All right. Hello, everybody. I'm thankful to be able to share a little bit of this exciting research with you today. First, a little bit of background. So, what is REBOA? REBOA stands for Resuscitative Endovascular Balloon Occlusion of the Aorta, and it's a life-saving tool used to treat non-compressible torso hemorrhages. So, non-compressible torso hemorrhages include anything from gunshot wounds, stab wounds, acute traumas to the abdomen, and even gynecologic emergencies like traumatic births. So, this is particularly useful in areas that are far from acute trauma centers. So, really rural areas or even on the battlefield. The way it works is a balloon catheter is fed up the femoral artery into the abdominal aorta. And with the occlusion of the aorta, it augments blood flow to vital organs. So, the blood flow is preserved for the heart and the brain, and it mitigates any further blood loss. Can we go, is it just going by itself? Okay. So, although the REBOA treatment is a life-saving tool, it unfortunately is not without injury to the body. So, as the balloon is inflated, it preserves blood flow to the vital organs, but below the occlusion, you can have ischemia reperfusion injury due to the hypoxic conditions. So, a little bit more into the ischemia reperfusion injury. Several studies have shown that, both cell studies and rat studies have shown mitochondria to be central to both mitigating ischemia reperfusion injury, and if sustained for a long period of time, actually causing some of the ischemia reperfusion injury. So, with the mitochondria being central to that role in leading to oxidation, the release of reactive oxygen species, we wanted to focus our research on stabilizing the mitochondria during REBOA treatment. So, GGA120K is an isoform of connexin 43, and connexins are junctional cell proteins that allow for intercellular communication. GGA120K, in particular, is an ischemic response protein. So, it does so by stabilizing actin filaments, and it has protective capabilities through two mechanisms. One, by stimulating mitochondrial fission, and also by shuffling the mitochondria around the cell to have a homogenous spread of mitochondria, and those two things have been shown to mitigate oxidative stress. So, we hypothesized that GGA120K would mitigate REBOA-associated ischemia reperfusion injury, and through this, it would make REBOA a more accepted treatment for resuscitative teams. Oops. Sorry. So, here's our study design. We had 12 Yorkshire pigs, and they were anesthetized and instrumented, and then subjected to hemorrhagic shock by removing 25% of their blood volume. At T60, we would feed the balloon catheter up the femoral artery into the aorta, and occlude it for a period of one hour. Twenty-five minutes into the occlusion period, we would give an IV infusion of either GGA120K or saline. At the end of the occlusion period, the one-hour occlusion period, the balloon would be deflated, and then critical care and resuscitation would continue until T360. The reason we started the infusion at 25 minutes into the REBOA occlusion was to mirror how it might happen in really rural areas or resource-deplete areas. Here are our results. So, first, we're looking at serum lactate concentration. On the y-axis, we have serum lactate concentration, and on the x-axis, over time, and you can see that there's effectively no difference between the treatment and the control group, which showed that both groups had similar ischemic conditions throughout the experiment. Next, we are looking at resuscitation requirements. So, our resuscitation requirements included both the addition of isotonic crystalloids and norepinephrine. So, we can see graph A is isotonic crystalloids, and graph B is norepinephrine, and this is kind of exciting results because we saw that in the isotonic crystalloids, in the treatment group, they required significantly less than the control group, and norepinephrine was insignificant. So, like I said, this treatment is very useful in areas that don't have a lot of resources. So, if we can reduce the isotonic crystalloids that are required to maintain the mean arterial pressure at 65, then areas are more able to use their resources to maintain blood pressure during these traumas. Of significance, we had two of the animals that required no fluid boluses at all, and one only required a single bolus of 10 mLs per kg. Next result is focusing on renal injury. The roboa balloon was placed above the renal artery, so during the entirety of the roboa occlusion, the kidneys were not being perfused. So, we first looked at urine to serum N-gal concentration, which is neutrophil gelatinase associated lipocalin, and it's a marker that's released in the urine during acute tubular injury, and we also looked at serum creatinine concentration, which is an indicator of renal function, and you can see in both the urine to serum N-gal concentration and serum creatinine concentration that the treatment group had a significant reduction in both of those, showing to us that GGA120K had protective capabilities in mitigating some renal injury during ischemia reperfusion. Our next result is serum IL-6 concentration. So, we looked and did a multiplex cytokine study that looked at a variety of cytokines. You can see on the y-axis is all of the cytokines we looked at and on the x-axis over time, and there was a log two-fold change from T0, so we're specifically looking at T105, T180, and T360 at the end of the experiment, and if we can go back a slide, that would be great. Well, I can just tell you a little bit about it while we're going back a slide. There we go. All right, so we're looking specifically at IL-6 concentration on graph A. You can see there's a significant reduction in IL-6 at T360, so this is indicating to us some level of immunomodulation with the addition of GGA120K. So, of note, IL-6 is produced in the liver, and it's been shown to be high in humans that experience severe traumas and is related to mortality, increased mortality, so there's definitely an association that we will look more into with IL-6 concentration and mortality. So, to conclude, we learned that with the addition of GGA120K in the context of REBOA that there was no significant difference in serum lactate concentration, so both groups experienced similar ischemic conditions. Despite the treatment group receiving significantly less fluids than the control group. We also saw a significant reduction in fluid requirements of the isotonic crystalloids received during that resuscitation period. So, this is an exciting finding for two reasons. One, to be able to, in resource-deplete areas, use their resources wisely. And secondly, in fluid responsiveness, we can mitigate some potential consequences of overloading patients with fluids, like abdominal compartment syndrome. Next, we saw that GGA120K mitigated renal injury. We saw a significant reduction in both urine-to-serum NGAL concentration and serum creatinine concentration. And last, we saw a decrease in serum IL-6 concentration, showing that with the addition of GGA120K, there was some level of amino modulation. And if we can go back one slide, we'll look at just a few more things. So, we learned that mitochondrial protection is a potential target for mitigating the REBOA-associated ischemia reperfusion injury. So, in future directions, focusing on the mitochondria, we want to do combination therapy with other known mitochondrial pharmaceuticals to see if, in more complex models, that we can have even more improved outcomes. We also want to do other studies looking at the pharmacokinetics, pharmacodynamics, and cellular mechanisms of GGA120K. Like I said before, the reason we chose to do the infusion of GGA120K after the point of occlusion was to mirror what it might be like in the field. But we do want to see in the context of if we gave it before the REBOA was inflated, so the tissues past the point of occlusion would receive some of that treatment, if the outcomes may be different. So, thank you for your time, and I'll take any questions.

REBOA

non-compressible torso hemorrhages

GGA120K

renal injury

immunomodulation