Abstract
No-reflow phenomenon, defined as inadequate perfusion of myocardium without evident artery obstruction, occurs at a high incidence after coronary revascularization. The mechanisms underlying no-reflow is only partially understood. It is commonly caused by the swelling of endothelial cells, neutrophil accumulation, and vasoconstriction, which are all related to acute inflammation. Persistent no-reflow can lead to hospitalization and mortality. However, an effective preventive intervention has not yet been established. We have previously found that paeonol, an active extraction from the root of Paeonia suffruticosa, can benefit the heart function by inhibiting tissue damage after ischemia, reducing inflammation, and inducing vasodilatation. To further investigate the potential cardioprotective action of paeonol on no-reflow, healthy male Wistar rats were randomly divided into four groups: sham, ischemia-reperfusion (I/R) injury (left anterior descending coronary artery was ligated for 4 h followed by reperfusion for 8 h), and I/R injury pretreated with paeonol at two different doses. Real-time myocardial contrast echocardiography was used to monitor regional blood perfusion and cardiac functions. Our data indicated that paeonol treatment significantly reduces myocardial infarct area and no-reflow area (n = 8; p < 0.05). Regional myocardial perfusion (A·β) and cardiac functions such as ejection fraction, stroke volume, and fractional shortening were elevated by paeonol (n = 8; p < 0.05). Paeonol also lowered the serum levels of lactate dehydrogenase, creatine kinase, cardiac troponin T, and C-reactive protein, as indices of myocardial injury. Paeonol exerts beneficial effects on attenuating I/R-associated no-reflow injuries, and may be considered as a potential preventive treatment for cardiac diseases or post-coronary revascularization in which no-reflow often occurs.
Highlights
Ischemic heart disease is a major cause of morbidity and mortality worldwide (Zuo et al, 2009, 2013; Zhu and Zuo, 2013; Sivaraman and Yellon, 2014)
The rats were randomly divided into four groups: (1) sham group, thoracotomy without left anterior descending coronary artery (LAD) occlusion or paeonol pretreatment; (2) I/R group, LAD occlusion for 4 h followed by reperfusion for 8 h; (3) Paeonol (100 mg/kg) + I/R group, oral administration of 100 mg/kg paeonol (1 mL/kg) for 7 days using a intragastric tube prior to I/R procedure; (4) Paeonol (200 mg/kg) + I/R group, oral administration of 200 mg/kg paeonol (1 mL/kg) for 7 days using a intragastric tube prior to I/R procedure
An ischemia group without reperfusion is not included since our present study mainly focuses on the effect of paeonol on the cardiac injuries after reperfusion, which is closely related to the real-world situation of no-reflow after coronary revascularization
Summary
Ischemic heart disease is a major cause of morbidity and mortality worldwide (Zuo et al, 2009, 2013; Zhu and Zuo, 2013; Sivaraman and Yellon, 2014). Paeonol Protection in No-Reflow caused by factors such as myocardial interstitial edema, microvascular spasm, endothelial cell injury/swelling, neutrophil accumulation, micro-thromboembolism, and vasoconstriction related to acute inflammation (Rezkalla and Kloner, 2002; Kaul, 2014; Shao et al, 2014). The persistence of these symptoms, termed no-reflow phenomena, can cause insufficient regional blood perfusion, left ventricular (LV) dysfunction, and even cardiac death (Kawano et al, 2005; Chan et al, 2012; Zeng et al, 2012). We hypothesize that paeonol exerts cardioprotective effects by attenuating I/R-associated no-reflow injuries and may be considered as a potential preventive treatment for cardiac diseases or post-coronary revascularization when no-reflow occurs
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