DL-3-n-butylphthalide improves ventricular function, and prevents ventricular remodeling and arrhythmias in post-MI rats.
Hui-Liang QiuJin MaHuanlin WuChunhua DingPublished in: Naunyn-Schmiedeberg's archives of pharmacology (2018)
DL-3-n-butylphthalide (NBP) is used in the treatment of ischemic stroke. It was demonstrated NBP also has a cardioprotective effect in acute myocardial infarction (MI) model. However, the chronic effects of NBP on ventricular function, remodeling, and arrhythmias in post-MI stage are unknown. This study was to investigate the effect of NBP on reducing ventricular remodeling and arrhythmias in post-MI stage. Post-MI rats were randomly treated with 100 mg/kg NBP daily (n = 21) or vehicle (n = 21) for 5 weeks. Sham-operated rats were treated with the same dose vehicle (n = 18). Echocardiographic assessment, ventricular arrhythmias inducibility test, morphological and collagen analysis, immunohistochemistry, and western blot were studied. NBP significantly improved cardiac function, inhibited the severity and inducibility of ventricular arrhythmias, reduced cardiac index, fibrosis and hypertrophy, improved the protein expression and distribution of Cx43 gap junction, and upregulated PI3k/Akt/Nrf2 pathway and the downstream antioxidant response elements (ARE), including heme oxygenase-1, Glutathione, Cu-Zn superoxide dismutase, and Fe/Mn superoxide dismutase. These results suggest NBP improves LV function and reduces ventricular arrhythmias by mitigating LV fibrosis, hypertrophy, and Cx43 gap junction remodeling. PI3k/Akt/Nrf2/ARE signaling pathway may contribute to its anti-ventricular remodeling effects.
Keyphrases
- left ventricular
- pi k akt
- signaling pathway
- heart failure
- catheter ablation
- acute myocardial infarction
- cell proliferation
- congenital heart disease
- cell cycle arrest
- oxidative stress
- risk assessment
- mitral valve
- physical activity
- acute coronary syndrome
- pulmonary hypertension
- cell death
- clinical trial
- coronary artery disease
- south africa
- room temperature
- nitric oxide
- mouse model