Regeneration of peripheral nerve through a preformed tissue space. Preliminary observations on the reorganization of regenerating nerve fibres and perineurium.
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Biomedical subjects
Publications and source records attributed to G Lundborg.
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The vascularization of the human flexor pollicis longus tendon was outlined by the use of microangiographic techniques, applied on freshly amputated arms. At the insertion of the tendon there was regularly a very well developed vinculum brevis, often extending proximally to the middle of the base phalanx of the thumb. Proximally to the metacarpo phalangeal joint there was a mesotenon of various shape, originating from the volar-ulnar (non-friction) side of the synovial tendon sheath. There seemed to exist a non-interrupted intrinsic longitudinal vascular system in the tendon, and the vessels were located in those parts of the tendon which are not subjected to friction.
The pathogenesis of the late post-traumatic rupture of the extensor pollicis longus tendon has never been satisfactorily explained. In the present series of fifty-nine ruptures two were partial, making possible an exact localization of the rupture. Microangiographic studies performed on amputated arms showed that this part of the tendon was poorly vascularized. Our study confirms earlier observations that ruptures most commonly occur after undisplaced fractures. It is suggested that increased pressure within the non-ruptured tendon sheath jeopardizes the blood flow in the already poorly vascularized parts of the tendon, leading to degeneration and rupture, usually within eight weeks. An haematoma inside the sheath interfering with the production of synovial fluid, could deprive the tendon of an alternative nutrition via diffusional pathways.
A combination of microangiographic and histological methods was used to analyse the intrinsic microvascular system of human peripheral nerves of freshly amputated arms. Special attention was paid to perineurial and intrafascicular vascular systems. The human nerves present a microvascular system analogous to the intraneural system of experimental animals. The fascicles are vascularized segmentally by epineurial vessels, and each fascicle presents a well-defined fascicular vascular organization composed of endoneurial and perineurial microvascular systems in combination. The possible effects of intraneural dissection on intrafascicular blood flow are discussed. It is suggested that intraneural dissection produces considerable trauma to the nerve and an inflammatory reaction in extrafascicular layers, but that due to the barrier function of the perineurium the effects on intrafascicular tissues can be limited.
Local anesthetics are designed for application in or close to nerve tissue. In spite of their wide clinical use, surprisingly few investigations deal with the neural toxicity of modern local anesthetics. In this experimental study, the effects were investigated of intrafascicular or topical application of the long-acting local anesthetic bupivacaine on the rabbit sciatic nerve. Axonal degeneration was histologically evaluated and a fluorescence-microscopic technique used to detect lesions in the blood-nerve barrier. Topical application of bupivacaine in clinically recommended concentrations around the nerve caused no detectable nerve injury, while intrafascicular injections caused considerable axonal degeneration and damaged the blood nerve barrier. Axonal degeneration was the same after injection of physiologic saline solution and bupivacaine 0.5%, but it increased with increasing bupivacaine concentration and especially with the addition of adrenaline. On the other hand, the acute effects of intrafascicular injection, as visualized in the barrier experiments, changed little with the addition of adrenaline, indicating that it is the injection trauma itself which is deleterious. It is concluded that intraneural injections should be avoided and that plain bupivacaine solutions should be routinely used.
The healing process of totally cut and subsequently resutured rabbit flexor tendons kept isolated in the knee joint cavity and free in the synovial fluid was studied by histological and ultrastructural techniques. This experimental model represents a "tissue culture in situ," where the tendon is nourished by diffusion from the synovial fluid only and where no adhesions are formed. Under these conditions there is a proliferation of tendon cells and deposition of collagen resulting in bridging of the suture line. On the basis of these findings, it is assumed that the tendon cells possess an intrinsic potential of repair, provided they obtain a sufficient nutritional supply. In the present experimental model, this nutrition was provided by way of diffusional pathways from the synovial fluid.
The intrinsic vascularization of human flexor tendons within the digital sheath region was studied on fresh amputation specimens with the aid of angiographic and histochemical techniques. In the flexor digitorum profundus tendon, three separate vascular systems of various origin and with no or very little communication could be verified. In the flexor digitorum superficialis tendon, two such systems were observed. The volar surface of both tendons is more or less devoid of vessels. Moreover, at the proximal interphalangeal joint level, the flexor digitorum profundus tendon has a volar avascular zone, constituting about 1 mm, i.e., about one-third to one-fourth of the thickness of the tendon. It is assumed that the synovial fluid is of importance for the nutrition of the tendons and that therefore the synovial sheath should be preserved as much as possible.
Nerve injury can arise as a complication peripheral nerve block anesthesia. Of the various factors involved, the trauma caused by the injection needle may be of significance. In this experimental study the frequency of fascicular injury was investigated immediately after needling isolated rabbit sciatic nerve preparations, and after intraneural injection with the nerve in situ. Two different injection needles were used, one with a bevel angle of 14 degrees and the other with a 45 degrees bevel angle. Fascicular injury was indicated by a fluorescence microscopy technique, tracing locally applied Evans Blue Albumin, The results show that a 45 degrees-beveled needle less frequently produces fascicular damage and should therefore be recommended for use in clinical anesthesia. It is also concluded that paresthesiae, when necessary, should be elicited gently, and that intraneural injections should be avoided.
Experimental compression lesions of peripheral nerves were induced by applying pressure direct to exposed rabbit nerve trunks. A specifically designed compression chamber was used, enabling application of graded pressures (50--600 mmHg) to the nerves for various periods of time (15 min to 6 hours). After releasing the pressure, analyses were performed concerning the intraneural microvascular permeability and the barrier function of the perineurium. The method used was fluorescence microscopic tracing of intravenously injected or locally applied albumin labelled with Evans blue. The results indicate that a slight trauma to a nerve (e.g. 50 mmHg during 2 hours) induced an epineurial oedema by increasing the permeability of the epineurial vessels, which were more susceptible to compression trauma than the endoneurial vessels. Compression at higher pressure levels or of prolonged duration caused injury also to the endoneurial vessels, leading to intrafascicular oedema formation, which generally was most prominent at the edges of the compressed nerve segment. The perineurial barrier was remarkably resistant to compression trauma. Possible pathophysiological effects of various degrees of post-traumatic intraneural oedema formation are discussed.
The gliding surfaces of the flexor tendons and the tendon sheath are delicate structures of the complex digital flexor system. Beside the fibrous parts, the tendon sheath also exhibits membranous synovial components, which represent a dialysing membrane producing a plasma ultrafiltrate--the synovial fluid. In this study, interest was focused on the vascularization of the synovial sheath. By a microangiographic method it was demonstrated that this membrane is richly vascularized and that the vascular plexus is in continuity on the outside of the fibrous pulleys. The friction surfaces of the system--the inside of the pulleys and the surface of the flexor tendons--are devoid of vessels, and here a differentiation into chondrocyte-like cells is observed. It is suggested that these tissue areas, in analogy to joint cartilage, are nourished by diffusion from the synovial fluid, and that the flexor system can be regarded as a specialized joint, sliding longitudinally and exhibiting an extremely large range of motion.
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The mechanism of tendon healing and the role played by the synovial sheath are still obscure and controversial. In the present experimental study free tendon grafts were nourished by synovial fluid only. By morphological and cytochemical techniques viable cells were found in the superficial zones of the tendon, capable of both proliferation and production and production of new collagen. This repair process affected predominantly the ends of the grafts. At the centre of the specimens degenerative changes appeared to an increasing extent throughout the observation period of 12 weeks. Adhesions to the surrounding tissues did not form. It is concluded that fibroblasts, most probably originated from the superficial cell layers of the tendon are capable of regeneration and synthesis of new collagen and that synovial fluid plays an important role in the metabolic exchange of the superficial scantily vascularized areas of the tendon. The observations are discussed in relation to the present concepts of tendon surgery.
An experimental model is presented enabling an analysis of the healing process of completely cut and re-sutured free segments of rabbit flexor tendons, kept avascular in a synovial milieu and completely isolated from adhesion formation. Under these conditions the cut tendons heal within a few weeks. It can be shown that this healing process is a result of intrinsic tendon cell activity only.
Surgical treatment of peripheral nerve lesions associated with intraneural fibrosis is sometimes extended to include internal neurolysis. This procedure is performed in order to release the individual nerve fascicles from interfascicular scar tissue which is believed to constrict nerve fibres and thereby interfere with their function and regenerative capacity. However, an internal neurolysis per se implies a significant trauma to the nerve and may induce microvascular damage and formation of new intraneural scar tissue. Considering this, such a procedure appears justified only when the preoperative intraneural fibrosis is more severe than the scarring which might be induced by the surgical procedure as such. In order to evaluate the tissue reactions following internal neurolysis an experimental investigation was carried out: internal neurolysis was performed on normal rabbit tibial nerve. After varying postoperative periods up to 6 months specimens of nerves were analysed. Reactive changes of connective tissue and myelin sheath lesions, indicating nerve fibre damage, were investigated in histological sections studied by light microscopy. Barrier function of perineurial membrane and endoneurial vessels was investigated by fluorescent microscopic tracing of locally applied or intravenously injected albumin labelled with Evans' blue. The results indicate that an experimental internal neurolysis per se may induce fibrosis in all layers of the nerve and may cause some nerve fibre damage. However, the barrier function of the perineurium and the endoneurial vessels seems to be generally well preserved. The findings are discussed in relation to indications for internal neurolysis.
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The mechanism of healing of a free tendon graft and also the role played by the synovial sheath is still obscure and debated. In the present study an effort is made to further elucidate these problems. In rabbits and dogs an experimental model was developed where a free tendon graft would be nourished by synovial fluid only. Macroscopically the grafts remained smooth, white and glistening without vascular ingrowth or adhesions during an observation period of 12 weeks. By histological and histochemical techniques the grafts as a whole were found viable up to 3 weeks. In a clinical series of 40 free flexor tendon grafts within the digital area as much as possible of the tendon sheath was preserved during grafting. The functional recovery was generally very good. The best results were obtained in those cases where most of the tendon sheath was preserved during grafting. The functional recovery was generally very good. The best results were obtained in those cases where most of the tendon sheath was preserved. No signs of defective graft survival were observed. Based on both experimental and clinical results from the present study it is concluded that there is no reason to excise the remaining tendon sheath within the critical zone in the digits. On the contrary preservation of the sheath contributes to survival of the graft and helps maintaining the integrity of gliding surfaces with maximal functional restoration and minimal formation of adhesions.
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