Physiology of Neonatal Post-Hypoxic Myocardial Failure: Insights from an Experimental Model for Postnatal Management

Introduction

Hemodynamic and myocardial alterations, as well as compensatory mechanisms during perinatal asphyxia, are not yet fully understood.

To investigate hemodynamic and myocardial function changes during prolonged umbilical cord occlusion (UCO).

Method

This is the first study with real time assessment of cardiac performance in alive sheep foetus. Five near-term fetal sheep were surgically instrumented under general anaesthesia. A venous central catheter was placed for blood sampling, a controlled occlusion system was positioned around the UC, and a 5 Fr. pressure-volume impendance catheter was inserted into the left ventricle through a 6Fr. introducer placed into the right carotid artery. The foetus was then repositioned into the uterus. Hemodynamic responses were assessed during long UCO (12 minutes) through analysis of ventricular pressures and volumes, pressure-volume loops, allowing estimation of ventricular (Ees) and arterial (Ea) elastance. Longer UCO was done to determine the time of hemodynamic failure.

Results

A biphasic response to complete cord occlusion was observed. An initial adaptive phase (30 s) was characterized by abrupt bradycardia (mean heart rate dropped from 175 bpm to 126, −28%), decreased stroke volume (4,43 mL to 2,8 mL, −35%) and cardiac output (775 to 348 mL/min, −52%), along with increased myocardial workload as reflected by a rise in Ea/Ees ratio (+12%) (Figure 1, A). This was followed by a transient compensatory phase with partial recovery of heart rate (+25%), SV (+20%), and CO (+25%), while the Ea/Ees ratio decreased but remained slightly elevated (+3%) compared to baseline. Left ventricular end-diastolic pressure progressively increased (+ 30%) despite volume reduction. (Figure 1, B and C). The hemodynamic parameters recovered quickly after UCO relieve (Figure 1, D). Hemodynamic markers remained stable during the compensatory phase. In prolonged UCO, lactic acidosis occurred at the 15^th minutes, before a hemodynamic collapse and severe systolic dysfunction at 17 minutes, marked by a 50% drop in SV and CO, and a significant Ea/Ees imbalance (−20%), ultimately resulting in irreversible arterial hypotension.

Conclusion

Umbilical cord blood flow interruption is associated with a rapid and sustained increase in myocardial workload and diastolic dysfunction before the systolic dysfunction. Diastolic function should be assessed in all newborns with perinatal asphyxia.