**6. Pulseless electrical activity in the porcine model of neonatal hypoxia-asphyxia**

Using our porcine model of neonatal hypoxia-asphyxia, we are able to describe an increasingly important clinical situation in the laboratory setting. Recent studies from our group have identified the presence of PEA rhythms in nearly half of neonatal pigs that were subjected to hypoxia-asphyxia in animal models of neonatal resuscitation [19–21]. In the study by Patel et al., 43% of piglets (23/54) had no CBF or HR on auscultation but had a HR of 15–80 bpm displayed on ECG, indicating PEA rhythm [20]. Luong et al. reported that 49% of piglets (22/45) presented with PEA rhythms, as indicated by no CBF or HR on auscultation but a HR of 17–75 bpm was displayed on ECG [19]. Solevag et al. also reported that 43% of piglets (9/21) presented with PEA rhythm on ECG, as confirmed by zero CBF and no audible HR/ pulse; however, only 56% of piglets with PEA rhythms achieved ROSC compared to 100% of piglets with non-PEA rhythms (p = 0.02) [21]. Furthermore, survival

**173**

*A Porcine Model of Neonatal Hypoxia-Asphyxia to Study Resuscitation Techniques in Newborn…*

to 4-hours post-ROSC occurred in only 33% of PEA piglets versus 58% of non-PEA piglets [21]. These studies indicate that cardiac arrest in the presence of a nonperfusing cardiac rhythm is common in asphyxiated neonatal piglets. Furthermore, this animal data is in agreeance with clinical observations of reduced CPR success in

Studies from other research groups have also reported on the presence of PEA rhythms in their porcine model [22, 23]. It is important to note, however, that these studies were conducted in older piglets (2-month old "infant/pediatric" pigs) and were subjected to asphyxial cardiac arrest without the preceding hypoxia period. In the study by Lopez-Herce et al., 62% of piglets (44/71) had a PEA rhythm at the time of cardiac arrest [23]. However, there was no significant difference in the rate of ROSC between piglets with PEA rhythm (43%; 19/44) and piglets with non-PEA rhythm (30%; 7/23). Another study by the same research group, Gonzalez et al., also reported the presence of PEA rhythm at the time of cardiac arrest: 45% of piglets (22/49) [22]. Interestingly, the rate of ROSC was greater in piglets with PEA rhythm (45%; 10/22) versus non-PEA rhythm piglets (20%; 4/20) (p = 0.037).

The apparent discordance in the rate of ROSC post-PEA event between neonatal piglets [21] and pediatric piglets [22, 23] highlights the need for strong scientific evidence obtained from appropriate neonatal models to further our knowledge of delivery room resuscitation, rather than extrapolating data gained from the pediatric or adult populations. The percentages of PEA in our above-described neonatal model indicate relative consistency and can therefore be generalizable as a methodology. In this neonatal animal model, PEA is confirmed by electrical activity recorded on ECG in combination with no HR/pulse detected by auscultation and pulse oximetry and zero CBF. This animal model is beneficial for research directed at the management of PEA in newborns. Due to the increased awareness of PEA events in newborn infants, it is necessary to further investigate specifically tailored resuscitation techniques or changes in the resuscitation guideline algorithms to improve their survival. This translational model will therefore serve as a valuable tool to bridge the knowledge gap and improve the outcome of newborns that

**7. Advantages and limitations of the porcine model of neonatal** 

hypoxia-asphyxia has provided a platform to extensively investigate neonatal resuscitation. The newborn piglet is equivalent to a human infant at 36–38 weeks of gestational age, and has a comparable size and weight (1.5–2 kg body weight). This allows for relatively easy instrumentation to invasively monitor hemodynamic and physiological measurements, such as blood pressure and blood gases, as well as the ability to monitor the degree of hypoxia-asphyxia and reoxygenation in the recovery phase. The large size of this animal model (compared to smaller rodent models) allows the repeated collection of biological samples (plasma, whole blood) during the experimental period for biochemical assays. The piglet's cerebral metabolic data and many of the body systems, including cerebrovascular and cardiovascular systems, are also comparable to the human counterparts. This allows for better interpretation of the findings and makes it an exceptional animal model to study resuscitation interventions. The porcine model of neonatal hypoxia-asphyxia closely simulates delivery room events, with the gradual onset of severe hypoxia-asphyxia leading to cardiac arrest. Bradycardia or asystole (cardiac arrest) in newborn infants is usually caused by hypoxia/asphyxia, rather than

Owing to its many advantages, the clinically relevant porcine model of neonatal

the presence of PEA in the delivery room in newborn infants [15, 16].

*DOI: http://dx.doi.org/10.5772/intechopen.89171*

experience PEA in the delivery room.

**hypoxia-asphyxia**

#### *A Porcine Model of Neonatal Hypoxia-Asphyxia to Study Resuscitation Techniques in Newborn… DOI: http://dx.doi.org/10.5772/intechopen.89171*

to 4-hours post-ROSC occurred in only 33% of PEA piglets versus 58% of non-PEA piglets [21]. These studies indicate that cardiac arrest in the presence of a nonperfusing cardiac rhythm is common in asphyxiated neonatal piglets. Furthermore, this animal data is in agreeance with clinical observations of reduced CPR success in the presence of PEA in the delivery room in newborn infants [15, 16].

Studies from other research groups have also reported on the presence of PEA rhythms in their porcine model [22, 23]. It is important to note, however, that these studies were conducted in older piglets (2-month old "infant/pediatric" pigs) and were subjected to asphyxial cardiac arrest without the preceding hypoxia period. In the study by Lopez-Herce et al., 62% of piglets (44/71) had a PEA rhythm at the time of cardiac arrest [23]. However, there was no significant difference in the rate of ROSC between piglets with PEA rhythm (43%; 19/44) and piglets with non-PEA rhythm (30%; 7/23). Another study by the same research group, Gonzalez et al., also reported the presence of PEA rhythm at the time of cardiac arrest: 45% of piglets (22/49) [22]. Interestingly, the rate of ROSC was greater in piglets with PEA rhythm (45%; 10/22) versus non-PEA rhythm piglets (20%; 4/20) (p = 0.037).

The apparent discordance in the rate of ROSC post-PEA event between neonatal piglets [21] and pediatric piglets [22, 23] highlights the need for strong scientific evidence obtained from appropriate neonatal models to further our knowledge of delivery room resuscitation, rather than extrapolating data gained from the pediatric or adult populations. The percentages of PEA in our above-described neonatal model indicate relative consistency and can therefore be generalizable as a methodology. In this neonatal animal model, PEA is confirmed by electrical activity recorded on ECG in combination with no HR/pulse detected by auscultation and pulse oximetry and zero CBF. This animal model is beneficial for research directed at the management of PEA in newborns. Due to the increased awareness of PEA events in newborn infants, it is necessary to further investigate specifically tailored resuscitation techniques or changes in the resuscitation guideline algorithms to improve their survival. This translational model will therefore serve as a valuable tool to bridge the knowledge gap and improve the outcome of newborns that experience PEA in the delivery room.
