[Show abstract][Hide abstract] ABSTRACT: Objective:
We hypothesized that labetalol and pindolol have no detrimental effects on fetal cardiac function and pulmonary hemodynamics when administered for norepinephrine-induced maternal hypertension in a chronic sheep model of increased placental vascular resistance. Specifically, we investigated the effects of labetalol and pindolol on fetal cardiopulmonary responses to acute hypoxemia.
Twenty chronically instrumented near-term ewes with increased placental vascular resistance after placental embolization were anesthetized and randomized to receive labetalol or pindolol for norepinephrine-induced hypertension. Thereafter, maternal inspiratory oxygen fraction was decreased to induce fetal hypoxemia. At the end of each phase, fetal hemodynamics were assessed by Doppler ultrasonography. The data were analyzed using repeated measures ANOVA.
Maternal administration of norepinephrine had no effect on fetal hemodynamics. Pindolol decreased fetal heart rate and weight-indexed left ventricular cardiac output and increased pulmonary vascular impedances, while labetalol had no effect on these parameters. During hypoxemia, fetal heart rate increased to baseline in the pindolol group and pulmonary vascular impedances increased in the labetalol group, with no changes in fetal cardiac outputs.
Pindolol decreased fetal left ventricular cardiac output and induced vasoconstriction in the pulmonary vasculature, but neither pindolol nor labetalol significantly modified fetal cardiopulmonary responses to acute hypoxemia.
Full-text · Article · Sep 2012 · European journal of obstetrics, gynecology, and reproductive biology
[Show abstract][Hide abstract] ABSTRACT: We investigated whether hypoxemia without acidemia affects ductus venosus (DV) blood velocity waveform pattern in sheep fetuses with intact placenta and whether worsening acidemia and impending fetal death are related to changes in DV velocimetry in fetuses with increased placental vascular resistance. A total of 34 fetuses were instrumented at 115-136/145 days of gestation. Placental embolization was performed in 22 fetuses on the fourth postoperative day, 24 h before the experiment. The control group was comprised of 12 fetuses with intact placenta. The experimental protocol consisted of fetal hypoxemia that was induced by replacing maternal inhaled oxygen with medical air. To further deteriorate fetal oxygenation and blood-gas status, uterine artery volume blood flow was reduced by maternal hypotension. Fetuses that underwent placental embolization were divided into two groups according to fetal outcome. Group 1 consisted of 12 fetuses that completed the experiment, and group 2 comprised 10 fetuses that died during the experiment. DV pulsatility index for veins (PIV) and fetal cardiac outputs (COs) were calculated. Placental volume blood flow, fetal blood pressures, and acid base and lactate values were monitored invasively. On the experimental day, the mean gestational age did not differ significantly between the groups. In groups 1 and 2, the baseline mean DV PIV and fetal COs were not statistically significantly different from the control group. In the control group, the DV PIV values increased significantly with hypoxemia. In groups 1 and 2, the DV PIV values did not change significantly, even with worsening acidemia and imminent fetal death in group 2. During the experiment, the fetal COs remained unchanged. We conclude that fetal hypoxemia increases the pulsatility of DV blood velocity waveform pattern. In fetuses with elevated placental vascular resistance, DV pulsatility does not increase further in the presence of severe and worsening fetal acidemia and impending fetal death.
[Show abstract][Hide abstract] ABSTRACT: We investigated the effects of labetalol and pindolol on uterine, placental, and fetal hemodynamics following norepinephrine-induced maternal hypertension in a sheep model of increased placental vascular resistance. Also, we examined fetal and placental hemodynamic responses to acute hypoxemia after antihypertensive medication. Norepinephrine increased maternal heart rate (HR), mean arterial pressure (MAP) and uterine vascular resistance (R(UtA)), and decreased uterine volume blood flow (Q(UtA)). Both labetalol and pindolol decreased maternal HR, MAP, and R(UtA), but did not restore Q(UtA). Fetal MAP was unaffected while fetal HR and placental volume blood flow (Q(UA)) decreased and placental vascular resistance increased. During hypoxemia, which was induced by decreasing maternal inspiratory oxygen fraction, all these parameters remained unchanged in the labetalol group while fetal HR increased and Q(UA) further decreased in the pindolol group. We conclude that labetalol and pindolol may compromise uterine and placental hemodynamics. Hypoxemic stress provokes divergent hemodynamic responses in fetuses exposed to these differently acting adrenoceptor antagonists.
No preview · Article · May 2009 · Reproductive sciences (Thousand Oaks, Calif.)
[Show abstract][Hide abstract] ABSTRACT: We studied the interactions between uterine and placental hemodynamics during maternal hypotension in chronically instrumented fetal sheep. In addition, we investigated maternal hemodynamic characteristics, fetoplacental hemodynamics and fetal acid-base status when a retrograde diastolic uterine artery blood flow pattern is present during maternal hypotension.
Invasive maternal and fetal hemodynamic parameters, uterine (Q(UtA)) and placental (Q(UA)) volume blood flows and acid-base values were examined in 24 chronically instrumented sheep at baseline and during epidural-induced maternal hypotension at 117-132 (term 145) days of gestation. Uterine artery blood flow velocity waveforms were obtained by Doppler ultrasonography.
Maternal hypotension decreased Q(UtA) without affecting Q(UA). During hypotension, eight out of 24 sheep demonstrated a retrograde diastolic blood flow velocity waveform pattern in the uterine artery. Maternal systolic, diastolic and mean arterial blood pressures were significantly lower in the retrograde group than in the antegrade group. No statistically significant differences in Q(UtA), Q(UA) and fetal blood gas values were detected between the two groups during hypotension.
An acute decrease in uterine artery volume blood flow during maternal hypotension is not compensated by increased placental volume blood flow. A retrograde diastolic blood flow pattern in the uterine artery is related to lower maternal arterial pressures, especially during diastole. A uterine artery retrograde diastolic blood flow pattern does not have any additional detrimental short-term effects on fetal acid-base status.
No preview · Article · Nov 2008 · Acta Anaesthesiologica Scandinavica
[Show abstract][Hide abstract] ABSTRACT: We hypothesized that acute fetal metabolic acidosis decreases fetal myocardial motion in a chronic sheep model of increased placental vascular resistance (R(ua)). Eleven ewes and fetuses were instrumented at 118-122 days of gestation. After 5 days of recovery and 24 h of placental embolization to increase R(ua), longitudinal myocardial velocities of the right and left ventricles and interventricular septum (IVS) were assessed at the level of the atrioventricular valve annuli via tissue Doppler imaging (TDI). Ventricular inflow (E and A waves) and outflow velocities were obtained, and cardiac outputs were calculated. All measurements were performed at baseline and during fetal acidosis caused by epidural anesthesia-induced maternal hypotension, which decreased uterine artery volume blood flow, fetal oxygenation, arterial pH, and base excess and increased lactate. Compared with baseline, the peak isovolumic myocardial contraction and relaxation velocities of the ventricles and IVS, early relaxation velocity (E') of the ventricles, and systolic velocity of the IVS decreased during metabolic acidosis. The proportion of isovolumic contraction time of the cardiac cycle increased but the isovolumic relaxation and ejection time proportions and the TDI Tei index did not change. The E-to-E' ratio for both ventricles was higher during metabolic acidosis than at baseline. During metabolic acidosis, right and left ventricular cardiac outputs remained unchanged compared with baseline. In sheep fetuses with increased R(ua) and acute metabolic acidosis, global cardiac function was preserved. However, acute metabolic acidosis impaired myocardial contractility during the isovolumic phase and relaxation during the isovolumic and early filling phases of the cardiac cycle.
Full-text · Article · Feb 2008 · AJP Heart and Circulatory Physiology
[Show abstract][Hide abstract] ABSTRACT: We hypothesized that the administration of ephedrine and phenylephrine for maternal hypotension modifies cardiovascular hemodynamics in near-term sheep fetuses.
At 115-136 days of gestation, chronically instrumented, anesthetized ewes with either normal placental function or increased placental vascular resistance after placental embolization were randomized to receive boluses of ephedrine (n = 12) or phenylephrine (n = 12) for epidural-induced hypotension after a short period of hypoxemia. Fetal cardiovascular hemodynamics were assessed by Doppler ultrasonography at baseline, during hypotension and after vasopressor treatment.
During hypotension, fetal PO(2) decreased and proximal branch pulmonary arterial and pulmonary venous vascular impedances increased. Additionally, in the embolized fetuses, the time-velocity integral ratio between the antegrade and retrograde blood flow components of the aortic isthmus decreased. These parameters were restored to baseline conditions by ephedrine but not by phenylephrine. With phenylephrine, weight-indexed left ventricular cardiac output and ejection force decreased in the non-embolized fetuses, and the proportion of isovolumetric contraction time of the total cardiac cycle was elevated in the embolized fetuses.
After exposure to hypoxemia and maternal hypotension, ephedrine restored all fetal cardiovascular hemodynamic parameters to baseline. Phenylephrine did not reverse fetal pulmonary vasoconstriction or the relative decrease in the net forward flow through the aortic isthmus observed in fetuses with increased placental vascular resistance. Moreover, fetal left ventricular function was impaired during phenylephrine administration.
[Show abstract][Hide abstract] ABSTRACT: To test the hypothesis that Doppler-derived (calculated) uterine artery volume blood flow (cQ(UtA)) reflects accurately volume blood flow measured directly (mQ(UtA)) in an experimental setting.
Five pregnant sheep were instrumented at 122-130 days of gestation under general anesthesia. After a 4-day recovery period, maternal hemodynamics were varied by administering to the sheep under general anesthesia noradrenaline, beta-blocker, low oxygen gas mixture, epidural bupivacaine and ephedrine, consecutively. The central venous pressure was obtained with the help of a thermodilution catheter. The mean arterial pressure and acid-base status were monitored using a 16-gauge polyurethane catheter inserted into the descending aorta via a femoral artery. A 6-mm transit-time ultrasonic perivascular flow probe was used to measure the mQ(UtA). Doppler ultrasonography of the uterine artery was performed and volume blood flow was obtained simultaneously by the transit-time ultrasonic perivascular flow probe during each phase of the experiment.
A total of 31 observations were made. The mQ(UtA) varied between 90 and 800 (mean +/- SD, 419 +/- 206) mL/min during the experiments. The corresponding values for the cQ(UtA) were 110 and 900 (mean +/- SD, 459 +/- 211) mL/min. There was a significant correlation (R = 0.76; P < 0.0001) between mQ(UtA) and cQ(UtA). The mQ(UtA) correlated positively with Doppler-derived uterine artery absolute velocities, i.e. peak systolic (R = 0.50; P = 0.004), end-diastolic (R = 0.53; P = 0.002) and time-averaged maximum (R = 0.69; P < 0.0001) and time-averaged intensity weighted mean (R = 0.75; P < 0.0001) velocities.
cQ(UtA) correlates well with volume blood flow measured directly. Doppler-derived uterine artery absolute blood flow velocities reflect uteroplacental volume blood flow in pregnant sheep. Published by John Wiley & Sons, Ltd.
Full-text · Article · Apr 2007 · Ultrasound in Obstetrics and Gynecology
[Show abstract][Hide abstract] ABSTRACT: We hypothesized that ephedrine and phenylephrine are equal with respect to uterine and placental haemodynamics and fetal acid-base status after exposure to maternal hypoxaemia and hypotension in a chronic sheep model of increased placental vascular resistance (R(UA)).
At 114-135 days gestation, chronically instrumented fetal sheep underwent placental embolization leading to increased R(UA). Twenty-four hours after embolization, the ewes were anaesthetized and randomized to receive boluses of ephedrine (n=7) or phenylephrine (n=6) for epidural-induced hypotension after maternal hypoxaemia. Uterine (Q(UtA)) and placental (Q(UA)) volume blood flows and uterine vascular resistance (R(UtA)) and R(UA) were recorded. Uterine (PI(UtA)) and umbilical artery (PI(UA)) pulsatility indices were obtained by Doppler ultrasonography. Fetal arterial blood samples were analysed for acid-base values and lactate concentrations.
During hypotension, Q(UtA), fetal pH, BE, and Po(2) decreased whereas R(UtA), PI(UtA), R(UA), and fetal lactate concentration increased. With ephedrine, Q(UtA), R(UtA), PI(UtA), R(UA), and fetal Po(2) returned to baseline. Fetal pH, BE, and lactate concentration did not change from hypotensive values. With phenylephrine, Q(UtA) remained lower (P=0.007) and R(UtA) (P=0.007), PI(UtA) (P=0.013), and R(UA) (P=0.050) higher than at baseline. Fetal Po(2) returned to baseline and fetal pH and BE did not change from hypotensive values. However, fetal lactate concentration increased further (mean difference 1.49, 95% confidence interval 0.72-2.26 mmol litre(-1); P=0.004).
In a chronic sheep model of increased placental vascular resistance, compared with ephedrine administration, phenylephrine administration was associated with impaired uterine and placental haemodynamics and increased fetal lactate concentrations.
Preview · Article · Mar 2006 · BJA British Journal of Anaesthesia
[Show abstract][Hide abstract] ABSTRACT: We hypothesized that a decrease in fetal oxygenation without acidemia in a near-term fetal sheep leads to cardiovascular hemodynamic changes that are detectable by Doppler ultrasonography.
Twelve ewes and fetuses were instrumented at 112 to 127 days of gestation. After a 5-day recovery period, experiments were performed with general anesthesia. Uterine and placental volume blood flows and fetal arterial and venous blood pressures were measured. Fetal cardiovascular hemodynamics was assessed by Doppler ultrasonography. All the measurements were performed at baseline, during fetal hypo-oxygenation, and at recovery phase.
A drop in fetal Po2 was related to increased (P < .05) weight-indexed right ventricular and combined cardiac outputs and proximal branch pulmonary artery pulsatility index values. The increase in proximal branch pulmonary artery pulsatility index values correlated (R = .59; P < .05) with the decrease in fetal oxygen saturation. In the aortic isthmus, the time-velocity integral ratio between antegrade and retrograde blood flow components decreased (P < .05) when fetal Po2 dropped.
During decreased fetal oxygenation Doppler ultrasonography demonstrated increased fetal cardiac output and pulmonary arterial vascular impedance and a relative increase in the retrograde blood flow component in the aortic isthmus.
No preview · Article · Feb 2006 · American journal of obstetrics and gynecology
[Show abstract][Hide abstract] ABSTRACT: Recent studies support the use of alpha-agonists during regional anaesthesia in uncomplicated term pregnancies. We hypothesized that ephedrine and phenylephrine, administered for maternal hypotension following fetal hypoxaemia, are equal in respect of fetal outcome.
At 117-132 days gestation, chronically instrumented, anaesthetized and mechanically ventilated ewes were randomized to receive boluses of ephedrine (n=9) or phenylephrine (n=8) for maternal epidural-induced hypotension after a period of fetal hypoxaemia. Uterine (QUtA) and placental (QUA) volume blood flows were measured with perivascular transit-time ultrasonic flow probes, and uterine (RUtA) and placental (RUA) vascular resistances were computed from volume blood flows and maternal and fetal mean arterial pressures. Uterine (PIUtA) and umbilical artery (PIUA) pulsatility indices were obtained by Doppler ultrasonography.
Ephedrine increased QUtA and decreased RUtA and PIUtA from a hypotensive to baseline level and had no significant effect on umbilical circulation. With phenylephrine, QUtA remained lower (P=0.011) and RUtA higher (P=0.043) than at baseline, although PIUtA decreased to baseline level. PIUA increased from baseline with phenylephrine (P=0.007), whereas QUA decreased (P=0.050). Maternal volume expansion with hydroxyethyl starch decreased RUtA significantly irrespective of the vasopressor used. There were no significant differences in fetal blood gas values or lactate concentrations between the ephedrine and phenylephrine groups.
Despite the more favourable effects on uterine and placental circulations of ephedrine over phenylephrine, no significant differences in fetal acid-base status or lactate concentrations were observed.
Preview · Article · Jan 2005 · BJA British Journal of Anaesthesia