Cardiopulmonary reference standards in the pregnant sheep (Ovis aries): A comparative study of ovine and human physiology in obstetrics

Cissik, John H.; Ehler, William J.; Hankins, Gary D.V.; Snyder, Rüssel R

doi:10.1016/0300-9629(91)90307-x

Cited by 15 publications

(12 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Maternal and fetal cardiovascular responses to dexmedetomidine are presented in Figures 2 and 3, respectively. Before drug infusion, maternal heart rate and blood pressure were within the normative range for pregnant sheep 33 (these ranges along with UBF match well with values for humans at a similar gestational stage 34 ). Baseline fetal heart rate also matched published reports 35 but the values (>160 beats/min) would be defined as tachycardia for a human fetus.…”

Section: Resultssupporting

confidence: 65%

Maternal and Preterm Fetal Sheep Responses to Dexmedetomidine

Uemura

Shimazutsu

McClaine

et al. 2013

Obstetric Anesthesia Digest

View full text Add to dashboard Cite

Topics: Pharmacology P regnant women may require sedation, anesthesia, or pain control for nonobstetric-related care. The a 2adrenergic receptor (a 2 AR) agonist dexmedetomidine (DEX) has sedative, anxiolytic, and analgesic actions and can reduce the dose requirements for other sedative and analgesic drugs through synergistic effects with opioids and benzodiazepines. Clinical investigations of DEX have not included significant numbers of pregnant patients; in fact, most studies have excluded pregnant women. This study was designed to determine the maternal and fetal responses to an intravenous infusion of DEX in sheep.The study was performed on 9 preterm pregnant ewes at gestational day 92, a time relatively equivalent to the end of the second trimester in humans. Surgical anesthesia was induced with IV sodium thiopental and maintained with isoflurane in oxygen. Standard surgical techniques were used to insert catheters into maternal femoral artery and jugular vein as well as bilateral fetal femoral arteries. A flow probe was placed around the left uterine artery to record uterine blood flow (UBF). The fetal head was exteriorized to install near-infrared spectroscopy probes to assess changes in fetal cerebral oxygenation during and after drug administration to the mother. The fetus was then returned to the uterus. After the procedure, infiltration of the surgical incision with bupivacaine and intramuscular nalbuphine hydrochloride were used to control postoperative pain. Animals recovered for 48 hours before the DEX-exposure experiment was conducted. Maternal and fetal cardiovascular data along with UBF were recorded. Fetal cerebral oxygenation, measured by changes in oxygenated, deoxygenated, and total hemoglobin (Hb) (oxyHb, deoxyHb, and totalHb, respectively), was quantitated with the near-infrared spectroscopy monitor. After a baseline recording period of 30 to 60 minutes, drug exposure was begun using human-dosing guidelines. Each ewe received an IV bolus injection of DEX, 1.0 mg/kg followed by a constant IV infusion of 1.0 mg/kg/h. The infusion was stopped after 3 hours and the experiment halted 2 hours later. Hemodynamic and fetal cerebral oxygenation data were continuously recorded during the study; maternal and fetal arterial blood samples were obtained at 30-minute intervals.The statistical analyses focused on the 3 primary endpoints: changes in fetal cerebral oxygenation, maternal and fetal cardiovascular status, and arterial blood gas status.All animals tolerated the DEX infusion with no complications during or after drug exposure. Profound sedation occurred within minutes of starting the infusion; consciousness returned within 30 to 60 minutes after discontinuation of the infusion. During the infusion, the sheep were unresponsive to painful stimuli. The ewes had a normal respiratory pattern throughout the exposure period, as evidenced by the arterial blood gas values that remained normal throughout the study. Only blood glucose levels in both the ewe and fetus continued to rise during DEX infusion, p...

show abstract

Section: Resultssupporting

confidence: 65%

Maternal and Preterm Fetal Sheep Responses to Dexmedetomidine

Uemura

Shimazutsu

McClaine

et al. 2013

Obstetric Anesthesia Digest

View full text Add to dashboard Cite

show abstract

“…Before drug infusion, maternal heart rate and blood pressure were within the normative range for pregnant sheep 33 (these ranges along with UBF match well with values for humans at a similar gestational stage 34 ). Baseline fetal heart rate also matched published reports 35 but the values (>160 beats/min) would be defined as tachycardia for a human fetus.…”

Section: Resultssupporting

confidence: 65%

Maternal and preterm fetal sheep responses to dexmedetomidine

Uemura

Shimazutsu

McClaine

et al. 2012

International Journal of Obstetric Anesthesia

View full text Add to dashboard Cite

Background The α2 adrenergic receptor agonist dexmedetomidine has some unique pharmacologic properties that could benefit pregnant patients (and their fetuses) when they require sedation, analgesia, and/or anesthesia during pregnancy. The purpose of the present study was to delineate maternal and fetal responses to an intravenous infusion of dexmedetomidine. Methods This study was conducted on surgically-recovered preterm sheep instrumented for physiologic recording and blood sampling. Maternal and fetal cardiovascular and blood gas parameters and fetal cerebral oxygenation levels were recorded before, during, and after 3 h of dexmedetomidine infusion to the ewe at a rate of 1 μg/kg/h. Results Drug infusion produced overt sedation but no apparent respiratory depression as evidenced by stable maternal arterial blood gases; fetal blood gases were also stable. The one blood parameter to change was serum glucose, By the end of the 3 h infusion, glucose increased from 49 ± 10 to 104 ± 33 mg/dL in the ewe and from 22 ± 3 to 48 ± 16 mg/dL in the fetus; it declined post-drug exposure but remained elevated compared to the starting levels (maternal, 63 ± 12 mg/dL, P = 0.0497; and fetal, 24 ± 4 mg/dL, P = 0.012). With respect to cardiovascular status, dexmedetomidine produced a fall in maternal blood pressure and heart rate with fluctuations in uterine blood flow but had no discernable effect on fetal heart rate or mean arterial pressure. Likewise, maternal drug infusion had no effect on fetal cerebral oxygenation, as measured by in utero near-infrared spectroscopy. Conclusions Using a clinically-relevant dosing regimen, intravenous infusion of dexmedetomidine produced significant maternal sedation without altering fetal physiologic status. Results from this initial acute assessment support the conduct of further studies to determine if dexmedetomidine has clinical utility for sedation and pain control during pregnancy.

show abstract

“…In addition, sheep are docile, inexpensive, and easy to handle, and multiple biopsies can be obtained in a single animal. Sheep have been used for many years in perinatal health and development studies and are well characterized for these purposes (34). …”

Section: Discussionmentioning

confidence: 99%

High Resolution Imaging of Epithelial Injury in the Sheep Cervicovaginal Tract: A Promising Model for Testing Safety of Candidate Microbicides

Vincent

Bourne²,

Bell

et al. 2009

Sexually Transmitted Diseases

View full text Add to dashboard Cite

Background Access to readily available large animal models and sensitive non-invasive techniques that can be used for the evaluation of microbicide-induced changes in tissue could significantly facilitate pre-clinical evaluations of microbicide safety. The sheep cervicovaginal tract, with stratified squamous epithelium similar to humans, holds promise as a large animal model used prior to non-human primates. In addition, optical coherence tomography (OCT) could enable high resolution visualization of tissue morphology and non-invasive assessment of microbicide-induced epithelial injury. Methods We evaluated the dose response of sheep cervicovaginal tract to benzalkonium chloride (BZK). Twenty sheep received treatment with phosphate buffered saline (PBS) or BZK solution (2%, 0.2%, or 0.02%). Pre- and post-treatment colposcopy and OCT images were collected and graded based on WHO criteria and a previously reported scoring system, respectively. Biopsies were collected and the degree of epithelial injury and its thickness was assessed based on histology and OCT. Results The sheep cervicovagina exhibited anatomical and microscopic features similar to the human. Extensive loss of the epithelium was noted on colposcopy and OCT following application of 2% BZK. Colposcopy detected findings in half of sheep and OCT in all sheep treated with 0.2% BZK. OCT detected differences in the 0.02% BZK-treated group compared to controls whereas colposcopy failed to detect any changes. Conclusions The sheep cervicovagina is similar to humans, and exhibits dose dependent epithelial changes following BZK treatment. These findings suggest that the sheep model and OCT may become valuable tools for the safety evaluation of candidate microbicides, and warrant continued development. Short summary Optical coherence tomography, a high resolution imaging method, used with colposcopy in the sheep cervicovaginal tract detected a dose-dependent response to benzalkonium chloride, demonstrating potential for microbicide safety evaluations.

show abstract

Cardiopulmonary reference standards in the pregnant sheep (Ovis aries): A comparative study of ovine and human physiology in obstetrics

Cited by 15 publications

References 1 publication

Maternal and Preterm Fetal Sheep Responses to Dexmedetomidine

Maternal and Preterm Fetal Sheep Responses to Dexmedetomidine

Maternal and preterm fetal sheep responses to dexmedetomidine

High Resolution Imaging of Epithelial Injury in the Sheep Cervicovaginal Tract: A Promising Model for Testing Safety of Candidate Microbicides

Contact Info

Product

Resources

About