Myocardial lipid metabolism in compensated and advanced stages of heart failure: evaluation by canine pacing model with BMIPP.
The normal myocardium uses primarily fatty acid as its energy source, but, as heart failure develops, the myocardial fatty acid metabolism is limited. In this study, impairment of the lipid metabolism in heart failure was serially evaluated with 123I-(rho-iodophenyl)3-(R,S)-methylpentadecanoic acid (BMIPP), a radioiodinated fatty acid analog.


METHODS
Rapid ventricular pacing was introduced in 10 beagle dogs. Dogs were subjected to hemodynamic assessment and measurement of catecholamine before and after pacing. After 1 wk (group A; n = 4) and 4 wk (group B; n = 6) of pacing, BMIPP was injected directly into the left anterior descending artery; its extraction, retention, and washout rate in the early phase were calculated, and the metabolites in the myocardium were evaluated using high-performance liquid chromatography. These factors were compared with those of healthy control animals (group C; n = 6).


RESULTS
The left ventricular ejection fraction and cardiac output decreased significantly in groups A and B after pacing. The pulmonary capillary wedge pressure did not change in group A but increased significantly in group B. Plasma norepinephrine increased progressively as heart failure developed but did not reach statistical significance. The washout rate in the early phase increased, significantly in groups A and B compared with that of group C. Extraction and retention of BMIPP did not change in group A. In group B, extraction tended to decrease and retention decreased significantly compared with that of group C. The levels of full metabolite formed by complete oxidation of BMIPP decreased, and backdiffusion of BMIPP increased significantly in groups A and B compared with that of group C. Myocardial blood flow did not change among the three groups.


CONCLUSIONS
Our study indicates that myocardial fatty acid oxidation begins to be inhibited and that washout of BMIPP increases in the compensated stage of left ventricular dysfunction but that myocardial extraction and retention of fatty acid are definitely impaired in the advanced stage of heart failure. Therefore, as assessed by BMIPP, the myocardial lipid metabolism is related to the pathophysiology of the development and worsening of heart failure.
Kataoka
K
K
Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Japan.
Nohara
R
R
Hosokawa
R
R
Hirai
T
T
Okuda
K
K
Li-Guang
C
C
Fujibayashi
Y
Y
Fujita
M
M
Konishi
J
J
Sasayama
S
S
D000818:Animals; D002304:Cardiac Pacing, Artificial; D004285:Dogs; D005227:Fatty Acids / Q000493:pharmacokinetics; D006333:Heart Failure / Q000000981:diagnostic imaging* / Q000378:metabolism; D006439:Hemodynamics / Q000502:physiology; D007457:Iodine Radioisotopes; D007462:Iodobenzenes / Q000493:pharmacokinetics; D050356:Lipid Metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011877:Radionuclide Imaging; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000378:metabolism
D005227:Fatty Acids; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; C049338:iodofiltic acid