Objective—To quantify changes in endothelium-derived factors and relate those changes to various aspects of digital hemodynamics during the prodromal stages of carbohydrate overload (CHO)-induced laminitis in horses.
Animals—20 adult horses without abnormalities of the digit.
Procedures—Digital and jugular venous blood samples were collected at 1-hour intervals (for assessment of endothelin-1 [ET-1] immunoreactivity and measurement of glucose, insulin, and nitric oxide [NO] concentrations) or 4-hour intervals (CBC and platelet-neutrophil aggregate assessment) for 8 hours or 16 hours after induction of CHO-associated laminitis in horses treated with an ET-1 antagonist. Effects of treatment, collection site, and time and the random effects of horse on each variable were analyzed by use of a repeated-measures model. Where treatment and collection site had no significant effect, data were combined.
Results—Compared with baseline values, CHO resulted in changes in several variables, including a significant increase from baseline in digital blood ET-like immunoreactivity at 11 hours; digital blood ET-like immunoreactivity was significantly greater than that in jugular venous blood at 8, 9, 11, and 12 hours. Digital and jugular venous blood concentrations of glucose increased from baseline significantly at 3, 4, and 5 hours; insulin concentration increased significantly at 5 hours; and the number of platelet-neutrophil aggregates increased significantly at 12 hours.
Conclusions and Clinical Relevance—In horses, concurrent increases in venous blood ET-1 immunoreactivity, insulin and glucose concentrations, and platelet-neutrophil aggregates support a role of endothelial dysfunction in the pathogenesis of CHO-induced laminitis.
Objective—To determine significant molecular and
cellular factors responsible for differences in secondintention
healing in thoracic and metacarpal wounds
Animals—6 adult mixed-breed horses.
Procedure—A full-thickness skin wound on the
metacarpus and another such wound on the pectoral
region were created, photographed, and measured,
and tissue was harvested from these sites weekly for
4 weeks. Gene expression of type-I collagen, transforming
growth factor (TGF)-β1, matrix metalloproteinase
(MMP)-1, and tissue inhibitor of metalloproteinase
(TIMP)-1 were determined by quantitative in
situ hybridization. Myofibroblasts were detected by
immunohistochemical labeling with α-smooth muscle
actin (α-SMA). Collagen accumulation was detected
by use of picrosirius red staining. Tissue morphology
was examined by use of H&E staining.
Results—Unlike thoracic wounds, forelimb wounds
enlarged during the first 2 weeks. Myofibroblasts,
detected by week 1, remained abundant with superior
organization in thoracic wounds. Type-I collagen
mRNA accumulated progressively in both wounds.
More type-I collagen and TGF-β1 mRNA were seen in
forelimb wounds. Volume of MMP-1 mRNA
decreased from day 0 in both wounds. By week 3,
TIMP-1 mRNA concentration was greater in thoracic
Conclusions and Clinical Relevance—Greater collagen
synthesis in metacarpal than thoracic wounds
was documented by increased concentrations of
myofibroblasts, type-I collagen mRNA, TGF-β1 mRNA,
and decreased collagen degradation (ie, MMP-1).
Imbalanced collagen synthesis and degradation likely
correlate with development of exuberant granulation
tissue, delaying healing in wounds of the distal portions
of the limbs. Factors that inhibit collagen synthesis
or stimulate collagenase may provide treatment
options for horses with exuberant granulation
tissue. (Am J Vet Res 2002;63:1564–1570)