UNLABELLED: Doxorubicin (DOX)-induced muscle dysfunction may contribute to patient fatigue, but the nature of this myotoxicity remains unclear. The purpose of this study was to characterize the muscle function dose-response to DOX. A secondary purpose was to compare the degree of DOX-induced muscle dysfunction to the observed cardiac dysfunction. MATERIALS AND METHODS: Rats received DOX at 10 mg/kg (DOX1), 12.5 mg/kg (DOX2), or 15 mg/kg (DOX3). Muscle and cardiac function were assessed 5 days, post injection. RESULTS: Compared to controls, DOX2 and DOX3 soleus and DOX3 extensor digitorum longus (EDL) had lower maximal twitch force (p<0.05). Soleus fatigue rate was altered by DOX, but EDL fatigue rate was not. Additionally, fractional shortening was lower in DOX2 and DOX3 compared to controls (p<0.05). CONCLUSION: DOX impaired muscle function in a dose-dependent manner. The degree of dysfunction was greater in the soleus and was consistent with the observed cardiac dysfunction.
UNLABELLED: Doxorubicin (DOX)-induced muscle dysfunction may contribute to patientfatigue, but the nature of this myotoxicity remains unclear. The purpose of this study was to characterize the muscle function dose-response to DOX. A secondary purpose was to compare the degree of DOX-induced muscle dysfunction to the observed cardiac dysfunction. MATERIALS AND METHODS:Rats received DOX at 10 mg/kg (DOX1), 12.5 mg/kg (DOX2), or 15 mg/kg (DOX3). Muscle and cardiac function were assessed 5 days, post injection. RESULTS: Compared to controls, DOX2 and DOX3 soleus and DOX3 extensor digitorum longus (EDL) had lower maximal twitch force (p<0.05). Soleus fatigue rate was altered by DOX, but EDL fatigue rate was not. Additionally, fractional shortening was lower in DOX2 and DOX3 compared to controls (p<0.05). CONCLUSION:DOX impaired muscle function in a dose-dependent manner. The degree of dysfunction was greater in the soleus and was consistent with the observed cardiac dysfunction.
Authors: Brittany N J Davis; Jeffrey W Santoso; Michaela J Walker; Catherine E Oliver; Michael M Cunningham; Christian A Boehm; Danielle Dawes; Samantha L Lasater; Kim Huffman; William E Kraus; George A Truskey Journal: Ann Biomed Eng Date: 2019-04-08 Impact factor: 3.934
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