Cardiovascular and endocrine responses to acute hypoxaemia during and following dexamethasone infusion in the ovine fetus

Abstract

This study investigated the effects of fetal treatment with dexamethasone on ovine fetal cardiovascular defence responses to acute hypoxaemia, occurring either during or 48 h following the period of glucocorticoid exposure. To address the mechanisms underlying these responses, chemoreflex function and plasma concentrations of catecholamines, neuropeptide Y (NPY) and vasopressin were measured. Under general halothane anaesthesia, 26 Welsh Mountain sheep fetuses were surgically prepared for long-term recording at between 117 and 120 days of gestation (dGA; term is approximately 145 days) with vascular catheters and a Transonic flow probe around a femoral artery. Following at least 5 days of recovery, fetuses were randomly assigned to one of two experimental groups. After 48 h of baseline recording, at 125 +/- 1 dGA, half of the fetuses (n = 13) were continuously infused I.V. with dexamethasone for 48 h at a rate of 2.06 +/- 0.13 microg kg-1 h-1. The remaining 13 fetuses were infused with heparinized saline at the same rate (controls). At 127 +/- 1 dGA, 2 days from the onset of infusions, seven fetuses from each group were subjected to 1 h of acute hypoxaemia. At 129 +/- 1 dGA, 2 days after the end of infusions, six fetuses from each group were subjected to 1 h of acute hypoxaemia. Similar reductions in fetal partial pressure of arterial oxygen occurred in control and dexamethasone-treated fetuses during the acute hypoxaemia protocols. In control fetuses, acute hypoxaemia led to transient bradycardia, femoral vasoconstriction and significant increases in plasma concentrations of catecholamines, vasopressin and NPY. In fetuses subjected to acute hypoxaemia during dexamethasone treatment, the increase in plasma NPY was enhanced, the bradycardic response was prolonged, and the plasma catecholamine and vasopressin responses were diminished. In fetuses subjected to acute hypoxaemia 48 h following dexamethasone treatment, femoral vasoconstriction and plasma catecholamine and vasopressin responses were enhanced, whilst the prolonged bradycardia and augmented plasma NPY responses persisted. These data show that fetal treatment with dexamethasone modifies the pattern and magnitude of fetal cardiovascular responses to acute oxygen deprivation. Modifications to different mechanisms mediating the fetal defence responses to acute hypoxaemia that occur during dexamethasone treatment may reverse, persist or even become enhanced by 48 h following the treatment period.

Figure 1. Fetal cardiovascular variables in the acute hypoxaemia protocol occurring during infusions

Absolute values of cardiovascular variables for the hypoxaemia protocol during saline infusion (n = 7) and during dexamethasone treatment (n = 7). Values are mean ±s.e.m. for each minute. The boxed area represents the period of hypoxaemia. FHR, fetal heart rate; FBP, fetal arterial blood pressure; FBF, fetal femoral blood flow; FVR, fetal femoral vascular resistance.

Figure 3. Fetal cardiovascular variables in the acute hypoxaemia protocol occurring following infusions

Absolute values of cardiovascular variables for the hypoxaemia protocol following saline infusion (n = 6) and following dexamethasone treatment (n = 6). Values are means ±s.e.m. for each minute. The boxed areas represent the period of hypoxaemia.

Figure 2. Statistical summary of changes from baseline for fetal cardiovascular responses to 1 h of hypoxaemia occurring during infusions

A, mean ±s.e.m. of the areas bounded by the curve for each variable, expressed per minute. B, line graphs representing mean ±s.e.m. of values for changes from individual baselines in fetal heart rate, arterial blood pressure, femoral blood flow and femoral vascular resistance during the following time periods: early (0–45 min) and late (46–60 min) normoxia, early (61–75 min) and late (76–120 min) hypoxaemia, and early (121–135 min) and late (136–180 min) recovery. Fetal cardiovascular responses during saline infusion (○; n = 7) and during dexamethasone treatment (•; n = 7) are represented by open and filled bars, respectively, in A. Significant differences (P < 0.05): a, differences by post hoc analysis indicating a significant main effect of time compared with normoxia; b, differences by post hoc analysis indicating a significant main effect of dexamethasone treatment compared with saline infusion (two-way repeated-measures ANOVA + Tukey test).

Figure 4. Statistical summary of changes from baseline for fetal cardiovascular responses to 1 h of hypoxaemia occurring following infusions

A, mean ±s.e.m. of the areas bounded by the curve, expressed per minute. B, line graphs representing the mean ±s.e.m. of values for changes from individual baselines in fetal heart rate, arterial blood pressure, femoral blood flow and femoral vascular resistance during the following time periods: early (0–45 min) and late (46–60 min) normoxia, early (61–75 min) and late (76–120 min) hypoxaemia, and early (121–135 min) and late (136–180 min) recovery. Fetal cardiovascular responses following saline infusion (○; n = 6) and following dexamethasone treatment (•; n = 6) are represented by open and filled bars, respectively. Significant differences (P < 0.05): a, differences by post hoc analysis indicating a significant main effect of time compared with normoxia; b, differences by post hoc analysis indicating a significant main effect of dexamethasone treatment compared with saline infusion (two-way repeated-measures ANOVA + Tukey test).

Figure 5. Fetal arterial plasma hormone concentrations during the acute hypoxaemia protocol

Arterial plasma concentrations of noradrenaline (NA), adrenaline (ADR), neuropeptide Y (NPY) and arginine vasopressin (AVP) in fetuses exposed to 1 h of hypoxaemia during saline infusion (n = 7), during dexamethasone treatment (n = 7), following saline treatment (n = 6) and following dexamethasone treatment (n = 6). Values are means ±s.e.m. at 15 min (N15) and 45 min (N45) of normoxia, 15 min (H15) and 45 min (H45) of hypoxaemia, and 45 min (R45) of recovery. The boxed area represents the period of hypoxaemia. Significant differences (P < 0.05): a, differences by post hoc analysis indicating a significant main effect of time compared with normoxic baseline; b, differences by post hoc analysis indicating a significant main effect of dexamethasone treatment compared with saline infusion (two-way repeated-measures ANOVA + Tukey test).