ABSTRACT The result of birth asphyxia is a huge burden on global health contributing to 1 million neonatal death each year. The current recommendations by the neonatal resuscitation program (NRP) to provide external chest compressions when a newborn’s heart rate remains below 60 beats per minute after providing effective external breaths for 30 seconds. This protocol is based on expert opinion, but not evidence. The objective of this proposal is to determine the heart rate range for starting external chest compression to optimize blood flow to the brain and the heart. Low heart rate at birth in a newborn is normally due to impaired gas exchange, and our preliminary studies show that performing external chest compressions (CC) could be harmful when the heart is still beating. We hypothesize that continuing external breaths for low heart rate (<60 per minute), along with medications like epinephrine and only initiating external cardiac compressions if there is a loss of pulse/heart rate. This approach could improve gas exchange, leading to better cerebral and myocardial perfusion, reducing time to establish a heart rate of ≥ 100 per minute, and decrease brain and heart injury. Our specific aims will help determine the best heart rate cut-off (HR 60-40 or 40-20bpm) for initiating external compressions using both a preterm and term lamb model by evaluating: 1. Gas exchange and blood flows to brain and heart; 2. The loss of intrinsic heart beat when external chest compressions are performed and time taken to achieve the desired heart rate; 3. The role of CC on cerebral and cardiac injury. We can measure coronary blood flow directly which has not been reported before, which will help establish normal and abnormal blood flow to the heart during transition and the influence of performing external chest compressions, which is a novel observation. The proposed research is significant to find out, if the current method of providing neonatal resuscitation, which is not evidence based, could be improved. Using a combination of hemodynamics, biomarkers and imaging techniques, these data could be translated to direct neonatal resuscitation. Use of electrocardiogram in the delivery room to detect heart rate has increased the frequency of providing chest compressions by 3-fold, and may be causing more damage if over used. It is also possible that resuscitation in preterm bradycardia could require different treatment protocols than at term gestation. It is important to understand the risk of brain and cardiac damage involved with the current practice. Focusing on providing external breaths with chest compressions when needed, with the objective to limit cardiac and asphyxia brain injury will have a great impact globally during resuscitation of 1.4 million newborns each year.