Abstract
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Objectives: ACE inhibitor (ACEI) improves both cardiac function and hemodynamics of failing heart. The details of the metabolism, however, still remain unclear. The purpose of this study was to examine the myocardial metabolism of pacing-induced failing heart with ACEI, using a fatty acid analog, I-123 BMIPP.
Methods: Using a canine model, failing heart was iuduced by 4 weeks over drive pacing (210-230 bpm). Cardiac output (CO), pulmonary capillary wedge pressure (PCWP), and ejection fraction of left ventricle (EF) were examined before and 4 weeks after pacing (hear failure dog, n=6). After 4 weeks of over drive pacing, canine chest was opened, and BMIPP was directly injected into left anterior descending coronary artery. Then the rapid extraction into myocardium and the subsequent retention in 30 min. were investigated, and further metabolites, including back diffusion of BMIPP, were evaluated using a HPLC technique. In addition to that, the effects of ACEI on these parameters were examined (n=5, lisinopril 30 mg/day, had been orally prescribed for 3 weeks from 1week after the beginning of over drive pacing).
Results: The decreased CO by 4weeks pacing improved in 9.6% and the elevated PCWP improved in 13.5% with ACEI. The decreased EF with heart failure also improved by ACEI (26±4% to 32±5%) with statistical significance (p<0.05). In metabolic study, the extraction improved in 31.3% and the retention also improved in 35.7% with ACEI. The metabolites of BMIPP consisted of back diffusion of BMIPP, alpha-oxidation metabolite, and beta-oxidation metabolites. Among these metabolites, beta-oxidation metabolites decreased to 50.2% heart failure compared to those with control, which were preserved 99.2% with ACEI (p<0.05).
Conclusions: These results indicated that ACEI improved not only cardiac function and hemodynamics, but also beta-oxidation in mitochondrias of failing heart, suggesting the reduced myocardial energy production by lipid was improved by ACEI, and this improvement might be strongly related to the betterment of cardiac function of failing heart.
- Society of Nuclear Medicine, Inc.