Terlipressin combined with conservative fluid management attenuates hemorrhagic shock-induced acute kidney injury in rats

Abstract

Hemorrhagic shock (HS), a major cause of trauma-related mortality, is mainly treated by crystalloid fluid administration, typically with lactated Ringer’s (LR). Despite beneficial hemodynamic effects, such as the restoration of mean arterial pressure (MAP), LR administration has major side effects, including organ damage due to edema. One strategy to avoid such effects is pre-hospitalization intravenous administration of the potent vasoconstrictor terlipressin, which can restore hemodynamic stability/homeostasis and has anti-inflammatory effects. Wistar rats were subjected to HS for 60 min, at a target MAP of 30–40 mmHg, thereafter being allocated to receive LR infusion at 3 times the volume of the blood withdrawn (liberal fluid management); at 2 times the volume (conservative fluid management), plus terlipressin (10 µg/100 g body weight); and at an equal volume (conservative fluid management), plus terlipressin (10 µg/100 g body weight). A control group comprised rats not subjected to HS and receiving no fluid resuscitation or treatment. At 15 min after fluid resuscitation/treatment, the blood previously withdrawn was reinfused. At 24 h after HS, MAP was higher among the terlipressin-treated animals. Terlipressin also improved post-HS survival and provided significant improvements in glomerular/tubular function (creatinine clearance), neutrophil gelatinase-associated lipocalin expression, fractional excretion of sodium, aquaporin 2 expression, tubular injury, macrophage infiltration, interleukin 6 levels, interleukin 18 levels, and nuclear factor kappa B expression. In terlipressin-treated animals, there was also significantly higher angiotensin II type 1 receptor expression and normalization of arginine vasopressin 1a receptor expression. Terlipressin associated with conservative fluid management could be a viable therapy for HS-induced acute kidney injury, likely attenuating such injury by modulating the inflammatory response via the arginine vasopressin 1a receptor.

Obesity aggravates acute kidney injury resulting from ischemia and reperfusion in mice

“…Tubular necrosis was quantified by a pathologist who was blinded to the groups. Tubular injury, characterized by loss of the renal brush border and cast formation, as well as tubular necrosis and dilation, was graded on the basis of the proportion of the corticomedullary region involved in 10 randomly selected, non-overlapping high-power fields (× 100 magnification), on a five-point scale 19 , as follows: 0 = none; 1 = 0–10%; 2 = 10–25%; 3 = 25–50%; 4 = 50–75%; and 5 = 75–100%. For each animal, the total value is expressed as the tubular injury score.…”

Hemorrhagic Shock Assessed by Tissue Microcirculatory Monitoring: A Narrative Review

“…Trauma seriously threatens the lives of young adults and accounts for a significant proportion of the global disease burden (1). Hemorrhagic shock (HS) is a common type of hypovolemic shock and posttraumatic complication and has a mortality rate of up to 40% (2,3). Hemorrhagic shock is also the leading cause of death and a potential preventable cause of death in trauma patients.…”