Vasopressin and Aldosterone Dysregulation of Renal Potassium Handling During Resuscitative Endovascular Balloon Occlusion of the Aorta and Vena Cava Following Hemorrhage

Resuscitative endovascular balloon occlusion of the aorta and vena cava (REBOAVC) may be used in trauma care to prevent blood loss from non-compressible torso hemorrhage. REBOAVC balloon catheters effectively separate the upper circulation above the diaphragm from the circulation below. Survivability after severe traumatic hemorrhage depends on maintenance of renal function and avoidance of extreme hyperkalemia that will cause cardiac arrest. We have previously shown in a pig model that non-survivors of severe hemorrhage develop hyperkalemia in association with insufficient vasopressin (VP)-mediated renal potassium excretion. The objective of this current study was to determine if REBOAVC would disrupt normal cardiovascular endocrine responses. We hypothesized that two main hormonal regulators of potassium homeostasis, VP and aldosterone (ALDO), may be disconnected from regulation of renal function by REBOAVC compartmentalization of VP secreted from the posterior pituitary in the upper circulation and ALDO secreted from the adrenal gland in the lower circulation. Anesthetized, mechanically ventilated adult Duroc-cross pigs (n=6, body weight = 52±4 kg) were catheterized for assessment of hemodynamics, regional blood flow, and urine flow. REBOAVC and extracorporeal membrane oxygenation (ECMO) catheters were placed to separate the lower circulation below the diaphragm while using ECMO in the lower body to maintain tissue perfusion during truncal vascular occlusion. Pigs were hemorrhaged to a 30% blood volume loss. REBOAVC was applied along with lower body ECMO for 90 minutes, resulting in a decrease in renal blood flow (4.82±0.14 to 0.08±0.02 ml/min/g), a decrease in glomerular filtration (3.4±1.0 to 0.2±0.1 ml/min/kg), and a corresponding decrease in urine output (5.3±2.7 to 1.0±0.1 ul/min/kg) after REBOAVC. Plasma potassium in the upper circulation above the REBOAVC occlusion was similar before and after occlusion (4.9±0.2 vs 5.2±0.2 mmol/L). In contrast, potassium in the lower body circulation (8.0 ±0.3 mmol/L) was elevated after REBOAVC. The renal transtubular potassium gradient (TTKG) was 9.4±2.3 before versus 5.5±1.7 after occlusion, indicating an insufficient renal response to elevated potassium levels in the lower body circulation. Vasopressin was elevated in the upper circulation (120±34 pg/ml), compared to the lower circulation (31±4 pg/ml). Conversely, ALDO levels were elevated (249±40 pg/ml) in the lower circulation compared to the upper circulation (53±8 pg/ml). Results suggest ALDO was stimulated by elevated potassium in the lower body circulation, but VP is still needed to regulate the renal TTKG. The VP response to hyperkalemia after hemorrhage is disrupted by REBOAVC sequestering VP to the upper circulation, resulting in dysregulation of VP mediated renal potassium excretion. The views expressed are those of the authors and do not reflect the official policy or position of the Defense Health Agency, Department of Defense, or the U.S. Government. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.