Wound repair in horse limbs is often complicated by exuberant granulation tissue, a condition characterized by excessive fibroplasia and scarring and that resembles hypertrophic scars and keloids in man. The aim of this study was to compare microvascular occlusion and apoptosis in wounds of the limb with those of the body, which heal normally. Five 6.25 cm(2) wounds were created on both forelimbs and on the body of six horses. One limb was bandaged to stimulate excessive fibroplasia. Weekly biopsies were evaluated histologically and immunohistochemically for mutant p53 protein by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling to localize and quantify apoptosis, and by electron microscopy to measure microvessel luminal diameters. Histologic examination revealed protracted inflammation as well as slowed epithelialization and deficient fibroblast orientation in limb wounds, particularly those with excessive fibroplasia. Microvessels were occluded significantly more often in limb wounds, and the balance of apoptotic signals was altered against apoptosis in the former, although this could not be confirmed quantitatively. Data suggest that microvascular occlusion and a dysregulated apoptotic process may be involved in the excessive accumulation of extracellular matrix within limb wounds. This might provide a basis for the development of targeted therapies to prevent and treat excessive fibroplasia and extensive scarring in horses.

The persistence of TGF-beta(1) expression in leg wounds may be related to the development of exuberant granulation tissue in this location, because TGF-beta(1) is profibrotic.

Topical application of autologous platelet-rich plasma did not accelerate or improve the quality of repair of small granulating wounds on limbs of horses. This treatment may better suit wounds with massive tissue loss or, alternatively, chronic wounds that would benefit from a fresh source of mediators to accelerate the healing process.

Impaired wound healing represents an enormous clinical and financial problem for companion animals and humans alike. Unfortunately, most models used to study healing rely on rodents, which have significant differences in the healing and scarring process and rarely develop complications. In order to better simulate impaired healing, the model should strive to reproduce the natural processes of healing and delayed healing. Wounds on the limbs of horses display similarities to wounds in humans in their epithelialization/contraction ratio, genetic influence as well as dysregulated cytokine profile and the spontaneous development of fibroproliferative disorders. Veterinarians have access to advanced wound therapies that are often identical to those provided to human patients. Wound research in large animals has resulted in new wound models as well as a better understanding of the physiology, immunology, and local environmental impact on both normal and aberrant wound healing. One such model reproduces the naturally occurring fibroproliferative disorder of horses known as exuberant granulation tissue. Comparisons between the normally healing and impaired wounds provide insight into the repair process and can facilitate product development. A better understanding of the wound healing physiopathology based on clinically accurate animal models should lead to the development of novel therapies thereby improving outcomes in both human and veterinary patients.

This study suggests that the production of EGT in bandaged wounds may be related to increased expression of fibrogenic TGF-beta1 and decreased expression of antifibrotic TGF-beta3. Further investigation of the roles of TGF-beta1 and -beta3 may be important in understanding the molecular control of EGT in horses.

Wound repair in horse limbs is often complicated by the development of exuberant granulation tissue (EGT) and excessive scarring while body wounds tend to repair uneventfully. EGT resembles the human keloid. While the events leading to keloid formation are not fully elucidated, tissue hypoxia has been proposed as a major contributing factor. The objective of this study was to investigate tissue oxygen saturation in healing full-thickness wounds created on the horse limb and body, using near-infrared spectroscopy. Spectroscopic reflectance data were collected from both anatomic sites at specific times following wounding. The oxygen saturation values of limb wounds were significantly inferior to those of body wounds during the early period of healing, indicating a temporary, relative state of hypoxia in the former during the inflammatory phase of repair. Horses present a weak, persistent inflammatory response to wounding, especially at the limb level. The relative hypoxia present acutely in limb wounds of horses may promote a feeble yet prolonged inflammatory response, which could interfere with and retard the subsequent phases of healing. Ongoing low-grade inflammation in horse wounds is accompanied by up-regulation of various inflammatory and profibrotic mediators, which might ultimately promote the development of fibroproliferative disorders such as EGT.

We compared the ability of 1.5 T magnetic resonance imaging (MRI), computed tomography (CT), and computed radiography (CR) to evaluate noncartilaginous structures of the equine metacarpophalangeal joint (MCP), and the association of imaging changes with gross cartilage damage in the context of osteoarthritis. Four CR projections, helical single-slice CT, and MRI (Ti-weighted gradient recalled echo [GRE], T2*-weighted GRE with fast imaging employing steady-state acquisition [FIESTA], T2-weighted fast spin echo with fat saturation, and spoiled gradient recalled echo with fat saturation ISPGR-FS]) were performed on 20 racehorse cadaver forelimbs. Osteophytosis, synovial effusion, subchondral bone lysis and sclerosis, supracondylar lysis, joint fragments, bone marrow lesions, and collateral desmopathy were assessed with each modality. Interexaminer agreement was inferior to intraexaminer agreement and was generally moderate (i.e., 0.4 < kappa < 0.6). Subchondral bone sclerosis scores using CT or MRI were correlated significantly with the reference quantitative CT technique used to assess bone mineral density (P < 0.0001). Scores for subchondral lysis and osteophytosis were higher with MRI or CT vs. CR (P < 0.0001). Although differences between modalities were noted, osteophytosis, subchondral sclerosis, and lysis as well as synovial effusion were all associated with the degree of cartilage damage and should be further evaluated as potential criteria to be included in a whole-organ scoring system. This study highlights the capacity of MRI to evaluate noncartilaginous changes in the osteoarthritic equine MCP joint.

The purpose was to evaluate the capacity of 1.5 T magnetic resonance (MR) imaging to assess articular cartilage in racehorses with naturally occurring metacarpophalangeal joint osteoarthritis. A sagittal, threedimensional spoiled gradient-recalled echo (SPGR) with fat saturation (FS) sequence was acquired ex vivo on 20 joints. Following joint dissection, specific areas on the third metacarpal condyle were designated for subsequent sampling for histologic cartilage thickness measurement and modified Mankin scoring. Cartilage thickness was measured and cartilage signal intensity was also graded (0-3) on MR images at these selected metacarpal sites. Cartilage structure was graded (0-3) macroscopically and on MR images by two examiners in defined subregions of the proximal phalanx, third metacarpal, and proximal sesamoid bones. There was good precision (mean error 0.11 mm) and moderate correlation (r ¼ 0.44; Po0.0001) of cartilage thickness measurements between MR images (0.90 AE 0.17 mm) and histology (0.79 AE 0.16 mm). There was moderate correlation between modified Mankin histologic score and signal intensity of cartilage (r ¼ 0.36; Po0.01) or MR cartilage structure assessment (r ¼ 0.49, P40.001) on SPGR-FS. The sensitivity to detect full-thickness cartilage erosion on MR was only moderate (0.56), and these lesions were often underestimated, particularly when linear in nature. However, the specificity to detect such lesions on MR was high (0.92). While few limitations were identified, the use of a clinically applicable SPGR-FS sequence allows a reasonably accurate method to assess structural changes affecting the articular cartilage of the equine metacarpophalangeal joint. r 2010