to evaluate the relationship between the arterial network of the posterior tibial artery perforators, the cutaneous nerves, and the superficial venous system in the lower one third of the leg. METHODS: Eighteen lower limbs from cadavers were used for this study. The arterial and venous compartment were selectively injected with a mixture of barium sulfate and epoxy. The specimen were CT scanned and the superficial veins, nerves, and the arterial perforators were dissected. RESULTS: A large perforator of the posterior tibial artery was found at a mean distance of 6.23 cm ± 0.88, with a 95% CI: 5.79-6.67, from the medial malleolus. The average diameter was 0.9 mm ± 0.17, with a 95% CI: 0.81-0.99. In 67% the connection of the venae comitantes to the superficial venous system was established with the GSV, in the other cases, with Leonardo's vein. Both dissection and imaging studies showed perineural interperforator connections along the branches of SN in all the specimens examined. CONCLUSIONS: The distribution pattern of posterior tibial artery perforators followed the superficial nerves in this region. There is an interperforator anastomotic network along the SN. The various patterns of the venous drainage system, in relationship to the distribution of the branches of posterior tibial artery perforators, have been clarified.

Myelinated mouse nerves studied by X-ray phase contrast zoom tomography.

We have used X-ray phase contrast tomography to resolve the structure of uncut, entire myelinated optic, saphenous and sciatic mouse nerves. Intrinsic electron density contrast suffices to identify axonal structures. Specific myelin labeling by an osmium tetroxide stain enables distinction between axon and surrounding myelin sheath. Utilization of spherical wave illumination enables zooming capabilities which enable imaging of entire sciatic internodes as well as identification of sub-structures such as nodes of Ranvier and Schmidt-Lanterman incisures.

Axonal morphological changes following impulse activity in mouse peripheral nerve in vivo: the return pathway for sodium ions.

KEY POINTS: Conduction in myelinated axons involves substantial ion movements that must be reversed to restore homeostasis. The pathway taken by sodium ions returning to their original location and the potential osmotic consequences are currently unknown. We report striking morphological changes in axons following sustained impulse conduction that appear to result from osmosis and to indicate accumulation of ions in the periaxonal space followed by their release at the paranode. We conclude that the morphological changes illustrate a hitherto unrecognized part of normal axonal physiology that may also indicate the return pathway for the sodium ions involved in impulse formation. ABSTRACT: Myelinated axons can conduct sustained trains of impulses at high frequency, but this involves substantial ion movements that must be reversed to restore homeostasis. Little attention has been paid to the potential osmotic consequences of the ion movements or to the pathway taken by sodium ions returning to their original endoneurial location, given that the axolemmal Na(+)-K(+)-ATPase extrudes these ions into the periaxonal space beneath the myelin rather than into the endoneurium. Serial confocal imaging of fluorescent axons conducting at sustained physiological frequencies in vivo has revealed surprising morphological changes that may illuminate these problems. Saphenous nerves and spinal roots of anaesthetized transgenic mice expressing axoplasmic yellow fluorescent protein were stimulated electrically or pharmacologically (veratridine). Within 2 h, the axon herniated on one or both sides of the nodal membrane, displacing the paranodal myelin and widening the nodal gap. The herniated axoplasm became directed back towards the internode, forming a 'cap' up to 30 µm long. Concurrently, the fluid in the expanded periaxonal space accumulated into droplets that appeared to travel to the paranode, where they escaped. No such alterations occurred in axons treated with sodium channel or Na(+)-K(+)-ATPase inhibitors. Remarkably, impulse conduction continued throughout, and all these changes reversed spontaneously over hours or days. The morphological changes were verified ultrastructurally, and occurred in virtually all myelinated axons. The findings appear to reveal an overlooked part of the physiological repertoire of nerve fibres, and here they are interpreted in terms of osmotic changes that may illuminate the pathway by which sodium ions return to the endoneurial space after they have entered the axon during impulse conduction.

Anatomical considerations of the sural nerve in the distal leg: Side branch patterns and significance in nerve harvesting procedures.

BACKGROUND: The sural nerve is a somatosensory nerve that provides sensation to the posterolateral aspect of the lower leg and the lateral part of the ankle and foot. Due to its location and anatomical properties, it is often used as an autologous nerve graft. However, the nerve harvest can be complicated by the presence of side branches. The objective of this study was to investigate the anatomy of the sural nerve and to map its side branches. This information can be used to predict the localization of separate incisions during the stair-step incisions technique for nerve harvest, thereby reducing the risk of complications. METHODS: The study involved the dissection of 50 adult cadaveric legs (25 left and 25 right) obtained from 27 Central European cadavers. The focus of the dissection was to identify the sural nerve, small saphenous vein, and surrounding anatomical structures. Detailed measurements were taken on the side branches of the sural nerve, tributaries of the small saphenous vein, and their interrelationship. RESULTS: The average number of sural nerve side branches in a single leg was 4.2±1.9. These side branches were categorized into six groups based on their location and course: mediodistal, medioproximal, lateroproximal, laterodistal, medial perpendicular, and lateral perpendicular. Specific patterns of combination of these side branches were also identified and described. The branching point of the sural nerve was found to be 5.8±2.7 cm proximal to the lateral malleolus, whereas the small saphenous vein branching point was located more distally, 4.5 ± 2.8 cm proximal to the lateral malleolus. The highest density of sural nerve side branches was found 2.1-6.0 cm above the lateral malleolus. CONCLUSION: This study presents valuable data about the relationship between the sural nerve and the surrounding anatomical structures in the distal part of the leg, including the identification of its side branches and their relevance during nerve harvest procedures. On the basis of the most frequent locations of side branches, a three-incision-technique for nerve harvest is proposed.

The anatomy of the small saphenous vein: fascial and neural relations, saphenofemoral junction, and valves.

PURPOSE: Varicose veins are a frequent burden, also in the small saphenous system. Yet its basic anatomy is not described consistently. We therefore investigated the fascial and neural relationships of the small saphenous vein (SSV) as well as the frequency and position of valves and the different junctional patterns, also considering the thigh extension. MATERIALS AND METHODS: We dissected the legs of 51 cadavers during the regular dissection course held in winter 2007 at Innsbruck Medical University, with a total of 86 SSVs investigable proximally and 94 SSVs distally. RESULTS: A distinct saphenous fascia is present in 93 of 94 cases. It starts with a mean distance of 5.1 cm (SD 1.2 cm) proximal to the calcaneal tuber, where the tributaries to the SSV join to form a common trunk. The neural topography at the level of the gastrocnemius muscle's origins shows the medial sural cutaneous nerve in 88% medially and in 12% laterally to the SSV, the tibial nerve in 64% medially and in 36% laterally, and the common fibular nerve in 98% medially and in 2% laterally to the vein. The saphenopopliteal junction (SPJ) resembled in about 37% type A (UIP-classification), 15% type B, and 24% type C. A total of 17% of specimens showed a venous web or star at the popliteal fossa and 6% had a doubled junction. A thigh extension could be demonstrated in about 84%. A most proximal valve was present in only 94% at a mean distance of 1.2 cm (SD 1.4 cm) to the SSVs orifice. A consecutive distal valve was only present in 65% with a mean distance of 5.1 cm (SD 2.3 cm). CONCLUSION: Two fascial points or regions can be described in the SSVs' course and its own saphenous fascia is demonstrated macroscopically in almost all cases. The neural topography is highly individual. The SPJ is highly individual where we found hitherto unclassified patterns in a remarkable number of veins. Venous valves are not as frequent as we supposed them to be. Furthermore, not all most proximal valves seem to be terminal valves.

Syndesmotic Fixation With Suture Button: Neurovascular Structures at Risk: A Cadaver Study.

OBJECTIVES: The objective of this study was to describe the anatomic variations in the saphenous nerve and risk of direct injury to the saphenous nerve and greater saphenous vein during syndesmotic suture button fixation. METHODS: Under fluoroscopic guidance, syndesmotic suture buttons were placed from lateral to medial at 1, 2, and 3 cm above the tibial plafond on 10 below-knee cadaver leg specimens. The distance and position of each button from the greater saphenous vein and saphenous nerve were evaluated. RESULTS: The mean distance of the saphenous nerve to the suture buttons at 1, 2, and 3 cm were 7.1 ± 5.6, 6.5 ± 4.6, and 6.1 ± 4.2, respectively. Respective rate of nerve compression was as follows, 20% at 1 cm, 20% at 2 cm, and 10% at 3 cm. Mean distance of the greater saphenous vein from the suture buttons at 1, 2, and 3 cm was 8.6 ± 7.1, 9.1 ± 5.3, and 7.9 ± 4.9 mm, respectively. Respective rate of vein compression was 20%, 10%, and 10%. A single nerve branch was identified in 7 specimens, and 2 branches were identified in 3 specimens. CONCLUSION: There was at least one case of injury to the saphenous vein and nerve at every level of button insertion at a rate of 10% to 20%. Neurovascular injury may occur despite vigilant use of fluoroscopy and adequate surgical technique. Further investigation into the use of direct medial visualization of these high-risk structures should be done to minimize the risk. Levels of Evidence: Therapeutic, Level II: Prospective, comparative study.

The saphenous vein as a bypass conduit: the potential role of vascular nerves in graft performance.

The saphenous vein is the most commonly used conduit in patients undergoing coronary artery bypass surgery. However, a high proportion of vein grafts occlude within the first year and over 50% patients require further grafting within 10 years. Using conventional harvesting techniques the saphenous vein is damaged due to considerable surgical and mechanical trauma, a situation that affects graft patency. As a superficial vessel located in the leg, the saphenous vein in man is subjected to variations in orthostatic pressure associated with exercise and alterations in posture. These conditions require the vein's calibre to be regulated predominantly by the autonomic nervous system. While posture-induced changes occur in man, and other bipeds, such alterations in pressure may not occur or be more subtle in other species, conditions that may limit the usefulness of various experimental models. The neural control of the saphenous vein is under the influence of a plethora of neurotransmitters and neuropeptides which, apart from affecting vascular tone, possess mitogenic properties that may contribute to morphological changes caused by vascular injury. In addition to their neurotransmitter role a number of factors have a direct action on vascular smooth muscle cells that affects neural blood flow with subsequent influence on peripheral nerve conduction. Such neurovascular actions may potentially play a role in the altered vein reactivity and structure involved in graft failure. In this review we discuss the pressure changes experienced by the saphenous vein, its innervation and use as a bypass graft for revascularization of ischaemic tissue, in particular the myocardium. Also, we consider the value of various common experimental techniques for studying vasoactive and mitogenic factors and their potential role in vein graft performance.

On the sympathetic innervation of the human greater saphenous vein: relevance to clinical practice.

This review focuses on sympathetic perivascular innervation of human saphenous vein. It shows the distribution of the nerves in the vein wall, including an association of the nerves with the vasa vasorum system. An account of a possible contribution of sympathetic nerves to the physiology of the saphenous vein, as well as their relevance to the outcome of coronary artery bypass surgery that uses the vein as a graft, is discussed.

Distally based saphenous nerve-great saphenous veno-fasciocutaneous compound flap with nutrient vessels: microdissection and clinical application.

Improvements were made by us in several distally based pedicled flaps of the nutrient vessels of the saphenous nerve with lower rotation points. However, these flaps are still insufficient for trauma complicated by bone defects. Accordingly, we conducted a systematic study of the anatomic theory on distally based pedicled compound flaps of the nutrient vessels of the saphenous nerve and great saphenous vein with 30 lower limbs of adult cadavers injected with red gelatin through the femoral artery. It is found that the nutrient vessels of the saphenous nerve-great saphenous vein consist of arteria saphena, fascial cutaneous branches of the inferior medial genicular artery intermuscular spatium branches of the posterior tibial artery, osteocutaneous perforators, superior ankle perforators, medial anterior malleolus perforators, and fascial perforators of the ankle tunnel region. Musculocutaneous perforators of the interior gastrocnemius muscle also enter the nutrient vessels of cutaneous nerve-superficial vein. From May 2004 to February 2007, 23 cases of skin flaps for treating defective and infectious wound, 10 cases of musculocutaneous flaps for treating ulcus in the lower segment of the leg, medullitis, and exposure of bone, 3 cases for medial calcaneus medullitis, 7 cases of skeletal flaps for treating tibial defects and nonunion of calcaneal bone. In 2-15-month follow-ups all cases presented with survived flaps, and healed surfaces of the wound and the osteomyelitis. For cases of bone nonunion, it showed that the nonunion healed after 18 weeks, with recovery of work ability after year. Three types of the distally based pedicled flaps or compound flaps of vessels of different perforating branches can be designed for repairing tissue defects caused by trauma, such as bone defects in the distal leg, nonunion, large necrotic space as well as traumatic surface of the foot and ankle.

Myxofibrosarcoma involving the external saphenous nerve: a case report.

Myxofibrosarcoma, also known as "myxoid malignant fibrous histiocytoma" is one of the most common soft tissue sarcomas in the extremities of adult patients. Most cases are characterized by a multinodular and/or infiltrative pattern with a tendency to infiltrate along fascial planes. We report a case of myxofibrosarcoma with an unusual presentation. Despite the clinical impression of a complete surgical resection, microscopic sarcomatous foci extended along the perineurium of the external saphenous nerve proximally up to 20 cm away from the main tumour. This unique case represents an extreme example of the locally agressive behaviour of soft tissue sarcomas and illustrates the microscopic tumour invasion along major nerves.

Saphenous nerve injury after endovenous laser ablation of incompetent greater saphenous vein: An electroneuromyography study.

AIM: To determine whether endovenous laser ablation of incompetent greater saphenous vein causes a detectable impairment in saphenous nerve conduction. MATERIAL AND METHODS: Thirty-five patients (mean age: 44.78 ± 8.6, male/female ratio: 16/19) who were operated on for incompetent greater saphenous veins, underwent electroneuromyography before and two weeks after the operation. Dysesthesia was questioned as to whether having unpleasant abnormal sensation after the operation. Positive electroneuromyography findings for saphenous nerve injury included a sensory nerve action potential amplitude <2 µV or a nerve conduction velocity <48.0 m/s or a latency onset >5.0 ms. RESULTS: Thirty-four patients were available at two-week follow-up. All patients achieved complete proximal closure. Three patients (8.8%) had dysesthesia at two weeks. Mean electroneuromyography values were not significantly different between preoperative and postoperative period. Postoperatively, none of the patients had abnormal sensory nerve action potential or latency onset, whereas nerve conduction velocity decreased below the lower limit in two patients. These two patients were not among those having dysesthesia and they had no other complaints. CONCLUSION: Injury to saphenous nerve seems not likely during endovenous laser ablation of incompetent greater saphenous veins, as evidenced by normal electroneuromyography values found after the operation.

Analgesic Effects of GpTx-1, PF-04856264 and CNV1014802 in a Mouse Model of NaV1.7-Mediated Pain.

Loss-of-function mutations of Na(V)1.7 lead to congenital insensitivity to pain, a rare condition resulting in individuals who are otherwise normal except for the inability to sense pain, making pharmacological inhibition of Na(V)1.7 a promising therapeutic strategy for the treatment of pain. We characterized a novel mouse model of Na(V)1.7-mediated pain based on intraplantar injection of the scorpion toxin OD1, which is suitable for rapid in vivo profiling of Na(V)1.7 inhibitors. Intraplantar injection of OD1 caused spontaneous pain behaviors, which were reversed by co-injection with Na(V)1.7 inhibitors and significantly reduced in Na(V)1.7(-/-) mice. To validate the use of the model for profiling Na(V)1.7 inhibitors, we determined the Na(V) selectivity and tested the efficacy of the reported Na(V)1.7 inhibitors GpTx-1, PF-04856264 and CNV1014802 (raxatrigine). GpTx-1 selectively inhibited Na(V)1.7 and was effective when co-administered with OD1, but lacked efficacy when delivered systemically. PF-04856264 state-dependently and selectively inhibited Na(V)1.7 and significantly reduced OD1-induced spontaneous pain when delivered locally and systemically. CNV1014802 state-dependently, but non-selectively, inhibited Na(V) channels and was only effective in the OD1 model when delivered systemically. Our novel model of Na(V)1.7-mediated pain based on intraplantar injection of OD1 is thus suitable for the rapid in vivo characterization of the analgesic efficacy of Na(V)1.7 inhibitors.

Unsuitability of the 86Rb+ uptake method for estimation of (Na+ + K+)-ATPase activity in innervated tissues.

(Na+ + K+)-ATPase activity was estimated by 86Rb+ uptake in dog saphenous vein to determine the validity of the technique in tissues that have a sympathetic innervation. When saphenous vein rings were incubated at 37 degrees C in Krebs' solution containing 86Rb+, the cardenolide acetylstrophanthidin caused a concentration-dependent inhibition of Rb+ uptake. The threshold for inhibition was approx. 10 nM acetylstrophanthidin and the maximum effect was obtained at 9 microM. In the upper part of this concentration range (greater than 1 microM) acetylstrophanthidin released noradrenaline from the sympathetic nerve terminals associated with the tissue. In this upper part of the acetylstrophanthidin concentration range the alpha-adrenoceptor antagonist phentolamine (8 microM) reduced, by up to 25%, the degree of 86Rb+ uptake inhibition caused by the cardenolide. In other experiments, saphenous vein strips were loaded with 86Rb+ and perifused with Krebs' solution containing acetylstrophanthidin. At concentrations which release noradrenaline, acetylstrophanthidin increased the efflux of 86Rb+. Phentolamine (8 microM) prevented the acetylstrophanthidin-evoked efflux of the isotope as did prior in vitro denervation of 86Rb+ loaded strips with 6-hydroxydopamine. Exogenous noradrenaline (1-100 microM) added to the perifusing fluid also caused an efflux of 86Rb+ that was attenuated by phentolamine. The data indicate for dog saphenous vein that with low concentrations of acetylstrophanthidin the extent of 86Rb+ accumulation might accurately reflect prevailing (Na+ + K+)-ATPase activity. At higher concentrations of acetylstrophanthidin, however, noradrenaline is released from the nerve endings and causes 86Rb+ efflux from the smooth muscle cells consequent upon alpha-adrenoceptor activation. Since this efflux reduces the extent of Rb+ accumulation, measurement of the latter does not adequately reflect uptake mediated by the activity of (Na+ + K+)-ATPase. This is significant because in most applications of the 86Rb+ uptake method it is the estimate of Rb+ accumulation made in the presence of a high concentration of cardenolide that forms the basis of all subsequent calculations with respect to (Na+ + K+)-ATPase activity.

Does chronic experimental head-down tilt alter intramural innervation density of limb blood vessels?

Earlier, substantial increases in the intramural sympathetic innervation density of rat hind-limb blood vessels were found after 2 weeks of experimental orthostasis with tubular 45 degrees head-up tilt cages. In the present study, we presumed that chronic head-down tilting induces opposite changes in the innervation density. Tilted rats were kept 45 degrees head-down in long tubular cages for either 2 or 4 weeks (HDT2, HDT4), and the control animals were maintained in horizontal tilt cages for the same period (HOR2, HOR4). Segments of the saphenous and brachial veins and arteries were used for quantitative electron microscopic examinations. Intramural innervation density was defined by nerve terminal density (NTD) and synaptic microvesicle count (SVC) within the vascular adventitia. Neither HDT2 nor HDT4 resulted in a decrease of NTD or SVC of the saphenous and brachial veins or arteries; instead, a tendency to increase was observed in some cases. Thus in contrast to the large increases we found earlier in hind-limb vascular innervation density after 2 weeks of head-up tilting, head-down tilting of the same duration-or even twice as long-did not decrease the adventitial innervation density in our model. We assume that the quasi-free locomotor exercise the tilted animals in the long tubular cages were allowed may counteract a possible suppressive effect of chronic head-down tilt on hind-limb vascular innervation density.

Neural reorganisation in porcine vein grafts: a potential role for endothelin-1.

Vein grafts are associated with adventitial remodelling which may influence innervation of the graft. Since there is also evidence that endothelin-1 (ET-1) plays a role in the adventitial remodelling process, we investigated neural distribution in porcine vein grafts 1 and 6 months after implantation, as well as the localisation of immunoreactive ET-1 and its receptors in the same tissues. Saphenous vein-carotid artery interposition grafting was performed in Landrace pigs. One and 6 months after surgery, vein grafts and ungrafted saphenous veins were excised; neural tissue and ET-1 were identified by immunocytochemistry and ET receptors were identified using in vitro autoradiography. In ungrafted saphenous veins, abundant perivascular nerves were located in the outer region of the media with only a few paravascular nerves in the adventitia. In vein grafts at 1 month after implantation, there was almost complete depletion of perivascular nerves in the media. In contrast, in the neoadventitia, there was an emphatic appearance of large paravascular nerve bundles and a marked increase in small paravascular nerves. These changes were more pronounced at 6 months after surgery, although the principal changes had occurred within 1 month. Immunoreactive ET-1 (index of ET-1 content) was associated with paravascular nerve bundles, appearing as a dark, dense ring at the perineurium. Furthermore, within the nerve bundles, positive ET-1 immunoreactivity was associated with positive alpha-actin staining, indicating that ET-1 is associated with (neural) microvessels. Also, dense 125I-labelled BQ3020 (ET(B)-selective) binding to nerve bundles was observed, indicating the presence of ET(B) receptor subtypes. ET(A) receptor subtypes were not detected in neural tissue. These data demonstrate neural reorganisation in vein grafts and indicate that ET-1 content and binding may play a role in this process. The functional consequences of these changes on neointima formation, a major cause of vein graft failure, remain to be determined.

Frequency dependent changes in mechanosensitivity of rat knee joint afferents after antidromic saphenous nerve stimulation.

The aim of the present study was to examine the effect of electrical saphenous nerve stimulation (14 V, 1-10 Hz) on the mechanosensitivity of rat knee joint afferents. The responses to passive joint rotations at defined torque were recorded from slowly conducting knee joint afferent nerve fibres (0.6-20.0 m/s). After repeated nerve stimulation with 1 Hz, the mechanosensitivity of about 79% of the units was significantly affected. The effects were most prominent at a torque close to the mechanical threshold. In about 46% of the examined nerve fibres a significant increase was obtained, whereas about 33% reduced their mechanosensitivity. The sensitisation was prevented by an application of 5 microM phentolamine, an alpha-adrenergic receptor blocker, together with a neuropeptide Y receptor blocker. An inhibition of N-type Ca(2+) channels by an application of 1 microM omega-conotoxin GVIA caused comparable changes of the mechanosensitivity during the electrical stimulation. Electrical nerve stimulation with higher frequencies resulted in a further reduction of the mean response to joint rotations. After stimulation with 10 Hz, there was a nearly complete loss of mechanosensitivity.In conclusion, antidromic electrical nerve stimulation leads to a frequency dependent transient decrease of the mechanosensitivity. A sensitisation was only obtained at 1 Hz, but this effect may be based on the influence of sympathetic nerve fibres.

Modulation of noradrenaline release from the sympathetic nerves of the human saphenous vein and pulmonary artery by presynaptic EP3- and DP-receptors.

1. Spirally cut strips of the human saphenous vein and pulmonary artery were used to determine the pharmacological properties of the presynaptic prostanoid receptors involved in the modulation of sympathetic [3H]-noradrenaline release. Strips preincubated with [3H]-noradenaline were superfused with physiological salt solution containing inhibitors of uptake1 and uptake2 and rauwolscine to eliminate involvement of presynaptic alpha 2-adrenoceptors. Tritium overflow was evoked by transmural electrical stimulation (standard frequency: 2 Hz). 2. In the saphenous vein, prostaglandin E2 (PGE2) inhibited the electrically-evoked tritium overflow; at the highest concentration investigated, tritium overflow was inhibited by more than 75% and the pEC50 value was 7.00. These effects were mimicked by prostaglandin E1, the EP1/EP3 receptor agonist, sulprostone and the EP2/EP3 receptor agonist, misoprostol with the rank order (pEC50): sulprostone (8.60) > PGE1 (7.25) > misoprostol (6.96). This rank order of potency suggests that the inhibitory effect of the drugs is mediated by presynaptic EP3-receptors. In contrast, PGF2 alpha did not inhibit evoked tritium overflow; the IP/EP1 receptor agonist iloprost and the stable thromboxane A2 analogue U 46619 (9, 11-dideoxy-11 alpha,9 alpha-epoxy-methanoprostaglandin F2 alpha) produced inhibition only at concentrations above 1 microM. 3. The EP1-receptor antagonist, AH 6809 (6-isopropoxy-9-oxoxanthene-2-carboxylic acid) had no effect on the evoked tritium overflow nor did it modify the inhibitory effect of PGE2, further excluding involvement of inhibitory presynaptic EP1-receptors. 4. PGD2 caused a facilitation of evoked tritium overflow in the saphenous vein; this facilitation is probably mediated by presynaptic DP-receptors, since it was abolished by the selective DP-receptor antagonist, BW A868C (3-benzyl-5-(6-carboxyhexyl)-1-(2-cyclohexyl-2-hydroxyethylamino)hydantoin).5. In the pulmonary artery, sulprostone (pECm value 8.35), misoprostol (7.70) and PGE2 (6.80)inhibited electrically-evoked tritium overflow. This rank order of potency is consistent with the involvement of inhibitory presynaptic EP3-receptors.6. These results suggest that the sympathetic nerve fibres of both human saphenous vein and pulmonary artery are endowed with presynaptic inhibitory EP3 receptors. The EP3-receptors do not interact with the alpha 2-autoreceptors. In addition, the human saphenous vein seems to be endowed with presynaptic facilitatory DP-receptors.

No evidence for differences between pre- and post-junctional alpha 2-adrenoceptors.

We have examined the pre- and post-junctional effects of a series of alpha-adrenoceptor agonists and antagonists at alpha 2-adrenoceptors in the pithed rat preparation and the human isolated saphenous vein. In the pithed rat, there was no difference in relative agonist and antagonist potencies between pre- and post-junctional alpha 2-adrenoceptors but the absolute potencies of antagonists differed: antagonists were more potent prejunctionally. In the human saphenous vein, the alpha 2-adrenoceptor antagonist yohimbine had pre- and post-junctional actions over the same concentration range. We have no evidence to suggest differences between pre- and post-junctional alpha 2-adrenoceptors: differences in absolute antagonist potencies in the pithed rat may be due to non-equilibrium conditions.

Sympathetic denervation caused by long-term noradrenaline infusions; prevention by desipramine and superoxide dismutase.

1. The effects of continuous intravenous infusion of noradrenaline (0.01 and 0.1 microgram kg-1 h-1) were studied in both the infused lateral saphenous vein and the contralateral saphenous vein of normal dogs. Noradrenaline, saline, noradrenaline + desipramine or noradrenaline + superoxide dismutase were infused using Alzet osmotic minipumps. 2. After a 5 day infusion period, the noradrenaline content in plasma and in both saphenous veins was determined, and the venous tissues submitted to light microscope morphometry and ultrastructural study and used for the determination of their O-methylation capacity (with [3H]-isoprenaline as a substrate). 3. Noradrenaline caused dose-dependent damage to the sympathetic nerve endings of the lateral saphenous veins. Concomitant changes in extraneuronal structure and function were observed (hypertrophy of smooth muscle cells, nuclear dysmorphy, thickening of the vessel wall, impairment in O-methylation capacity). 4. Desipramine and superoxide dismutase prevented or reduced the effects of noradrenaline on both the morphological and the biochemical parameters; the protection afforded by superoxide dismutase was more marked than that by desipramine. 5. It is concluded that moderately high doses of noradrenaline exert a 6-hydroxydopamine-like effect and that this chemical sympathectomy is partially or totally prevented by desipramine or superoxide dismutase. The data suggest that a substance derived from noradrenaline, in the formation of which free oxygen radicals are involved and which is subject to neuronal uptake, is the chemical entity responsible for the neurotoxic effect observed.