Muscle necrosis has been frequently observed in cardiomyoplasty patients and in experimental animal studies. The purpose of this study was to determine if heat shock could provide protection to skeletal muscle as has been shown in cardiac muscle. A 15-minute heat shock at 42 degrees C resulted in an immediate increase in HSP72 mRNA and was followed within 3 hours by a two-fold increase in HSP72. Surgical dissection of the latissimus dorsi muscle (LDM) followed by an ischemic period resulted in a two-fold increase in HSP72 in control LDM, whereas the already high levels in the heat-shocked LDM increased only slightly with surgery and ischemia. Citrate synthase activity and tissue histology indicated that heat shock did not protect the LDM from the imposed surgical trauma and ischemia insults used in this study.
This study determined effects of surgical dissection and chronic stimulation on degeneration of the latissimus dorsi muscle (LDM), the muscle used for contractile assistance in cardiomyoplasty. LDMs from 10 goats were allocated into four groups: N-LDM (normal), D-LDM (dissected muscle and collateral vessels ligated, muscle remained in original anatomic location), S-LDM (electrically stimulated for 65-75 days), and DS-LDM (dissected and stimulated). S-LDM had nearly a complete transformation to type I fibers throughout the lengths of the muscle. Both groups of dissected muscles (D-LDM and DS-LDM) showed lesser transformation and significant damage. Type I myosin heavy chain and citrate synthase activity were less in the distal compared with the proximal LDM. Morphology of the N-LDM and S-LDM was normal, whereas dramatic morphological abnormalities were observed in the D-LDM and DS-LDM, including lipid-containing ghostlike fibers, atrophied and hypertrophied fibers within the same fascicle. In conclusion, muscle degeneration associated with the cardiomyoplasty procedure was caused by surgical dissection, which was exacerbated by chronic stimulation but was not caused by stimulation alone.
Cardiomyoplasty has the potential to become an alternative therapy for congestive heart failure patients and is presently in Phase III clinical trials. In experimental studies, it is necessary to use an animal with muscle characteristics that resemble those of humans. Therefore, the purpose of this study was to compare morphological and biochemical characteristics of the latissimus dorsi muscle (LDM) of three common large mammals with those of human. Of the three mammals studied, the goat had the most overall similarities to the human when comparing mitochondrial capacity, percent fiber types, fiber areas, myofibrillar (MF)-AT-Pase activity, and 72-kDa heat shock protein (HSP) content. The pig was dissimilar to the human in its fiber-type arrangement, glycolytic capacity, percent fiber type, MF-ATPase activity, and HSP-72 content. The dog differed from the human in that it had high-mitochondrial enzyme activity, a fiber-type profile consisting of all high-aerobic fibers, and fiber cross-sectional areas that were nearly half those of humans. These findings show that the LDM of the goat most resembles that of the human.
Locke, M.; Laughlin, H.; lanuzzo, S. E.; Feild, M.; lanuzzo, CD. FACSM Author Information