Dataset Information

Cardiac function and tolerance to ischemia-reperfusion injury in chronic kidney disease.

ABSTRACT:

Background

Cardiac dysfunction is an independent risk factor of ischemic heart disease and mortality in chronic kidney disease (CKD) patients, yet the relationship between impaired cardiac function and tolerance to ischemia-reperfusion (IR) injury in experimental CKD remains unclear.

Methods

Cardiac function was assessed in 5/6 ablation-infarction (AI) and sham male Sprague-Dawley rats at 20 weeks of age, 8 weeks post-surgery using an isolated working heart system. This included measures taken during manipulation of preload and afterload to produce left ventricular (LV) function curves as well as during reperfusion following a 15-min ischemic bout. In addition, LV tissue was used for biochemical tissue analysis.

Results

Cardiac function was impaired in AI animals during preload and afterload manipulations. Cardiac functional impairments persisted post-ischemia in the AI animals, and 36% of AI animals did not recover sufficiently to achieve aortic overflow following ischemia (versus 0% of sham animals). However, for those animals able to withstand the ischemic perturbation, no difference was observed in percent recovery of post-ischemic cardiac function between groups. Urinary NOx (nitrite + nitrate) excretion was lower in AI animals and accompanied by reduced LV endothelial nitric oxide synthase and NOx. LV antioxidants superoxide dismutase-1 and -2 were reduced in AI animals, whereas glutathione peroxidase-1/2 as well as NADPH-oxidase-4 and H(2)O(2) were increased in these animals.

Conclusions

Impaired cardiac function appears to predispose AI rats to poor outcomes following short-duration ischemic insult. These findings could be, in part, mediated by increased oxidative stress via nitric oxide-dependent and -independent mechanisms.

SUBMITTER: Kuczmarski JM

PROVIDER: S-EPMC4106638 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Publications

Cardiac function and tolerance to ischemia-reperfusion injury in chronic kidney disease.

Kuczmarski James M JM Martens Christopher R CR Lennon-Edwards Shannon L SL Edwards David G DG

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 20131022 8

<h4>Background</h4>Cardiac dysfunction is an independent risk factor of ischemic heart disease and mortality in chronic kidney disease (CKD) patients, yet the relationship between impaired cardiac function and tolerance to ischemia-reperfusion (IR) injury in experimental CKD remains unclear.<h4>Methods</h4>Cardiac function was assessed in 5/6 ablation-infarction (AI) and sham male Sprague-Dawley rats at 20 weeks of age, 8 weeks post-surgery using an isolated working heart system. This included m ...[more]

PMID: 24151020

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Project description:BackgroundUremic cardiomyopathy is a common cardiovascular complication of chronic kidney disease (CKD) characterized by left ventricular hypertrophy (LVH) and fibrosis enhancing the susceptibility of the heart to acute myocardial infarction. In the early stages of CKD, approximately 60% of patients are women. We aimed to investigate the influence of sex on the severity of uremic cardiomyopathy and the infarct size-limiting effect of ischemic preconditioning (IPRE) in experimental CKD.MethodsCKD was induced by 5/6 nephrectomy in 9-week-old male and female Wistar rats. Two months later, serum and urine laboratory parameters were measured to verify the development of CKD. Transthoracic echocardiography was performed to assess cardiac function and morphology. Cardiomyocyte hypertrophy and fibrosis were measured by histology. Left ventricular expression of A- and B-type natriuretic peptides (ANP and BNP) were measured by qRT-PCR and circulating BNP level was measured by ELISA. In a subgroup of animals, hearts were perfused according to Langendorff and were subjected to 35 min global ischemia and 120 min reperfusion with or without IPRE (3 × 5 min I/R cycles applied before index ischemia). Then infarct size or phosphorylated and total forms of proteins related to the cardioprotective RISK (AKT, ERK1,2) and SAFE (STAT3) pathways were measured by Western blot.ResultsThe severity of CKD was similar in males and females. However, CKD males developed more severe LVH compared to females as assessed by echocardiography. Histology revealed cardiac fibrosis only in males in CKD. LV ANP expression was significantly increased due to CKD in both sexes, however, LV BNP and circulating BNP levels failed to significantly increase in CKD. In both sexes, IPRE significantly decreased the infarct size in both the sham-operated and CKD groups. IPRE significantly increased the phospho-STAT3/STAT3 ratio in sham-operated but not in CKD animals in both sexes. There were no significant differences in phospho-AKT/AKT and phospho-ERK1,2/ERK1,2 ratios between the groups.ConclusionThe infarct size-limiting effect of IPRE was preserved in both sexes in CKD despite the more severe uremic cardiomyopathy in male CKD rats. Further research is needed to identify crucial molecular mechanisms in the cardioprotective effect of IPRE in CKD.

Dataset Information

Cardiac function and tolerance to ischemia-reperfusion injury in chronic kidney disease.

Background

Methods

Results

Conclusions

Publications

Cardiac function and tolerance to ischemia-reperfusion injury in chronic kidney disease.

Similar Datasets

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