The effect of creatine supplementation on myocardial metabolism and function in sedentary and exercised rats

[摘要] ENGLISH ABSTRACT: Background: There has been a dramatic increase in the use of dietary creatinesupplementation among sports men and women, and by clinicians as a therapeuticagent in muscular and neurological diseases. The effects of creatine have been studiedextensively in skeletal muscle, but knowledge of its myocardial effects is limited.Objectives: To investigate the effects of dietary creatine supplementation with andwithout exercise on 1) basal cardiac function, 2) susceptibility to ischaemia/reperfusioninjury and 3) myocardial protein expression and phosphorylation and 4) mitochondrialoxidative function.Methods: Male Wistar rats were randomly divided into control or creatine supplementedgroups. Half of each group was exercise trained by swimming for a period of 8 weeks, 5days per week. At the end of the 8 weeks the open field test was performed and bloodcorticosterone levels were measured by RIA to determine whether the swim trainingprotocol had any effects on stress levels of the rats. Afterwards hearts were excised andeither freeze-clamped for biochemical and molecular analysis or perfused on theisolated heart perfusion system to assess function and tolerance to ischaemia andreperfusion. Five series of experiments were performed: (i) Mechanical function wasdocumented before and after 20 minutes global ischaemia using the work heart model,(ii) A H2O filled balloon connected to a pressure transducer was inserted into the leftventricle to measure LVDP and ischaemic contracture in the Langendorff model, (iii)The left coronary artery was ligated for 35 minutes and infarct size determined after 30minutes of reperfusion by conventional TTC staining methods. (iv) Mitochondrialoxidative capacity was quantified. (v) High pressure liquid chromatography (HPLC) andWestern Blot analysis were performed on blood and heart tissue for determination ofhigh energy phosphates and protein expression and phosphorylation.Results: Neither the behavioural studies nor the corticosterone levels showed anyevidence of stress in the groups investigated. Hearts from creatine supplementedsedentary (33.5 ± 4.5%), creatine supplemented exercised rats (18.22 ± 6.2%) as wellas control exercised rats (26.1 ± 5.9%) had poorer aortic output recoveries than thesedentary control group (55.9 ± 4.35% p < 0.01) and there was also greater ischaemiccontracture in the creatine supplemented exercised group compared to the sedentarycontrol group (10.4 ± 4.23 mmHg vs 31.63 ± 4.74 mmHg). There were no differences ineither infarct size or in mitochondrial oxygen consumption between the groups. HPLCanalysis revealed elevated phosphocreatine content (44.51 ±14.65 vs 8.19 ±4.93nmol/gram wet weight, p < 0.05) as well as elevated ATP levels (781.1 ±58.82 vs 482.1±75.86 nmol/gram wet weight, p<0.05) in blood from creatine supplemented vs controlsedentary rats. These high energy phosphate elevations were not evident in hearttissue and creatine tranporter expression was not altered by creatine supplementation.GLUT4 and phosphorylated AMPK and PKB/Akt were all significantly higher in thecreatine supplemented exercised hearts compared to the control sedentary hearts.Conclusion: This study suggests that creatine supplementation has no effects on basalcardiac function but reduces myocardial tolerance to ischaemia in hearts from exercisetrained animals by increasing the ischaemic contracture and decreasing reperfusionaortic output. Exercise training alone also significantly decreased aortic output recovery.However, the exact mechanisms for these adverse myocardial effects are unknown andneed further investigation.

[发布机构] Stellenbosch University