Assessment of myocardial triglyceride oxidation with PET and 11C-palmitate

Zulfia Kisrieva-Ware, Andrew R. Coggan, Terry L. Sharp, Carmen S. Dence, Robert J. Gropler, Pilar Herrero

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22 Scopus citations

Abstract

Background: The goal of this study was to test whether myocardial triglyceride (TG) turnover including oxidation of TG-derived fatty acids (FA) could be assessed with PET and 11C-palmitate. Methods and Results: A total of 26 dogs were studied fasted (FAST), during Intralipid infusion (IL), during a hyperinsulinemic-euglycemic clamp without (HIEG), or with Intralipid infusion (HIEG + IL). 11C-palmitate was injected, and 45 minutes were allowed for labeling of myocardial TG pool. 3D PET data were then acquired for 60 minutes, with first 15 minutes at baseline followed by 45 minutes during cardiac work stimulated with constant infusion of either phenylephrine (FAST, n = 6; IL, n = 6; HIEG + IL, n = 6) or dobutamine (FAST, n = 4; HIEG, n = 4). Myocardial 11C washout during adrenergic stimulation (AS) was fitted to a mono-exponential function (Km(PET)). To determine the source of this 11C clearance, Km(PET) was compared to direct coronary sinus-arterial measurements of total 11C activity, 11C-palmitate, and 11CO2. Before AS, PET curves in all groups were flat indicating absence of net clearance of 11C activity from heart. In both FAST groups, AS resulted in negligible net 11C activity and 11CO2 production higher than net 11C-palmitate uptake. AS with phenylephrine resulted in net myocardial uptake of total 11C activity and 11C- palmitate in IL and HIEG + IL, and 11CO2 production lower than 11C-palmitate uptake. In contrast, AS with dobutamine in HIEG resulted in net clearance of all 11C metabolites (total 11C activity, 11C-palmitate and 11CO2) with 11CO2 contributing 66% to endogenous FA oxidation. The AS resulted in significant Km(PET) in all the groups, except HIEG + IL. However, positive correlation between Km(PET) and 11CO2 was observed only in HIEG (R2 = 0.83, P = .09). Conclusions: This is the first study to demonstrate that using PET and pre-labeling of intracardiac TG pool with 11C-palmitate, noninvasive assessment of myocardial TG use is feasible under metabolic conditions that favor endogenous TG use such as increased metabolic demand (β-adrenergic stimulation of cardiac work) with limited availability of exogenous substrate (HIEG).

Original languageEnglish
Pages (from-to)411-421
Number of pages11
JournalJournal of Nuclear Cardiology
Volume16
Issue number3
DOIs
StatePublished - 2009

Keywords

  • 3DPET
  • C-palmitate
  • Mono-exponential clearance
  • Myocardial triglyceride turnover
  • β-adrenergic stimulation

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