<?xml version="1.0" encoding="utf-8"?>
<!DOCTYPE article SYSTEM "archivearticle3.dtd">
<article dtd-version="3.0" article-type="Invited Methods Article - JoVE Produced Video">
  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher">jove</journal-id>
      <journal-id journal-id-type="email">peerreview@jove.com</journal-id>
      <journal-title-group>
        <journal-title>Journal of Visualized Experiments</journal-title>
      </journal-title-group>
      <issn pub-type="ppub">1940-087X</issn>
      <issn pub-type="epub"></issn>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id">JoVE50392</article-id>
      <article-id pub-id-type="manuscript">JoVE50392</article-id>
      <article-categories>
        <subj-group subj-group-type="Article Type">
          <subject>Invited Methods Article - JoVE Produced Video</subject>
        </subj-group>
        <subj-group subj-group-type="Category">
          <subject>JoVE Clinical and Translational Medicine</subject>
        </subj-group>
        <subj-group subj-group-type="Classification">
          <subject>Fetal Therapies</subject>
          <subject>Obstetric Surgical Procedures</subject>
          <subject>Fetal Development</subject>
          <subject>Surgical Procedures, Operative</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Fetal echocardiography and pulsed-wave Doppler ultrasound in a rabbit model of intrauterine growth restriction.</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author" corresp="yes">
          <role content-type="1" />
          <name>
            <surname>Hodges</surname>
            <given-names>Ryan</given-names>
            <prefix>Dr.</prefix>
          </name>
          <degrees>MD PhD</degrees>
          <email>ryan.hodges@monash.edu</email>
          <xref ref-type="aff" rid="aff1" />
        </contrib>
        <contrib contrib-type="author">
          <role content-type="2" />
          <name>
            <surname>Endoh</surname>
            <given-names>Masa</given-names>
          </name>
          <email>mendoh1125@hotmail.com</email>
          <xref ref-type="aff" rid="aff2" />
        </contrib>
        <contrib contrib-type="author">
          <role content-type="3" />
          <name>
            <surname>La Gerche</surname>
            <given-names>Andre</given-names>
          </name>
          <email>andre.lagerche@uzleuven.be</email>
          <xref ref-type="aff" rid="aff3" />
        </contrib>
        <contrib contrib-type="author">
          <role content-type="4" />
          <name>
            <surname>Eixarch</surname>
            <given-names>Elisenda</given-names>
          </name>
          <email>elisendaeixarch@gmail.com</email>
          <xref ref-type="aff" rid="aff4" />
        </contrib>
        <contrib contrib-type="author">
          <role content-type="5" />
          <name>
            <surname>DeKoninck</surname>
            <given-names>Philip</given-names>
          </name>
          <email>philipdekoninck@gmail.com</email>
          <xref ref-type="aff" rid="aff5" />
        </contrib>
        <contrib contrib-type="author">
          <role content-type="6" />
          <name>
            <surname>Ferferieva</surname>
            <given-names>Vessilina</given-names>
          </name>
          <email>vesselina.ferferieva@uzleuven.be</email>
          <xref ref-type="aff" rid="aff6" />
        </contrib>
        <contrib contrib-type="author">
          <role content-type="7" />
          <name>
            <surname>D'hooge</surname>
            <given-names>Jan</given-names>
          </name>
          <email>jan.dhooge@uzleuven.be</email>
          <xref ref-type="aff" rid="aff7" />
        </contrib>
        <contrib contrib-type="author">
          <role content-type="8" />
          <name>
            <surname>wallace</surname>
            <given-names>euan</given-names>
          </name>
          <email>euan.wallace@monash.edu</email>
          <xref ref-type="aff" rid="aff8" />
        </contrib>
        <contrib contrib-type="author">
          <role content-type="9" />
          <name>
            <surname>Deprest</surname>
            <given-names>Jan</given-names>
          </name>
          <email>jan.deprest@uzleuven.be</email>
          <xref ref-type="aff" rid="aff9" />
        </contrib>
        <contrib contrib-type="editor">
          <name>
            <surname>Meehan</surname>
            <given-names>Alexa</given-names>
          </name>
          <email>alexa.meehan@jove.com</email>
          <xref ref-type="aff" rid="aff10" />
        </contrib>
        <aff id="aff1">
          <institution>KU Leuven</institution>
          <institution content-type="position">Research Fellow</institution>
          <institution content-type="dept">Obstetrics and Gynaecology</institution>
          <addr-line content-type="addrline1">University Hospitals Leuven</addr-line>
          <country>BELGIUM</country>
          <addr-line content-type="city">Leuven</addr-line>
          <addr-line content-type="state">Leuven</addr-line>
          <addr-line content-type="zipcode">B-3000</addr-line>
          <phone content-type="primary">+32489151511</phone>
          <institution>KU Leuven</institution>
        </aff>
        <aff id="aff2">
          <institution>UZ Leuven</institution>
          <institution content-type="dept">Obstetrics and Gynaecology</institution>
          <addr-line content-type="addrline1">UZ Leuven Hospital</addr-line>
          <addr-line content-type="city">Leuven</addr-line>
          <addr-line content-type="zipcode">B-3000</addr-line>
          <institution>UZ Leuven</institution>
        </aff>
        <aff id="aff3">
          <institution>UZ Leuven</institution>
          <institution content-type="dept">Cardiology</institution>
          <addr-line content-type="addrline1">UZ Leuven Hospital</addr-line>
          <addr-line content-type="city">Leuven</addr-line>
          <addr-line content-type="zipcode">B-3000</addr-line>
          <institution>UZ Leuven</institution>
        </aff>
        <aff id="aff4">
          <institution>University of Barcelona, Barcelona, Spain</institution>
          <institution content-type="dept">Maternal fetal medicine</institution>
          <addr-line content-type="addrline1">Hospital Clinic and Institut d’Investigacions Biomèdiques August Pi i Sunyer (I</addr-line>
          <addr-line content-type="city">Barcelona</addr-line>
          <addr-line content-type="zipcode">n/a</addr-line>
          <institution>University of Barcelona, Barcelona, Spain</institution>
        </aff>
        <aff id="aff5">
          <institution>UZ Leuven</institution>
          <institution content-type="dept">Obstetrics and Gynaecology</institution>
          <addr-line content-type="addrline1">UZ Leuven Hospital</addr-line>
          <addr-line content-type="city">Leuven</addr-line>
          <addr-line content-type="zipcode">B-3000</addr-line>
          <institution>UZ Leuven</institution>
        </aff>
        <aff id="aff6">
          <institution>UZ Leuven</institution>
          <institution content-type="dept">Cardiology</institution>
          <addr-line content-type="addrline1">UZ Leuven Hospital</addr-line>
          <addr-line content-type="city">Leuven</addr-line>
          <addr-line content-type="zipcode">B-3000</addr-line>
          <institution>UZ Leuven</institution>
        </aff>
        <aff id="aff7">
          <institution>UZ Leuven</institution>
          <institution content-type="dept">Cardiology</institution>
          <addr-line content-type="addrline1">UZ Leuven Hospital</addr-line>
          <addr-line content-type="city">Leuven</addr-line>
          <addr-line content-type="zipcode">B-3000</addr-line>
          <institution>UZ Leuven</institution>
        </aff>
        <aff id="aff8">
          <institution>MIMR</institution>
          <institution content-type="dept">Obstetrics and Gynaecology</institution>
          <addr-line content-type="addrline1">Monash Medical Centre</addr-line>
          <addr-line content-type="addrline2">Clayton, VIC</addr-line>
          <addr-line content-type="city">Clayton</addr-line>
          <addr-line content-type="zipcode">3168</addr-line>
          <institution>Monash University</institution>
        </aff>
        <aff id="aff9">
          <institution>UZ Leuven</institution>
          <institution content-type="dept">Obstetrics and Gynaecology</institution>
          <addr-line content-type="addrline1">UZ Leuven Hospital</addr-line>
          <addr-line content-type="city">Leuven</addr-line>
          <addr-line content-type="zipcode">B-3000</addr-line>
          <institution>UZ Leuven</institution>
        </aff>
        <aff id="aff10">
          <institution>Journal of Visualized Experiments</institution>
          <addr-line>17 Sellers St</addr-line>
          <addr-line>Cambridge, MA  02139</addr-line>
          <country>UNITED STATES</country>
        </aff>
      </contrib-group>
      <history>
        <date date-type="received">
          <day>21</day>
          <month>09</month>
          <year>2012</year>
        </date>
        <date date-type="rev-recd">
          <day>14</day>
          <month>11</month>
          <year>2012</year>
        </date>
        <date date-type="accepted">
          <day>15</day>
          <month>11</month>
          <year>2012</year>
        </date>
      </history>
      <abstract>
        <p>Fetal intrauterine growth restriction (IUGR) results in abnormal cardiac function that is apparent antenatally due to advances in fetoplacental Doppler ultrasound and fetal echocardiography. Increasingly, these imaging modalities are being employed clinically to examine cardiac function and assess wellbeing in utero, thereby guiding timing of birth decisions. Here, we used a rabbit model of IUGR that allows analysis of cardiac function in a clinically relevant way. Using isoflurane induced anesthesia, IUGR is surgically created at gestational age day 25 by performing a laparotomy, exposing the bicornuate uterus and then ligating 40-50% of uteroplacental vessels supplying each gestational sac in a single uterine horn. The other horn in the rabbit bicornuate uterus serves as internal control fetuses. Then, after recovery at gestational age day 30 (full term), the same rabbit undergoes examination of fetal cardiac function.  Anesthesia is induced with ketamine and xylazine intramuscularly, then maintained by a continuous intravenous infusion of ketamine and xylazine to minimize iatrogenic effects on fetal cardiac function. A repeat laparotomy is performed to expose each gestational sac and a microultrasound examination (VisualSonics VEVO 2100) of fetal cardiac function is performed. Placental insufficiency is evident by a raised pulsatility index or an absent or reversed end diastolic flow of the umbilical artery Doppler waveform. The ductus venosus and middle cerebral artery Doppler is then examined. Fetal echocardiography is performed by recording B mode, M mode and flow velocity waveforms in lateral and apical views. Offline calculations determine standard M-mode cardiac variables, tricuspid and mitral annular plane systolic excursion, speckle tracking and strain analysis, modified myocardial performance index and vascular flow velocity waveforms of interest. This small animal model of IUGR therefore affords examination of in utero cardiac function that is consistent with current clinical practice and is therefore useful in a translational research setting.</p>
      </abstract>
      <kwd-group>
        <kwd>intrauterine growth restriction, fetal echocardiography, Doppler ultrasound, fetal hemodynamics.</kwd>
      </kwd-group>
      <counts>
        <fig-count count="0" />
      </counts>
      <custom-meta-group>
        <custom-meta>
          <meta-name>Please indicate the full address at which this article will be filmed.</meta-name>
          <meta-value>UZ Leuven Gasthuisberg campus
Herestraat 49
3000 Leuven
Belgium</meta-value>
        </custom-meta>
        <custom-meta>
          <meta-name>Please indicate whether this article will be standard or open access. For information on the differences, &lt;a href="http://www.jove.com/authors#costs" target="_blank"&gt;click here&lt;/a&gt;</meta-name>
          <meta-value>Standard Access (US$2,400)</meta-value>
        </custom-meta>
        <custom-meta>
          <meta-name>Please include a short abstract below.  The short abstract should be no more than 50 words and will be featured in search results.</meta-name>
          <meta-value>We describe examination of fetal cardiac function with contemporary functional fetal echocardiography and fetoplacental Doppler ultrasound using the VisualSonics VEVO 2100 microultrasound in a surgically induced model of intrauterine fetal growth restriction in a rabbit. </meta-value>
        </custom-meta>
        <custom-meta>
          <meta-name>If the protocol section of this manuscript is longer than 3 pages, are the most important steps highlighted?</meta-name>
          <meta-value>Yes</meta-value>
        </custom-meta>
        <custom-meta>
          <meta-name>If this article is currently under review by another publication, please explain where.</meta-name>
          <meta-value>No</meta-value>
        </custom-meta>
        <custom-meta>
          <meta-name>Black and White Image Count</meta-name>
          <meta-value>0</meta-value>
        </custom-meta>
        <custom-meta>
          <meta-name>Color Image Count</meta-name>
          <meta-value>0</meta-value>
        </custom-meta>
        <custom-meta>
          <meta-name>Acquisitions Editor</meta-name>
          <meta-value>Alexa Meehan</meta-value>
        </custom-meta>
        <custom-meta>
          <meta-name>Assistant who entered lead</meta-name>
          <meta-value>Joni Williams</meta-value>
        </custom-meta>
      </custom-meta-group>
    </article-meta>
  </front>
  <body>
    <fig>
      <label>*Figure</label>
      <graphic xlink:href="Figure 1 creation of IUGR (reduced file size).pdf" xmlns:xlink="http://www.w3.org/1999/xlink" />
    </fig>
    <fig>
      <label>*Figure</label>
      <graphic xlink:href="Figure 2 UA Dopplers.pdf" xmlns:xlink="http://www.w3.org/1999/xlink" />
    </fig>
    <fig>
      <label>*Figure</label>
      <graphic xlink:href="Figure 3 DV MCA Dopplers.pdf" xmlns:xlink="http://www.w3.org/1999/xlink" />
    </fig>
    <fig>
      <label>*Figure</label>
      <graphic xlink:href="Figure 4 M mode.pdf" xmlns:xlink="http://www.w3.org/1999/xlink" />
    </fig>
    <fig>
      <label>*Figure</label>
      <graphic xlink:href="Figure 5 strain.pdf" xmlns:xlink="http://www.w3.org/1999/xlink" />
    </fig>
    <table-wrap>
      <label>*Table of Reagents/ Materials Used</label>
      <graphic xlink:href="JoVE_Materials.xlsx" xmlns:xlink="http://www.w3.org/1999/xlink" />
    </table-wrap>
  </body>
</article>