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      Physiological effects of partial amniotic carbon dioxide insufflation with cold, dry vs heated, humidified gas in a sheep model

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          ABSTRACT

          Objective

          Partial amniotic carbon dioxide (CO 2) insufflation (PACI) is used to improve visualization and facilitate complex fetoscopic surgery. However, there are concerns about fetal hypercapnic acidosis and postoperative fetal membrane inflammation. We assessed whether using heated and humidified, rather than cold and dry, CO 2 might reduce the impact of PACI on the fetus and fetal membranes in sheep.

          Methods

          Twelve fetal lambs of 105 days' gestational age (term = 145 days) were exteriorized partially, via a midline laparotomy and hysterotomy, and arterial catheters and flow probes were inserted surgically. The 10 surviving fetuses were returned to the uterus, which was then closed and insufflated with cold, dry (22 °C at 0–5% humidity, n = 5) or heated, humidified (40 °C at 100% humidity, n = 5) CO 2 at 15 mmHg for 180 min. Fetal membranes were collected immediately after insufflation for histological analysis. Physiological data and membrane leukocyte counts, suggestive of membrane inflammation, were compared between the two groups.

          Results

          After 180 min of insufflation, fetal survival was 0% in the group which underwent PACI with cold, dry CO 2, and 60% ( n = 3) in the group which received heated, humidified gas. While all insufflated fetuses became progressively hypercapnic (PaCO 2 > 68 mmHg), this was considerably less pronounced in those in which heated, humidified gas was used: after 120 min of insufflation, compared with those receiving cold, dry gas ( n = 3), fetuses undergoing heated, humidified PACI ( n = 5) had lower arterial partial pressure of CO 2 (mean ± standard error of the mean, 82.7 ± 9.1 mmHg for heated, humidified CO 2 vs 170.5 ± 28.5 for cold, dry CO 2 during PACI, P < 0.01), lower lactate levels (1.4 ± 0.4 vs 8.5 ± 0.9 mmol/L, P < 0.01) and higher pH (pH, 7.10 ± 0.04 vs 6.75 ± 0.04, P < 0.01). There was also a non‐significant trend for fetal carotid artery pressure to be higher following PACI with heated, humidified compared with cold, dry CO 2 (30.5 ± 1.3 vs 8.7 ± 5.5 mmHg, P = 0.22). Additionally, the median (interquartile range) number of leukocytes in the chorion was significantly lower in the group undergoing PACI with heated, humidified CO 2 compared with the group receiving cold, dry CO 2 (0.7 × 10 –5 (0.5 × 10 –5) vs 3.2 × 10 –5 (1.8 × 10 –5) cells per square micron, P = 0.02).

          Conclusions

          PACI with cold, dry CO 2 causes hypercapnia, acidosis, hypotension and fetal membrane inflammation in fetal sheep, raising potential concerns for its use in humans. It seems that using heated, humidified CO 2 for insufflation partially mitigates these effects and this may be a suitable alternative for reducing the risk of fetal acid–base disturbances during, and fetal membrane inflammation following, complex fetoscopic surgery. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

          Abstract

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          Most cited references25

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          The Solubility of Carbon Dioxide in Water at Low Pressure

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            Carbon dioxide transport and carbonic anhydrase in blood and muscle.

            G Gros, C Geers (2000)
            CO(2) produced within skeletal muscle has to leave the body finally via ventilation by the lung. To get there, CO(2) diffuses from the intracellular space into the convective transport medium blood with the two compartments, plasma and erythrocytes. Within the body, CO(2) is transported in three different forms: physically dissolved, as HCO(3)(-), or as carbamate. The relative contribution of these three forms to overall transport is changing along this elimination pathway. Thus the kinetics of the interchange have to be considered. Carbonic anhydrase accelerates the hydration/dehydration reaction between CO(2), HCO(3)(-), and H(+). In skeletal muscle, various isozymes of carbonic anhydrase are localized within erythrocytes but are also bound to the capillary wall, thus accessible to plasma; bound to the sarcolemma, thus producing catalytic activity within the interstitial space; and associated with the sarcoplasmic reticulum. In some fiber types, carbonic anhydrase is also present in the sarcoplasm. In exercising skeletal muscle, lactic acid contributes huge amounts of H(+) and by these affects the relative contribution of the three forms of CO(2). With a theoretical model, the complex interdependence of reactions and transport processes involved in CO(2) exchange was analyzed.
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              The physiology of fetal membrane weakening and rupture: Insights gained from the determination of physical properties revisited.

              Rupture of the fetal membranes (FM) is precipitated by stretch forces acting upon biochemically mediated, pre-weakened tissue. Term FM develop a para-cervical weak zone, characterized by collagen remodeling and apoptosis, within which FM rupture is thought to initiate. Preterm FM also have a weak region but are stronger overall than term FM. Inflammation/infection and decidual bleeding/abruption are strongly associated with preterm premature FM rupture (pPROM), but the specific mechanisms causing FM weakening-rupture in pPROM are unknown. There are no animal models for study of FM weakening and rupture. Over a decade ago we developed equipment and methodology to test human FM strength and incorporated it into a FM explant system to create an in-vitro human FM weakening model system. Within this model TNF (modeling inflammation) and Thrombin (modeling bleeding) both weaken human FM with concomitant up regulation of MMP9 and cellular apoptosis, mimicking the characteristics of the spontaneous FM rupture site. The model has been enhanced so that test agents can be applied directionally to the choriodecidual side of the FM explant consistent with the in-vivo situation. With this enhanced system we have demonstrated that the pathways involving inflammation/TNF and bleeding/Thrombin induced FM weakening overlap. Furthermore GM-CSF production was demonstrated to be a critical common intermediate step in both the TNF and the Thrombin induced FM weakening pathways. This model system has also been used to test potential inhibitors of FM weakening and therefore pPROM. The dietary supplement α-lipoic acid and progestogens (P4, MPA and 17α-hydroxyprogesterone) have been shown to inhibit both TNF and Thrombin induced FM weakening. The progestogens act at multiple points by inhibiting both GM-CSF production and GM-CSF action. The use of a combined biomechanical/biochemical in-vitro human FM weakening model system has allowed the pathways of fetal membrane weakening to be delineated, and agents that may be of clinical use in inhibiting these pathways to be tested.

                Author and article information

                Contributors
                philip.dekoninck@monash.edu
                Journal
                Ultrasound Obstet Gynecol
                Ultrasound Obstet Gynecol
                10.1002/(ISSN)1469-0705
                UOG
                Ultrasound in Obstetrics & Gynecology
                John Wiley & Sons, Ltd. (Chichester, UK )
                0960-7692
                1469-0705
                05 March 2019
                March 2019
                : 53
                : 3 ( doiID: 10.1002/uog.2019.53.issue-3 )
                : 340-347
                Affiliations
                [ 1 ] The Ritchie Centre, Hudson Institute of Medical Research Melbourne Victoria Australia
                [ 2 ] Department of Obstetrics and Gynaecology Monash University Melbourne Victoria Australia
                [ 3 ] Institute of Woman's Health University College London London UK
                [ 4 ] Department of Development and Regeneration, Cluster Organ Systems, Faculty of Medicine KU Leuven Leuven Belgium
                [ 5 ] Department of Obstetrics and Gynaecology Erasmus MC‐Sophia Children's Hospital Rotterdam The Netherlands
                Author notes
                [*] [* ] Correspondence to: Dr P. L. J. DeKoninck, The Ritchie Centre, Hudson Institute of Medical Research, 27–31 Wright St, Clayton, Victoria, 3168, Australia (e‐mail: philip.dekoninck@ 123456monash.edu )
                [†]

                K.J.C. and P.L.J.D. are joint senior authors.

                Author information
                https://orcid.org/0000-0002-4385-487X
                https://orcid.org/0000-0002-4920-945X
                Article
                UOG20180 UOG-2018-0620.R2
                10.1002/uog.20180
                6635737
                30461102
                c3edb14a-8cfe-4cef-8a55-48713f06e108
                © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 03 August 2018
                : 30 October 2018
                : 09 November 2018
                Page count
                Figures: 3, Tables: 2, Pages: 8, Words: 4558
                Funding
                Funded by: Royal Australian and New Zealand College of Obstetricians
                Funded by: National Health and Medical Research Council
                Categories
                Original Paper
                Original Papers
                Custom metadata
                2.0
                uog20180
                March 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.5 mode:remove_FC converted:17.07.2019

                Obstetrics & Gynecology
                carbon dioxide,fetal membrane inflammation,fetoscopic surgery,myelomeningocele,paci,partial amniotic co2 insufflation

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