Myosin heavy chain and physiological adaptation of the rat diaphragm in elastase-induced emphysema

BACKGROUND: Several physiological adaptations occur in the respiratory muscles in rodent models of elastase-induced emphysema. Although the contractile properties of the diaphragm are altered in a way that suggests expression of slower isoforms of myosin heavy chain (MHC), it has been difficult to demonstrate a shift in MHCs in an animal model that corresponds to the shift toward slower MHCs seen in human emphysema. METHODS: We sought to identify MHC and corresponding physiological changes in the diaphragms of rats with elastase-induced emphysema. Nine rats with emphysema and 11 control rats were studied 10 months after instillation with elastase. MHC isoform composition was determined by both reverse transcriptase polymerase chain reaction (RT-PCR) and immunocytochemistry by using specific probes able to identify all known adult isoforms. Physiological adaptation was studied on diaphragm strips stimulated in vitro. RESULTS: In addition to confirming that emphysematous diaphragm has a decreased fatigability, we identified a significantly longer time-to-peak-tension (63.9 ± 2.7 ms versus 53.9 ± 2.4 ms). At both the RNA (RT-PCR) and protein (immunocytochemistry) levels, we found a significant decrease in the fastest, MHC isoform (IIb) in emphysema. CONCLUSION: This is the first demonstration of MHC shifts and corresponding physiological changes in the diaphragm in an animal model of emphysema. It is established that rodent emphysema, like human emphysema, does result in a physiologically significant shift toward slower diaphragmatic MHC isoforms. In the rat, this occurs at the faster end of the MHC spectrum than in humans

Effects of different thyroid treatments on the biochemical characteristics of rabbit myocardium

It is well established that extreme dysthyroidism drastically alters the biochemical character of cardiac muscle. The purpose of this study was to determine if minor thyroid treatments would result in significant changes in the character of three major biochemical systems of muscle: metabolic; calcium regulating; and contractile systems. Different groups of New Zealand white rabbits had continuous time release propylthiouracil (PTU) pellets (500, 300, 200 and 100 mg) or triiodothyronine (T3) pellets (15 and 25 mg) subcutaneously implanted for 21 days. The ventricular myosin phenotypes shifted from 92% V3 myosin in the control rabbit hearts to 55% V3 and 10% V3 in the 15 mg and 25 mg T3 groups, respectively. PTU treatment resulted in a complete shift to the V3 myosin isoform. The sarcoplasmic reticulum Ca2+-ATPase activity increased with T3 and decreased with PTU treatments, except in the 500 mg PTU group. Ca2+-ATPase activity in the groups either side of the euthyroid group (100 mg PTU and 15 mg T3) did not change significantly. The glycolytic or aerobic potentials of the myocardium did not change with any of these minor thyroid treatments. It was concluded that the metabolic, enzymes, sarcoplasmic reticulum Ca2+-ATPase and myosin isozymes have different sensitivities to thyroid treatment and that minor thyroid treatments do result in significant changes in the biochemical character of the myocardium. These findings indicate that subclinical deviations in euthyroid status may affect myocardial biochemical character