The Dynamics of Vasopressin Release and Blood Volume Regulation During Fetal Hemorrhage in the Lamb Fetus

Summary Experiments were performed on 11 long-term fetal lamb prep- arations (103-138 days of gestation) to investigate the sensitivity and relative responsiveness of the fetal volume receptors in mod- ulating fetal plasma arginine vasopressin (pAVP) secretion and plasma renin activity (PRA) secretion during fetal hypovolemia and after fetal blood volume replacement. During fetal hemorrhage there were significant decreases (P < 0.05) in fetal hematocrit (34.7 f 2.58 to 27.0 f 1.64%), plasma proteins (3.14 f 0.15 to 2.78 f 0.19 g/100 ml), mean arterial blood pressure (MABP) (58.1 f 2.59 to 52.2 f 2.60 mmHg) and fetal arterial pH (7.38 f 0.01 to 7.35 f 0.01). A significant increase in fetal pAVP concentration from 0.73 f 0.21 to 34.9 f 10.04 pU/ml (P < 0.01) and fetal PRA from 4.78 2.22 to 40.4 f 18.31 ng/ml/hr (P < 0.05) was demonstrated at the peak of fetal hemorrhage. Two hr after correction of the fetoplacental blood volume, these values were back to base line levels. No change in either maternal pAVP or PRA was seen during fetal hemorrhage. When individual values for log pAVP and log PRA were plotted as a function of percent of fetoplacental blood volume removed the correlation coefficients were 0.82 and 0.60, respectively. A multiple regression analysis showed a high correlation of log pAVP and log PRA with the volume of blood removed and a low partial correlation with the fetal MABP. This suggests the decrease in fetal MABP was not the primary factor explaining the increase in pAVP and PRA during fetoplacental blood volume depletion. The data indicate that the fetal volume receptors for control of arginine vasopressin secretion are fullv functional in the last trimester of gestation and suggests that fetal pAVP and PRA are released as a; exponential function of the wrcent of feto~lacental blood volume de~letion. Finally, an isosmotic water shift from the fetal interstitial space to the fetal vascular space is described during fetal hemorrhage. Speculation It is suggested that a change in the equilibrium between the forces regulating fluid movement through the fetal capillary mem- branes, in accordance with Starling's principle, activates isosmotic water fluxes from the fetal interstitial space to the fetal vascular compartment counteracting the effects of fetal blood volume de- pletion. Therefore, the role of arginine vasopressin (AVP) release during fetal hemorrhage, if any, will be to act as a pressor substance helping to maintain fetal blood pressure. No major effect of AVP on placental membranes was demonstrated in vivo. Available information suggests that the newborn is capable of secreting vasopressin at birth and that both the osmoreceptors and volume control systems are fully functional (14, 21, 22). During fetal life, the increase in concentration of circulating vasopressin has been evoked by either osmolar or volume stimuli, using short-term fetal lamb preparations (exteriorized fetuses) (3, 32). However, the effects of surgical stress and anesthesia on the fetus may themselves have influenced this response (15, 17). Recently, using long-term fetal lamb preparations (chronically catheterized) and avoiding the effects of surgical stress on the fetus, we demonstrated that the fetal osmoreceptor system for control of AVP secretion is fully functional in the last trimester of pregnancy (38). The present protocol was designed to study the responsiveness of the fetal hypothalamic neurohypophyseal system to a hemor- rhagic stimulation under conditions that approximate the usual physiologic situation using long-term fetal lamb preparations. Using a specific and sensitive radioimmunoassay for AVP (34), we were able to assess the sensitivity and relative responsiveness of the fetal volume receptors in modulating fetal AVP secretion during fetal hypovolemia and after fetal blood volume replace- ment. Finally, this model permitted us to investigate the physio- logic mechanisms regulating the fetal blood volume during fetal hemorrhage.