Acute Kidney InjuryIschemia-Reperfusion Injury

Development of a novel porcine ischemia/reperfusion model inducing different ischemia times in bilateral kidneys-effects of hydrogen gas inhalation

by Motoaki Sano, Eiji Kobayashi, Kohsuke Shirakawa, Haruki Kume, Takashi Yokoo, Yoshitaka Kinoshita

Abstract:

Background: Acute kidney injury and its central pathology, renal ischemia reperfusion injury (IRI), have been studied in many animal models. Although renal IRI has been induced in pig models in many ways, simultaneous bilateral ischemia or unilateral ischemia along with contralateral nephrectomy models only provide data on the renal response to a single ischemia time. Moreover, it has been reported that prolonged renal ischemia time in pigs for 120 min or more can cause irreversible renal damage and increase animal mortality. Methods: We developed a model that induces prolonged ischemia time and subsequent reperfusion injury without threatening the lives of pigs by subjecting the left and right kidneys to ischemia for 120 and 60 min, respectively. Using this novel model, we investigated whether hydrogen gas inhalation could alleviate renal IRI. Results: All animals (n=4) survived until the end of the observation period of 3 months in this model. Evaluation of the left and right kidneys immediately before and after IRI could be performed separately by blood sampling from each renal vein and renal biopsy during surgery, although the results of peripheral blood sampling during the follow-up were the mixed results of bilateral kidneys. The release of degraded DNA from the kidneys immediately after IRI and subsequent renal fibrosis at 3 months increased in response to ischemia time. Although the effect of hydrogen gas on pathological findings was not obvious, the release of degraded DNA from the kidney, an acute marker of IRI, appeared to be suppressed. Conclusions: We have developed a novel model in which IRI of different ischemia times is induced in the bilateral kidney that provides two-fold information and allows for safe long-term observation experiments in pigs. Using this model, hydrogen gas inhalation appeared to reduce acute renal IRI, although the effect was not statistically significant. Keywords: Animal model; chronic kidney disease; hydrogen gas; ischemia reperfusion injury (IRI); porcine.


Read more:

https://doi.org/10.21037/tau-21-1164


Related Articles:

Inhalation of 4% and 67% hydrogen ameliorates oxidative stress, inflammation, apoptosis, and...

Acute kidney injury (AKI) is the major complication of rhabdomyolysis (RM) clinically, which is usually mimicked by glycerol injection in basic research. Oxidative stress, inflammatory response and apoptosis are recognized to play important roles in development of this disease. Recently,...

Year Published: 2023KidneyAcute Kidney InjuryPositive
Efficacy of inhaled hydrogen on neurological outcome following brain ischaemia during post-cardiac...

Background: Inhaled molecular hydrogen gas (H2) has been shown to improve outcomes in animal models of cardiac arrest (CA). H2 inhalation is safe and feasible in patients after CA. We investigated whether inhaled H2 would improve outcomes after out-of-hospital CA...

Year Published: 2023BrainCardiac ArrestPositive
Hypothermic Machine Perfusion with Hydrogen Gas Reduces Focal Injury in Rat Livers...

Background: We have previously reported the efficacy of post-reperfusion H2 gas treatment in cold storage (CS) and subsequent reperfusion of the rat liver. The present study aimed to evaluate the effect of H2 gas treatment during hypothermic machine perfusion (HMP)...

Year Published: 2023LiverSurgery/TransplantationPositive
Combination of Cold Storage in a Heavy Water-Containing Solution and Post-Reperfusion Hydrogen...

We previously reported the efficacy of cold storage (CS) using a heavy water-containing solution (Dsol) and post-reperfusion hydrogen gas treatment separately. This study aimed to clarify the combined effects of these treatments. Rat livers were subjected to 48-hour CS and...

Year Published: 2023LiverSurgery/TransplantationPositive