Renoprotective effects of levosimendan on acute kidney injury following cardiac arrest via anti‐inflammation, anti‐apoptosis, and ERK activation

Tian, Lei; Wang, Shiwei; Zhao, Li; Lu, Xinya; Zhu, Changqing; Gong, Hao; Yang, Weiqiang

doi:10.1002/2211-5463.13227

Cited by 5 publications

(3 citation statements)

References 42 publications

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“…These are markedly augmented after ROSC in CA hospital patients and in an induced-CA rat model (26). Previous studies have also reported that BUN and creatine levels are increased at 1 day and 2 days after ROSC in an asphaxial CA rat model (31,32). Our experimental data were also similar to studies using a traditional I/R model.…”

Section: Discussionsupporting

confidence: 87%

Changes of antioxidant enzymes in the kidney after cardiac arrest in the rat model

Lee

Islam

Yoo

et al. 2023

Braz J Med Biol Res

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Globally, cardiac arrest (CA) is a leading cause of death and disability. Asphyxial CA (ACA)-induced kidney damage is a crucial factor in reducing the survival rate. The purpose of this study was to investigate the role of antioxidant enzymes in histopathological renal damage in an ACA rat model at different time points. A total of 88 rats were divided into five groups and exposed to ACA except for the sham group. To evaluate glomerular function and oxidative stress, serum levels of blood urea nitrogen (BUN) and creatinine (Crtn) and malondialdehyde (MDA) levels in renal tissues were measured. To determine histopathological damage, hematoxylin and eosin staining, periodic acid-Schiff staining, and Masson's trichrome staining were performed. Expression levels of antioxidant enzymes including superoxide dismutase-1 (SOD-1), superoxide dismutase-2 (SOD-2), catalase (CAT), and glutathione peroxidase (GPx) were measured by immunohistochemistry (IHC). Survival rate of the experimental rats was reduced to 80% at 6 h, 55% at 12 h, 42.9% at 1 day, and 33% at 2 days after return of spontaneous circulation. Levels of BUN, Crtn, and MDA started to increase significantly in the early period of CA induction. Renal histopathological damage increased markedly from 6 h until two days post-CA. Additionally, expression levels of antioxidant enzymes were significantly decreased at 6 h, 12 h, 1 day, and 2 days after CA. CA-induced oxidative stress and decreased levels of antioxidant enzymes (SOD-1, SOD-2, CAT, GPx) from 6 h to two days could be possible mediators of severe renal tissue damage and increased mortality rate.

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Section: Discussionsupporting

confidence: 87%

Changes of antioxidant enzymes in the kidney after cardiac arrest in the rat model

Lee

Islam

Yoo

et al. 2023

Braz J Med Biol Res

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“…Levosimendan can effectively protect liver and kidney functions while preserving heart function, regardless of the presence of hepatic or renal impairment before it is used [23][24][25][26][27][28]. Partly of these protective effects due to their antiinflammatory and anti-apoptotic properties [29,30].…”

Section: Discussionmentioning

confidence: 99%

Preoperative Levosimendan Administration in Heart Transplant Patients with Severe Hepatic and Renal Impairment: A Retrospective Study

Qiang

Lan

Guo

et al. 2023

HSF

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Background: The cardio-renal syndrome and hepatic impairment play a critical role in end-stage heart failure (HF). Levosimendan is an effective inotropic agent used to maintain cardiac output similar to classic cardiotonic like dobutamine/dopamine. This current research aims to investigate the clinical outcomes of levosimendan and dobutamine/dopamine in Chinese heart transplant awaiting patients with severe hepatic or renal impairment. Methods: We performed a retrospective analysis of 568 heart transplant awaiting individuals with severe hepatic or renal impairment who treated with levosimendan or dobutamine/dopamine in our institution between January 2015 and December 2020. Univariate Cox proportional hazard models and Kaplan-Meier survival curves were applied. The primary endpoint was defined as death included inhospital mortality and the mortality at 30 days, 90 days, 180 days and 1 year after heart transplantation. Results: There were no significant differences in mortality rate at 30, 90, 180 days and 1 years after heart transplantation between the levosimendan and non-levosimendan groups, or between subgroups of patients with severe hepatic impairment or renal impairment. The results were consistent before and after propensity score matching. Conclusions: In the population with advanced heart failure awaiting heart transplantation, levosimendan did not increase short- or long-term mortality rates after surgery compared to dobutamine/dopamine, regardless of their hepatic or renal function. Severe hepatic or renal impairment were not necessarily considered a contraindication for levosimendan in these patients.

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“…Despite the increasing success rate of ROSC, the incidence and mortality of post-resuscitation AKI remain significant ( 31 , 32 ). Some substances were proven to partly alleviate post-CPR AKI to some extent in animal model ( 33 , 34 ); however, there is insufficient evidence to demonstrate that their pharmacological effects can improve long-term survival. Therefore, there is an urgent need to explore novel and feasible therapeutic strategies to prevent AKI and improve outcomes after CPR.…”

Section: Discussionmentioning

confidence: 99%

Protection Against Post-resuscitation Acute Kidney Injury by N-Acetylcysteine via Activation of the Nrf2/HO-1 Pathway

et al. 2022

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Background and ObjectiveAcute kidney injury (AKI), the common complication after cardiopulmonary resuscitation (CPR), seriously affects the prognosis of cardiac arrest (CA) patients. However, there are limited studies on post-resuscitation AKI. In addition, it has been demonstrated that N-acetylcysteine (N-AC) as an ROS scavenger, has multiorgan-protective effects on systemic and regional ischaemia-reperfusion injuries. However, no studies have reported its protective effects against post-resuscitation AKI and potential mechanisms. This study aimed to clarify the protective effects of N-AC on post-resuscitation AKI and investigate whether its potential mechanism was mediated by activating Nrf-2/HO-1 pathway in the kidney.MethodsWe established cardiac arrest models in rats. All animals were divided into four groups: the sham, control, N-AC, and ZnPP groups. Animals in each group except for the ZnPP group were assigned into two subgroups based on the survival time: 6 and 48 h. The rats in the control, N-AC, and ZnPP groups underwent induction of ventricular fibrillation (VF), 8 min untreated VF and cardiopulmonary resuscitation. Renal function indicators, were detected using commercial kits. Renal pathologic changes were assessed by haematoxylin–eosin (HE) staining. Oxidative stress and inflammatory responses were measured using the corresponding indicators. Apoptosis was evaluated using terminal uridine nick-end labeling (TUNEL) staining, and expression of proteins associated with apoptosis and the Nrf-2/HO-1 pathway was measured by western blotting.ResultsN-AC inhibited post-resuscitation AKI. We observed that N-AC reduced the levels of biomarkers of renal function derangement; improved renal pathological changes; and suppressed apoptosis, oxidative stress, and inflammatory response. Additionally, the production of ROS in the kidneys markedly decreased by N-AC. More importantly, compared with the control group, N-AC further upregulated the expression of nuclear Nrf2 and endogenous HO-1 in N-AC group. However, N-AC-determined protective effects on post-resuscitation AKI were markedly reversed after pretreatment of the HO-1 inhibitor zinc protoporphyrin (ZnPP).ConclusionsN-AC alleviated renal dysfunction and prolonged survival in animal models of CA. N-AC partially exerts beneficial renal protection via activation of the Nrf-2/HO-1 pathway. Altogether, all these findings indicated that N-AC as a common clinical agent, may have the potentially clinical utility to improve patients the outcomes in cardiac arrest.

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Renoprotective effects of levosimendan on acute kidney injury following cardiac arrest via anti‐inflammation, anti‐apoptosis, and ERK activation

Abstract: Renoprotective effects of levosimendan on acute kidney injury following cardiac arrest via anti-inflammation, anti-apoptosis and ERK activation

Cited by 5 publications

References 42 publications

Changes of antioxidant enzymes in the kidney after cardiac arrest in the rat model

Changes of antioxidant enzymes in the kidney after cardiac arrest in the rat model

Preoperative Levosimendan Administration in Heart Transplant Patients with Severe Hepatic and Renal Impairment: A Retrospective Study

Protection Against Post-resuscitation Acute Kidney Injury by N-Acetylcysteine via Activation of the Nrf2/HO-1 Pathway

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