Effect of Different Cardioprotective Methods on Extracorporeal Circulation in Fetal Sheep: A Randomized Controlled Trial

Abstract

Background Congenital heart disease is one of the leading causes of death in newborns and infants. The development of fetal cardiac surgery is inextricably linked to extracorporeal circulation. We aimed to compare the effects of heart-stopping solutions and extracorporeal circulation on fetal sheep myocardium.Methods Eighteen pregnant sheep were divided into the non-stop group, St. Thomas stopping solution group, and histidine–tryptophan–ketoglutarate stopping solution group. The three groups underwent the extracorporeal circulation. The right atrial myocardial tissue was removed from the fetal sheep at specific time points, and apoptosis was detected by TUNEL staining. Creatine kinase‒muscle band (CKMB), troponin I (cTnI), and troponin T (cTnT) were measured as indicators of myocardial damage.Results There were no significant differences in the serum cTnT, cTnI, and CKMB concentrations of fetal sheep among the three groups before starting extracorporeal circulation (P = 0.430, P = 0.391, P = 0.071). Changes in the serum cTnI (ng/L) concentrations were not significantly different among the three groups before and during the extracorporeal circulation (P > 0.05). The cTnI in the St. Thomas solution group at 1 hour post extracorporeal circulation was significantly higher than prior to it (P < 0.05), and cTnI in the non-stop group and histidine–tryptophan–ketoglutarate group after 2 hours was higher than in the pre-bypass value (P < 0.05). The cTnI in the histidine–tryptophan–ketoglutarate group at 1 and 2 hours after the extracorporeal circulation was lower than in the St. Thomas solution group. The number of TUNEL-positive cells in the two solution groups was higher than in the non-stop group (P = 0.001 and P = 0.048, respectively). The number of TUNEL-positive cells in the St. Thomas solution group was higher than in the histidine–tryptophan–ketoglutarate group (P = 0.007).Conclusion Myocardial protection in fetal sheep undergoing extracorporeal circulation was significantly better with non-stop beating than when the beating was stopped. Compared to the St. Thomas arrest solution, histidine‒tryptophan‒ketoglutarate stopping solution was associated with significantly reduced markers of myocardial damage in fetal sheep. Less cardiomyocyte apoptosis was observed when the beating was not stopped.