Effects of carnitine in ischemic and fatty acid supplemented swine hearts.
Effects of carnitine in ischemic and fatty acid supplemented swine hearts.
复制标题
肉碱对缺血和补充脂肪酸的猪心脏的影响。
DOI：
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发表时间：
1979
影响因子：
15.9
通讯作者：
G. Copenhaver
中科院分区：
文献类型：
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作者：
A. Liedtke;S. Nellis;G. Copenhaver
过量的游离脂肪酸（FFA）：白蛋白摩尔比已被确定会额外损害缺血性心脏的机械性能。肉毒碱是游离脂肪酸的细胞内载体，也是在缺血期间丢失到心脏的一种药物，已经被假定通过其替代部分恢复功能。为了测试其益处是否在过量FFA的情况下也有效，进行了这些研究。在主要方案中，四组灌注猪心（n = 45）进行了比较，在50分钟的控制流量（179.7 ml/min）和40分钟的全脑缺血（106.1 ml/min）。初始基线血清FFA：白蛋白摩尔比和肉毒碱水平在所有组分别为1.3：1和8.5 nmol/ml。在其中两组中，FFA：白蛋白比率在持续输注Intralidid的情况下增加至5.9：1。在两个交替组（一个与一个没有额外的FFA补充剂）DL-肉碱提供，足以增加血清水平近200倍。14颗心脏的缺血本身显着降低了整体和局部机械功能的多个参数，包括左心室（LV）和平均主动脉压、LV等容压发展（最大dp/dt）、LV心外膜运动和LV功，以及伴随的心肌耗氧量降低。12例FFA升高的心脏表现出类似的缺血性，进一步降低了机械功能（左室压：-20.8%，P < 0.05;平均主动脉压：-26.9%，P < 0.05;左室最大dp/dt：-39%，P < 0.05;左室局部缩短：-51.1%，P < 0.05;左室做功：-50.3%，P < 0.05）。在9个心脏中，没有补充额外FFA的dl-肉毒碱治疗在改善总体血流动力学性能方面没有明显效果。然而，在10个高FFA缺血心脏中，与未治疗组相比，dl-卡尼汀实现了几项改善：LV压力增加25.6%，P < 0.025;平均主动脉压：+43.5%，P < 0.05; LV最大dp/dt：+41.5%，P < 0.05;局部LV缩短：+241.3%，P < 0.001;以及LV功：在心肌耗氧量相当的水平下，+76.2%，P < 0.05。在一个单独的协议，立体特异性的影响进行了研究，通过比较左旋肉碱与dl-在全球灌注，棕榈酸补充心脏（5个心脏，每个治疗组）。在类似的条件下的流量和血清游离脂肪酸，机械功能的变化是可比的，除了倾向于执行更大的左心室工作在减少流量的左旋肉碱治疗的心脏。因此，它被证明，肉毒碱在缺血性心脏是能够保留机械功能的条件下过量FFA，大概是通过修改FFA中间体的毒性作用。主要的治疗作用似乎来自左旋异构体的肉毒碱。
FREE FATTY ACIDS (FFA) IN EXCESS FFA: albumin molar ratios have been determined to additionally compromise mechanical performance in ischemic hearts. Carnitine, an intracellular carrier of FFA and an agent which is lost to the heart during ischemia, has been postulated to in part restore function with its replacement. To test whether its benefits are also operative in a setting of excess FFA, these studies were performed. In the main protocol, four groups of perfused swine hearts (n = 45) were compared during 50 min of control flow (179.7 ml/min) and 40 min of global ischemia (106.1 ml/min). Initial base-line serum FFA:albumin molar ratios and carnitine levels in all groups were 1.3:1 and 8.5 nmol/ml, respectively. In two of these groups FFA:albumin ratios were increased to 5.9:1 with constant infusions of Intralipid. In two alternate groups (one with and one without extra FFA supplements) dl-carnitine was supplied, sufficient to increase serum levels nearly 200-fold. Ischemia per se in 14 hearts significantly decreased several parameters of global and regional mechanical function including left ventricular (LV) and mean aortic pressures, LV isovolumetric pressure development (max dp/dt), LV epicardial motion, and LV work, together with concomitant decreases in myocardial oxygen consumption. Elevated FFA in 12 hearts rendered similarly ischemic further decreased mechanical function (LV pressure: -20.8%, P < 0.05; mean aortic pressure -26.9%, P < 0.05; LV max dp/dt: -39%, P < 0.05; regional LV shortening: -51.1%, P < 0.05; and LV work: -50.3%, P < 0.05) as compared with nonsupplemented hearts. dl-Carnitine treatments in nine hearts, not supplemented with extra FFA were without apparent effect in improving overall hemodynamic performance. However, dl-carnitine in 10 high FFA-ischemic hearts effected several improvements as compared with the untreated group: LV pressure was increased 25.6%, P < 0.025; mean aortic pressure: +43.5%, P < 0.05; LV max dp/dt: +41.5%, P < 0.05; regional LV shortening: +241.3%, P < 0.001; and LV work: +76.2%, P < 0.05 at comparable levels of myocardial oxygen consumption. In a separate protocol, the effects of stereospecificity were also studied by comparing l- with dl-carnitine in globally perfused, palmitate-supplemented hearts (five hearts in each treatment group). At similar conditions of flow and serum FFA, changes in mechanical function were comparable, except for a tendency to perform greater LV work at reduced flows in the l-carnitine-treated hearts. Thus, it was demonstrated that carnitine in ischemic hearts is capable of preserving mechanical function under conditions of excess FFA, presumably by modifying the toxic effects of FFA intermediates. The major therapeutic actions appeared to derive from the l-isomer of carnitine.