Peripheral chemoreflex activation and cardiac function during hypoxemia in near-term fetal sheep without placental compromise.

Abstract

A drop in arterial oxygen content activates fetal chemoreflex including an increase in sympathetic activity leading to peripheral vasoconstriction and redistribution of blood flow to protect the brain, myocardium, and adrenal glands. By using a chronically instrumented fetal sheep model with intact placental circulation at near-term gestation, we investigated the relationship between peripheral chemoreflex activation induced by hypoxemia and central hemodynamics. A total of 17 Åland landrace sheep fetuses at 115-128/145 gestational days were instrumented. Carotid artery was catheterized in 10 fetuses and descending aorta in 7 fetuses. After a 4-day recovery, baseline measurements of fetal arterial blood pressures, blood gas values, and fetal cardiovascular hemodynamics by pulsed Doppler ultrasonography were obtained under isoflurane anesthesia. Comparable data to baseline were collected 10 min (acute hypoxemia) and 60 min (prolonged hypoxemia) after maternal hypo-oxygenation to saturation level of 70%-80% was achieved. During prolonged hypoxemia, pH and base excess (BE) were lower and lactate levels were higher in the descending aorta than in the carotid artery. During hypoxemia mean arterial blood pressure (MAP) in the descending aorta increased, whereas in the carotid artery, MAP decreased. In addition, right pulmonary artery pulsatility index values increased, and the diastolic component in the aortic isthmus blood flow velocity waveform became more retrograde, thus decreasing the aortic isthmus antegrade/retrograde blood flow (AoI Net Flow) ratio. Both fetal ventricular cardiac outputs were maintained even during prolonged hypoxemia when significant fetal metabolic acidemia developed. Fetal chemoreflex activation induced by hypoxemia decreased the perfusion pressure in the cerebral circulation. Fetal weight-indexed left ventricular cardiac output (LVCO) or AoI Net Flow ratio did not correlate with a drop in carotid artery blood pressure.NEW & NOTEWORTHY During fetal hypoxemia with intact placental circulation, peripheral chemoreflex was activated, as demonstrated by an increase in the descending aorta blood pressure, pulmonary vasoconstriction, and an increase in retrograde diastolic AoI blood flow, while both ventricular cardiac outputs remained stable. However, perfusion pressure in the cerebral circulation decreased. These changes were seen even during prolonged hypoxemia when significant metabolic acidosis developed. Weight-indexed LVCO or AoI Net Flow ratio did not correlate with a drop in carotid artery blood pressure.