Name: the perinatal asphyxiated lamb model: a model for newborn resuscitation
Uploaded: 2018-08-15T12:30:00
Description: Watch this Scientific Journal Video about The Perinatal Asphyxiated Lamb Model: A Model for Newborn Resuscitation at JoVE.com

All protocols have been approved by the Institutional Animal Care and Use Committee (IACUC) by the State University of New York Buffalo. An illustration of the methodology depicting invasive and non-invasive monitoring is shown in Figure 1.
1. Animals
<ol>
	<li>Use time-dated, Q-fever seronegative, pregnant ewes (mixed-breed, Suffolk-Dorset-Katahdin breed) with fetal lambs at 127&#8211;143 days gestation. 
	NOTE: Sheep term gestation is 145 days and 127 ges...

<ol>
	<li>Wyckoff, M. H., Berg, R. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Optimizing+chest+compressions+during+delivery-room+resuscitation.">Optimizing chest compressions during delivery-room resuscitation.</a> Semin Fetal Neonatal Med. 13 (6), 410-415 (2008).</li><li>Black, R. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Global,+regional,+and+national+causes+of+child+mortality+in+2008:+a+systematic+analysis.">Global, regional, and national causes of child mortality in 2008: a systematic analysis.</a> Lancet. 375 (9730), 1969-1987 (2010).</li><li>Guglani, L., Lakshminrusimha, S., Ryan, R. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transient+tachypnea+of+the+newborn.">Transient tachypnea of the newborn.</a> Pediatr Rev. 29 (11), e59-e65 (2008).</li><li>Brown, M. J., Olver, R. E., Ramsden, C. A., Strang, L. B., Walters, D. V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+adrenaline+and+of+spontaneous+labour+on+the+secretion+and+absorption+of+lung+liquid+in+the+fetal+lamb.">Effects of adrenaline and of spontaneous labour on the secretion and absorption of lung liquid in the fetal lamb.</a> J Physiol. 344, 137-152 (1983).</li><li>Lakshminrusimha, S., Saugstad, O. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+fetal+circulation,+pathophysiology+of+hypoxemic+respiratory+failure+and+pulmonary+hypertension+in+neonates,+and+the+role+of+oxygen+therapy.">The fetal circulation, pathophysiology of hypoxemic respiratory failure and pulmonary hypertension in neonates, and the role of oxygen therapy.</a> J Perinatol. 36 Suppl 2, S3-S11 (2016).</li><li>Wyckoff, M. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Part+13:+Neonatal+Resuscitation:+2015+American+Heart+Association+Guidelines+Update+for+Cardiopulmonary+Resuscitation+and+Emergency+Cardiovascular+Care.">Part 13: Neonatal Resuscitation: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.</a> Circulation. 132 (18 suppl 2), S543-S560 (2015).</li><li>Bhatt, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Delaying+cord+clamping+until+ventilation+onset+improves+cardiovascular+function+at+birth+in+preterm+lambs.">Delaying cord clamping until ventilation onset improves cardiovascular function at birth in preterm lambs.</a> J Physiol. 591 (Pt 8), 2113-2126 (2013).</li><li>Katheria, A. C., Brown, M. K., Rich, W., Arnell, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Providing+a+Placental+Transfusion+in+Newborns+Who+Need+Resuscitation).">Providing a Placental Transfusion in Newborns Who Need Resuscitation).</a> Front Pediatr. 5 (1), (2017).</li><li>Kapadia, V. S., Wyckoff, M. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Drugs+during+delivery+room+resuscitation--what,+when+and+why?.">Drugs during delivery room resuscitation--what, when and why?.</a> Semin Fetal Neonatal Med. 18 (6), 357-361 (2013).</li><li>Barcroft, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Researches on Pre-natal Life. 1, 292 (1946).</li><li>Dawes, G. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Foetal and Neonatal Physiosolgy. A Comparative Study of the Changes at Birth. , (1968).</li><li>Rudolph, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Congenital Diseases of the Heart: Clinical-Physiological Considerations. , 1-24 (2009).</li><li>Sobotka, K. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+initial+sustained+inflation+improves+the+respiratory+and+cardiovascular+transition+at+birth+in+preterm+lambs.">An initial sustained inflation improves the respiratory and cardiovascular transition at birth in preterm lambs.</a> Pediatr Res. 70 (1), 56-60 (2011).</li><li>Polglase, G. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Positive+end-expiratory+pressure+differentially+alters+pulmonary+hemodynamics+and+oxygenation+in+ventilated,+very+premature+lambs.">Positive end-expiratory pressure differentially alters pulmonary hemodynamics and oxygenation in ventilated, very premature lambs.</a> J Appl Physiol (1985). 99 (4), 1453-1461 (2005).</li><li>Lakshminrusimha, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Oxygen+concentration+and+pulmonary+hemodynamics+in+newborn+lambs+with+pulmonary+hypertension.">Oxygen concentration and pulmonary hemodynamics in newborn lambs with pulmonary hypertension.</a> Pediatr Res. 66 (5), 539-544 (2009).</li><li>Lakshminrusimha, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pulmonary+hemodynamics+in+neonatal+lambs+resuscitated+with+21%,+50%+and+100%+oxygen.">Pulmonary hemodynamics in neonatal lambs resuscitated with 21%, 50% and 100% oxygen.</a> Pediatr Res. 62 (3), 313-318 (2007).</li><li>Hooper, S. B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cardiovascular+transition+at+birth:+a+physiological+sequence.">Cardiovascular transition at birth: a physiological sequence.</a> Pediatr Res. 77 (5), 608-614 (2015).</li><li>Vali, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Evaluation+of+Timing+and+Route+of+Epinephrine+in+a+Neonatal+Model+of+Asphyxial+Arrest.">Evaluation of Timing and Route of Epinephrine in a Neonatal Model of Asphyxial Arrest.</a> J Am Heart Assoc. 6 (2), (2017).</li><li>Vali, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Continuous+Chest+Compressions+During+Sustained+Inflations+in+a+Perinatal+Asphyxial+Cardiac+Arrest+Lamb+Model.">Continuous Chest Compressions During Sustained Inflations in a Perinatal Asphyxial Cardiac Arrest Lamb Model.</a> Pediatr Crit Care Med. , (2017).</li><li>Vali, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hemodynamics+and+gas+exchange+during+chest+compressions+in+neonatal+resuscitation.">Hemodynamics and gas exchange during chest compressions in neonatal resuscitation.</a> PLoS One. 12 (4), e0176478 (2017).</li><li>Tana, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Determination+of+Lung+Volume+and+Hemodynamic+Changes+During+High-Frequency+Ventilation+Recruitment+in+Preterm+Neonates+With+Respiratory+Distress+Syndrome.">Determination of Lung Volume and Hemodynamic Changes During High-Frequency Ventilation Recruitment in Preterm Neonates With Respiratory Distress Syndrome.</a> Crit Care Med. 43 (8), 1685-1691 (2015).</li><li>Morin, F. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ligating+the+ductus+arteriosus+before+birth+causes+persistent+pulmonary+hypertension+in+the+newborn+lamb.">Ligating the ductus arteriosus before birth causes persistent pulmonary hypertension in the newborn lamb.</a> Pediatr Res. 25 (3), 245-250 (1989).</li><li>Morin, F. C., Egan, E. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pulmonary+hemodynamics+in+fetal+lambs+during+development+at+normal+and+increased+oxygen+tension.">Pulmonary hemodynamics in fetal lambs during development at normal and increased oxygen tension.</a> J Appl Physiol (1985). 73 (1), 213-218 (1992).</li><li>Morin, F. C., Egan, E. A., Ferguson, W., Lundgren, C. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Development+of+pulmonary+vascular+response+to+oxygen.">Development of pulmonary vascular response to oxygen.</a> Am J Physiol. 254 (3 Pt 2), H542-H546 (1988).</li><li>Rawat, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neonatal+resuscitation+adhering+to+oxygen+saturation+guidelines+in+asphyxiated+lambs+with+meconium+aspiration.">Neonatal resuscitation adhering to oxygen saturation guidelines in asphyxiated lambs with meconium aspiration.</a> Pediatr Res. , (2015).</li><li>Chandrasekharan, P. K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Continuous+End-Tidal+Carbon+Dioxide+Monitoring+during+Resuscitation+of+Asphyxiated+Term+Lambs.">Continuous End-Tidal Carbon Dioxide Monitoring during Resuscitation of Asphyxiated Term Lambs.</a> Neonatology. 109 (4), 265-273 (2016).</li><li>Lakshminrusimha, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tracheal+suctioning+improves+gas+exchange+but+not+hemodynamics+in+asphyxiated+lambs+with+meconium+aspiration.">Tracheal suctioning improves gas exchange but not hemodynamics in asphyxiated lambs with meconium aspiration.</a> Pediatr Res. 77 (2), 347-355 (2015).</li><li>Meuli, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+utero+surgery+rescues+neurological+function+at+birth+in+sheep+with+spina+bifida.">In utero surgery rescues neurological function at birth in sheep with spina bifida.</a> Nat Med. 1 (4), 342-347 (1995).</li><li>Meuli, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Creation+of+myelomeningocele+in+utero:+a+model+of+functional+damage+from+spinal+cord+exposure+in+fetal+sheep.">Creation of myelomeningocele in utero: a model of functional damage from spinal cord exposure in fetal sheep.</a> J Pediatr Surg. 30 (7), 1028-1032 (1995).</li><li>Adzick, N. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Correction+of+congenital+diaphragmatic+hernia+in+utero.+IV.+An+early+gestational+fetal+lamb+model+for+pulmonary+vascular+morphometric+analysis.">Correction of congenital diaphragmatic hernia in utero. IV. An early gestational fetal lamb model for pulmonary vascular morphometric analysis.</a> J Pediatr Surg. 20 (6), 673-680 (1985).</li><li>Harrison, M. R., Bressack, M. A., Churg, A. M., de Lorimier, A. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Correction+of+congenital+diaphragmatic+hernia+in+utero.+II.+Simulated+correction+permits+fetal+lung+growth+with+survival+at+birth.">Correction of congenital diaphragmatic hernia in utero. II. Simulated correction permits fetal lung growth with survival at birth.</a> Surgery. 88 (2), 260-268 (1980).</li><li>Turley, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intrauterine+cardiothoracic+surgery:+the+fetal+lamb+model.">Intrauterine cardiothoracic surgery: the fetal lamb model.</a> Ann Thorac Surg. 34 (4), 422-426 (1982).</li><li>Reddy, V. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+utero+placement+of+aortopulmonary+shunts.+A+model+of+postnatal+pulmonary+hypertension+with+increased+pulmonary+blood+flow+in+lambs.">In utero placement of aortopulmonary shunts. A model of postnatal pulmonary hypertension with increased pulmonary blood flow in lambs.</a> Circulation. 92 (3), 606-613 (1995).</li><li>Hemway, R. J., Christman, C., Perlman, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+3:1+is+superior+to+a+15:2+ratio+in+a+newborn+manikin+model+in+terms+of+quality+of+chest+compressions+and+number+of+ventilations.">The 3:1 is superior to a 15:2 ratio in a newborn manikin model in terms of quality of chest compressions and number of ventilations.</a> Arch Dis Child Fetal Neonatal Ed. 98 (1), F42-F45 (2013).</li><li>Solev&#229;g, A. L., Schm&#246;lzer, G. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Optimal+Chest+Compression+Rate+and+Compression+to+Ventilation+Ratio+in+Delivery+Room+Resuscitation:+Evidence+from+Newborn+Piglets+and+Neonatal+Manikins.">Optimal Chest Compression Rate and Compression to Ventilation Ratio in Delivery Room Resuscitation: Evidence from Newborn Piglets and Neonatal Manikins.</a> Frontiers in Pediatrics. 5 (3), (2017).</li><li>Solev&#229;g, A. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chest+compressions+in+newborn+animal+models:+A+review.">Chest compressions in newborn animal models: A review.</a> Resuscitation. 96, 151-155 (2015).</li></ol>

The lamb model is comparable in size to human newborns and allows easy instrumentation to measure invasive hemodynamic variables. The fetal/newborn lamb model has been an invaluable research tool that has richly contributed to understanding the transitioning circulation, as well as the newborn&#39;s pulmonary and cardiovascular physiology. Several experimental lamb models have been established over the years to study optimal ventilation strategies in preterm lambs13,14...

Perinatal asphyxia occurs in roughly 4 per 1,000 term births in the United States and is responsible for approximately 25% of the 4 million neonatal deaths worldwide1,2. Throughout the fetus&#39;s natural development, several adaptations must take place during labor and at birth to allow for a seamless transition from the intra- to the extrauterine environment when the lungs take on the role of the placenta as the organ of gas exchange. Any failure of the newborn to adequately transition at birth further compromises resuscitative efforts. Instances when fetal lung clearance is incomplete or delayed3,4, and circumstances that result in a persistent high pulmonary vascular resistance (PVR)5 impact the efficacy of ventilation, which remains the most important intervention in the resuscitation of the asphyxiated newborn6. In addition, immediate clamping of the umbilical cord and removal of the low-resistance placenta can lead to abrupt changes in cardiac output that may cause myocardial dysfunction7,8.
Owing to the infrequent need for aggressive resuscitation (need for chest compressions and/or epinephrine administration)1,9, there is a lack of strong evidence from large randomized clinical trials to support the current neonatal resuscitation program (NRP) guidelines. Many translational research studies in neonatal resuscitation are conducted using postnatal animal models (particularly piglets) that fail to adequately depict the transitioning fetal circulation and fluid-filled lungs inherent to the newborn in the delivery room. Given the unique challenges related to transition from fetal circulation to neonatal circulation, the perinatal asphyxiated cardiac arrest fetal lamb model is ideal to study newborn resuscitative physiology.
The studies by Joseph Barcroft on fetal lambs, as early as the 1930&#39;s, laid the foundation for fetal and neonatal physiology10. In the second half of the 20th century, Geoffrey Dawes&#39; innovative and meticulous experiments on fetal lamb models, and later those by Abraham Rudolph have tremendously contributed to the knowledge of cardiovascular and pulmonary physiology in the fetus11,12. In recent years, studies on fetal/neonatal lamb models have provided a better understanding of the impact of ventilation on hemodynamics13,14, the effects of oxygenation on PVR15,16, as well as the circulatory changes that occur during cord clamping7,17. Finally, in the past year, the newborn lamb has served as a novel model to study the hemodynamic effects during resuscitation18,19,20. A step-by-step narrative of what is involved in conducting a lamb experiment, as well as a detailed description of the surgical instrumentations and the experimental methodology will be presented.

<table border="0" cellpadding="0" cellspacing="0" width="819">
	<tbody>
		<tr height="20">
			<td height="20" style="height:20px;">Babcock forceps</td>
			<td>Miltex</td>
			<td>16-44</td>
			<td style="width:200px;"></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:216px;">Blood pressure transducer</td>
			<td style="width:192px;">Becton Dickinson</td>
			<td style="width:211px;">P23XL-1</td>
			<td style="width:200px;">Used with saline filled diaphragm domes</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Blunt tipped scissors</td>
			<td style="width:192px;">Miltex</td>
			<td style="width:211px;">98SCS50-56</td>
			<td style="width:200px;"></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:216px;">Capnograph</td>
			<td style="width:192px;">Philips</td>
			<td style="width:211px;">7900</td>
			<td style="width:200px;">Used with Neonatal Flow Sensors</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Cautery pencil</td>
			<td style="width:192px;">Valley Lab</td>
			<td style="width:211px;">287879</td>
			<td style="width:200px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Cautery unit</td>
			<td style="width:192px;">Valley Lab</td>
			<td style="width:211px;">SSE2K</td>
			<td style="width:200px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Curved Forceps</td>
			<td style="width:192px;">Everost</td>
			<td style="width:211px;">711714</td>
			<td style="width:200px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Data acquisition software</td>
			<td style="width:192px;">Biopac Systems Inc.</td>
			<td style="width:211px;">ACK100W</td>
			<td style="width:200px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">EKG</td>
			<td style="width:192px;">Biopac Systems Inc.</td>
			<td style="width:211px;">ECG100C</td>
			<td style="width:200px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Endotracheal tube -cuffed</td>
			<td style="width:192px;">Rusch</td>
			<td style="width:211px;">111780035</td>
			<td style="width:200px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Flow modulator</td>
			<td style="width:192px;">Transonic Systems Inc.&#160;</td>
			<td style="width:211px;">T403</td>
			<td style="width:200px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Flow-probe</td>
			<td style="width:192px;">Transonic Systems Inc.&#160;</td>
			<td style="width:211px;">MC4PSS-LS-WC100-CM4B-GA</td>
			<td style="width:200px;"></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Gastric tube</td>
			<td style="width:192px;">Jorgensen Labs Inc.</td>
			<td style="width:211px;">J0106LE</td>
			<td style="width:200px;">To decompress and drain ewe stomach</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Hair clipper</td>
			<td style="width:192px;">Andis Company</td>
			<td style="width:211px;">65340</td>
			<td style="width:200px;">&#160;# 40 Clipper Blade</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Infant radiant warmer</td>
			<td>GE healthcare</td>
			<td>7810</td>
			<td style="width:200px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Intravenous catheters</td>
			<td>Becton Dickinson</td>
			<td>381234</td>
			<td style="width:200px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Iris surgical scissors</td>
			<td style="width:192px;">Patterson</td>
			<td style="width:211px;">510585</td>
			<td style="width:200px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Kelly Foreceps</td>
			<td style="width:192px;">Patterson</td>
			<td style="width:211px;">510535</td>
			<td style="width:200px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Mosquito Forceps</td>
			<td style="width:192px;">RICA Surgical Products INC</td>
			<td style="width:211px;">1-74</td>
			<td style="width:200px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Near-infrared spectroscopy</td>
			<td style="width:192px;">Nonin Medical Inc.&#160;</td>
			<td style="width:211px;">X-100M</td>
			<td style="width:200px;">Sensmart Equanox &#38; PureSAT</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">RSO2 Sensor</td>
			<td style="width:192px;">Nonin Medical Inc.&#160;</td>
			<td style="width:211px;">8004CB-NA</td>
			<td style="width:200px;">Neonatal&#160;</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Scalpel handle and blade</td>
			<td style="width:192px;">Everost</td>
			<td>707203</td>
			<td style="width:200px;"></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Sutures -silk 2-0</td>
			<td style="width:192px;">Covidien</td>
			<td style="width:211px;">SS-695</td>
			<td style="width:200px;">Used for tying catheters to vessels</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Sutures -vicryl&#160; 2-0</td>
			<td style="width:192px;">Ethicon</td>
			<td style="width:211px;">J269H</td>
			<td style="width:200px;">Used for closing thoracotomy&#160;</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">T-piece resuscitator</td>
			<td>Neo-Tee</td>
			<td>MCM1050812</td>
			<td style="width:200px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Umbilical ties</td>
			<td style="width:192px;">Jorgensen Labs Inc.</td>
			<td>J0025UA</td>
			<td style="width:200px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Weitlander Retractor</td>
			<td style="width:192px;">Miltex</td>
			<td style="width:211px;">11-625</td>
			<td style="width:200px;"></td>
		</tr>
	</tbody>
</table>

the perinatal asphyxiated lamb model: a model for newborn resuscitation

Birth asphyxia accounts for nearly one million deaths worldwide each year, and is one of the primary causes of early neonatal morbidity and mortality. Many aspects of the current neonatal resuscitation guidelines remain controversial given the difficulties in conducting randomized clinical trials owing to the infrequent and often unpredictable need for extensive resuscitation. Most studies on neonatal resuscitation stem from manikin models that fail to truly reflect physiologic changes or piglet models that have cleared their lung fluid and that have completed the transition from fetal to neonatal circulation. The present protocol provides a detailed step-by-step description on how to create a perinatal asphyxiated fetal lamb model. The proposed model has a transitioning circulation and fluid-filled lungs, which mimics human newborns following delivery, and is, therefore, an excellent animal model to study newborn physiology. An important limitation to lamb experiments is the higher associated cost.

Following instrumentation of the fetal lambs, hemodynamic variables can be recorded (Figure 3 and Figure 4), then analyzed and interpreted (Figure 5). Frequent blood samples can be collected, and Figure 6 shows the pH and PaCO2 data from one of the experiments. Occasionally, catheters or flow probes may malfunction or get dislodged and data can, therefore, not...

Watch this Scientific Journal Video about The Perinatal Asphyxiated Lamb Model: A Model for Newborn Resuscitation at JoVE.com

The Perinatal Asphyxiated Lamb Model: A Model for Newborn Resuscitation

Invasive instrumentation of the fetal lamb provides accurate physiologic measurements of the transitioning circulation in a model that closely mimics the newly born infant.

Birth asphyxia accounts for nearly one million deaths worldwide each year, and is one of the primary causes of early neonatal morbidity and mortality. ...

This model can help answer key questions in the field of neonatal resuscitation and birth asphyxia. The main advantage of this model is that we can accurately study the physiological changes during fetal to neonatal transition with our known instrumentation. The implications of this technique extend towards the therapy of birth asphyxia as well as hypoxic ischemic encephalopathy.Researchers new to this method may struggle because there are many steps designed specifically for this species and our intended instrumentational goal. Visual demonstration of this method is critical as particular care is needed for the placement of the pulmonary and ductal flow probes during the open-chest procedure. To perform the Caesarian section, use cautery to make a 15 to 18-centimeter abdominal skin incision over the linea alba of an anesthetized pregnant ewe to expose the fascia and use blunt-tipped scissors to create and extend the incision.After locating and exteriorizing the fetal head, hold the head with one hand and use the cautery to make a 10-centimeter incision through the uterine wall over the animal's forehead. Use a 3 1/2 to 4 1/2-millimeter cuffed endotracheal tube to intubate the partially exposed animal and inflate the cuff, then tilt the head to the side to allow the excess fetal lung fluid to drain passively and occlude the endotracheal tube to limit spontaneous breathing. For neck vessel instrumentation, tent the skin and administer subcutaneous analgesia on each side of the neck of the fetal animal approximately six centimeters distal to the head adjacent to the trachea and make a single, three-centimeter skin incision on each side of the neck by cautery.Isolate the right external jugular vein and right common carotid artery by blunt dissection of the fascia and place two 20-centimeter zero silk sutures one centimeter apart under both vessels. Gently lift each suture to restrict the blood flow and use Iris surgical scissors to make a partial one to two-millimeter transverse cut into the vessel between the sutures. Insert one 15 or 17 gauge catheter into the right carotid artery caudally toward the aortic arch for blood pressure monitoring and blood sampling.Insert a 14 or 16 gauge pre-flushed catheter seven to 10 centimeters caudally within the jugular vein towards the right atrium for fluid and medication administration. Then, insert a second catheter approximately five centimeters rostrally to collect blood from the cerebral circulation. Next, extend the left incision one to two centimeters into a T shape.Isolate the carotid artery and place a two-millimeter perivascular flow probe around the vessel to measure the blood flow. Stabilize the probe with a flexible, one-centimeter polymer sleeve and place the flow probe cable line into the T-shaped incision so that the cable runs parallel with the vessel. Then close the skin incision, tying the cable with a loop to ensure appropriate position and minimal risk of displacement.For great vessel instrumentation, extend the left forelimb behind the neck to extract the fetal lamb, fully exposing the left side of the chest and cover the animal with polyethylene wrap to prevent heat loss. Subcutaneously infiltrate three milliliters of analgesia along the fourth intercostal space and use cautery to make a six-centimeter skin incision into the same region. Use blunt, curved forceps to carefully pierce the intercostal muscle, circling the tips under the third rib and coming out between the next intercostal space.Open the forceps to grasp a piece of zero silk and pull the suture back through the incision to encircle the rib, then clamp the ties around the rib. Next, gently pull up both silk ties and insert a cotton-tipped applicator into the chest under the fourth intercostal space to protect the chest contents while using cautery and blunt dissection to extend the intercostal space to six to eight centimeters. Place a rib spreader into the chest opening to reveal the left upper lobes of the lung and of the heart covered by the pericardium.Envelop the lung with a two-by-two inch gauze and gently push any exposed tissue away from the surgical area. Using forceps, lift the pericardium and cut along the main pulmonary artery, taking care not to cut the vagal nerve. Use an applicator stick to keep the right atrium from interfering with the lateral cut of the pericardium along the vagal nerve.Now that the pericardium is open, it reveals the main pulmonary artery, which splits into the ductus arteriosus and the left and right branches of the pulmonary artery. Effective transition at birth is evaluated by study of the change in flow as blood passes into the lung rather than continuing fetal circulation through the ductus. Locate the ductal pulmonary artery notch and move Gemini forceps carefully around and behind the left pulmonary artery to encircle the artery carefully, avoiding the right pulmonary artery notch and advancing the forceps only when there is no resistance.When the tip of the forceps is observed on the other side of the vessel, open the tips just far enough to grab one end of a pre-moistened piece of umbilical tape and gently retract the forceps to pull the tape into position. Ties are placed around vessels in preparation for a flow probe insertion. Gently lift the umbilical tape to allow the L-bracket of a four to eight-millimeter perivascular flow probe to be guided around each vessel along the opening established by the tape and redirect the tape toward the back of the probe to help move the flow probe into place.When the end of the L-bracket is visible, secure the sliding closure and carefully cut one end of the umbilical tape close to the probe, gently pulling the other end of the tape to remove it from the vessel. Instrumentation complete, measurement of these flows following birth gives insight to lung function and effective transition to air breathing. Use a tapered needle and a 2-0 synthetic monofilament suture to close the chest in layers and a cutting needle and 2-0 silk suture to secure the cables of the flow probes to the outer skin with a loop.To initiate the experimental protocol, check that the endotracheal tube is occluded and tie and cut the umbilical cord. Move the lamb to a radiant warmer and insert umbilical venous and arterial catheters. After asphyxial arrest, initiate the neonatal resuscitation program guidelines with 30 seconds of ventilation followed by three-to-one chest compressions and epinephrine administration every three minutes.Following instrumentation, hemodynamic variables can be recorded, analyzed, and interpreted. Frequent blood samples can be collected to allow, for example, the assessment of the pH and the partial pressure of oxygen of the samples at different time points throughout the resuscitation procedure. Occasionally the catheters or flow probes may malfunction or get dislodged, preventing data collection and analysis.Once mastered, instrumentation can be completed in two hours. It's also important to work with a trained team with assigned roles to ensure that all tasks are completed consistently. The animal in this model has a transitioning circulation and fluid-filled lungs simulating human newborns following delivery and is therefore an excellent model for studying newborn physiology.This perinatal lamb model resembles a depressed newborn baby in the delivery room. Studies on this model will optimize resuscitation of asphyxiated neonates worldwide.

Research

JoVE Journal

Medicine

Normothermic Cardiac Arrest and Cardiopulmonary Resuscitation: A Mouse Model of Ischemia-Reperfusion Injury

Acute Kidney Injury (AKI) is a common, highly lethal, complication of critical illness which has a high mortality1-4 and which is most 
frequently caused ...

A Rat Model of Ventricular Fibrillation and Resuscitation by Conventional Closed-chest Technique

A rat model of electrically-induced ventricular fibrillation followed by cardiac resuscitation using a closed chest technique that incorporates the basic ...

A Piglet Model of Neonatal Hypoxic-Ischemic Encephalopathy

Birth asphyxia, which causes hypoxic-ischemic encephalopathy (HIE), accounts for 0.66 million deaths worldwide each year, about a quarter of the ...

Breast Milk Enhances Growth of Enteroids: An Ex Vivo Model of Cell Proliferation

Breast Milk Enhances Growth of Enteroids: An Ex Vivo Model of Cell Proliferation

Human small intestinal enteroids are derived from the crypts and when grown in a stem cell niche contain all of the epithelial cell types. The ability to ...

Isometric Contractility Measurement of the Mouse Mesenteric Artery Using Wire Myography

The wire myograph technique is used to assess the contractility of vascular smooth muscles in response to depolarization, GPCR agonists/inhibitors and ...

The Lower Body Positive Pressure Treadmill for Knee Osteoarthritis Rehabilitation

Here, based on a clinician&rsquo;s point-of-view, we propose a two-model lower body positive pressure (LBPP) protocol (walking and squatting models) in ...

Noninvasive Electrocardiography in the Perinatal Mouse

Electrocardiography (ECG) has long been relied upon as an effective and reliable method of assessing cardiovascular (and cardiopulmonary) function in both ...

A Murine Model of Fetal Exposure to Maternal Inflammation to Study the Effects of Acute Chorioamnionitis on Newborn Intestinal Development

Chorioamnionitis is a common precipitant of preterm birth and is associated with many of the morbidities of prematurity, including necrotizing ...

Effect of Hyaluronic Acid 35 kDa on an In Vitro Model of Preterm Small Intestinal Injury and Healing Using Enteroid-Derived Monolayers

Effect of Hyaluronic Acid 35 kDa on an In Vitro Model of Preterm Small Intestinal Injury and Healing Using Enteroid-Derived Monolayers

In vitro scratch wound assays are commonly used to investigate the mechanisms and characteristics of epithelial healing in a variety of tissue types. ...

In Vitro Apical-Out Enteroid Model of Necrotizing Enterocolitis

In Vitro Apical-Out Enteroid Model of Necrotizing Enterocolitis

Necrotizing enterocolitis (NEC) is a devastating disease affecting preterm infants, characterized by intestinal inflammation and necrosis. Enteroids have ...