Summary Although short‐term survival rates following small intestinal resection reportedly range from 48–88%, there is little information on predicting which horse may or may not survive small intestinal (SI) resection and anastomosis. The aim of this study was to identify factors that contribute to nonsurvival in horses following small intestinal resection. Medical records of horses which recovered from anaesthesia following SI resection were reviewed. Clinical and surgical variables were evaluated for their association with short‐term survival using logistic regression and were reported as odds ratios (OR), including the 95% confidence interval (CI), indicating the likelihood of horses not surviving to hospital discharge. Ninety‐two records met the criteria for inclusion. Thirty‐six (81.8%) of the horses that underwent jejunojejunostomy (JJ) and 34 (70.8%) of the horses that underwent jejunocaecostomy (JC) survived to discharge. Multiple logistic analysis indicated that postoperative ileus (OR = 29.7; 95% CI 2.5–354.6), repeat celiotomy (OR = 18; CI 1.7–187.6), and an elevated heart rate of ≥ 60 beats/min (OR = 5.6; CI 1.5–20.6) were the principal factors associated with nonsurvival. A low total plasma protein of <55 g/l (OR = 1.8; CI 0.5–7.6) was incorporated in the final model because its inclusion improved the overall validity of the model Clinicians should be aware of the factors associated with the greatest likelihood of nonsurvival following small intestinal resection, so that they can institute aggressive treatment and accurately inform owners on the likelihood of survival.

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An animal suspension model has been used to simulate the weightlessness experienced during space travel. This procedure results in a reduction in the normal shortening (i.e. hypokinesia) and force generation functions of hind limb muscles (i.e. hypodynamia). The ensuing muscle atrophy was studied over 12 days in different muscle types. Slow muscles (e.g. the soleus) underwent a more pronounced atrophy than intermediate (i.e. gastrocnemius) and fast phasic muscles (e.g. extensor digitorum longus). In all muscle types inactivity resulted in a smaller accumulation of DNA and losses of RNA and protein after 5 days. The latter arose from a decrease in the rate of protein synthesis (measured in vivo) and an increase in protein breakdown. Increased specific activities of cathepsins B and D also supported the view that there is an increased proteolysis after hypokinesia and hypodynamia. When the inactive soleus was simultaneously held in a lengthened (stretched) state the atrophy was prevented through a large increase in the fractional rate of protein synthesis. Protein degradation remained elevated with stretch, thereby slowing the growth of these muscles relative to those in pair-fed, ambulatory controls. The much smaller atrophy of the tibialis anterior and extensor digitorum longus muscles in suspended only limbs represented an underestimate of the true atrophic effects of hypokinesia and hypodynamia. In this model gravity pulls the suspended foot into a plantar flexed position, thereby permanently stretching and protecting such flexor muscles. When this influence of stretch was removed a greater atrophy ensued, mainly due to the loss of the stretch-induced stimulation of protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Toward the treatment of osteoarthritis (OA), the authors have been investigating self-complementary adeno-associated virus (scAAV) for intra-articular delivery of therapeutic gene products. As OA frequently affects weight-bearing joints, pharmacokinetic studies of scAAV gene delivery were performed in the joints of the equine forelimb to identify parameters relevant to clinical translation in humans. Using interleukin-1 receptor antagonist (IL-1Ra) as a secreted therapeutic reporter, scAAV vector plasmids containing codon-optimized cDNA for equine IL-1Ra (eqIL-1Ra) were generated, which produced eqIL-1Ra at levels 30- to 50-fold higher than the native sequence. The most efficient cDNA was packaged in AAV2.5 capsid, and following characterization in vitro, the virus was injected into the carpal and metacarpophalangeal joints of horses over a 100-fold dose range. A putative ceiling dose of 5 × 10 viral genomes was identified that elevated the steady-state eqIL-1Ra in the synovial fluids of injected joints by >40-fold over endogenous levels and was sustained for at least 6 months. No adverse effects were seen, and eqIL-1Ra in serum and urine remained at background levels throughout. Using the 5 × 10 viral genome dose of scAAV, and green fluorescent protein as a cytologic marker, the local and systemic distribution of vector and transduced cells following intra-articular injection scAAV.GFP were compared in healthy equine joints and in those with late-stage, naturally occurring OA. In both cases, 99.7% of the vector remained within the injected joint. Strikingly, the pathologies characteristic of OA (synovitis, osteophyte formation, and cartilage erosion) were associated with a substantial increase in transgenic expression relative to tissues in healthy joints. This was most notable in regions of articular cartilage with visible damage, where foci of brilliantly fluorescent chondrocytes were observed. Overall, these data suggest that AAV-mediated gene transfer can provide relatively safe, sustained protein drug delivery to joints of human proportions.