Changes in fetal ovine metabolism and oxygen delivery with fetal bypass.

Since the 1980s, attempts at experimental fetal cardiac bypass for the purpose of correcting severe congenital heart defects in the womb have been hampered by deterioration of placental function. This placental pathophysiology in turn affects transplacental transport of nutrients and gas exchange. To date, the effects of bypass on fetal metabolism and oxygen delivery have not been studied.

Fetal stress response to fetal cardiac surgery.

Background: A deleterious fetal stress response, although not fully elucidated, may account for poor outcomes after experimental fetal cardiac surgery. We set out to characterize this fetal stress response and its potential role in placental dysfunction.

Methods: Fifteen ovine fetuses at gestational day 100 to 114 were placed on extracorporeal support for 30 minutes and were then followed 2 hours after cardiopulmonary bypass.

Umbilical blood flow during pregnancy: evidence for decreasing placental perfusion.

Objective: The present study was designed to determine the relation of umbilical venous blood flow (UmbBF) to fetal weight (FW) at different times in late pregnancy, and to assess fetal O2 supply near term.

Study Design: In 46 pregnant women, UmbBF was calculated just before delivery using the product of flow velocity and the cross section of the umbilical vein determined by pulsed Doppler technique and measuring of the diameter of the vessel, respectively. Based on the gestational age at delivery (range, 29-42 weeks), infants were divided into a preterm group (PT; < or = 36 weeks, n = 13) and a full-term group (FT; > 36 weeks, n = 33).

Hemodynamic effects of acute and repeated exposure to raloxifene in ovariectomized sheep.

We hypothesize that administration of acute and daily doses of raloxifene will have significant effects on ovine coronary and uterine hemodynamics and that these changes are estrogen receptor dependent. Eleven ovariectomized sheep were instrumented to measure mean arterial pressure, heart rate (HR), cardiac output (CO), and coronary (CBF) and uterine artery blood flows (UBF). A dose-response curve was generated for raloxifene (1, 3, and 10 microg/kg) and compared with a standard dose of estradiol-17beta (1 microg/kg) given intravenously.

Vacuum-assisted venous drainage during fetal cardiopulmonary bypass.

Fetal bypass presents several perfusion challenges, including the need for high arterial flow rates using flexible arterial and small venous cannulae. We hypothesized that vacuum-assisted venous drainage (VAVD) would improve drainage and allow perfusion at higher flow rates which are thought to prevent placental dysfunction induced by fetal bypass. We conducted bypass for 60 minutes in 14 fetal lambs (90-105 days gestation; approximately 1-1.

Expression of phosphodiesterase 5 in maternal and fetal sheep.

Objective: Ovine pregnancy is associated with elevated levels of nitric oxide. Nitric oxide stimulates cyclic guanosine monophosphate (cGMP), which results in vascular smooth muscle relaxation/vasodilation. Phosphodiesterase type 5 regulates cGMP in the urogenital track.

Effects of combined use of sildenafil citrate (Viagra) and 17beta-estradiol on ovine coronary and uterine hemodynamics.

Objective: This study was undertaken to determine whether Viagra (Pfizer, New York, NY), a type 5 phosphodiesterase (PDE-5) inhibitor, increases baseline coronary and uterine blood flow or potentiates estrogen-induced increases in blood flow.

Study Design: Seven nonpregnant ovariectomized ewes were chronically instrumented to measure blood pressure, heart rate, cardiac output, and coronary and uterine blood flow. Estradiol-17beta (E2, 0.

Differential effects of selective estrogen receptor modulators and estrogens on mammary blood flow in the ovine.

Objective: Hormone replacement therapy has been implicated in the increased incidence of breast cancer, although selective estrogen receptor modulators have been shown to be effective in the prevention of breast cancer. Breast cancers are associated with increased mammary blood flow compared to benign breast lesions. However, few studies have examined the hemodynamic effects of hormonal agents on the mammary circulation that promote or reduce the risk of breast cancers.

Estrogen increases iNOS expression in the ovine coronary artery.

Estrogen is believed to protect postmenopausal women from coronary vascular disease, in part by increasing production of nitric oxide (NO). In this study, we investigated the possibility that transcriptional activation of inducible NO synthase (iNOS) is responsible for a component of the estrogen-induced increase in coronary blood flow. Twenty-two ewes were instrumented with Doppler flow probes on their left circumflex coronary and pulmonary arteries.

Fetal umbilical vascular response to chronic reductions in uteroplacental blood flow in late-term sheep.

Objective: The present study was designed to determine the effects of chronic reduction in uterine blood flow (UBF) on umbilical blood flow (UmbBF) and fetal cardiovascular hemodynamics and oxygenation.

Study Design: Sixteen sheep with singleton pregnancies were instrumented on gestational day (GD) 110; an externally adjustable vascular occluder was placed on the common internal iliac artery. UBF in control animals rose from 867 +/- 61 mL/min on GD 115 to 1520 +/- 158 mL/min (n = 8) on GD 138, whereas UBF in restricted animals was maintained at 750 +/- 50 mL/min (n = 8).

Effect of Ro 61-1790, a selective endothelin-A receptor antagonist, on systemic and uterine hemodynamics and fetal oxygenation in sheep.

Objective: Endothelin-1 is reportedly elevated in preeclampsia, and studies in our laboratory have shown that infusion of endothelin-1 produces increased mean arterial pressure, hemoconcentration, and proteinuria, while decreasing uterine blood flow. If a role in preeclampsia is confirmed for endothelin-1, therapeutic intervention may involve selective endothelin-A receptor blockers. Thus, this study was designed to determine the effects of Ro 61-1790, a selective endothelin-A receptor inhibitor, on mean arterial pressure, heart rate, and uteroplacental blood flow in pregnant and nonpregnant sheep.