Abstract
The accumulation of oxygen free radicals and activation of neutrophils are strongly implicated as pathophysiological mechanisms mediating myocardial ischemia/reperfusion injury. Heme oxygenase-1 (HO-1) has been reported to play a protective role in oxidative tissue injuries. In this study, the cardioprotective activity of tetramethylpyrazine (TMP), an active ingredient of Chinese medicinal herb Ligusticum wallichii Franchat, was evaluated in an open-chest anesthetized rat model of myocardial ischemia/reperfusion injury. Pretreatment with TMP (5 and 10 mg/kg, i.v.) before left coronary artery occlusion significantly suppressed the occurrence of ventricular fibrillation. After 45 min of ischemia and 1 h of reperfusion, TMP (5 and 10 mg/kg) caused a significant reduction in infarct size and induced HO-1 expression in ischemic myocardium. The HO inhibitor ZnPP (50 μg/rat) markedly reversed the anti-infarct action of TMP. Superoxide anion production in ischemic myocardium after 10 min reperfusion was inhibited by TMP. Furthermore, TMP (200 and 500 μM) significantly suppressed fMLP (800 nM)-activated human neutrophil migration and respiratory burst. In conclusion, TMP suppresses ischemia-induced ventricular arrhythmias and reduces the infarct size resulting from ischemia/reperfusion injury in vivo. This cardioprotective activity of TMP may be associated with its antioxidant activity via induction of HO-1 and with its capacity for neutrophil inhibition.
| Original language | English |
|---|---|
| Pages (from-to) | 731-740 |
| Number of pages | 10 |
| Journal | Journal of Biomedical Science |
| Volume | 13 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Sept 2006 |
Keywords
- Arrhythmias
- HO-1
- Myocardial ischemia
- Neutrophils
- Oxidative stress
- Reperfusion injury
- Tetramethylpyrazine
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Molecular Biology
- Clinical Biochemistry
- Cell Biology
- Biochemistry, medical
- Pharmacology (medical)
