A step forward toward establishing a novel preclinical porcine model to study ischemia/reperfusion-induced acute and chronic kidney injures

Zhou, Xiaoming

doi:10.21037/tau-22-176

Cited by 1 publication

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“…An animal model closely mimicking the clinical setting is important to understanding pathophysiology and testing therapeutic approaches. Although pigs are more similar to humans in physical size, physiology and immunology than rodents (Packialakshmi et al, 2020;Zhou, 2022), rodents are easy to handle, quickly reproduce and have contributed significantly to deciphering pathophysiology and developing novel therapies. As such, a majority of tourniquet-induced lower limb ischemia/ reperfusion (TILLIR) injury in the literature has been produced in rodents, and a variety of therapies have been tested using rodent models (Klausner et al, 1989;Adachi et al, 2006;Hsu et al, 2012;Mansour et al, 2014;Kao et al, 2015a;Kao et al, 2015b;Karahan et al, 2016;Onody et al, 2016;Foster et al, 2017;Shih et al, 2018;İnce et al, 2019).…”

Section: Figurementioning

confidence: 99%

A clinically-relevant mouse model that displays hemorrhage exacerbates tourniquet-induced acute kidney injury

Packialakshmi,

Burmeister,

Anderson

et al. 2023

Front. Physiol.

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Hemorrhage is a leading cause of death in trauma. Tourniquets are effective at controlling extremity hemorrhage and have saved lives. However, tourniquets can cause ischemia reperfusion injury of limbs, leading to systemic inflammation and other adverse effects, which results in secondary damage to the kidney, lung, and liver. A clinically relevant animal model is critical to understanding the pathophysiology of this process and developing therapeutic interventions. Despite the importance of animal models, tourniquet-induced lower limb ischemia/reperfusion (TILLIR) models to date lack a hemorrhage component. We sought to develop a new TILLIR model that included hemorrhage and analyze the subsequent impact on kidney, lung and liver injuries. Four groups of mice were examined: group 1) control, group 2) hemorrhage, group 3) tourniquet application, and group 4) hemorrhage and tourniquet application. The hemorrhagic injury consisted of the removal of 15% of blood volume through the submandibular vein. The tourniquet injury consisted of orthodontic rubber bands applied to the inguinal area bilaterally for 80 min. Mice were then placed in metabolic cages individually for 22 h to collect urine. Hemorrhage alone did not significantly affect transcutaneous glomerular filtration rate (tGFR), blood urea nitrogen (BUN) or urinary kidney injury molecule-1 (KIM-1) levels. Without hemorrhage, TILLIR decreased tGFR by 46%, increased BUN by 162%, and increased KIM-1 by 27% (p < 0.05 for all). With hemorrhage, TILLIR decreased the tGFR by 72%, increased BUN by 395%, and increased urinary KIM-1 by 37% (p < 0.05 for all). These differences were statistically significant (p < 0.05). While hemorrhage had no significant effect on TILLIR-induced renal tubular degeneration and necrosis, it significantly increased TILLIR-induced lung total injury scores and congestion, and fatty liver. In conclusion, hemorrhage exacerbates TILLIR-induced acute kidney injury and structural damage in the lung and liver.

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Section: Figurementioning

confidence: 99%

A clinically-relevant mouse model that displays hemorrhage exacerbates tourniquet-induced acute kidney injury

Packialakshmi,

Burmeister,

Anderson

et al. 2023

Front. Physiol.

Self Cite

View full text Add to dashboard Cite

show abstract

A step forward toward establishing a novel preclinical porcine model to study ischemia/reperfusion-induced acute and chronic kidney injures

Abstract: Cite this article as: Zhou X. A step forward toward establishing a novel preclinical porcine model to study ischemia/ reperfusion-induced acute and chronic kidney injures. Transl

Cited by 1 publication

References 21 publications

A clinically-relevant mouse model that displays hemorrhage exacerbates tourniquet-induced acute kidney injury

A clinically-relevant mouse model that displays hemorrhage exacerbates tourniquet-induced acute kidney injury

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