Effective gene therapy for muscular dystrophy will likely require intravascular administration. Although plasmid DNA (pDNA) contained within a large volume and rapidly infused into a major artery can achieve gene transfer within downstream muscles, this is associated with substantial muscle edema. Here we hypothesized that excessive edema-related increases in intramuscular pressure (IM pressure) developed during intraarterial pDNA injections could hinder successful gene delivery. Accordingly, we monitored IM pressure during injection of pDNA carrying a LacZ transgene into the femoral artery of rats and pigs. Large variations in IM pressure were found between different muscles. There was a significant inverse relationship between IM pressure and the subsequent level of gene transfer to muscle. Modification of the injection protocol to reduce IM pressure led to greatly increased pDNA-mediated gene expression and reduced muscle damage in pigs. Under the most optimized conditions, average transfection within eight different muscles of the pig hind limb amounted to 22% of all fibers, attaining a maximum of 60% in the gastrocnemius muscle. We conclude that IM pressure monitoring is a simple and useful procedure, which can be applied in both small and large animals to help optimize pDNA-mediated gene transfer to skeletal muscles by the intraarterial route.

Proximal suspensory desmopathy (PSD) is a common cause of hindlimb lameness in sports horses; anecdotally there is an association with straight hock conformation. The objective of this prospective observational study is to describe hindlimb conformation in horses with and without bilateral PSD. Horses examined over one year with a definitive diagnosis for lameness (based on clinical assessment, response to diagnostic anaesthesia, radiography, ultrasonography AE MRI or scintigraphy), were included (n = 193). Markers were placed on predefined landmarks. Lateral photographs were acquired from the left and right sides with the horse standing squarely, using standardised techniques, with each metatarsus perpendicular to the ground, aligned to the tuber ischii marker. Before data acquisition, repeatability studies for marker placement, horse positioning and angle measurements were performed. The tarsal and metatarsophalangeal angles were measured using Image Measurement. Orthopaedic diagnosis, breed, work discipline, weight, height and age were recorded. Z-tests, Fisher's exact tests, Chi-squared tests and multivariable logistic regression were used to determine the associations between diagnosis, tarsal angles and possible confounding variables. Mann Whitney U tests were used to evaluate the relationship between metatarsophalangeal joint angle and suspensory ligament injury. Horses with PSD had larger tarsal angles than controls (P = 0.003). The proportions of Warmblood-type horses and dressage horses with PSD were different to those of other breeds and work disciplines (P = 0.001, 0.02 respectively). A final logistic regression model demonstrated a significant effect of mean tarsal angle on outcome when breed and weight-height product were accounted for. There was a an 11% increase in the odds of PSD for every degree increase in tarsal angle (CI 1.006-1.223, P = 0.04). There was no association between suspensory ligament injury and metatarsophalangeal joint angle. Assessment of tarsal angles at prepurchase examinations and prior to surgical treatment of PSD may be advisable.