Effects of reducing fatty acid metabolism on mechanical function in regionally ischemic hearts.
Effects of reducing fatty acid metabolism on mechanical function in regionally ischemic hearts.
复制标题
减少脂肪酸代谢对局部缺血心脏机械功能的影响。
DOI：
10.1152/ajpheart.1984.247.3.h387
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
Mjos,OD
中科院分区：
文献类型：
--
作者：
Liedtke,AJ;Nellis,SH;Mjos,OD
过量的脂肪酸损害缺血心脏的机械功能和电稳定性。本研究的目的是测试奥非尼辛（一种能够降低脂肪酸代谢的药物）是否可以预防这些后果，从而改善血流动力学性能。两组工作猪心（n = 15），体外灌注全血，比较超过90分钟的控制冠状动脉灌注。全身给予含肝素的三酰甘油乳剂（Intradenoid），使血清脂肪酸增加3倍（0.30 - 0.92 mumol/ml）。标记的[U14 C]棕榈酸酯选择性地给予左前降支冠状动脉循环，以跟踪脂肪酸氧化。在最后30分钟的灌注中，该床中的冠状动脉流量减少了50%。在30分钟灌注时向安慰剂或治疗的动物施用盐水（n = 7）或氧非尼辛（17-33 mg/kg，n = 8）。标记棕榈酸酯的14 CO2产生在正常血流时减少了55%（P小于0.025），在缺血期间进一步减少。在有氧和缺血心肌中，奥非尼辛处理的心脏中酰基肉毒碱的组织水平显著降低，乙酰辅酶A水平显著增加。这些变化与机械功能的改善有关。与安慰剂心脏相比，在缺血结束时，左心室收缩压和发展压以及最大左心室dP/dt分别增加36 δ %，P <0.01; 46 δ %，P <0.025;和41 δ %，P <0.025。（250字处删节）
Fatty acids in excess impair mechanical function and electrical stability in ischemic hearts. The purpose of the present studies was to test whether oxfenicine, an agent capable of reducing fatty acid metabolism, can prevent these consequences and in so doing improve hemodynamic performance. Two groups of working swine hearts (n = 15), extracorporeally perfused with whole blood, were compared over 90 min of controlled coronary perfusion. An emulsion of triacylglycerols (Intralipid) with heparin were administered systemically to augment serum fatty acids threefold (0.30 to 0.92 mumol/ml). Labeled [U14C]palmitate was administered selectively into the left anterior descending coronary circulation to follow fatty acid oxidation. Coronary flow in this bed was decreased by 50% over the final 30 min of perfusion. Saline (n = 7) or oxfenicine (17-33 mg/kg, n = 8) was administered to placebo or treated animals at 30 min perfusion. 14CO2 production from labeled palmitate was decreased by 55% (P less than 0.025) at normal flows in oxfenicine-treated hearts and was reduced further during ischemia. Tissue levels of acyl carnitine were significantly reduced and acetyl CoA levels significantly increased in oxfenicine-treated hearts both in aerobic and ischemic myocardium. These changes were associated with an improvement in mechanical function. Left ventricular systolic and developed pressures and maximum left ventricular dP/dt were increased by 36 delta %, P less than 0.01; 46 delta %, P less than 0.025; and 41 delta %, P less than 0.025, respectively, at end ischemia as compared with placebo hearts.(ABSTRACT TRUNCATED AT 250 WORDS)