Fasudil, a Rho-Kinase Inhibitor, Exerts Cardioprotective Function in Animal Models of Myocardial Ischemia/Reperfusion Injury: A Meta-Analysis and Review of Preclinical Evidence and Possible Mechanisms.

Fasudil, a Rho-kinase inhibitor, has shown outstanding therapeutic effects against cerebral vasospasm after subarachnoid hemorrhage (SAH) in humans. Studies show various biological effects of fasudil in the cardiovascular system. We conducted a preclinical systematic review to determine the efficacy and possible mechanisms of fasudil on animal models of myocardial ischemia/reperfusion (I/R) injury. Nineteen studies involving 400 animals were identified after searching 8 databases for articles published till June 2018. The methodological quality was assessed by the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES) 10-item checklist. The data were analyzed using Rev-Man 5.3 software, and the score of study quality ranged from 3 to 6 points. Compared to the control group, fasudil treated animals showed reduced myocardial infarct size (P < 0.05), lower levels of cardiac enzymes (P < 0.05) and cardiac troponin T (P < 0.05), improved systolic and diastolic functions (P < 0.05), and increased degree of decline in the ST-segment (P < 0.05). The possible mechanisms of fasudil action against myocardial I/R injury are improvement in coronary vasodilation, inhibition of apoptosis and oxidative stress, relieving inflammation, and reduction in endoplasmic reticulum stress and metabolism. In conclusion, fasudil exerts a cardio-protective function through multiple signaling pathways in animal models of myocardial I/R injury.

[Implication of N-terminal pro-B-type natriuretic peptide and Tei index of left ventricle changes in children with ventricular septal defect treated by transcatheter interventional therapy].

OBJECTIVE: To explore the implication of the dynamic changes of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) level and Tei index of left ventricle (LV) in children with ventricular septal defect (VSD) treated by transcatheter closure. METHODS: Sixty children with VSD treated by transcatheter closure with VSD occluder (Group VSD) and 30 healthy children (Group C) were included in this study. The plasma concentration of NT-proBNP, Tei index of LV and left ventricle ejection fraction (LVEF) were measured in Group C and at before, 5th minute, 4th hour, 1st month, 3rd month and 6th month after VSD closure in Group VSD. RESULTS: (1) The concentration of plasma NT-proBNP was significantly increased in children with VSD before transcatheter closure compared with Group C [(229.45 ± 57.75) ng/L vs. (99.21 ± 46.86) ng/L, P < 0.01], significantly increased at 5th minute and 24th hour after transcatheter closure [(356.27 ± 96.78) ng/L and (356.38 ± 91.95) ng/L vs. (229.45 ± 57.75) ng/L, all P < 0.01], and significantly decreased at 1st month, 3rd months and 6th months after transcatheter closure [(131.33 ± 34.79) ng/L, (96.56 ± 31.55) ng/L and (93.39 ± 29.46) ng/L vs. (229.45 ± 57.75) ng/L, P < 0.05 or P < 0.01]. (2) The Tei indexes of LV in Group VSD before transcatheter closure were significantly higher than in Group C (0.45 ± 0.05 vs. 0.33 ± 0.08, P < 0.01) and Tei index was significantly increased at 24th hour, 1st month after transcatheter closure (P < 0.01) while significantly decreased at 3rd and 6th month compared with those before transcatheter closure (0.34 ± 0.07 and 0.34 ± 0.06 vs. 0.45 ± 0.05, all P < 0.01). (3) There is a positive correlation between the changes of the plasma concentration of NT-proBNP and the change of Tei index of LV before and after transcatheter closure (r = 0.653, P < 0.05). CONCLUSION: Tei index of LV and NT-proBNP can monitor cardiac function changes in children with VSD before and after transcatheter closure.