Supplemental arginine vasopressin during the resuscitation of severe hemorrhagic shock preserves renal mitochondrial function

Abstract

Arginine vasopressin (AVP), a hormone secreted by the posterior pituitary, plays a vital role in maintaining vasomotor tone during acute blood loss. We hypothesized that decompensated hemorrhagic shock is associated with decreased AVP stores and supplementation during resuscitation would improve both blood pressure and renal function. Using a decompensated hemorrhagic shock model, male Long-Evans rats were bled to mean arterial blood pressure (MAP) of 40mmHg and maintained until the MAP could not be sustained without fluid. Once 40% of the shed volume was returned in lactated Ringer’s (Severe Shock), animals were resuscitated over 60 minutes with 4x the shed volume in lactated Ringer’s (LR) or the same fluids with AVP (0.5 units/kg+ 0.03 units/kg/min). Animals (n = 6-9/group) were sacrificed before hemorrhage (Sham), at Severe Shock, following resuscitation (60R, 60R with AVP) or 18 hours post-resuscitation (18hr, 18hr with AVP). Blood samples were taken to measure AVP levels and renal function. Pituitaries were harvested and assayed for AVP. Kidney samples were taken to assess mitochondrial function, histology, and oxidative damage. Baseline pituitary AVP stores (30,364 ± 5311 pg/mg) decreased with severe shock and were significantly depressed post-resuscitation (13,910 ± 3016 pg/ml. p<0.05) and at 18hr (15,592 ±1169 pg/ml, p<0.05). Resuscitation with LR+AVP led to higher serum AVP levels at 60R (31±8 vs 79±12; p<0.01) with an improved MAP both at 60R (125±3 vs 77±7mmHg; p<0.01) and 18hr (82±6 vs 69±5mmHg;p<0.05). AVP supplementation preserved complex I respiratory capacity at 60R and both complex I and II function at 18hr (p<0.05). AVP was also associated with decreased reactive oxygen species at 60R (856±67 vs 622±48F RFU) and significantly decreased oxidative damage as measured by mitochondrial lipid peroxidation (0.9±0.1 vs 1.7±0.1 fold change, p<0.01) and nitrosylation (0.9±0.1 vs 1.4±0.2 fold change, p<0.05). With AVP, renal damage was mitigated at 60R and histologic architecture was conserved at 18 hours. In conclusion, pituitary and serum AVP levels decrease during severe hemorrhage and may contribute to the development of decompensated hemorrhagic shock. Supplementing exogenous AVP during resuscitation improves blood pressure, preserves renal mitochondrial function, and mitigates acute kidney injury.

Early vasopressor use following traumatic injury: a systematic review

“…34 35 One highly cited observational study on vasopressor use in trauma was excluded because it addressed vasopressor use exclusively after patient arrival in the ICU. 36 We identified two ongoing clinical trials ( https://clinicaltrials.gov/show/NCT01611935 ; https://clinicaltrials.gov/ct2/show/NCT00379522 ), 37 38 but after contacting study personnel, the investigators preferred not to provide clinical data for this review. A PRISMA flow chart illustrates the selection process ( figure 1 ).…”

“…Currently, the degree of uncertainty precludes any recommendation regarding vasopressor use in trauma ( https://www.magicapp.org/app #/guideline/1273). Two clinical trials currently underway 37 38 may provide useful insights on this question. However, they have not been designed a priori to capture long-term neurological or quality of life-related outcomes.…”

Therapeutic interventions to restore microcirculatory perfusion following experimental hemorrhagic shock and fluid resuscitation: A systematic review

“…Mitochondrial dysfunction following hemorrhagic shock and fluid resuscitation is characterized by increased ROS formation 73 and decreased ATP production, 12,74 partly due to increased calcium content during ischemia 75 . Several studies focused on improving ATP content, 21,30‐33 or reducing calcium levels with the use of a calcium antagonist, 21 and all restored microcirculatory blood flow while using comparable models of moderate hemorrhagic shock.…”

Robot‐assisted partial nephrectomy is associated with early recovery of renal function: Comparison of open, laparoscopic, and robot‐assisted partial nephrectomy using DTPA renal scintigraphy

“…In our study, RAPN was associated with the lowest EBL, which agrees with previous research. 9,10 Blood loss could be associated with apoptosis caused by hypoxic damage and mitochondrial dysfunction caused by reactive oxygen species 17 ; robotic surgery minimizes both of these factors and also increases intraabdominal pressure, which could help to reduce bleeding. Another advantage of robotic surgery is that it is minimally invasive with a small incision.…”