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.

METHODS AND 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: Luong Cong Thuc, Yasushi Teshima, Naohiko Takahashi, Satoru Nishio, Akira Fukui, Osamu Kume, Kaori Ezaki, Hiroko Miyazaki, Kunio Yufu, Masahide Hara, Mikiko Nakagawa, Tetsunori Saikawa
• Journal: Circulation journal : official journal of the Japanese Circulation Society (Circ J) Vol. 75 Issue 7 Pg. 1601-8 ( 2011) ISSN: 1347-4820 [Electronic] Japan
• PMID: 21613743 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cardiotonic Agents
• Pravastatin
• Calcium

Topics

• Administration, Oral
• Animals
• Calcium (metabolism)
• Cardiotonic Agents (administration & dosage, pharmacology, therapeutic use)
• Cells, Cultured
• Coronary Vessels (physiopathology)
• Heart Ventricles (drug effects, metabolism, pathology)
• Ligation
• Male
• Membrane Potential, Mitochondrial (drug effects, physiology)
• Models, Animal
• Myocardial Reperfusion Injury (complications)
• Myocytes, Cardiac (drug effects, metabolism, pathology)
• Pravastatin (administration & dosage, pharmacology, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Tachycardia, Ventricular (etiology, physiopathology, prevention & control)
• Treatment Outcome
• Ventricular Fibrillation (etiology, physiopathology, prevention & control)