Muscular dystrophy is a disease characterized by skeletal muscle weakness and wasting, but little is known of alterations in the vascular system that occur with this disease. The culprit in many muscular dystrophies is a defective dystrophin-glycoprotein complex (DGC). The DGC is a group of transmembrane proteins that connects the cytoskeleton of muscle cells to the extracellular matrix; it plays a role in mechanotransduction and the maintenance of structural integrity of these cells, and includes the proteins dystrophin and sarcoglycan-delta. The absence of these proteins results in severe muscular dystrophies in humans, and thus knockout mice lacking the genes encoding for dystrophin (mdx mice) and sarcoglycan-delta (sgcd-/- mice) were studied to detect any vascular alterations that occur as a result of a defective DGC. Acute biaxial biomechanical data were obtained through pressure-diameter and axial force-length tests on common carotid arteries of mdx, sgcd-/-, and wild-type mice in the active and passive smooth muscle state. Functional response to the vasoreactive compounds phenylephrine, carbamylcholine chloride, and sodium nitroprusside was also tested. We found significant biomechanical differences between the knockout and wild-type mouse arteries: the mdx and sgcd-/- arteries had decreased distensibilities in pressure-diameter tests, with mdx arteries also having increased circumferential stresses, and the knockout arteries generated increased axial loads and stresses in the axial force-length tests. The mdx and sgcd-/- arteries also differed from the wild-type in that their ‘homeostatic’ axial stretch, at which the axial force remains constant upon pressurization, was significantly decreased. We conclude that the loss of DGC proteins does trigger changes in vascular smooth muscle cells or their interactions with the extracellular matrix, yet that the altered vascular system was able to adapt and function without the DGC. Knowledge of alterations to the vascular system (and adaptations to these changes) of patients with muscular dystrophy could help physicians customize their treatment to extend and enhance their lives, especially as medical advances extend the lifespan of these patients and they begin to suffer from diseases such as hypertension and atherosclerosis that affect the normal aging population.

Thèse de doctorat : Sciences pharmaceutiques. Pharmacologie cellulaire et moléculaire : Strasbourg 1 : 2006. / Titre provenant de l'écran-titre. Bibliogr. 24 p.

Thesis (Ph. D.)--University of Texas at Austin, 2000. / Vita. Includes bibliographical references (leaves 119-126). Available also in a digital version from Dissertation Abstracts.

Thesis (Ph. D.)--York University, 1999. Graduate Programme in Biology. / Typescript. Includes bibliographical references (leaves 135-144). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://wwwlib.umi.com/cr/yorku/fullcit?pNQ39261.

Thesis (M. Phil.)--University of Hong Kong, 1974. / Mimeographed.

The purpose of this study was to determine whether ischemia would enhance muscle spindle responses to tendon tap and vibration during submaximal fatiguing contractions in the soleus muscle of able-bodied individuals. Nine healthy adults attended two experimental sessions approximately 48 hours apart. Both sessions were identical except that the fatigue task in one was performed with a pressure cuff placed above the knee and inflated to 180 mm Hg. Three 5s maximum voluntary contractions (MVCs) were performed prior to and after the fatigue task. Each participant held a target force of 20% MVC until endurance time (peak-to-peak tremor amplitude exceeded 5% MVC or target force dropped by 2% for 3s). Muscle spindle responses were evaluated using the peak-to-peak EMG amplitude of tendon taps (delivered by a custom-made tapper) and the Motor Unit Firing Rates (MUFR) during 15 s of vibration, recorded with fine-wire intramuscular electrodes. H reflex responses were measured before and after fatigue for each condition, to measure the net excitability of the spinal cord. There were no significant differences (p>0.05) in the P-P EMG of tendon taps or the MUFR across any conditions. The post-fatigue Maximal Voluntary Contraction forces were measured and were less than the pre-fatigue values under both conditions (and significantly different in the non-ischemic condition (p=0.01)). Absence of significant differences in the Hmax:Mmax ratios (p=0.94 in non-ischemic/fatigue and p=0.43 in ischemic condition) indicated that the spinal excitability was relatively unchanged across the conditions. Therefore, we could not conclude that ischemia enhanced the muscle spindle response. / text

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

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