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Effect of verapamil on experimental septic cardiomyopathy induced by cecal ligation and puncture
Author(s) -
Celes Mara Rubia,
Prado Cibele M,
Campos Erica C,
Blefari Valdecir,
Malvestio Lygia M,
Cunha Fernando Q,
Tanowitz Herbert B,
Rossi Marcos A
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.614.5
Objective This study was designed to determine the effect of verapamil (VP), an L‐type voltage‐dependent calcium channel inhibitor, on septic cardiomyopathy induced by cecal ligation and puncture (CLP). Methods and Results Male C57Bl/6 mice were subjected to sham or severe septic injury (SSI) induced by CLP and, 2 hours after sham or SSI procedure the mice were treated with verapamil (SSI+VP). The SSI+VP mice presented reduced serum levels of TNF‐alpha, IL‐1b and IL‐6 when compared with SSI mice. The myocardium of SSI+VP mice presented reduced foci of myocytolysis and tumefaction of cardiac cells compared with SSI myocardium. Consonantly, reduced amounts of NF‐kB and calpain‐1 were detected in SSI+VP myocardium associated with increase of actin and myosin expression when compared with SSI mice. An improvement of ejection fraction and fractional shortening was observed in SSI+VP mice. Conclusions The results support the concept that increased calcium concentrations may be an important mechanism of sepsis‐induced cardiac muscle proteolysis. The data also indicate that the decreased levels of TNF‐alpha may contribute to the anti‐catabolic effects of verapamil during sepsis. These observations are important from a clinical standpoint suggesting that the catabolic response in myocardial muscle during sepsis may be prevented by treatment with a calcium antagonist. Supported by FAPESP.