The influence of dressings on the healing of normal and ischaemic wounds and flap survival.

The effects of dressing with Duoderm (occlusive hydrocolloid) and Mepore (permeable viscose) on the healing of normal and ischaemic incisional wounds, and on flap survival, were investigated in 60 rats. The biomechanical properties of dressed normal wounds after 14 days did not differ from those of the undressed controls. In contrast, energies at maximum and breaking (load*S, stress*S) of dressed ischaemic wounds decreased by 30%-42% after 14 days of healing, compared with undressed ischaemic controls. Dressing decreased the shrinkage of ischaemic wounds and necrosis length of ischaemic flaps. Normal incisional wounds can safely be dressed for 14 days without the wound strength being affected. Dressings may be useful clinically in preventing superficial dermal necroses. One must, however, be aware of the impairment of the wound strength of ischaemic incisional wounds.

Ischemic wound healing and possible treatments.

The present review describes the major steps in wound healing, the factors that clinically cause ischemia including the changes found in diabetes mellitus and the possible interventions and treatments of ischemic wounds. The number of randomized, double-blind, controlled clinical trials is scarce, especially on the healing of chronic ischemic soft tissue wounds. Experimental and clinical studies to date have demonstrated that hyperbaric oxygen may be an effective treatment of chronic hypoxic wounds and that certain growth factors (e.g., recombinant platelet-derived growth factor-BB) are likely to enhance the healing of such wounds. Other treatments are discussed, among them vasoactive drugs (e.g., pentoxifylline), occlusive dressings and surgical treatment, including delayed primary closure of acute ischemic wounds.

The influence of occlusive dressing and hyperbaric oxygen on flap survival and the healing of ischaemic wounds.

The effect of dressing with Duoderm (hydrocolloid) and treatment with hyperbaric oxygen was investigated on the healing of ischaemic incisional wounds and on flap survival in rats. After 10 days, Duoderm dressing of ischaemic wounds decreased all strength parameters (load*S, stress*S) by 41%-44% and the improvement of ischaemic wound healing by hyperbaric oxygen treatment shown in our previous study was not seen. After removal of Duoderm on day 10 the biomechanical properties had improved but not returned to normal on day 20. In the dressed animals the shrinkage of ischaemic wounds and the extension of necrosis on the ischaemic flaps were reduced. Dressing may be useful clinically in preventing superficial dermal necroses. One must, however, be aware of the impairment of the wound strength of the incisional wounds.

The effect of recombinant basic fibroblast growth factor (bFGF) in fibrin adhesive vehicle on the healing of ischaemic and normal incisional skin wounds.

Normal and ischaemic incisional wounds in rats were treated with recombinant human basic fibroblast growth factor (rbFGF) in fibrin adhesive vehicle. After 10 days of healing the maximum load*S and stress*S (S denotes correction for shrinkage) of ischaemic wounds were increased by 45% and 39%, respectively, after treatment with 20 micrograms rbFGF and by 67% and 56% after treatment with 60 micrograms rbFGF. After 20 days only 20 micrograms rbFGF had any effect and increased maximum load*S by 31% and energy at maximum (load*S, stress*S) by 40%-48%. In normal wounds 0.6-20 micrograms and 60 micrograms rbFGF decreased the strength parameters by 19%-34% and 49%-52%, respectively, after 10 days. After 20 days there was no negative influence but 60 micrograms rbFGF increased the biomechanical properties by 15%-24%. Treatment with the fibrin adhesive vehicle alone decreased the biomechanical properties of ischaemic wounds after 20 days, and of normal wounds after both 10 and 20 days. In conclusion, rbFGF can improve the healing of ischaemic wounds and may be used in the treatment of ischaemic wounds in patients, but it can have negative effects on normal wound healing.

Diclofenac and indomethacin influence the healing of normal and ischaemic incisional wounds in skin.

The influence of diclofenac and indomethacin on the healing of normal (non-ischaemic) incisional wounds, and of ischaemic incisional wounds using a flap model, was studied in 192 rats. Both drugs improved the strength of normal wounds as the energies at maximum load and stress increased by 23% - 33% after 10 days. After 20 days the treated normal wounds were stiffer. In ischaemic wounds neither drug influenced the biomechanical properties after 10 days, which reflects the healing of the deep dermis, but both countered the ischaemia of the superficial skin as the necroses on the skin flaps decreased. After 20 days the drugs decreased some of the strength parameters of ischaemic wounds, indomethacin in particular, which decreased these parameters by about 20% - 35%. In conclusion, in certain doses the drugs improved the healing of normal wounds. The healing of ischaemic wounds was unaffected after 10 days but decreased after 20 days. The drugs may, however, be used for reducing superficial necroses of skin flaps.

Effect of delayed primary closure on the healing of ischemic wounds.

OBJECTIVE: To study the influence of delayed primary closure on the healing of ischemic wounds in rats. METHODS: Wounds sutured after a delay of 3 days were compared with primary closed wounds by biomechanical testing. RESULTS: The delayed wounds were as strong as primary closed wounds when tested 10 days after wounding. Thirteen days after wounding (10 days after closure), nearly all the biomechanical parameters of the delayed wounds were increased, compared with those of primary closed wounds that had healed for 10 days. The wounds closed after a delay were weaker, however, when tested 20 days after wounding. CONCLUSION: An ischemic wound can safely be left open for 3 days before suturing, i.e., for prevention of infection in contaminated wounds, without affecting the biomechanical properties at the time of removing the sutures, which is often performed clinically 10 to 12 days after the operation.

The impact of ischemia on wound healing is increased in old age but can be countered by hyperbaric oxygen therapy.

The healing of normal incisional wounds and ischemic flap wounds was investigated in young (10 weeks) and old (102-104 weeks) rats, together with the effect of treatment with hyperbaric oxygen on day 0-3 of healing. After 10 days of healing all biomechanical strength parameters of normal wounds were decreased by 30-40% and of ischemic wounds by 40-51% in the old animals compared with the young controls. After 20 days all strength parameters of normal wounds and ischemic wounds were decreased by 29-37% and 46-58%, respectively, in the old rats compared with those of the young ones. Treatment with hyperbaric oxygen of ischemic wounds in old animals increased all strength parameters by 36-50% after 10 days and by 67-88% after 20 days. For young animals, the corresponding increase was only 21-35% after 10 days and no effect was seen after 20 days. The shrinkage of ischemic wounds was decreased by 48% in the old animals compared with the young ones. It can be concluded that ischemia intensifies the impairment of the healing seen in old age. On the other hand, treatment of ischemia with hyperbaric oxygen is much more effective in old animals, despite the fact that it also has a pronounced effect in young animals. Furthermore, the results suggest a decreased wound contraction with age.

Failure of buflomedil to improve wound healing in ischaemic skin flaps.

The effect of buflomedil and isoxsuprine on the healing of ischaemic wounds was investigated using an ischaemic flap model previously evaluated on rats. The drugs were given twice daily intraperitoneally for a total of nine days starting on the day before operation. The wounds were tested biomechanically after 10 and 20 days of healing, respectively, and the length of surface necrosis on the flaps was measured after 10 days. The study showed no differences in any of the biomechanical (functional) parameters of the ischaemic wounds compared with the control groups, either after 10 or 20 days of healing. There were no differences in the length of surface necrosis on the flaps. Neither of these drugs has so far convincingly proved to be effective in the treatment of ischaemic wounds or flaps.

The effect of hyperbaric oxygen on different phases of healing of ischaemic flap wounds and incisional wounds in skin.

Several studies have revealed a positive effect of treatment of ischaemic wounds and flaps with hyperbaric oxygen. We studied the effect of 100% oxygen (2.4 ATA) for 90 min daily on different phases of healing ischaemic and normal incisional wounds in rats. Hyperbaric oxygen on day 0-3 significantly increased almost all the force parameters of ischaemic flap wounds by 41-57% after 10 days of healing. On the other hand, when the treatment was continued until day 9 the positive effect on the wound healing was abolished. Furthermore, when hyperbaric oxygen was given on days 4-9 there was a tendency towards a decrease in the biomechanical parameters. Hyperbaric oxygen had no effect on the healing of normal incisional wounds.

Bladder diverticula in patients with prostatism.

The incidence of bladder diverticula was investigated in a patient material referred for prostatism. Out of 104 referred patients 69 were examined by cystography and urography. Fifty-one per cent had diverticula on cystography but only 30% on urography. Diverticula were significantly related to age. They were significantly associated with upper tract dilatation and tended to relate to residual urine volume and bladder instability. There was no relation to the bladder neck-verumontanum distance, maximal flow rate or bladder capacity.

[Research on aging: biological perspectives]. / Aeldreforskning: biologiske perspektiver.

Aging is a part of the continuous process from conception to death and is strongly modulated by environmental factors throughout the lifespan. Variability in functional capacity between different organs and between individuals therefore increases with aging. This review will discuss two tissues of importance for the fitness of the aging human being: connective tissue and bone. Connective tissues become stiffer with age, which can be mitigated by physical exercise. The physical-chemical stability of collagen is a precise measure for the functional age of the organism. While in the aged, the healing (formation of connective tissue scar) of uncomplicated incisional wounds is slightly impaired, the healing of ischemic wounds is endangered. The clinical observation that "simple" wounds also heal less well in the aged might be due to the presence of diseases with ischemia and other pathologies. During normal aging bone loses mass, structural continuity, and strength. When pronounced, these changes cause osteopenia and osteoporotic fractures. The age-adjusted incidence of osteoporotic fractures is increasing on account of changes in our lifestyle. Preventive efforts, with increased physical activity as the main feature, must be implemented to alter this trend. Our knowledge of the mechanisms of aging is not yet sufficient to formulate a policy containing preventive measures enabling man to achieve his maximum biological lifespan with good physical health and a high quality of life. Multidisciplinary efforts by biologists, clinicians and epidemiologists are warranted to achieve this goal.

Ischemia in wound healing. II: Design of a flap model--biomechanical properties.

A standardized reproducible H-shaped double flap model for biomechanical testing of ischemic wounds was developed in rats. After 10 days of healing all the biomechanical parameters of the flap wounds decreased significantly, compared with normal healing incisional wounds. After 20 days of healing the extensibility as well as the most important biomechanical parameters were still significantly decreased. In part I of this study we showed that on day 1 the blood flow had decreased to 7% of the flow in normal incisional wounds, though it returned to normal on day 16. Here we show that this drop in blood flow results in a significant decrease in all the biomechanical parameters and thereby caused significant delay in the healing of the test wounds. There was no correlation between any of the biomechanical parameters and the length of surface necrosis on the flaps. These necroses thus do not necessarily reflect necrosis of the dermis, where the healing is responsible for the continuity and strength of the skin.

Ischemia in wound healing. I: Design of a flap model--changes in blood flow.

A standardized ischemic, H-shaped, double flap model in rats was developed for investigating the influence of different factors that could potentially increase flap survival. The blood flow was measured in the flaps as well as in normal healing incisional wounds on day -1 (intact skin) and on days 1, 4, 8, and 16 by the xenon-133 (133Xe) clearance technique. The flow in normal healing incisional wounds remained the same as the flow in intact skin. The flow in the flaps, however, initially decreased to ischemic levels, but afterwards gradually increased to that of normal healing incisional wounds and intact skin. Further, the cutaneous blood flow in both the cranially and the caudally based ischemic dorsal flap was independent of the width of the flap.

The influence of age on the healing of normal and ischemic incisional skin wounds.

Experimental studies have not shown that the 'common' clinical experience, which suggests that wound healing is impaired in an old organism, is valid for healthy old experimental animals. We have developed a model in the rat for ischemic wound healing by using an H-shaped double skin flap, where the test wound is the horizontal line in the H. Our previous studies have shown that the blood flow in this wound is only 7% of that of a normally vascularized wound on the first postoperative day. Functional (biomechanical) properties of this wound are decreased by up to 67% after 10 days of healing and certain key properties by up to 64% after both 10 and 20 days. This study reports on the effect of aging, using 3- and 24-month-old rats. The 'normal' incisional wounds healed equally well in both groups. On the other hand, the ischemic wounds in the old animals were found to be impaired by 40-65% compared to similar wounds in the young animals. It is concluded that ischemia is deleterious for wound healing in old age and that one of the key elements of the clinical experience of impaired wound healing in old age is probably based on concomitant diseases in old patients, contributing to varying degrees of ischemia in the traumatized tissue.

Freezing for postmortal storage influences the biomechanical properties of linear skin wounds.

Specimens for biomechanical investigations are often stored frozen between sampling and testing. Several authors have analysed the effects of freezing on a variety of intact tissues; while some have found mostly minor changes, others have reported no adverse effects. Healing wounds contain more fragile tissue components than other tissues and are therefore more sensitive to possible adverse effects. This study on rat skin wounds (healed for 10 and 20 days) demonstrates that freezing has a significant adverse influence on the mechanical properties. It is concluded that fresh tissue should be used whenever possible. In case storage in a freezer is necessary great care should be taken when designing the experimental protocol.