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Biomedical subjects

W A Morrison

Publications and source records attributed to W A Morrison.

At least 55 records · Page 3Linked to original sources
PubMed1999

The beneficial antiinflammatory effect of dexamethasone administration prior to reperfusion on the viability of cold-stored skin flaps.

The main purpose of this study was to investigate the possible protective effect of a single dose of glucocorticoid dexamethasone administered just before reperfusion on the viability of cold-stored inferior epigastric rat skin flaps. We also sought evidence for the antiinflammatory mechanism of action of dexamethasone involved in this model of cold ischemia-reperfusion. The viability of flaps on reperfusion day 7, after 1, 2, 3, 4, or 5 days of cold ischemia, was 80, 74, 60, 47 and 12% respectively. Four days' cold ischemia time was chosen to test the effect of intraperitoneal dexamethasone administration (2.5 mg/kg) 30 min prior to reperfusion. Flap survival after 4 days' cold ischemia/7 days' reperfusion increased significantly from a mean of 37.0% survival in saline-treated controls to 73.3% in dexamethasone-treated rats (p < 0.05). Dexamethasone treatment also resulted in significantly lower skin flap water content (a measure of edema) and myeloperoxidase activity (an indicator of neutrophil infiltration) but had no significant effect on skin levels of hydroperoxides (a measure of free radical activity). In conclusion, dexamethasone attenuates ischemia-reperfusion injury in cold-stored skin flaps by reducing the tissue levels of several proinflammatory mediators.

Animals↗
PubMed1998

HIV-1 selection by epidermal dendritic cells during transmission across human skin.

Macrophage tropic HIV-1 is predominant during the initial viremia after person to person transmission of HIV-1 (Zhu, T., H. Mo, N. Wang, D.S. Nam, Y. Cao, R.A. Koup, and D.D. Ho. 1993. Science. 261:1179-1181.), and this selection may occur during virus entry and carriage to the lymphoid tissue. Human skin explants were used to model HIV-1 selection that may occur at the skin or mucosal surface. Macrophage tropic, but not T cell line tropic strains of HIV-1 applied to the abraded epidermis were recovered from the cells emigrating from the skin explants. Dermis and epidermis were separated by dispase digestion after virus exposure to determine the site of viral selection within the skin. Uptake and transmission to T cells of all HIV-1 isolates was found with the dermal emigrant cells, but only macrophage tropic virus was transferred by emigrants from the epidermis exposed to HIV-1, indicating selection only within the epidermis. CD3+, CD4+ T cells were found in both the dermal and epidermal emigrant cells. After cell sorting to exclude contaminating T cells, macrophage tropic HIV-1 was found in both the dermal emigrant dendritic cells and in dendritic cells sorted from the epidermal emigrants. These observations suggest that selective infection of the immature epidermal dendritic cells represents the cellular mechanism that limits the initial viremia to HIV-1 that can use the CCR5 coreceptor.

CD4-Positive T-Lymphocytes↗
PubMed1998

A model of bridging angiogenesis in the rat.

A model of angiogenesis has been developed in the rat. The epigastric vascular pedicle was exposed in the groin, a 7 mm segment of epigastric artery was excised leaving the vein intact and, after a variable period of time for angiogenesis to occur between the ends of the artery, a skin flap was elevated on the epigastric vascular pedicle so that it depended completely for its blood supply on bridging angiogenesis across the created gap. Skin flap survival and vessel counts were measured as indices of the angiogenic response. In this model we observed a spontaneous increase in vessel counts between the ends of the artery, and a corresponding increase in skin flap tissue survival until day 10 after which time vessel counts plateaued whilst tissue survival continued to increase until day 14. In the angiogenic pedicle, a time-dependent development of granulation tissue containing numerous macrophages and mast cells, and capillary sprouting were documented. When flap elevation was performed 7 days after arterial excision skin flap survival was 42%. Thus, in this model, 7 days is a suitable interval for the future evaluation of the effects of either pro- or anti-angiogenic agents.

Animals↗
PubMed1998

Late occlusion of microvascular vein grafts in replantation.

Two cases are described in which patients presented 16 and 17 years, respectively, after complete or incomplete amputation/replantation of the arm. In case 1, the patient complained of coldness, pain, and tingling in the replanted arm in the previous 24 hours and noticed that his fingers had gone white. Arteriography and subsequent surgery revealed obliteration of the vein graft (inserted in the distal brachial artery) by neointimal thickening and atherosclerotic plaque, which was confirmed in a subsequent morphologic examination. In case 2, the patient presented with discomfort and a pulsatile swelling on the inner aspect of his upper arm. Arteriography and surgery revealed an aneurysm in the previously inserted vein graft in the brachial artery, with some atherosclerotic degeneration. Both vein grafts were successfully replaced with a fresh autologous vein graft and the patients remain well several years later. The 2 cases suggest that as part of replantation surgery of a limb, it is essential to maintain postoperative clinical monitoring for signs of graft degeneration in all patients with long-term vein graft insertion.

Adolescent↗
PubMed1998

The prefabrication of a bone graft in a rat model.

The prefabrication of bone grafts in a rat model was investigated. In 26 Sprague-Dawley rats, free iliac crest bone graft was harvested, bivalved, and reinserted heterotopically into the groin, where it was closed around the mobilized superficial inferior epigastric vascular bundle. In half the animals, the vascular bundle remained in continuity as a flow-through pedicle (group 1); in the remaining animals, the pedicle was ligated and divided distal to the bone graft. All grafts were isolated from other tissues by a silicone sheet envelope. At 3 or 6 weeks, the grafts were re-explored and analyzed by India ink perfusion and histologic examination for evidence of viability and neovascularization. Three weeks after insertion, India ink perfusion of the group 1 and 2 grafts revealed neovascularization extending to the periphery of the graft, and histologic examination showed extensive new bone formation on endosteal, periosteal, and trabecular surfaces of the graft. Six weeks after insertion, creeping substitution had almost completely remodelled the cortical and cancellous bone of both group 1 and 2 grafts to create a viable vascularized bone graft on a pedicle. In 3 control nonvascularized grafts (free iliac cortical bone without an implanted pedicle), all pre-existing bone of the graft was dead 3 weeks after insertion, and only very limited new bone formation was present within the graft.

Animals↗
PubMed1998

Motor collateral sprouting through an end-to-side nerve repair.

The outcome of end-to-side repair of peripheral nerves was investigated. The sciatic nerve in 10 male Sprague-Dawley rats was dissected to its tibioperoneal junction. The nerve to the medial gastrocnemius muscle, branching from the tibial nerve, was ligated at its origin and divided. Its distal end was sutured to an epineurial window on the side of the intact tibial nerve 1 cm distally. At 12 weeks, physiologic evaluation of the medial gastrocnemius muscle and analyses of histologic preparations of nerve and muscle were performed. The results showed that reinnervation successfully occurred in 8 rat media gastrocnemii. The mean weight of the reinnervated medial gastrocnemius was 73% of the contralateral normal muscle, the mean muscle fiber cross-sectional area of the reinnervated muscle was 72%, and the force of contraction was 60%. Analyses of histologic preparations revealed evidence of myelinated axons in the medial gastrocnemius nerve and no evidence of damage to axons of the donor tibial nerve.

Anastomosis, Surgical↗
PubMed1998

Long-term studies of cold-stored rabbit femoral artery and vein autografts.

UNLABELLED: In previous studies we have shown that 80-100% of rabbit femoral vascular autografts cold-stored at 4 degrees C for 3 weeks remain patent 3 weeks after reinsertion in the femoral artery. The present study reports the effect on graft patency of increasing either the period of cold storage prior to reinsertion or the duration of reperfusion to 6 months. Rabbit femoral blood vessels were cold-stored (CS) at 4 degrees C for varying periods. CS autografts were reinserted into the contralateral leg for 3 weeks or 6 months. Graft patency was determined and grafts examined by histological, immunohistochemical and electron microscopical techniques. Six months after reinsertion patency of 4-week CS arterial and 1-week CS venous grafts was 40% and 27% respectively, very much lower than the 80-100% seen after 3 weeks reperfusion. Arterial grafts CS for 6 months had a patency rate of 70% after 3 weeks reperfusion but 0% after 6 months. Morphological examination suggests that the delayed failure of cold-stored vascular grafts is caused by thrombus superimposed on intimal hyperplasia within the graft. CONCLUSIONS: Cold-stored vascular grafts are useful prostheses when only 3-4 weeks graft patency is required. They are not suitable for use when long-term graft patency is needed.

Animals↗
PubMed1998

Dexamethasone treatment prior to reperfusion improves the survival of skin flaps subjected to secondary venous ischaemia.

The potential use of the anti-inflammatory glucocorticoid, dexamethasone, to treat ischaemic skin flaps prior to reperfusion was investigated. Island flaps were raised in rats, subjected to arteriovenous ischaemia for 2 h, normal blood flow for 24 h, secondary venous ischaemia for 4 h and secondary reperfusion for 7 days. This sequence mimics the clinical sequence of free flap transfer followed by a subsequent venous thrombosis. Groups of 10 rats were administered with an intraperitoneal dose of either saline (controls) or dexamethasone (2.5 mg/kg) 30 min before the end of the venous ischaemia. Compared with viability of 70.0% in controls, dexamethasone treatment increased viability significantly to 92.0% (P < 0.01). In skin flap tissue harvested at 24 h reperfusion, dexamethasone treatment resulted in significant attenuation of tissue water content, tissue myeloperoxidase activity and tissue hydroperoxide levels. Thus the protective effect of this agent may be explained by the combined reduction of oedema formation, neutrophil infiltration and free radical production, respectively. We conclude that a single systemic dose of dexamethasone prior to reperfusion may be beneficial in treating skin flaps that have undergone secondary venous ischaemia.

Animals↗
PubMed1998

The tensor fasciae latae myocutaneous flap closure of major chest and abdominal wall defects.

BACKGROUND: The usual methods of closure of major chest and abdominal wall defects have significant disadvantages. Skin grafts provide no structural support and result in incisional hernias. Synthetic mesh requires skin cover and is prone to infection and wound breakdown. The tensor fasciae latae (TFL) myocutaneous flap offers skin cover and a semi-rigid fascial layer. We document our unit's experience in pedicled and free TFL flaps. METHODS: The TFL flap closure of trunk defects was undertaken in 10 patients between August 1989 and April 1997. All cases were not amenable to primary closure and repair with synthetic mesh or skin grafts. RESULTS: The defect was satisfactorily repaired in all cases without subsequent herniation. The closure techniques using a pedicled TFL flap and a TFL flap for a free-tissue transfer are described. CONCLUSIONS: We conclude that the TFL flap is the method of choice for repairs of major truncal defects.

Abdominal Muscles↗
PubMed1998

Mode of vascularization of control and basic fibroblast growth factor-stimulated prefabricated skin flaps.

This study, using 62 rabbits, examines the rate and pattern of vascular outgrowth from a subcutaneously implanted vascular pedicle, how the newly formed vessels connect to preexisting skin vessels, and whether local application of basic fibroblast growth factor can accelerate the angiogenic process. When the femoral artery and vein of rabbits are implanted beneath the skin, angiogenesis from both the pedicle and small blood vessels within the adjacent skin begins within 3 days. Perfusion with India ink reveals connections between the pedicle and dermal vessels as early as 5 days after implantation of the pedicle. Provided the pedicle does not thrombose, skin flaps based on it may survive completely when elevated as early as 2 weeks after implantation. Flap survival depends on the development of a small number of vascular connections between vessels arising from the pedicle and preexisting dermal vessels. If elevation is delayed until 4 weeks after implantation a flap may survive even if its pedicle has thrombosed. Prolonged release of basic fibroblast growth factor adjacent to the pedicle significantly increases the survival of flaps elevated 1 week after implantation but does not alter the survival of flaps elevated at 2 and 4 weeks.

Animals↗
PubMed1997

Ischaemia-reperfusion injury in mouse skeletal muscle is reduced by N omega-nitro-L-arginine methyl ester and dexamethasone.

We have developed a model of ischaemia-reperfusion injury in C57BL/6 mice involving ischaemia for 0.5 to 2.5 h with an elastic tourniquet on one hind limb and reperfusion for 24 h, analogous to a well-established model of ischaemia-reperfusion injury in the rat. Viability was assessed in tissue homogenates of the gastrocnemius muscles from the affected and contralateral control limb by a triphenyl tetrazolium chloride dye reaction, measuring the activity of the oxidative mitochondrial enzymes. After 1.5 h ischaemia and 24 h reperfusion, viability in the ischaemic-reperfused limb was 13%, with the control muscle regarded as 100% viable. Significant improvements in viability to 86% (P < 0.05) and 56% (P < 0.05) were achieved, with administration 30 min prior to tourniquet release, of the nitric oxide (NO) synthase inhibitor nitro-L-arginine methyl ester (L-NAME, 30 mg/kg) and the anti-inflammatory glucocorticoid dexamethasone (2.5 mg/kg) respectively, with similar findings in the rat tourniquet model.

Animals↗
PubMed1997

Leukemia inhibitory factor enhances the regeneration of transected rat sciatic nerve and the function of reinnervated muscle.

The cytokine leukemia inhibitory factor (LIF) favors the survival and growth of axons in vitro and in vivo. Fibronectin has been shown to enhance nerve regeneration when added in combination with various growth factors including LIF. The goal of this study was to evaluate the effect of LIF plus fibronectin on the regeneration of transected nerve and functional recovery of reinnervated skeletal muscle, in one experimental model of peripheral nerve repair, at two recovery times. The rat sciatic nerve was cut at mid-thigh level and a silicone cuff containing either saline (control), LIF, or LIF plus fibronectin (L+F) was used to bridge the proximal and distal nerve stumps leaving a 1 cm gap between them. Rats were then explored at 6 or 12 weeks following the initial surgery. Regenerating nerves were assessed by measuring the diameter of myelinated axons, conduction velocity, and number of myelinated fibers. Muscle reinnervation was assessed by measuring muscle mass, force of contraction, and histologically for changes in muscle fiber type (type I and type II). In this report we demonstrate that at 6 weeks there were significant increases in 1) nerve conduction velocity, 2) myelinated axon diameter, and 3) number of myelinated axons over that of control (saline-treated) animals. Both LIF groups demonstrated a shift in type II muscle fiber area compared to saline-treated controls, with the L+F group having a significant increase in muscle mass. At 12 weeks there was an improved recovery over and above that demonstrated at 6 weeks. Muscle mass was 65% and 42% greater than control for LIF and L+F, respectively. Force of contraction, conduction velocity, myelinated fiber number, and diameter were also significantly greater for both LIF- and L+F-treated rats than saline-treated rats. These results demonstrate that LIF significantly improves the regeneration of damaged peripheral nerves and the preservation of muscle viability, resulting in greatly enhanced recovery of skeletal muscle function.

Analysis of Variance↗
PubMed1997

Mild hypothermia protects against ischaemia-reperfusion injury in rabbit skeletal muscle.

In three groups of rabbits, the rectus femoris muscle was subjected to 4 hours of total ischaemia. In Group 1 (normothermia, n = 5) the core temperature was maintained within the range 36-38 degrees C for the duration of ischaemia. In Group 2 (total hypothermia, n = 5) the core temperature was allowed to fall to 31.5-33.5 degrees C. In Group 3 (muscle only hypothermia, n = 5) core temperature was maintained as in Group 1 but the muscle temperature was allowed to fall to 29.5-31.5 degrees C. After 24 hours of reperfusion the muscles were harvested and measurements made of muscle viability, oedema and myeloperoxidase content. The mean (s.e.m.) muscle viability of Group 1, 19.5 (3.8)%, was significantly less than that of both Group 2, 86.0 (2.0)%, and Group 3, 87 (4.1)%, (P < 0.001). Muscle oedema and myeloperoxidase levels were elevated in all experimental groups, but differences were not significant. These findings indicate that ischaemia-reperfusion injury in skeletal muscle in this model is highly temperature-sensitive, small reductions in muscle temperature during ischaemia providing significant protection against ischaemia-reperfusion injury.

Animals↗
PubMed1997

Timing of administration of dexamethasone or the nitric oxide synthase inhibitor, nitro-L-arginine methyl ester, is critical for effective treatment of ischaemia-reperfusion injury to rat skeletal muscle.

1. The effects of the nitric oxide synthase (NOS) inhibitors, NG-nitro-L-arginine-methyl ester (L-NAME), nitroiminoethyl-L-ornithine and S. methylisothiourea on skeletal muscle survival following 2 h of tourniquet ischaemia and 24 h of reperfusion were compared with those of the anti-inflammatory steroid, dexamethasone. 2. Administration of each of the NOS inhibitors or dexamethasone 30 min before reperfusion reduced the degree of skeletal muscle necrosis 24 h after reperfusion. 3. The influence of timing of drug administration was investigated. L-NAME administered 30 min before reperfusion, at 3 h after reperfusion, but not thereafter, significantly improved muscle survival compared with saline-treated controls. Dexamethasone administered 30 min before, or at 3 or 8 h after reperfusion, but not at 16 h, significantly improved muscle survival, but neither agent had protective effects when administered before ischaemia. 4. After 8 h of reperfusion of ischaemic skeletal muscle, cell-free homogenates contained Ca(2+)-independent (inducible) NOS activity which was reduced in dexamethasone-treated (2.5 mg/kg) rats. Furthermore, inducible NOS mRNA levels, as detected by reverse transcriptase-PCR, were increased after 8 h of reperfusion in saline, but not in dexamethasone-treated rats. 5. These data suggest a significant deleterious effect of endogenous NO which may be restricted to the first 3 h of the reperfusion phase of ischaemia-reperfusion injury, and raise the possibility of effective treatment of incipient reperfusion injury, even after several hours of reperfusion.

Animals↗
PubMed1997

Clinical applications and technical limitations of prefabricated flaps.

Vascular pedicle implantation into the subdermal level of the skin induces an angiogenic response that can be sufficient to artificially create or "prefabricate" an axial-pattern flap suitable for island pedicle or free-flap transfer. This technique allows the creation of large, thin skin flaps that retain the qualities of the donor-site skin. Three cases are presented in which such thin flaps have been created to cover defects, one on the knee and two on the face. While the reconstructions are satisfactory, difficulties were encountered with venous insufficiency in the flaps after the second-stage transfer. We believe that the complexity and staged nature of these procedures limit their application to highly selected patients, but their role probably lies in the transfer of supraclavicular skin for the reconstruction of facial defects.

Adult↗
PubMed1996

Influence of postischemic administration of oxyradical antagonists on ischemic injury to rabbit skeletal muscle.

The aim of this study was to determine whether the administration of free radical antagonists, immediately before and during the early minutes of reperfusion, improves muscle survival 24 hr after a period of ischemia. Rabbit rectus femoris muscles were isolated, made ischemic for 3 1/2 hr and treated with either desferrioxamine (DFX), an Fe3+ chelator, superoxide dismutase and catalase (SOD & CAT), which quench superoxide and hydrogen peroxide, or allopurinol, an inhibitor of xanthine oxidase (XO). After 24 hr reperfusion, muscle viability (+/-s.e.m.), measured by the nitro blue tetrazolium (NBT) vital staining technique, was 41.6 +/- 11.3% for saline-treated ischemic controls, 30.6 +/- 7.6% for DFX-treated, 46.7 +/- 10.3% for SOD & CAT-treated, and 43.3 +/- 9.5% for allopurinol-treated muscles. None of the treated groups differed significantly from the ischemic control group. Tissue myeloperoxidase, ATP and reduced glutathione levels, and plasma lactate dehydrogenase (LDH) and aspartate transaminase (AST) levels were increased by ischemia and reperfusion in all groups, but the changes did not differ between the treatment groups. Levels of XO in the rabbit muscle were determined and found to be very low in both normal and postischemic muscle. As XO is the target enzyme of allopurinol, its absence provides a basis for the lack of effect of this agent. However, it is not clear why DFX and SOD & CAT had no protective effect.

Allopurinol↗
PubMed1996

Effects of low dose intra-arterial monoclonal antibodies to ICAM-1 and CD11/CD18 on local and systemic consequences of ischaemia-reperfusion injury in skeletal muscle.

The aim of this study was to investigate the effects of intra-arterial infusion of low doses of monoclonal antibodies (Mabs) against adhesion molecules (the neutrophil CD18 integrins, and the endothelial adhesion molecule, ICAM-1) on reperfusion injury in skeletal muscle. The rabbit rectus femoris muscle was rendered ischaemic for 2 1/2 hours. Mabs were infused (approximately 0.5 mg/kg) commencing 20 minutes before the end of ischaemia and for the first hour of reperfusion. 24 hours after reperfusion, the muscle was assessed for viability, oedema and neutrophil infiltration (myeloperoxidase (MPO) levels). The results of the viability assessment (control--20.9 (0-47.5)% [median (range)], anti-CD18--30.5 (3.0-89.4)%, anti-ICAM-1--27.9 (7.8-78.1)% and anti-CD18 combined with anti-ICAM-1--45.2 (15.6-92.3)%) showed no significant differences between groups, while analysis of MPO in the postischaemic muscle showed that the anti-ICAM-1 Mab reduced neutrophil infiltration significantly. Furthermore, in contralateral unoperated muscles MPO levels were elevated 24 hours after ischaemia in the contralateral muscle. This increased neutrophil infiltration was prevented by pretreatment with anti-ICAM-1. These results suggest that low doses of anti-CD18 and anti-ICAM-1 Mabs do not reduce reperfusion injury in skeletal muscle but may help to protect against systemic effects of severe trauma. The evidence suggests that reperfusion injury in this skeletal muscle model may be largely independent of neutrophil involvement.

Animals↗