title: Cardioprotective effects of pravastatin against lethal ventricular arrhythmias induced by reperfusion in the rat heart.
abstract: BACKGROUND
  Statins are reported to reduce mortality in patients with coronary artery disease and that mortality benefit might be related to the drugs' antiarrhythmic properties.
  
  
  RESULTS
  Male rats were fed with or without pravastatin (0.1 mg·kg⁻¹·day⁻¹) for 7 days, and thereafter subjected to 10 min of ischemia by coronary artery ligation followed by 20 min reperfusion. Treatment with pravastatin reduced the frequency and duration of ventricular tachycardia and fibrillation (VT/VF) and improved the arrhythmia score after reperfusion. To investigate the rapid effects of pravastatin, isolated perfused rat hearts were subjected to 20 min of global ischemia followed by 30 or 60 min of reperfusion. Treatment with pravastatin (10 nmol/L) from 10 min before ischemia shortened the total duration of reperfusion-induced VT/VF. Interestingly, pravastatin administered from the beginning of reperfusion also exerted antiarrhythmic effects. These results indicate that pravastatin exerts antiarrhythmic effects not only with daily oral intake but also when administered just before ischemia or even after ischemia. Intracellular calcium ([Ca²⁺](i)) overload and collapse of mitochondrial inner membrane potential (Δψ(m)) are associated with the arrhythmogenesis during ischemia-reperfusion. In cultured cardiomyocytes, pretreatment with pravastatin (10 nmol/L) suppressed [Ca²⁺](i) overload and prevented Δψ(m) loss induced by H₂O₂.
  
  
  CONCLUSIONS
  Pravastatin attenuated reperfusion-induced lethal ventricular arrhythmias. Inhibition of [Ca²⁺](i) overload and preserving Δψ(m) may be the mechanisms of the observed antiarrhythmic effects of pravastatin.
authors: Department of Laboratory Examination and Diagnostics, Faculty of Medicine, Oita University, Yufu, Japan.
authors: Luong Cong
authors: LC
authors: Thuc
authors: Yasushi
authors: Y
authors: Teshima
authors: Naohiko
authors: N
authors: Takahashi
authors: Satoru
authors: S
authors: Nishio
authors: Akira
authors: A
authors: Fukui
authors: Osamu
authors: O
authors: Kume
authors: Kaori
authors: K
authors: Ezaki
authors: Hiroko
authors: H
authors: Miyazaki
authors: Kunio
authors: K
authors: Yufu
authors: Masahide
authors: M
authors: Hara
authors: Mikiko
authors: M
authors: Nakagawa
authors: Tetsunori
authors: T
authors: Saikawa