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Ryanodine Receptor Modulator, Dantrolene Sodium, Improves Survival Following Ventricular Fibrillation

Background: Ventricular fibrillation (VF) is associated with dysfunctional cardiac calcium cycling and poor survival. We hypothesized dantrolene improves survival following VF by stabilizing calcium dysregulation.
Methods: VF was induced in 26 healthy Yorkshire pigs and left untreated for 4 min followed by 3 min of CPR and defibrillation. Dantrolene was infused during CPR. Rabbit hearts (n=14) were studied to evaluate the effect of dantrolene on VF-induced calcium cycling dysfunction. Results: Survival was higher in the dantrolene group. (85% vs. 39%, P=0.01) Dantrolene-treated pigs required significantly lower defibrillation energy level. (150J vs. 650J, P<0.05) Systolic pressure was significantly higher during the post-defibrillation period in the dantrolene group. (P=0.001) In rabbit hearts, dantrolene significantly mitigated the amplitude of VF-induced diastolic calcium elevations and increased the calcium alternans threshold. (P<0.05) Conclusion: Our findings suggest dantrolene facilitates successful defibrillation, prevents myocardial stunning and improves survival following VF. The effects are mediated through normalizing the VF-induced dysfunctional calcium cycling.

Identiferoai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/44069
Date19 March 2014
CreatorsZamiri, Nima
ContributorsNanthakumar, Kumaraswamy
Source SetsUniversity of Toronto
Languageen_ca
Detected LanguageEnglish
TypeThesis

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