The Perinatal Asphyxiated Lamb Model: A Model for Newborn Resuscitation

Summary

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

Abstract

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.

Introduction

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 worldwide^1,2. Throughout the fetus'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 delayed

Protocol

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

1. Use time-dated, Q-fever seronegative, pregnant ewes (mixed-breed, Suffolk-Dorset-Katahdin breed) with fetal lambs at 127–143 days gestation.
   NOTE: Sheep term gestation is 145 days and 127 gestation lambs behave like extreme premature infants.

2. Pre-surgical Preparation

1. Withhold food from the ....

Results

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.......

Discussion

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's pulmonary and cardiovascular physiology. Several experimental lamb models have been established over the years to study optimal ventilation strategies in preterm lambs^13,14.......

Materials

List of materials used in this article

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