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

Author(s):Show less -

Castro, Leticia Urbano Cardoso ; Otsuki, Denise Aya ; Sanches, Talita Rojas ; Souza, Felipe Lima ; Santinho, Mirela Aparecida Rodrigues ; da Silva, Cleonice ; Noronha, Irene de Lourdes ; Duarte-Neto, Amaro Nunes ; Gomes, Samirah Abreu ; Malbouisson, Luiz-Marcelo Sa ; Andrade, Lucia

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 12, n. 1, p. 13-pg., 2022-11-28.

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at a target MAP of 30-40 mmHg, thereafter being allocated to receive LR infusion at 3 times the volume of the blood withdrawn (liberal fluid management); at 2 times the volume (conservative fluid management), plus terlipressin (10 mu g/100 g body weight); and at an equal volume (conservative fluid management), plus terlipressin (10 mu g/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 At 15 min after fluid resuscitation/treatment, the blood previously withdrawn was reinfused.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. (AU)

• FAPESP's process: 19/19433-0 - Pollution is the motor of premature ageing of the kidney
• Grantee: Lucia da Conceição Andrade
• Support Opportunities: Research Projects - Thematic Grants