title: A novel method for controlled and reversible long term compression of the umbilical cord in fetal sheep.
abstract: 1. 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. 2. 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. 3. 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, P(a,O2), percentage O(2) saturation of haemoglobin, and hindlimb oxygen delivery, and increases in P(a,CO2), haemoglobin concentration, arterial blood oxygen carrying capacity and in blood glucose and lactate concentrations. While the reductions in P(a,O2), percentage saturation of haemoglobin and hindlimb oxygen delivery and the increase in P(a,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. 4. 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. 5. 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.
authors.affiliation: The Physiological Laboratory, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK.
authors.forename: D S
authors.initials: DS
authors.lastname: Gardner
authors.forename: A J
authors.initials: AJ
authors.lastname: Fletcher
authors.forename: A L
authors.initials: AL
authors.lastname: Fowden
authors.forename: D A
authors.initials: DA
authors.lastname: Giussani
mesh_terms: D000818:Animals; D001158:Arteries; D001769:Blood / Q000378:metabolism; D002319:Cardiovascular System / Q000196:embryology / Q000503:physiopathology; D002908:Chronic Disease; D003251:Constriction, Pathologic; D004195:Disease Models, Animal; D004703:Endocrine System / Q000196:embryology / Q000503:physiopathology; D005260:Female; D005312:Fetal Blood; D005333:Fetus / Q000502:physiology; D005740:Gases / Q000097:blood; D008722:Methods; D011247:Pregnancy; D012756:Sheep; D014470:Umbilical Cord / Q000503:physiopathology*
chemical_list: D005740:Gases