Unmasking the Confounder- Inherent Physiological Variability in Swine During Automated Ischemia-Reperfusion Injury​

Background: Swine are often used in translational research of shock and resuscitation. To fully understand the effects of a given intervention, external variability must be minimized. The purpose of this study was to determine the magnitude of the inherent inter animal variability when external factors are minimized by automating a porcine experimental protocol of shock. 

 Hypothesis: We hypothesize that, as physiologic impact increases, the inherent variability between animals will be uncovered and magnified. 

 Methods: Swine underwent a 30-minute controlled hemorrhage of 30% blood volume, followed by 30 minutes of complete REBOA to create an ischemic insult (ischemic phase). Automated reperfusion (REBOA modulated to maintain target proximal MAP of 65mmHg) occurred over five minutes and shed blood was transfused to produce the ischemia-reperfusion shock state. Physiologic parameters were collected and plasma was stored for later analysis. The variance between time points was analyzed retrospectively using an F-test (p<.001) and differences between gender or weights were measured with a t-test (p<.05). 

 Results: There was no difference in baseline physiology. Proximal blood pressure trends showed that variability within groups increased slightly from baseline to the hemorrhagic phase, followed by a large increase in inter animal variability from the hemorrhagic phase to the ischemic phase and a drastic decrease from the time points after the balloon wean within the reperfusion phase. Variability in distal pressures generated by the automated REBOA catheter increased slightly from baseline to the hemorrhagic phase, followed by a steep decline during the ischemic phase, and a sudden increase and plateau after balloon weaning. 

 Conclusions: Despite leveraging automation to minimal external variability, we noted that the greater the physiologic derangement, the greater the inter-animal hemodynamic variability. Given the significant role of swine in resuscitation research, the increasing inter-animal variability increasing physiologic compromise that we observed warrants further investigation.