Abstract
ObjectiveThis study tested the hypothesis that verapamil (VP), an L‐type voltage‐dependent calcium channel inhibitor, and dantrolene (DT), a sarcoplasmic reticulum calcium inhibitor, could attenuate calpain overexpression, dystrophin loss/reduction and cardiac dysfunction in experimental sepsis by CLP.Methods and ResultsMale C57Bl/6 mice were subjected to sham and severe septic injury (SSI) induced by CLP; half of animals from each group were treated with either verapamil (5mg/kg, SSI+VP) or dantrolene (10mg/kg, SSI+DT). Reduced myocardial levels of NF‐kB and calpain‐1 were detected in SSI+DT and SSI+VP mice associated with increased actin and myosin expression as compared to SSI mice. Consonantly, DT and VP significantly prevented the loss of dystrophin in comparison with SSI mice. Concurrently, SSI+DT and SSI+VP mice presented ejection fraction and fractional shortening improvement associated with increased survival rate.ConclusionsThese observations give support to the opinion that increased intracellular calcium concentration induces calpain activation that causes dystrophin loss/reduction and consequent myocardial dysfunction in CLP experimental sepsis. Studies are needed to further elucidate these new possible interventional pathways to prevent septic cardiomyopathy/heart failure.
Published Version
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