Inhibition of fatty acid metabolism alters myocardial high-energy phosphates in vivo.
Inhibition of fatty acid metabolism alters myocardial high-energy phosphates in vivo.
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DOI：
10.1152/ajpheart.1994.267.1.h224
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发表时间：
1994-07
期刊：
影响因子：
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通讯作者：
G. Schwartz;C. Greyson;J. Wisneski;J. García
中科院分区：
文献类型：
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作者：
G. Schwartz;C. Greyson;J. Wisneski;J. García
我们以前观察到，异丙肾上腺素（ISO）刺激原位猪右心室（RV）增加磷酸肌酸（PCr）ATP的比例，伴随着心肌游离脂肪酸（FFA）摄取显着增加。我们假设增加FFA的摄取和利用导致PCr/ATP的增加，ISO期间抑制FFA代谢可以防止这种增加。在开胸猪中，在不存在（n = 6）和存在（n = 6）肉毒碱棕榈酰转移酶I抑制剂奥非尼辛（65 mg/kg iv）的情况下，ISO（0.15 μ g.kg-1.min-1 iv）可增加RV游离壁的心肌耗氧量（MVO 2）。ISO导致MVO 2和动脉FFA浓度增加两倍。在不存在奥非尼辛的情况下，ISO使RV FFA摄取从对照的0.01 +/- 0.01增加至0.11 +/- 0.02（SE）mumol.g-1.min-1。通过31 P-核磁共振光谱测量的PCr/ATP从1.75 +/- 0.05上升到2.22 +/- 0.10（P < 0.05）。在存在氧非尼辛的情况下，尽管动脉FFA浓度升高，但FFA摄取并未随ISO增加。PCr/ATP从1.65 +/- 0.05下降到1.53 +/- 0.07（P < 0.01，与无奥非尼辛的反应相比）。在另外4头猪中，在不存在ISO的情况下，通过输注Intraperoid和肝素钠增加了动脉FFA浓度。PCr/ATP值均升高。当奥非尼辛与Intraperoid一起给药时，每头猪的PCr/ATP降低。我们的结论是，增加FFA的利用率提高RV PCr/ATP的比例在体内。抑制FFA代谢可防止在ISO或高动脉FFA时观察到的PCr/ATP升高。（250字处删节）
We previously observed that isoproterenol (ISO) stimulation of the in situ porcine right ventricle (RV) increases the ratio of phosphocreatine (PCr) to ATP, accompanied by marked augmentation of myocardial free fatty acid (FFA) uptake. We hypothesized that increased FFA uptake and utilization cause the increase in PCr/ATP and that inhibition of FFA metabolism during ISO would prevent such an increase. In open-chest pigs, myocardial oxygen consumption (MVO2) of the RV free wall was increased with ISO (0.15 microgram.kg-1.min-1 iv) in the absence (n = 6) and presence (n = 6) of oxfenicine (65 mg/kg iv), an inhibitor of carnitine palmitoyltransferase I. ISO caused twofold increases in MVO2 and arterial FFA concentration. In the absence of oxfenicine, ISO increased RV FFA uptake from a control of 0.01 +/- 0.01 to 0.11 +/- 0.02 (SE) mumol.g-1.min-1. The PCr/ATP, measured by 31P-nuclear magnetic resonance spectroscopy, rose from 1.75 +/- 0.05 to 2.22 +/- 0.10 (P < 0.05). In the presence of oxfenicine, FFA uptake did not increase with ISO, despite elevated arterial FFA concentration. PCr/ATP fell from 1.65 +/- 0.05 to 1.53 +/- 0.07 (P < 0.01 vs. response without oxfenicine). In four additional pigs, arterial FFA concentration was increased in the absence of ISO by infusion of Intralipid and heparin sodium. PCr/ATP increased in each pig. When oxfenicine was administered with Intralipid, PCr/ATP decreased in each pig. We conclude that increased utilization of FFA raises the RV PCr/ATP ratio in vivo. Inhibition of FFA metabolism prevents the rise in PCr/ATP otherwise observed with ISO or with high arterial FFA.(ABSTRACT TRUNCATED AT 250 WORDS)