Myocardial carnitine and carnitine palmitoyltransferase deficiencies in patients with severe heart failure

We studied myocardial tissue from 25 cardiac transplant recipients, who had end-stage congestive heart failure (CHF), and from 21 control donor hearts . Concentrations of total carnitine (TC), free carnitine (FC, short-chain a cylcarnitines, long-chain acylcarnitines (LCAC) as well as carnitine palmit oyltransferase (CPT) activities were measured in myocardial tissue homogena tes and referred to the concentration of non-collagen protein. Compared to controls, the concentrations of TC and FC as well as total CPT activities w ere significantly lower in patients. LCAC levels and the LCAC to FC ratio v alues were significantly greater in patients than in controls. While the ma lonyl-CoA sensitive fraction of CPT, which represents CPT I activity, was s imilar in patients and controls, the residual CPT activity after inhibition by malonyl-CoA, representing CPT II activity, was significantly reduced in patients compared to controls. Moreover, the activity of CPT in the presen ce of Triton X-100, which also represents the activity of CPT II, was signi ficantly lower in patients than in controls. Malonyl-CoA concentrations req uired for half-maximal inhibition of CPT activity were significantly greate r in patients than in controls. There was a linear relationship between eje ction fraction (EF) values and concentrations of TC, FC, or total CPT activ ities. Values for LCAC and the LCAC to FC ratio were inversely related to E F values. We conclude that failing heart shows decreased total CPT and CPT II activities and carnitine deficiency that may be related to ventricle fun ction. (C) 2000 Elsevier Science B.V. All rights reserved.