title: Impairment of cardiac function and energetics in experimental renal failure.
abstract: Cardiac function and energetics in experimental renal failure in the rat (5/6 nephrectomy) have been investigated by means of an isolated perfused working heart preparation and an isometric Langendorff preparation using 31P nuclear magnetic resonance (31P NMR). 4 wk after nephrectomy cardiac output of isolated hearts perfused with Krebs-Henseleit buffer was significantly lower (P < 0.0001) at all levels of preload and afterload in the renal failure groups than in the pair-fed sham operated control group. In control hearts, cardiac output increased with increases in perfusate calcium from 0.73 to 5.61 mmol/liter whereas uremic hearts failed in high calcium perfusate. Collection of 31P NMR spectra from hearts of renal failure and control animals during 30 min normoxic Langendorff perfusion showed that basal phosphocreatine was reduced by 32% to 4.7 mumol/g wet wt (P < 0.01) and the phosphocreatine to ATP ratio was reduced by 32% (P < 0.01) in uremic hearts. During low flow ischemia, there was a substantial decrease in phosphocreatine in the uremic hearts and an accompanying marked increase in release of inosine into the coronary effluent (14.9 vs 6.1 microM, P < 0.01). We conclude that cardiac function is impaired in experimental renal failure, in association with abnormal cardiac energetics and increased susceptibility to ischemic damage. Disordered myocardial calcium utilization may contribute to these derangements.
authors.affiliation: Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, England.
authors.forename: A E
authors.initials: AE
authors.lastname: Raine
authors.forename: A M
authors.initials: AM
authors.lastname: Seymour
authors.forename: A F
authors.initials: AF
authors.lastname: Roberts
authors.forename: G K
authors.initials: GK
authors.lastname: Radda
authors.forename: J G
authors.initials: JG
authors.lastname: Ledingham
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003404:Creatinine / Q000494:pharmacology; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000503:physiopathology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D015999:Multivariate Analysis; D009206:Myocardium / Q000378:metabolism*; D009392:Nephrectomy; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D014508:Urea / Q000494:pharmacology
chemical_list: D010710:Phosphates; D010725:Phosphocreatine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D014508:Urea; D003404:Creatinine