ABSTRACT
The feasibility of transabdominal near-infrared (NIR) spectroscopy for detecting and quantifying fetal hypoxia in utero is demonstrated in a pregnant ewe model. A frequency domain NIR spectroscopy probe, consisting of two detectors and six sources operating at three wavelengths (675, 786, and 830 nm), was placed on the maternal abdomen directly above the fetal head. Fetal hypoxia was indirectly induced through occlusion of uterine blood flow for approximately 3 min. NIR photon diffusion measurements were made during a baseline period, during hypoxia of the fetus, and during recovery. Fetal blood samples were drawn from the fetal brachial artery and jugular veins at several time points during the cycle. Seven hypoxic cycles were induced in a total of five pregnant ewes. The NIR measurements were analyzed by using a two-layer diffusion model to deconvolve the fetal blood saturation from that of the pregnant ewe. Fetal hypoxia was detected. Good agreement was found between fetal blood saturation determined by the transabdominal NIR method and arterial and venous fetal blood saturation quantified from fetal blood samples by using a hemoximeter.
Subject(s)
Brain , Hypoxia/blood , Oximetry/instrumentation , Oximetry/methods , Abdomen , Animals , Cerebrovascular Circulation , Equipment Design , Models, Animal , Sheep , Spectrophotometry, InfraredABSTRACT
We investigated long-term cardiovascular effects in the offspring of sheep exposed to prenatal dexamethasone (DM). We assessed in vitro vascular responsiveness and evaluated endothelial nitric oxide synthase (eNOS) message and protein levels in femoral muscle removed from 5-month-old sheep. Dexamethasone was administered i.m. to pregnant ewes as 3 weekly courses (4 x 2 mg at 12 h intervals), starting on day 103 of gestation (term approximately 149 days). Ewes were allowed to lamb. At 5 months of age a carotid catheter was placed for blood pressure measurement and hamstring muscle was removed from the lambs under general anaesthesia. We demonstrate that following prenatal DM exposure in the 5-month-old offspring: (1) blood pressure is unchanged; (2) as previously reported in the fetus, sensitivity to endothelin-1 (ET) is increased; (3) acetylcholine-induced relaxation is increased; (4) L-NAME suppressible vasodilatory response to ET is abolished; (5) there is no change in endothelium-independent vasodilatation; and (6) there is no change in eNOS RNA and protein levels, when compared to saline treated controls. We speculate that decreased agonist-induced NO release is not due to alteration in gene expression, but is more likely to be a post-transcriptional event. In summary, the lack of a difference in resting mean arterial pressure (MAP) between DM and control lambs indicates that the compensation we have previously demonstrated in the fetus following glucocorticoid exposure persists to 5 months postnatal age. Compensation is likely due to non-NO-dependent mechanisms, since no evidence was found of upregulated NOS.
Subject(s)
Dexamethasone/pharmacology , Endothelium, Vascular/drug effects , Glucocorticoids/pharmacology , Prenatal Exposure Delayed Effects , Vasodilation/drug effects , Animals , Blood Pressure/physiology , Endothelium, Vascular/enzymology , Enzyme Inhibitors/pharmacology , Female , Gene Expression Regulation, Enzymologic , Microcirculation/drug effects , Microcirculation/physiology , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide/metabolism , Nitric Oxide Synthase/genetics , Nitric Oxide Synthase/metabolism , Nitric Oxide Synthase Type III , Pregnancy , Reverse Transcriptase Polymerase Chain Reaction , Vascular Resistance/physiology , Vasodilation/physiologyABSTRACT
Dexamethasone (DM) was administered to pregnant ewes as three weekly courses of four injections of 2 mg at 12-h intervals. DM (n = 7) or saline (n = 7) was given starting at 103 days of gestation (dGA; term approximately 149 days). Fetal femoral arteries (approximately 300-microm internal diameter) were evaluated using wire myography at 119 dGA. DM-exposed fetuses were significantly smaller than saline-exposed fetuses. DM exposure increased maximal contraction to 125 mM KCl, and maximum tension developed along with sensitivity to endothelin-1 and relaxation to bradykinin. Preincubation with the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester shifted the dose-response curves to endothelin-1 and acetylcholine to the right in controls but not in the DM-exposed group. Relaxation to acetylcholine and to the nitric oxide donor sodium nitroprusside was similar in both groups. The combination of enhanced endothelin-induced vasoconstriction, abnormal endothelium-dependent relaxation, and normal endothelium-independent relaxation indicates microvessel dysfunction following antenatal DM administration. Because such dysfunction is associated with several forms of adult hypertension, our results indicate the potential for consequences of antenatal glucocorticoid exposure on adult cardiovascular health.
