Considerations in selecting postoperative analgesia for pregnant sheep following fetal instrumentation surgery

Varcoe, Tamara J.; Darby, Jack R. T.; Gatford, Kathryn L.; Holman, Stacey L.; Cheung, Pearl; Berry, Mary J.; Wiese, Michael; Morrison, Janna L.

doi:10.1093/af/vfz019

Cited by 29 publications

(31 citation statements)

References 49 publications

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“…This decreased fetal motion but may have reduced cardiac function to some degree (Varcoe et al . 2019). However, our previous studies of blood flow using 2D PC‐MRI resulted in values that were similar to those determined in conscious ewes using other methods (Duan et al .…”

Section: Discussionmentioning

confidence: 99%

Technique for comprehensive fetal hepatic blood flow assessment in sheep using 4D flow MRI

Schrauben

Darby

Saini³

et al. 2020

The Journal of Physiology

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Key points The comprehensive visualization and quantification of in vivo fetal hepatic haemodynamics, particularly the shunting of ductus venosus blood, has been elusive and is not yet fully understood. We introduce the combination of chronically instrumented fetal sheep and 4D flow MRI of the whole fetal liver, which allows retrospective blood flow measurement in all visible vessels as well as qualitative assessment. The applicability and usefulness of this technique is exhibited in normally grown fetal Merino sheep in mid‐ and late‐gestation with detailed dynamic distribution of hepatic blood flow presented. The feasibility of this approach in clinical pathology is demonstrated in two growth‐restricted fetuses at mid‐gestation. Further exemplification of blood flow quantification is performed over major hepatic vessels. Abstract Although the fetal vasculature has been demarcated and well understood for several decades, the corresponding haemodynamics permitting oxygen‐ and nutrient‐rich blood delivery to the fetal organs has been comparatively difficult to study. We married two well‐established methods: 4D flow MRI, a volumetric and dynamic blood‐flow measurement technique, and chronically instrumented sheep to broadly assess fetal hepatic circulation. We performed this technique in mid‐ and late‐gestation fetal Merino sheep under normoxemic conditions and major hepatic vasculature was segmented to quantify blood flow and related parameters. Dynamic blood flow was visualized, exhibiting an acceleration of umbilical vein blood through the ductus venosus as well as spiralling into the inferior vena cava where its stream remained separate from that of the hepatic veins and lower body. Ductus venosus changes from mid‐ to late‐gestation included larger diameter (mid: 5.8 ± 0.9 vs. late: 7.1 ± 1.1 mm; P = 0.003) and cross‐sectional area (mid: 27.1 ± 8.6 vs. late: 40.4 ± 11.8 mm2; P = 0.003), and lower velocity averaged over the cardiac cycle (mid: 15.7 ± 5.4 vs. late: 9.8 ± 7.0 cm s‐1; P = 0.020). This resulted in higher magnitude blood flow (indexed to umbilical vein input) at mid‐gestation in the ductus venosus (mid: 0.73 ± 0.21; late: 0.46 ± 0.21; P = 0.008). The visualization and quantification results support the further use of this technique to better understand regional blood flow changes during normal or abnormal fetal growth, as well as to observe acute haemodynamic responses to physiological challenges or drug interventions.

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Section: Discussionmentioning

confidence: 99%

Technique for comprehensive fetal hepatic blood flow assessment in sheep using 4D flow MRI

Schrauben

Darby

Saini³

et al. 2020

The Journal of Physiology

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“…Antibiotics were administered intramuscularly to each ewe for 3 days after surgery and intra‐amniotically (500 mg Ampicillin, Clifford Hallam Healthcare, Adelaide, Australia) for 4 days after surgery. Analgesia was administered subcutaneously at 16:00 hr on the day prior to surgery and repeated 24 hr later (meloxicam, subcutaneous, 0.5 mg·ml −1 , Lyppards, Melbourne, Australia (Varcoe et al, ). Clinical record sheets were completed daily to monitor behavior (appetite, thirst, defecation, urination, and alertness) and fetal arterial blood collected daily for blood gas analysis.…”

Section: Methodsmentioning

confidence: 99%

Fetal cardiovascular response to acute hypoxia during maternal anesthesia

et al. 2020

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Preclinical imaging studies of fetal hemodynamics require anesthesia to immobilize the animal. This may induce cardiovascular depression and confound measures under investigation. We compared the impact of four anesthetic regimes upon maternal and fetal blood gas and hemodynamics during baseline periods of normoxia, and in response to an acute hypoxic challenge in pregnant sheep. Merino ewes were surgically prepared with maternal and fetal vascular catheters and a fetal femoral artery flow probe at 105–109 days gestation. At 110–120 days gestation, ewes were anesthetized with either isoflurane (1.6%), isoflurane (0.8%) plus ketamine (3.6 mg·kg−1·h−1), ketamine (12.6 mg·kg−1·h−1) plus midazolam (0.78 mg·kg−1·h−1), propofol (30 mg·kg−1·h−1), or remained conscious. Following 60 min of baseline recording, nitrogen was administered directly into the maternal trachea to displace oxygen and induce maternal and thus fetal hypoxemia. During normoxia, maternal PaO2 was ~30 mmHg lower in anesthetized ewes compared to conscious controls, regardless of the type of anesthesia (p < .001). There was no effect of anesthesia on fetal mean arterial blood pressure (MAP; p > .05), but heart rate was 32 ± 8 bpm lower in fetuses from ewes administered isoflurane (p = .044). During maternal hypoxia, fetal MAP increased, and peripheral blood flow decreased in all fetuses except those administered propofol (p < .05). Unexpectedly, hypoxemia also induced fetal tachycardia regardless of the anesthetic regime (p < .05). These results indicate that despite maternal anesthesia, the fetus can mount a cardiovascular response to acute hypoxia by increasing blood pressure and reducing peripheral blood flow, although the heart rate response may differ from when no anesthesia is present.

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“…Therefore, pain management and anti-microbial management have to be planned carefully and adapted to meet the special requirements of sheep (Lizarraga and Chambers, 2012;Varcoe et al, 2019). Sheep guidelines for pain assessment by facial expression are available (Hager et al, 2017) which may help managing pain.…”

Section: Additional Considerations Regarding Sheepmentioning

confidence: 99%

Large Animal Models in Regenerative Medicine and Tissue Engineering: To Do or Not to Do

Ribitsch

Baptista

Consiglio

et al. 2020

Front. Bioeng. Biotechnol.

147

110

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Rapid developments in Regenerative Medicine and Tissue Engineering has witnessed an increasing drive toward clinical translation of breakthrough technologies. However, the progression of promising preclinical data to achieve successful clinical market authorisation remains a bottleneck. One hurdle for progress to the clinic is the transition from small animal research to advanced preclinical studies in large animals to test safety and efficacy of products. Notwithstanding this, to draw meaningful and reliable conclusions from animal experiments it is critical that the species and disease model of choice is relevant to answer the research question as well as the clinical problem. Selecting the most appropriate animal model requires in-depth knowledge of specific species and breeds to ascertain the adequacy of the model and outcome measures that closely mirror the clinical situation. Traditional reductionist approaches in animal experiments, which often do not sufficiently reflect the studied disease, are still the norm and can result in a disconnect in outcomes observed between animal studies and clinical trials. To address these concerns a reconsideration in approach will be required. This should include a stepwise approach using in vitro and ex vivo experiments as well as in silico modeling to minimize the need for in vivo studies for screening and early development studies, followed by large animal models which more closely resemble human disease. Naturally occurring, or spontaneous diseases in large animals remain a largely untapped resource, and given the similarities in pathophysiology to humans they not only allow for studying new treatment strategies but also disease etiology and prevention. Naturally occurring disease models, particularly for longer lived large animal species, allow for studying disorders at an age when the disease is most prevalent. As these diseases are usually also a concern in the chosen veterinary species they would be beneficiaries of newly developed therapies. Improved awareness of the progress

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Considerations in selecting postoperative analgesia for pregnant sheep following fetal instrumentation surgery

Cited by 29 publications

References 49 publications

Technique for comprehensive fetal hepatic blood flow assessment in sheep using 4D flow MRI

Technique for comprehensive fetal hepatic blood flow assessment in sheep using 4D flow MRI

Fetal cardiovascular response to acute hypoxia during maternal anesthesia

Large Animal Models in Regenerative Medicine and Tissue Engineering: To Do or Not to Do

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