A Swine Model of Neonatal Asphyxia

Annually more than 1 million neonates die worldwide as related to asphyxia. Asphyxiated neonates commonly have multi-organ failure including hypotension, perfusion deficit, hypoxic-ischemic encephalopathy, pulmonary hypertension, vasculopathic enterocolitis, renal failure and thrombo-embolic complications. Animal models are developed to help us understand the patho-physiology and pharmacology of neonatal asphyxia. In comparison to rodents and newborn lambs, the newborn piglet has been proven to be a valuable model. The newborn piglet has several advantages including similar development as that of 36-38 weeks human fetus with comparable body systems, large body size (˜1.5-2 kg at birth) that allows the instrumentation and monitoring of the animal and controls the confounding variables of hypoxia and hemodynamic derangements.We here describe an experimental protocol to simulate neonatal asphyxia and allow us to examine the systemic and regional hemodynamic changes during the asphyxiating and reoxygenation process as well as the respective effects of interventions. Further, the model has the advantage of studying multi-organ failure or dysfunction simultaneously and the interaction with various body systems. The experimental model is a non-survival procedure that involves the surgical instrumentation of newborn piglets (1-3 day-old and 1.5-2.5 kg weight, mixed breed) to allow the establishment of mechanical ventilation, vascular (arterial and central venous) access and the placement of catheters and flow probes (Transonic Inc.) for the continuously monitoring of intra-vascular pressure and blood flow across different arteries including main pulmonary, common carotid, superior mesenteric and left renal arteries. Using these surgically instrumented piglets, after stabilization for 30-60 minutes as defined by Z<10% variation in hemodynamic parameters and normal blood gases, we commence an experimental protocol of severe hypoxemia which is induced via normocapnic alveolar hypoxia. The piglet is ventilated with 10-15% oxygen by increasing the inhaled concentration of nitrogen gas for 2h, aiming for arterial oxygen saturations of 30-40%. This degree of hypoxemia will produce clinical asphyxia with severe metabolic acidosis, systemic hypotension and cardiogenic shock with hypoperfusion to vital organs. The hypoxia is followed by reoxygenation with 100% oxygen for 0.5h and then 21% oxygen for 3.5h. Pharmacologic interventions can be introduced in due course and their effects investigated in a blinded, block-randomized fashion.Download video file.^{(66M, mov)}     

Exhaled CO2 Parameters as a Tool to Assess Ventilation-Perfusion Mismatching during Neonatal Resuscitation in a Swine Model of Neonatal Asphyxia

Background

End-tidal CO₂ (ETCO₂), partial pressure of exhaled CO₂ (PECO₂), and volume of expired CO₂ (VCO₂) can be continuously monitored non-invasively to reflect pulmonary ventilation and perfusion status. Although ETCO₂ ≥14mmHg has been shown to be associated with return of an adequate heart rate in neonatal resuscitation and quantifying the PECO₂ has the potential to serve as an indicator of resuscitation quality, there is little information regarding capnometric measurement of PECO₂ and ETCO₂ in detecting return of spontaneous circulation (ROSC) and survivability in asphyxiated neonates receiving cardiopulmonary resuscitation (CPR).

Methods

Seventeen newborn piglets were anesthetized, intubated, instrumented, and exposed to 45-minute normocapnic hypoxia followed by apnea to induce asphyxia. Protocolized resuscitation was initiated when heart rate decreased to 25% of baseline. Respiratory and hemodynamic parameters including ETCO₂, PECO₂, VCO₂, heart rate, cardiac output, and carotid artery flow were continuously measured and analyzed.

Results

There were no differences in respiratory and hemodynamic parameters between surviving and non-surviving piglets prior to CPR. Surviving piglets had significantly higher ETCO₂, PECO₂, VCO₂, cardiac index, and carotid artery flow values during CPR compared to non-surviving piglets.

Conclusion

Surviving piglets had significantly better respiratory and hemodynamic parameters during resuscitation compared to non-surviving piglets. In addition to optimizing resuscitation efforts, capnometry can assist by predicting outcomes of newborns requiring chest compressions.     

血清CyPA、sCLU、HO-1与新生儿窒息复苏后发生脑损伤的关系研究

摘要 目的：探讨血清亲环素A（CyPA）、丛生蛋白（sCLU）、血红素氧化酶-1（HO-1）与新生儿窒息复苏后发生脑损伤的关系。方法：选择2020年6月至2023年3月湖北民族大学附属民大医院收治的172例窒息新生儿,根据复苏后是否发生脑损伤分为脑损伤组（80例）和无脑损伤组（92例）,复苏治疗前检测并对比两组血清CyPA、sCLU、HO-1水平。多因素Logistic回归分析新生儿窒息复苏后发生脑损伤的影响因素,受试者工作特征（ROC）曲线分析血清CyPA、sCLU、HO-1预测新生儿窒息复苏后发生脑损伤的价值。结果：脑损伤组血清CyPA、sCLU、HO-1水平高于无脑损伤组（P＜0.05）。胎盘早剥、母体妊娠高血压疾病、重度窒息、高水平CyPA、高水平sCLU、高水平HO-1是新生儿窒息复苏后发生脑损伤的危险因素（P＜0.05）。血清CyPA、sCLU、HO-1预测新生儿窒息复苏后发生脑损伤的曲线下面积为0.797、0.832、0.779,联合预测的曲线下面积为0.941,高于各指标单独预测。结论：新生儿窒息复苏后发生脑损伤的危险因素包括胎盘早剥、母体妊娠高血压疾病、重度窒息、CyPA升高、sCLU升高、HO-1升高,联合检测血清CyPA、sCLU和HO-1对新生儿窒息复苏后发生脑损伤具有较高的预测价值。