As a result,the paw of the distal pelvic limb pulled or pushed against a pedal affixed to a transducer,providing a measure of iso metric torque.Supramaximal 150 V,100 us pulses were applied in a tetanic run of 250 pulses.The site of contact for the paw with the lever was estimated to be 75% of the dis tance between the point of the hock first and the distal digit.Torque was divided by the moment arm to convert to force.Eccentric contraction decrement Eccentric contractions were induced Inhibitors,Modulators,Libraries by stimulating the peroneal nerve using square wave pulses of 100 us dur ation in a tetanic run for 1 s at a frequency of 50 Hz while simultaneously extending the TTJ with a servo motor.The contraction was held isometric at the optimal joint angle,expressed as Lo here,for the first 900 ms.

For the final 100 ms,the muscles of the cranial tibial compartment were stretched by the servomotor at 0.7 Lo s,such that the muscles were dis placed to 107% of Lo.Thus,the muscles of the cranial tibial compartment were repeatedly stretched to Inhibitors,Modulators,Libraries induce mechanical damage.Three sets of 10 stretches for a total of 30,each set separated by 4 min,were performed.Contraction induced injury was quantified by the force deficit using the following equation,Fd before stretch Po after stretch Po before stretch �� 100.Joint angles We previously reported that 6 month old GRMD dogs have abnormally acute TTJ angles while po sitioned in dorsal recumbence for force measurements.Other investigators have subsequently described methods to measure joint angles at maximal flexion and extension,with associated range of motion,in wild type dogs.

The method of Jaegger et al.is now utilized to measure pelvic limb tibiotarsal,stifle,and coxofemoral joint angles for on going natural history and preclinical trials in our labora tory.In each case,dogs Inhibitors,Modulators,Libraries were anesthetized and positioned in lateral recumbence.Angles at rest,max imal flexion,and maximal extension were measured.To objectively characterize the cranioventral shift of the pel vis typically seen in GRMD dogs,we also measured the pelvic angle formed by two lines extending cranially from the tuber ischium,one drawn parallel to the lumbar spine and the Inhibitors,Modulators,Libraries other extending to the midpoint of the tuber coxae.Magnetic resonance imaging Studies were done on a Siemens 3 T Allegra Head Only MRI scanner with a circular polarization head coil or Siemens 3 T Tim Trio Whole Body MRI scanner with a 32 channel body coil at the Inhibitors,Modulators,Libraries UNC CH Biomedical Research Imaging Center.Dogs were anesthetized,placed on an MRI gantry in the sternal position with the pelvic limbs extended,and positioned Multiple myeloma in the coil centered at the midpoint of the femur.The proximal pelvic limbs from the coxofe moral joint to the stifle were imaged bilaterally.Scans were completed using a published protocol.