Myocardial function after fetal cardiac bypass in an ovine model

Abstract

Objective Fetal cardiac surgery may improve the prognosis of certain complex congenital heart defects that have significant associated mortality and morbidity in utero or after birth. An important step in translating fetal cardiac surgery is identifying potential mechanisms leading to myocardial dysfunction following bypass. The hypothesis was that fetal cardiac bypass results in myocardial dysfunction, possibly due to perturbation of calcium cycling and contractile proteins. Methods Mid-term sheep fetuses (n=6) underwent 30 minutes of cardiac bypass and 120 minutes of monitoring after bypass. Sonomicrometry and pressure catheters inserted in left (LV) and right ventricles (RV) measured myocardial function. Cardiac contractile and calcium cycling proteins, along with calpain, were analyzed by immunoblot. Results Preload recruitable stroke work (slope of the regression line) was reduced at 120 min after bypass (RV – baseline vs. 120 min after bypass, 38.6±6.8 vs. 20.4±4.8 (P=.01); LV – 37±7.3 vs. 20.6±3.9 (P=.01). Tau (msec), a measure of diastolic relaxation, was elevated in both ventricles (RV – baseline vs. 120 min after bypass, 32.7±4.5 vs. 67.8±9.4 (P<.01); LV – 26.1±3.2 vs. 63.2±11.2 (P=.01). Cardiac output was lower and end-diastolic pressures were higher in the RV, but not the LV, after bypass compared with baseline. RV troponin I was degraded by elevated calpain activity and protein levels of sarco(endo)plasmic reticulum calcium ATPase (SERCA2a) were reduced in both ventricles. Conclusions Fetal cardiac bypass was associated with myocardial dysfunction and disruption of calcium cycling and contractile proteins. Minimizing myocardial dysfunction after cardiac bypass is important for successful fetal surgery to repair complex congenital heart defects.

Assessing the impact of total extracorporeal circulation on hemodynamics in an ovine fetal model

“…However, cardiac output was found to be lower and end-diastolic pressures were higher in the RV, though not in the LV, post-bypass (29). In the present study, the Tei index increased significantly in the ventricles post-arrest (P<0.05).…”

“…In a previous study utilizing fetal cardiac bypass in an ovine model, fetal systolic dysfunction (with lower preload recruitable stroke work) and diastolic dysfunction (with increased time constant of isovolumic relaxation and a lower derivative of pressure/change over time) was observed post-bypass in the ventricles (29). However, cardiac output was found to be lower and end-diastolic pressures were higher in the RV, though not in the LV, post-bypass (29).…”

“…Similarly, in a late third-trimester goat model, LV and RV myocardial dysfunction was observed (30), with an increased Tei index value 1 h after CPB. The separate evaluation of RV and LV dysfunction provides information on the sensitivity of each ventricle to hemodynamic alterations during bypass, which may then affect fetal blood composition (29). Although CPB and fetal cardiac arrest may collectively cause left and right ventricular dysfunction, changes in LV function following CPB are not identical to changes in RV function, and deterioration of RV diastolic function is also more apparent (17,21,29).…”

“…The separate evaluation of RV and LV dysfunction provides information on the sensitivity of each ventricle to hemodynamic alterations during bypass, which may then affect fetal blood composition (29). Although CPB and fetal cardiac arrest may collectively cause left and right ventricular dysfunction, changes in LV function following CPB are not identical to changes in RV function, and deterioration of RV diastolic function is also more apparent (17,21,29). The applications of ventricular function data in ovine models are limited, due to the sheep heart having greater ventral tilted along the long axis compared with the human heart.…”

Anesthetic Techniques for Fetal Surgery

“…The chronically instrumented fetal-maternal sheep model is a well-established model for fetal-maternal physiologic and hemodynamic studies. [7][8][9] The first aim of this prospective and controlled sheep study was to compare the maternal and fetal effects of two commonly used fetal anesthetic techniques, HD-DES and SIVA. We hypothesized that compared with HD-DES, the SIVA technique provides more stable maternal-fetal hemodynamic parameters, less fetal acidosis, and less fetal cardiac dysfunction.…”