Fetal acidosis and hypotension during repeated umbilical cord occlusions are associated with enhanced chemoreflex responses in near-term fetal sheep

Abstract

This study examined the hypothesis that repeated episodes of brief but severe hypoxia would not attenuate the chemoreflex-mediated rapid initial fall in fetal heart rate (FHR) and, further, that greater hypoxic stress, as shown by hypotension and metabolic acidosis, would be associated with an enhanced chemoreflex response. Chronically instrumented, near-term fetal sheep received 1 min total umbilical cord occlusion either every 5 min for 4 h (1:5 group; n = 8) or every 2.5 min (1:2.5 group; n = 8) until mean arterial blood pressure fell to <20 mmHg on two successive occlusions. Umbilical cord occlusion caused variable decelerations, with sustained hypertension in the 1:5 group and little change in acid-base status (pH 7.34 +/- 0.03 after 4 h). In contrast, the 1:2.5 group showed progressive hypotension and metabolic acidemia (pH 6.92 +/- 0.04 after the last occlusion). The 1:2.5 group showed a significant increase in the rate of initial fall in FHR during the occlusion series, which was greater than the 1:5 group in the last 30 min of the occlusion series (9.4 +/- 1.4 vs. 3.5 +/- 0.3 beats.min(-1).s(-1); P < 0.01), with a greater fall in FHR (71.9 +/- 6.5 vs. 47.0 +/- 8.7 beats/min; P < 0.05). In summary, this study demonstrated that repetitive laborlike cord occlusions, which led to severe fetal compromise, were associated with an increase in the slope and magnitude of the initial FHR deceleration. These findings support the concept of the chemoreflex as a central, robust component of fetal adaptation to severe hypoxia.

Mathematical Model of Cardiovascular and Metabolic Responses to Umbilical Cord Occlusions in Fetal Sheep

“…The recovery time for 1-min complete occlusion, that is, the UCO frequency, influences the system behavior significantly. Based on our in silico experiments, for 1:2.5 UCO, FHR overshoot appears after about two and half hours with developing acidosis, as demonstrated in vivo (Westgate et al 1999(Westgate et al , 2001Bennet et al 2005). In contrast, 1:5 UCO scenario does not show any significant FHR overshoots and acidosis, as shown in the literature (Westgate et al 2001).…”

“…Figure 6 shows several experimentally measurable quantities over 4-h occlusions. Agreement is shown when comparing with the data extracted from Bennet et al (2005). Corresponding to the FHR overshoot instability for 1:2.5 UCO in Fig.…”

“…The pronounced FHR overshoot occurs only after a delay of approximately 3 h, in agreement with experiments (Westgate et al 2001). This is accompanied by an eventual decline in MABP after approximately 2 h. At the early stage of the occlusions, MABP rises as soon as the occlusion starts (de Haan et al 1997;Bennet et al 2005). The inset in the bottom panel of Fig.…”

“…The resulting increased risk of ischemic brain injury can be associated with acidemia (Liston et al 2007). The sudden compression of the umbilical cord leads to fetal hypertension and fetal heart rate (FHR) decelerations, which are mediated through chemoreflex and sympathetic stimulation (Low et al 1995;Westgate et al 1999;Bennet et al 2005). Fetal oxygen delivery via the umbilical cord is interrupted and leads to hypoxemia and acute cerebral hypoxia (Mallard et al 1995;Koos et al 1995;Bishai et al 2003;Hunter et al 2003;Westgate et al 2007;Thakor and Giussani 2008).…”

“…These activities, in turn, via efferent signaling, regulate FHR and systemic arterial blood pressure. Furthermore, prolonged cord compression and/or repeated cord compressions may cause accumulation of metabolites, such as CO 2 and lactate, in the fetus, which contributes to acidemia (Bennet et al 2005;Frasch et al 2009b), as well as prolonged cerebral hypoperfusion (Yan et al 2009). A comprehensive discussion on the dynamic changes of the fetal circulation and blood flow distribution during hypoxia and asphyxia due to different experimental disturbances can be found in the review paper (Jensen et al 1999).…”