BACKGROUND: The incidence of and mortality due to acute kidney injury (AKI) is high in patients with traumatic shock. However, it is unclear how hemorrhage and trauma synergistically affect renal function, especially when timely volume resuscitation is not available. METHOD: We hypothesized that trauma impairs renal tolerance to prolonged hemorrhagic hypotension. Sprague Dawley rats were randomized into 6 groups: control, extremity trauma (ET), hemorrhage at 70 mmHg (70-H), hemorrhage at 55 mmHg (55-H), ET + 70 mmHg (70-ETH), and ET + 55 mmHg (55-ETH). Animals were anesthetized and ET was induced via soft tissue injury and closed fibula fracture. Hemorrhage was performed via catheters 5 minutes after ET with target MAP clamped at 70 mmHg or 55 mmHg for up to 3 hours. Blood and urine samples were collected to analyze plasma creatinine (Cr), creatinine clearance (CCr), renal oxygen delivery (DO2), urinary albumin, and kidney injury molecule-1 (KIM-1). RESULTS: ET alone did not alter renal hemodynamics, DO2, or function. In 70-H, CCr was increased following hemorrhage, while Cr, renal vascular resistance (RVR), KIM-1, and albumin levels remained unchanged. Compared to 70-H, 70-ETH exhibited increases in Cr and RVR with decreases in CCr and DO2. In addition, ET decreased the blood volume loss required to maintain MAP = 70 mmHg by ~50%. 55-H and 55-ETH exhibited a marked and similar decrease in CCr and increases in RVR, Cr, KIM-1, and albumin. However, ET greatly decreased the blood volume loss required to maintain MAP at 55 mmHg and led to 50% mortality. CONCLUSIONS: These results suggest that ET impairs renal and systemic tolerance to prolonged hemorrhagic hypotension. Thus, traumatic injury should be considered as a critical component of experimental studies investigating outcomes and treatment following hemorrhagic shock. LEVEL OF EVIDENCE: This is an original article on basic science and does not require a level of evidence.
BACKGROUND: The incidence of and mortality due to acute kidney injury (AKI) is high in patients with traumatic shock. However, it is unclear how hemorrhage and trauma synergistically affect renal function, especially when timely volume resuscitation is not available. METHOD: We hypothesized that trauma impairs renal tolerance to prolonged hemorrhagic hypotension. Sprague Dawley rats were randomized into 6 groups: control, extremity trauma (ET), hemorrhage at 70 mmHg (70-H), hemorrhage at 55 mmHg (55-H), ET + 70 mmHg (70-ETH), and ET + 55 mmHg (55-ETH). Animals were anesthetized and ET was induced via soft tissue injury and closed fibula fracture. Hemorrhage was performed via catheters 5 minutes after ET with target MAP clamped at 70 mmHg or 55 mmHg for up to 3 hours. Blood and urine samples were collected to analyze plasma creatinine (Cr), creatinine clearance (CCr), renal oxygen delivery (DO2), urinary albumin, and kidney injury molecule-1 (KIM-1). RESULTS:ET alone did not alter renal hemodynamics, DO2, or function. In 70-H, CCr was increased following hemorrhage, while Cr, renal vascular resistance (RVR), KIM-1, and albumin levels remained unchanged. Compared to 70-H, 70-ETH exhibited increases in Cr and RVR with decreases in CCr and DO2. In addition, ET decreased the blood volume loss required to maintain MAP = 70 mmHg by ~50%. 55-H and 55-ETH exhibited a marked and similar decrease in CCr and increases in RVR, Cr, KIM-1, and albumin. However, ET greatly decreased the blood volume loss required to maintain MAP at 55 mmHg and led to 50% mortality. CONCLUSIONS: These results suggest that ET impairs renal and systemic tolerance to prolonged hemorrhagic hypotension. Thus, traumatic injury should be considered as a critical component of experimental studies investigating outcomes and treatment following hemorrhagic shock. LEVEL OF EVIDENCE: This is an original article on basic science and does not require a level of evidence.
Authors: Lusha Xiang; Alfredo S Calderon; Harold G Klemcke; Carmen Hinojosa-Laborde; Sandra C Becerra; Kathy L Ryan Journal: J Appl Physiol (1985) Date: 2022-08-25