Key result
Cecal ligation and puncture reduces LVEF by ~22% vs sham in septic rats.
Why the study?
Autophagy is involved in sepsis-induced myocardial dysfunction, but its changes and relationship with the mTOR pathway in CLP-induced myocardial dysfunction remain unclear.
RCT (n=12)
randomly divided
Absolute Event Rate: 0.59% vs 0.76%
p-value: p=<0.01
Rat sepsis model impairs LVEF with autophagy acceleration; leaves open translation to human septic cardiomyopathy.
BACKGROUND: Recent studies have indicated that autophagy is involved in sepsis-induced myocardial dysfunction. This study aimed to investigate the change of autophagy in cecal ligation and puncture (CLP)-induced myocardium dysfunction and its relationship with mammalian target of rapamycin (mTOR) pathway. METHODS: Totally, 12 rats were randomly divided into CLP group or sham-operated (SHAM) group. Cardiac tissues were harvested 18 h after CLP or sham operation. Pathology was detected by hematoxylin and eosin staining, cardiac functions by echocardiography, distribution of microtubule-associated protein light chain 3 type II (LC3II) by immunohistochemical staining, and autophagic vacuoles by transmission electron microscopy. Moreover, phosphorylation of mTOR (p-mTOR), phosphorylation of S6 kinase-1 (PS6K1), and LC3II and p62 expression were measured by western blotting. Pearson's correlation coefficient was used to analyze the correlation of two parameters. RESULTS: The results by pathology and echocardiography revealed that there was obvious myocardial injury in CLP rats (left ventricle ejection fraction: SHAM 0.76 ± 0.06 vs. CLP 0.59 ± 0.11, P < 0.01; fractional shortening: SHAM 0.51 ± 0.09 vs. CLP 0.37 ± 0.06, P < 0.05). We also found that the autophagy process was elevated by CLP, the ratio of LC3II/LC3I was increased (P < 0.05) while the expression of p62 was decreased (P < 0.05) in the CLP rats, and there were also more autophagosomes and autolysosomes in the CLP rats. Furthermore, the mTOR pathway in CLP myocardium was inhibited when compared with the sham-operated rats; p-mTOR (P < 0.01) and PS6K1 (P < 0.05) were both significantly suppressed following CLP challenge. Interestingly, we found that the mTOR pathway was closely correlated with the autophagy processes. In our study, while p-mTOR in the myocardium was significantly correlated with p62 (r = 0.66, P = 0.02), PS6K1 was significantly positively correlated with p62 (r = 0.70, P = 0.01) and negatively correlated with LC3II (r = -0.71, P = 0.01). CONCLUSIONS: The autophagy process in the myocardium was accelerated in CLP rats, which was closely correlated with the inhibition of the mTOR pathway.
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Wang et al. (2018) conducted an RCT in sepsis-induced myocardial dysfunction (n=12). Cecal ligation and puncture (CLP) vs. Sham operation was evaluated on left ventricle ejection fraction (p=<0.01). Cecal ligation and puncture significantly reduced left ventricle ejection fraction compared to sham operation in rats (0.59 vs 0.76; P<0.01) and accelerated myocardial autophagy.
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