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Increased Inducibility of Ventricular Tachycardia in the Type I Diabetic Akita Mouse is Associated with Abnormalities of Ca2+ Homeostasis and Reversed by Pravastatin.
Author(s) -
Jin Hongwei,
Rajab Mohammad,
Aronovitz Mark,
Wang Bo,
Park HoJin,
Link Mark,
Galper Jonas
Publication year - 2013
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.27.1_supplement.1169.1
Subject(s) - pravastatin , medicine , endocrinology , ventricular tachycardia , calcineurin , afterdepolarization , glucose homeostasis , homeostasis , chemistry , diabetes mellitus , transplantation , insulin resistance , electrophysiology , cholesterol , repolarization
Diabetes mellitus is associated with increased risk of sudden cardiac death. It's relationship to the development of Ventricular Tachycardia (VT) is not understood. It has recently been suggested that Inhibitors of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase (statins) might exert anti arrhythmic effects. It is hypothesized that treatment of Type I diabetic Akita mice with Pravastatin decreases the inducibility of VT. Inducibility of VT in Akita mice in response to programmed ventricular stimulation was significantly increased (78.6%) compared to WT (28.6%, p=0.006). Pravastatin treatment for one week (i.p. 20mg/day) decreased the inducibility of VT to 36.84% (p<0.01). Whole cell patch clamp studies of isolated ventricular myocytes from Akita mice demonstrated a high frequency of early and delayed afterdepolarizations ( EADs and DADs) compared to WT type. Pravastatin treatment significantly decreased occurrence of EADs and DADs. Ca 2+ reuptake as measured by Ca 2+ transient decay time (Tau) was increased in cells from Akita (170.9±10.3 ms) vs WT (138.6±7.3ms, p<0.05) and cytosolic free Ca 2+ was increased. Pravastatin significantly improved SR Ca 2+ reuptake (Tau=142±5.9ms, p<0.05), decreased cytosolic free Ca 2+ . Hence Pravastatin might exert and anti‐arrhythmic effect in Type I diabetes by improving Ca 2+ homeostasis.