The object of this animal study was to examine and further develop the expanded polytetrafluoroethylene wound healing model. The goal was to increase its potential for assessing wound healing by increasing yield, reducing variability, establishing the elements of a standard technique, and further testing its ability to detect variations of healing which have clinical significance. Expanded polytetrafluoroethylene implants of various dimensions and fabrications and several implantation and sterilization techniques were compared in rats. Hydroxyproline, DNA, and protein deposition into the expanded polytetrafluoroethylene implants as parameters for wound healing were assessed. Additionally, a 4 cm skin incision for tensile strength assessment was created. Wound healing was assessed under normal and corticosteroid-impaired healing conditions. The highest yield of collagen was found in the stiffer fabrication of expanded polytetrafluoroethylene with the larger pore size and after the more traumatic implantation technique of incisional placement. Variability was unaffected by fabrication, implantation technique, indexing by various geometric dimensions of the implant, sterilization, or sampling techniques. Variability was the same in the individual animals as in groups of animals. The expanded polytetrafluoroethylene method also detects the influence of antiinflammatory corticosteroids and reflects the tensile strength of incisional wounds made in other sites in the same animal.

Journal Article↗

PubMedDate not supplied

Centrally and locally mediated thermoregulatory responses alter subcutaneous oxygen tension.

Mild perianesthetic hypothermia decreases resistance to infections. Decreased resistance likely results in part from direct immune inhibition. However, decreased tissue oxygen partial pressure also decreases resistance to infection by impairing oxidative killing by neutrophils and collagen deposition. Thermoregulatory vasoconstriction decreases skin blood flow and may also decrease subcutaneous tissue oxygen tension. Accordingly, we determined the influence of centrally and locally mediated thermoregulatory vasomotion on subcutaneous oxygen tension. We also compared subcutaneous oxygen tension to other potential markers of tissue perfusion: laser Doppler flowmetry and transcutaneous oxygen tension. Arterial oxygen tension was maintained near 325 mm Hg in five volunteers. Control subcutaneous oxygen tension values were recorded after 1 hour of euthermia (no sweating or vasoconstriction). Volunteers were then cooled with a circulating-water mattress positioned under the trunk and legs. After 1.5 hours of cooling sufficient to produce shivering, the right upper arm was covered for 1 hour with a small circulating water blanket set to 40 degrees C while systemic cooling continued. The volunteers were then systematically warmed to produce sweating, and the right arm was locally cooled. There was no correlation among laser Doppler flowmetry, transcutaneous oxygen tension, and subcutaneous oxygen tension. Systemic cooling significantly decreased subcutaneous oxygen tension, but subcutaneous oxygen tension in the right arm returned to control values during local heating. Systemic warming significantly increased subcutaneous oxygen tension, and 1 hour of local cooling failed to fully reverse the increase. These data indicate that thermoregulatory vasoconstriction significantly decreases tissue oxygen availability. Decreased subcutaneous oxygen tension may be one mechanism by which mild perianesthetic hypothermia facilitates development of surgical wound infections.

Journal Article↗

PubMedDate not supplied

Long-term results of aggressive management of diabetic foot ulcers suggest significant cost effectiveness.

This study was undertaken to examine the hypothesis that the initial high limb salvage rate in patients with diabetes who are treated aggressively with a multidisciplinary approach to management of severe, chronic lower extremity wounds is durable and cost effective. In 1991 a cohort of 41 patients with diabetes with severe, chronic foot wounds was selected by a neutral, blinded observer who had no knowledge of the outcomes from a group of 101 consecutive such patients who had been treated at our wound center from 1983 to 1990. All had limb-threatening lesions, scoring 3 to 4 on the Wagner scale, were treated for at least 7 days with adjunctive hyperbaric oxygen, and had photographic and medical documentation. Durability of wound repair was examined in 1991 and 1993. Initial limb salvage was 85%. Mean hospital charges were $31,264, including average hyperbaric charges of $15,000. At the initial review, 28 of the patients with previously salvaged limbs (80%) were contacted. Of the 28 patients, 27 remained intact (96%). The mean durability of repair was 2.6 years. At the second review, the mean duration of repair in surviving patients was 4.6 years with no further expenditures relative to the salvaged limb. In patients who died, average durability was 3.4 years, also without additional expenditure referable to the salvaged extremity. Most complex lower extremity lesions were healed by a comprehensive wound care program which included vascular surgery and hyperbaric oxygen. The results were durable, and the treatment was cost effective and humane compared with early amputation.

Journal Article↗

PubMedDate not supplied

Tissue gas tensions and oxygen consumption in healing bone defects.

A technique for measuring the gaseous environment during the reconstitution of a large bone defect is described. Extensive testing of this system over the past 10 years has demonstrated its validity in measuring the average extracellular tissue pO-2 and pCO-2. Histology of the tissue surrounding the tonometer was obtained and correlated with the gaseous measurements. New bone formation in the healing segmental bone defects has been shown to take place under hypoxic conditions. The oxygen consumption of the surrounding tissue was determined and correlated with the histology and tissue gas measurements. It was demonstrated that the oxygen consumption was not elevated during the period of new bone formation, reflecting a state of anaerobic metabolism. The hypoxic conditions persist until the vascularity increases to match the cellularity. Thephysiological role of oxygen in osseous repair is presented. The present technique as well as the previously published microelectrode technique have demonstrated bone formation in vivo can take place under hypoxic conditions but the mechanism is not known and requires further investigation.

Animals↗

PubMedDate not supplied

External localization of experimental sterile abscesses.

Explore the source record for details and available documents.

Abscess↗

PubMedDate not supplied

Natural resistance to infection: leukocyte functions.

The nonspecific immune system has an extraordinarily important role in prevention of and response to wound infection. In the presence of injury or contamination, leukocytes adhere to local endothelial cells in response to complement signals through an integrin mechanism; they then migrate to the affected tissue site to locate, ingest, and kill microbes. Clinically, the major weaknesses in this system are impairment of cell recruitment and depression of microbial killing mechanisms; intracellular killing is the most problematic step in the process. Provided that leukocytes are able to migrate and ingest bacteria, nonoxidative killing proceeds in a normal fashion. Oxidative killing, however, can be profoundly impaired by poor blood perfusion and oxygenation. Low oxygen tension is a common clinical problem in surgical sites and wounds. There are a number of ways in which oxidative killing can be supported and facilitated in the clinical arena in a manner that is likely to enhance the effects of antibiotics in the treatment and prevention of infection.

Burns↗

PubMedDate not supplied

Lactate elicits vascular endothelial growth factor from macrophages: a possible alternative to hypoxia.

Macrophages respond to various stimuli to produce angiogenic factors but few mechanistic details are known. We examined the effects of hypoxia, lactate and nicotinamide on the expression of vascular endothelial growth factor by cultured macrophages. These agents were chosen because they down-regulate polyadenosine diphosphoribose levels. Following exposure, conditioned media were analyzed for vascular endothelial growth factor protein. Nicotinamide adenine dinucleotide, polyadenosine diphosphoribose, and vascular endothelial growth factor mRNA were measured in the cellular fraction. Angiogenic capacity of the conditioned media was tested in rabbit corneas and Matrigel implants. All three agents, hypoxia, lactate and nicotinamide, elicited significantly increased levels of vascular endothelial growth factor mRNA and vascular endothelial growth factor in the conditioned media, and these levels were paralleled by their angiogenic activity. Polyadenosine diphosphoribose in the cellular fraction was correspondingly depressed. Anti-vascular endothelial growth factor antibody inhibited most of the angiogenic response whereas anti-basic fibroblast growth factor antibody had little effect. We propose that redox changes associated with the alteration of cellular nicotinamide adenine dinucleotide and polyadenosine diphosphoribose are involved in lactate-mediated VEGF expression.

Animals↗

PubMedDate not supplied

Relaxin induces vascular endothelial growth factor expression and angiogenesis selectively at wound sites.

Relaxin is a reproductive hormone that has historically been characterized as being responsible for pubic ligament loosening and cervical ripening. Recently, relaxin has been associated with neovascularization of the endometrial lining of the uterus, potentially via specific induction of vascular endothelial growth factor. Previously conducted clinical studies using partially purified porcine relaxin have described relaxin's ability to stimulate the healing of ischemic wounds, suggesting that relaxin may also have angiogenic effects at sites of ischemic wound healing. In the present study, relaxin's angiogenic effects in the context of wound repair were tested in rodent models of angiogenesis and wound healing. Relaxin showed an ability to stimulate new blood vessel formation, particularly at ischemic wound sites, and to induce both vascular endothelial growth factor and basic fibroblast growth factor specifically in cells, presumably including macrophages, collected from wound sites. Resident macrophages collected from nonwound sites, such as the lung, did not show altered expression of these cytokines following relaxin administration. Because angiogenic wound cells are frequently macrophages, THP-1 cells, a cell line of monocyte lineage that binds relaxin specifically, were tested for and shown to induce vascular endothelial growth factor and basic fibroblast growth factor in response to relaxin. In conclusion, relaxin may be useful in the treatment of ischemic wounds by stimulating angiogenesis via the induction of vascular endothelial growth factor and basic fibroblast growth factor in wound macrophages.

Animals↗

PubMedDate not supplied

Physiology of wound healing.

Wound healing is a complicated process that recruits at least 4 distinct cell types. Though the process is continuous, it is commonly referred to as occurring in "phases." The main phases of wound healing include coagulation, which begins immediately after injury; inflammation, which initiates shortly thereafter; a migratory and proliferative process, which begins within days and includes the major processes of healing; and a remodeling process, which may last for up to a year and is responsible for scar tissue formation and development of new skin. Wound healing is affected by several factors. These include local factors (growth factors, edema and ischemia, low oxygen tension, and infection), regional factors (arterial insufficiency, venous insufficiency, and neuropathy), systemic factors (inadequate perfusion and metabolic disease), and other miscellaneous factors, such as nutritional state, preexisting illnesses, exposure to radiation therapy, and smoking. In general, chronic wounds may be managed by preventing or medically treating infections through debridement and occlusive dressings. For wounds that are unresponsive to such interventions, the use of skin replacements is becoming a viable option. In this regard, a product such as Graftskin (APLIGRAF, Organogenesis Inc, Canton, MA, and Novartis Pharmaceuticals Corporation, East Hanover, NJ), a bilayered living skin construct with allogeneic dermis and epidermis, is a positive development.

Blood Coagulation↗

PubMedDate not supplied

Adjuvant hyperbaric oxygen therapy (HBO2)for treatment of necrotizing fasciitis reduces mortality and amputation rate.

OBJECTIVE: A retrospective analysis of 42 patients with necrotizing soft tissue infections treated with adjunctive HBO2 to ascertain efficacy and safety. Overall mortality was 11.9% and morbidity 5%. SUMMARY BACKGROUND DATA: Necrotizing soft tissue infections have historically high rates of mortality and morbidity, including amputation. Common misconceptions that prevent widespread use of adjunctive HBO2 for this diagnosis include delays to surgery, increased morbidity, and significant complications. METHODS: Forty-two consecutive patients (average age 56.1) with necrotizing fasciitis presenting to a major referral center were treated with adjunctive HBO2 as part of an aggressive program of surgery, antibiotics, and critical care. Involved areas included the lower abdomen (15 patients), thigh and perineum (9 patients), flank (4 patients), lower leg (3 patients), and arm, shoulder, and axilla (2 patients). Co-morbidities included diabetes mellitus, chronic renal failure, intravenous drug abuse, peripheral vascular disease, and malignancy. RESULTS: Mortality was 11.9% (5 patients). Both amputations (a finger and a penis), occurred prior to transport to our facility. The average number of surgical debridements was 2.8 per patient; 1.25 performed prior to the start of HBO. The infectious process was controlled after an average of 7 HBO2 treatments were administered to ensure successful wound closure. Complications consisted of only mild ear barotrauma in 3 patients (7%), and confinement anxiety in 17 (41%) but did not prevent treatment. CONCLUSION: Compared to national reports of outcomes with "standard" regimens for necrotizing fasciitis, our experience with HBO2, adjunctive to comprehensive and aggressive management, demonstrates reduced mortality (34% v. 11.9%), and morbidity (amputations 50% v. 0%). The treatments were safe and no delays to surgery or interference with standard therapy could be attributed to HBO2.

Adult↗