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- W2068204188 abstract "Background: Heart failure with preserved ejection fraction (HFPEF) and renal impairment are often associated but the underlying pathomechanisms are largely unknown. We investigated tissue fibrosis and cardiomyocyte contractile function in a rat model with HFPEF and compensated renal failure.Methods: Seventy young male Wistar rats were subjected to subtotal nephrectomy (NXT) or sham operation (SOP). Blood/urine samples, echocardiography, pressure-volume loops were performed after 8 and 24 weeks. Left ventricular (LV) hypertrophy, fibrosis (picosirius-red-staining) and NCX protein expression (Western blot) were determined after sacrification. Cardiomyocyte function (Ca2+ transients, cell shortening) was quantified in isolated cardiomyocytes without and with the NCX inhibitor SEA0400 (300nM).Results: NXT rats showed stable renal impairment with preserved urine excretion and elevated arterial pressure (148±8 and 154±7 vs. 105±3 and 109±2 mmHg, p<0.01) at 8 and 24 weeks, respectively. LV in NXT were significantly hypertrophied at 8 and 24 weeks, but LV systolic function (EF, dP/dt) were preserved. LVEDP, LA size and lung weight were significantly increased indicating HFPEF with pulmonary congestion. Fibrosis was increased in LV from NXT. LV cardiomyocytes showed significantly prolonged time for early (50%) relaxation and decay of the Ca2+ transient. Time constant of the caffeine-induced Ca2+ transient (TAU) was significantly prolonged indicating reduced NCX forward mode activity, while NCX protein expression was upregulated. Acute treatment with SEA0400 (300nM) significantly accelerated early relaxation in cardiomyocytes from NXT (8 weeks).Conclusion: In this model of compensated renal failure and HFPEF cardiomyocyte relaxation was prolonged already at an early stage. Our results suggest increased NCX activity may contribute to contractile dysfunction, likely through reverse mode Ca2+ influx. NCX represents a potential target to treat cardiomyocyte dysfunction in HFPEF." @default.
- W2068204188 created "2016-06-24" @default.
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- W2068204188 date "2014-01-01" @default.
- W2068204188 modified "2023-09-30" @default.
- W2068204188 title "Inhibition of the NA+/CA2+ Exchanger (Ncx) Improves Cardiomyocyte Contractile Dysfunction in a Rat Model with Compensated Renal Failure and Heart Failure with Preserved Ejection Fraction" @default.
- W2068204188 doi "https://doi.org/10.1016/j.bpj.2013.11.697" @default.
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