(+)-Pinoresinol diacetate

11507171

In fetal sheep during late gestation the aims of the present study were to (1) develop a technique for inducing prolonged but reversible periods of controlled compression of the umbilical cord and (2) characterise the cardiovascular, endocrine and metabolic responses to this challenge.

Under 1-2 % halothane anaesthesia, 16 Welsh Mountain sheep fetuses were chronically instrumented at 118 ± 2 days of gestation (term is ca 145 days) with an inflatable occluder cuff around the umbilical cord, amniotic and femoral vascular catheters and with transit-time flow probes around the contra-lateral femoral artery and an umbilical artery. At 125 days, umbilical blood flow was reduced by 30 % from a pre-determined 24 h baseline for 3 days by automated servo-controlled inflation of the occluder cuff (n = 8). The occluder was then deflated allowing return of umbilical blood flow to baseline. The remaining eight fetuses were used as sham-operated controls in which the occluder was not inflated throughout the protocol. Fetal cardiovascular variables were recorded at 8 s intervals and arterial blood samples taken for measurement of blood gases, glucose and lactate and plasma adrenaline, noradrenaline and vasopressin concentration throughout the study.

Automated servo-controlled inflation of the occluder cuff, programmed to reduce umbilical blood flow by 30 % from baseline, reduced umbilical blood flow by 30.2 ± 1.7 %, with a coefficient of variation during compression of 6.5 ± 1.1 %. Sustained partial compression of the umbilical cord produced falls in fetal arterial pH, Pa,O2, percentage O2 saturation of haemoglobin, and hindlimb oxygen delivery, and increases in Pa,CO2, haemoglobin concentration, arterial blood oxygen carrying capacity and in blood glucose and lactate concentrations. While the reductions in Pa,O2, percentage saturation of haemoglobin and hindlimb oxygen delivery and the increase in Pa,CO2 were sustained throughout compression, the reduction in arterial pH and the increase in arterial oxygen carrying capacity had returned towards baseline values by 48 h compression. Fetal blood lactate concentrations reached a peak at 8 h of compression and, thereafter, were maintained at an elevated level relative to baseline.

Partial compression of the umbilical cord produced fetal hypertension, a reduction in femoral blood flow and, consequently, an increase in calculated fetal femoral vascular resistance for the duration of the challenge. In addition, the fall in heart rate measured in sham control fetuses by the end of the study, did not occur in cord-compressed fetuses. Cosinor analysis on 24 h rhythms of cardiovascular data indicated a significant increase in the amplitude of the 24 h rhythm in heart rate in cord-compressed fetuses relative to sham controls during the period of compression or sham-compression. Furthermore, cord compression led to an increase in fetal plasma noradrenaline, but not adrenaline and vasopressin concentrations relative to sham control fetuses.

In conclusion, a novel reversible method for controlled, long-term compression of the umbilical cord in sheep has been developed. The data show that sustained, partial compression of the umbilical cord produced moderate but sustained asphyxia, which resolved after the end of the compression period, and induced changes in fetal cardiovascular, endocrine and metabolic functions.

A novel method for controlled and reversible long term compression of the umbilical cord in fetal sheep

D S Gardner, A J W Fletcher, A L Fowden, and D A Giussani

2001 Aug 15

12456840

This study investigated the effects on ovine fetal basal cardiovascular and endocrine functions of fetal intravenous dexamethasone treatment, resulting in circulating concentrations that were one-fifth of the values measured clinically in human infants following maternal antenatal glucocorticoid therapy. Between 117-120 days gestation (dGA; term: ca 145 dGA), 26 Welsh Mountain sheep fetuses were surgically prepared under general anaesthesia with vascular catheters and a Transonic flow probe positioned around a femoral artery. At 125 ± 1 dGA, fetuses were infused with dexamethasone (2.06 ± 0.13 μg kg−1 h−1i.v.; n = 13) or saline (n = 13) for 48 h. Daily fetal arterial blood samples were taken and cardiovascular data were recorded continuously (data acquisition system). Pressor, vasoconstrictor and chronotropic responses to exogenously administered doses of phenylephrine, angiotensin II and arginine vasopressin (AVP) were determined at 124 ± 1 (pre-infusion), 126 ± 1 (during infusion) and 128 ± 1 (post-infusion) dGA. Fetal cardiac baroreflex curves were constructed using peak pressor and heart rate responses to phenylephrine. Dexamethasone treatment elevated fetal mean arterial blood pressure by 8.1 ± 1.0 mmHg (P < 0.05), increased femoral vascular resistance by 0.65 ± 0.12 mmHg (ml min−1)−1 (P < 0.05), depressed plasma noradrenaline concentrations and produced a shift in set-point, but not sensitivity, of the cardiac baroreflex (P < 0.05). Elevations in fetal arterial blood pressure, but not femoral vascular resistance and the shift in baroreflex set-point, persisted at 48 h following dexamethasone treatment. By 48 h following dexamethasone infusion, basal plasma noradrenaline concentration was restored, whilst plasma adrenaline and neuropeptide Y (NPY) concentrations were enhanced, compared with controls (P < 0.05). Fetal dexamethasone treatment did not alter the fetal pressor or femoral vasoconstrictor responses to adrenergic, vasopressinergic or angiotensinergic agonists. These data show that fetal treatment with low concentrations of dexamethasone modifies fetal basal cardiovascular and endocrine functions. Depending on the variable measured, these changes may reverse, persist or become enhanced by 48 h following the cessation of treatment.

Effects of low dose dexamethasone treatment on basal cardiovascular and endocrine function in fetal sheep during late gestation

Andrew J W Fletcher, Hugh H G McGarrigle,* C Mark B Edwards,† Abigail L Fowden, and Dino A Giussani

2002 Dec 1