James M Kuczmarski1, Christopher R Martens2, Shannon L Lennon-Edwards3, David G Edwards1. 1. Department of Kinesiology and Applied Physiology, University of Delaware, 25 N College Avenue, McDowell Hall, Newark, DE 19716, USA Department of Biological Sciences, University of Delaware, Newark, DE, USA. 2. Department of Kinesiology and Applied Physiology, University of Delaware, 25 N College Avenue, McDowell Hall, Newark, DE 19716, USA. 3. Department of Kinesiology and Applied Physiology, University of Delaware, 25 N College Avenue, McDowell Hall, Newark, DE 19716, USA Department of Behavioral Health and Nutrition, University of Delaware, Newark, DE, USA.
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.
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.
Authors: A Levin; C R Thompson; J Ethier; E J Carlisle; S Tobe; D Mendelssohn; E Burgess; K Jindal; B Barrett; J Singer; O Djurdjev Journal: Am J Kidney Dis Date: 1999-07 Impact factor: 8.860
Authors: Karen A Griffin; Maria M Picken; Monique Churchill; Paul Churchill; Anil K Bidani Journal: J Am Soc Nephrol Date: 2000-03 Impact factor: 10.121
Authors: Christopher R Martens; James M Kuczmarski; Jahyun Kim; John J Guers; M Brennan Harris; Shannon Lennon-Edwards; David G Edwards Journal: Am J Physiol Renal Physiol Date: 2014-06-25
Authors: James M Kuczmarski; Christopher R Martens; Jahyun Kim; Shannon L Lennon-Edwards; David G Edwards Journal: J Appl Physiol (1985) Date: 2014-07-24