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The effects of diltiazem in dystrophic hamsters
Insights
Diltiazem reduced muscle calcium accumulation in dystrophic hamsters, showing potential for treating muscular dystrophy and similar conditions. This calcium antagonist was well-tolerated and beneficial for heart and skeletal muscles.
Area of Science:
- Biochemistry
- Pharmacology
- Physiology
Background:
- Calcium accumulation in muscles is a hallmark of muscular dystrophy.
- Calcium antagonists have shown mixed results in treating dystrophic cardiomyopathy and skeletal muscle issues.
Purpose of the Study:
- To investigate the effects of a novel calcium antagonist, diltiazem, on muscle calcium levels and related markers in dystrophic hamsters.
- To assess the therapeutic potential of diltiazem in conditions characterized by excessive tissue calcium accumulation.
Main Methods:
- Dystrophic and normal hamsters were administered diltiazem (25 mg/kg/day orally) from 37 to 92 days of age.
- Muscle calcium content, plasma creatine kinase (CK) levels, and protein synthesis rates were measured.
- Histological examination focused on calcium deposits in cardiac tissue.
Main Results:
- Diltiazem significantly reduced muscle calcium in dystrophic hamsters: 73% in the heart, 61% in the diaphragm, and 48% in the rectus femoris.
- Plasma CK levels decreased by 37% in treated dystrophic hamsters.
- Histology confirmed a notable reduction in cardiac calcium deposits; noncollagen protein synthesis in the diaphragm was unaffected.
Conclusions:
- Diltiazem effectively lowers muscle calcium accumulation in dystrophic hamsters.
- The drug was well-tolerated and demonstrated potential therapeutic value for muscular dystrophy and other calcium-related tissue disorders.
- Diltiazem's impact on cardiac calcium deposits suggests specific benefits for cardiomyopathy associated with muscular dystrophy.
Abstract:
Calcium accumulates in muscles of dystrophic hamsters (DH) and patients with Duchenne muscular dystrophy. Various Ca antagonists were beneficial to the cardiomyopathy of DH, but had only minor effects on skeletal muscle. We administered a new Ca antagonist, diltiazem, 25 mg/kg/day orally to normal and dystrophic hamsters from ages 37 to 92 days. We observed a marked reduction in muscle Ca in DH treated with diltiazem: 73% in the heart, 61% in the diaphragm, and 48% in the rectus femoris. Plasma CK was significantly lower (by 37%) in treated DH, while the elevated rate of noncollagen protein synthesis in the diaphragm was not diminished. Histologically, the most important change was a reduction in Ca deposits in the heart. Diltiazem was well-tolerated by all animals and did not modify Ca content in normal hamsters. This study suggests that diltiazem may have therapeutic value in those conditions that are accompanied by excessive accumulation of Ca in tissues, such as muscular dystrophy.