ABSTRACT
OBJECTIVE: In the present study we examined the effects of low-dose endotoxin (lipopolysaccharides, LPS) on continuously recorded umbilical blood flow. METHODS: Twenty fetal sheep were catheterized at a gestational age of 107 +/- 1 days. A flow probe was placed around either the common umbilical artery or one single umbilical artery. Three days later fetuses received either 100 or 500 nanograms of LPS (n = 14) or 2 mL saline (n = 6) intravenously. Six fetuses died within 12 hours after LPS. Fetal heart rate (FHR), mean arterial pressure (MAP), and umbilical blood flow (Q(umb)) were monitored for 3 days. RESULTS: FHR increased by 25 +/- 4% at 4-5 hours after LPS (P <.01) and was elevated for 15 hours after LPS. MAP increased by 18 +/- 5% 1 hour after LPS (P <.01) and returned to control value 4-5 hours after LPS. Q(umb) began to decrease 1 hour after LPS and was minimal (-30 +/- 7%, P <.001) at 4-5 hours after LPS. Q(umb) slowly returned to the control value at 12 hours after LPS. Placental vascular resistance increased by 73 +/- 37% (P <.01), whereas pH did not appreciably change. CONCLUSION: Intravenous application of endotoxin caused a substantial and long-lasting decrease in umbilical blood flow resulting in fetal hypoxemia without acidemia. These effects may be of significance in the development of fetal brain damage associated with intrauterine infection.
Subject(s)
Endotoxins/toxicity , Fetus/physiology , Lipopolysaccharides/toxicity , Placenta/blood supply , Umbilical Arteries/pathology , Umbilicus/blood supply , Animals , Blood Flow Velocity/drug effects , Brain Damage, Chronic/embryology , Dose-Response Relationship, Drug , Female , Fetus/drug effects , Gestational Age , Injections, Intravenous , Lipopolysaccharides/administration & dosage , Pregnancy , Sheep , Umbilical Arteries/drug effectsABSTRACT
OBJECTIVE: The role of nitric oxide in control of fetal cardiovascular functions and of cerebral blood flow during normoxia and acute hypoxia is only partially known. We studied the effects of nitric oxide synthase inhibition on the distribution of cardiac output in preterm sheep using N(omega)-nitro-L-arginine methyl ester (L-NAME). METHODS: Thirteen fetal sheep were instrumented at a gestational age of 107 days. Three days later fetuses received L-NAME (n = 7) or vehicle infusion (n = 6). At 0 minutes, acute hypoxia was induced by occlusion of the maternal aorta for 2 minutes. Organ blood flows (microsphere method) and physiologic variables (fetal heart rate, mean arterial pressure [MAP], oxygen saturation, and pH) were measured at -75, -1, +2, +4, and +30 minutes. RESULTS: L-NAME caused bradycardia and an increase in MAP. A significant decrease in cardiac output by 32% occurred in the control group during the control period, which was consequently reflected in organ blood flows. L-NAME injection reduced cardiac output by 64% during normoxia. Blood flow to the fetal body, placenta, and cerebrum decreased by 62%, 66%, and 55%, respectively. During acute hypoxia, L-NAME did not change the redistribution of cardiac output toward the central organs. In the L-NAME group MAP increased, and fetal heart rate was maintained; in contrast, in controls MAP initially decreased and then returned to control values while fetal heart rate decreased. After hypoxia L-NAME delayed the recovery of cardiac output and blunted the increase in blood flow to the brain and heart. CONCLUSIONS: Although influenced by fetal stress after extensive instrumentation, the results of this study indicate that nitric oxide plays a role in fetal cardiovascular control during normoxia and acute hypoxia. Nitric oxide also mediates the increase in blood flow to the brain and heart immediately after hypoxia.
