## 6 Swine Animal Trials Using the Prototype in Hemorrhagic Shock
### Partial REBOA without VPA  
An exemplary data set measured by the SCISCCO system with the swine undergoing a pREBOA procedure is illustrated in Figure 34. The red curve corresponds to the HbO concentration, the blue curve corresponds to the HbR concentration, and the green curve corresponds to the CCO concentration. The vertical lines and their labels represent key events during the swine experiments, and the data were collected over more than 8 h continuously. The words at each stage in Figure 33 help to describe the behavior observed using the SCISCCO instrument. The measured HbR and HbO concentration changes across different clinical phases were consistent with our expectations based on physiological principles. As hemorrhaging begins, SCISCCO detects that the HbO concentration increases, which indicates increased oxygen supply to brain due to the body's regulation mechanisms in response to hemorrhage, such as tachycardia. Next, we observed that the HbR concentration increased sharply while the HbO concentration dropped abruptly at the same time as when hemorrhaging ensued  
Figure 34: HbO, HbR, and CCO concentration changes during pREBOA-only swine HS test. Figure 33: Expected behavior of CCO, HbO, and HbR in various physiological states. until shortly after the blood loss was halted. This corresponded to oxygen deprivation to the brain, as the rate of hemorrhage outpaced the compensatory mechanisms, termed \"stage 4 shock\". Interestingly, the CCO concentration switched from negatively correlating to positively correlating with HbO before the initially increasing HbO reached the maximum, and this lasted throughout the first hour of REBOA. This could represent the limit of cerebral autoregulation, as the CCO redox state no longer reflected the ability of compensatory regulation to meet the metabolic demands. Instead ATP generation passively followed the oxygen supply as indicated by the tissue HbO concentration. When the REBOA was applied (occlusion was initiated), oxygenated blood was prevented from going to the abdomen and lower extremities, and more oxygenated blood was then shunted to the brain. There was a 10-min period of complete aortic occlusion that was followed by the onset of pREBOA, which was reflected in the increase in HbO at occlusion that then dipped and recovered throughout the intervention phase. During the first 80 min of the REBOA period, we observed oscillation of the animal's blood pressure, and this was captured by the SCISCCO system (e.g., Figure 35b). During this period, the mean arterial pressure (MAP) showed a clear correlation with HbR and negative correlation with HbO and CCO. In the third hour of the pREBOA period, the HbO started to decrease, as the persistent insufficient blood supply led to degenerating body function and an exhaustion of all compensatory mechanisms. The CCO redox state gradually and continuously decreased throughout the REBOA period, indicating the lowered but stable demand of an anesthetized animal and the gradually degenerating blood supply. It is also noteworthy that at the end of the REBOA period, CCO switched back to correlating with HbO concurrent with the administration of blood transfusion, which improved the blood supply and tissue oxygenation. After 3 h of pREBOA, massive transfusion of fresh whole blood was initiated (resuscitation), and the balloon was deflated, which increased flow past the balloon site and circulated distal ischemic metabolites. This initial reperfusion injury is notable with the surge of deoxygenated blood that initially returns upon balloon deflation and then washes out as transfusion restores oxygenated blood. At \(\sim\)30 min after the transfusion ended, the HbO was restored to a relatively high level, and this corresponded to the animal being successfully resuscitated. These findings suggest that the novel SCISCCO instrument detected rapid changes in swine cerebral metabolism that were consistent with the expected physiological principles. What remained unclear was the metabolic demand of the distal tissue beds.