Effect of different cardioprotective methods on extracorporeal circulation in fetal sheep: a randomized controlled trial

Jin-sheng Cai,Qian-biao Wu,Shuo Shi,Yi-bo Yan,Bin-feng Lei

doi:10.1186/s13019-021-01486-y

Abstract

BackgroundCongenital heart disease is a leading cause of death in newborns and infants. The feasibility of fetal cardiac surgery is linked to extracorporeal circulation (ECC); therefore, cardioplegic solutions need to be effective and long-lasting.MethodsEighteen pregnant sheep were divided into an ECC-only group, St. Thomas’ Hospital cardioplegic solution (STH1) group (STH group), and HTK preservation solution (Custodiol®) group (HTK group). Markers of myocardial injury including troponin I (cTnI), troponin T (cTnT) and creatine kinase myocardial band (CKMB) were measured at specific time points (T1: pre-ECC, T2: 30 min of ECC, T3: 60 min of ECC, T4: 60 min post-ECC, T5: 120 min post-ECC). Myocardial tissue was removed from the fetal sheep at T5, and apoptosis was detected by TUNEL staining.ResultsChanges in the serum cTnI, cTnT and CKMB concentrations were not significantly different among the three groups before and during the ECC(T1,T2,T3). At 60 min after ECC shutdown(T4), cTnI and cTnT concentrations were significantly higher in the STH group than before the start of ECC. The concentration of cTnI was higher in the STH group than in the HTK and ECC-only groups. The concentration of cTnT was higher in the STH group than in the ECC-only group. At 120 min after ECC shutdown(T5), cTnI and cTnT concentrations were significantly higher in the ECC and HTK groups than before the start of ECC, and CKMB concentration was significantly higher in STH and HTK groups. The concentrations of cTnT, cTnI and CKMB was higher in the STH group than in the HTK and ECC-only groups. The number of TUNEL-positive cells in the HTK and STH groups was higher than in the ECC-only group. The number of TUNEL-positive cells in the STH group was higher than in the HTK group. There was no statistically significant difference among the groups in the heart rate and mean arterial pressure after ECC.ConclusionThe HTK preservation solution was significantly better than STH1 in reducing the release of cardiomyocyte injury markers and the number of apoptotic cells in fetal sheep ECC. Fetal sheep receiving ECC-only had an advantage in all indicators, which suggests ECC-only fetal heart surgery is feasible.

Highlights

Congenital heart disease is a leading cause of death in newborns and infants
When perfusing the hearts of fetal sheep in the St Thomas’ Hospital cardioplegic solution (STH) and HTK preservation solution (HTK) groups, we considered that a lower temperature cardioplegic solution (4 °C) might influence the body temperature of the fetal sheep, so we perfused at a slower rate of 30 mL/min, with 50–100 mL per perfusion until the heart arrested
One fetal sheep was intubated into the main pulmonary artery between the outer and middle membranes, which was not detected in time, and it died of cardiac arrest after the start of extracorporeal circulation (ECC)

Summary

Introduction

Congenital heart disease is a leading cause of death in newborns and infants. The feasibility of fetal cardiac surgery is linked to extracorporeal circulation (ECC); cardioplegic solutions need to be effective and long-lasting. Congenital heart disease is one of the leading causes of death in newborns and infants and accounts for about 1% of all congenital malformations [1]. If congenital heart disease can be operated on during the fetal period, the transformation of an abnormality into a complex one can be prevented, complex postnatal cardiac surgery can be avoided, the heart can be given a chance to develop further in utero, and secondary morphologic damage can be avoided [7,8,9]. Because of the fetus’s unique characteristics, the need for the protection of immature fetal myocardium is much higher than that in the adults. Based on many experiments on fetal sheep and a thorough understanding of fetal sheep physiology, the technology for ECC in fetal sheeps is largely mature [13]

Methods

Results

Conclusion