Cancer is the leading cause of deaths around the world, especially in low- and middle- income countries. Pirarubicin (THP) is an effective drug for treatment of cancer, however, there still exists cardiotoxic effects of THP. Rutin is a kind of antioxidative compound extracted from plants, and might be a protective compound for cardiomyocytes. Phosphatidylinositol 3-hydroxy kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway is critical for cellular survival, proliferation and metabolism, and thus we speculated rutin might perform a protective role in cardiomyocytes via PI3K/AKT/mTOR signaling pathway. And in this experiment, we first established a cardiotoxicity model of THP in mice model and cell models, and then found that rutin treatment could increase the proliferation of cells at low concentration. Then we explored the possible mechanism of the protective effect of rutin using Western blotting, quantitative polymerase chain reaction (qPCR) and ELISA methods, and found that the activation of PI3K/AKT/mTOR/nuclear factor-κB (NF-κB) signaling pathway was increased, and expression of downstream molecules involved in antioxidative stress were also increased. We further noticed that concentration of angiogenesis promoting factors were also increased in medium of cultured cells. Thus, we speculated that rutin could increase the activation of PI3K/AKT/mTOR signaling pathway, further decrease the oxidative stress level via increasing the expression of antioxidative stress enzymes with the increasing concentration of angiogenesis promoting factors, resulting in the protective role in cardiomyocytes and cardiac function.

BACKGROUND: There is lack of outcomes of transaortic shallow septal myectomy with mitral valve(MV) repair comparing with extended Morrow procedure in treatment of hypertrophic obstructive cardiomyopathy (HOCM) with severe interstitial fibrosis. OBJECTIVES: We report a 4-year single-center experience with transaortic shallow septal myectomy in combination with MV repair and compare it with extended Morrow surgery in a cohort of HOCM patients with severe interstitial fibrosis. METHODS: 36 patients who received surgery have been enrolled in current study. Their perioperative characteristics with echocardiographic results, myocardial histopathology and follow up outcomes had been graded and analyzed. We included two groups:13 patients who received shallow septal myectomy concomitant with mitral valvuloplasty (MVP) due to the intrinsic abnormalities of MV apparatus (Shallow septal myectomy + MVP group), and 23 patients who only received extended Morrow procedure without any intrinsic MV abnormalities (Extended Morrow group). RESULTS: Preoperative results revealed that left ventricular end-diastolic dimension (LVEDD) (46.9±1.41mm vs. 11.4±2.17mm, p＜0.05), posterior wall thickness (PWT) (13.3±2.66mm vs. 11.4±2.17mm, p＜0.05), left ventricular mass (LVM) (440.2±78.9g Vs. 310.9±127.6g, p＜0.05), left ventricular mass index (LVMI) (231.7±75.39g/m2 Vs. 180.2±65.07g/m2, p＜0.05 ) and late gadolinium enhancement (LGE) (72.73% Vs. 27.27%, p＜0.01 ) had showed the significant difference between the two group. In the myocardial histopathological evaluation, more severe interstitial fibrosis of the resected myocardium in Shallow septal myectomy + MVP group had showed statistical significant difference compared with Extended Morrow group (p＜0.05). Shallow septal myectomy + MVP procedure sufficiently release left ventricular outflow tract obstruction(LVOTO) and decrease mitral regurgitation (MR) with no increase of postoperative arrhythmia compared with Extended Morrow surgery. CONCLUSIONS: Shallow septal myectomy associated with concomitant MVP provided excellent results offering adequate treatment of LVOTO with no increase of postoperative arrhythmia complication for HOCM patients with severe interstitial fibrosis.