Distribution of carbon flux within fatty acid utilization during myocardial ischemia and reperfusion.
Distribution of carbon flux within fatty acid utilization during myocardial ischemia and reperfusion.
复制标题
心肌缺血和再灌注期间脂肪酸利用中碳通量的分布。
DOI：
10.1161/01.res.69.3.779
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发表时间：
1991
影响因子：
20.1
通讯作者：
Renstrom,B
中科院分区：
文献类型：
--
作者：
Nellis,SH;Liedtke,AJ;Renstrom,B
对29个完整的工作猪心进行体外灌注，并分为两个研究组（16个有氧心脏和13个缺血/再流心脏）。使用阶跃函数，[14 C]棕榈酸盐平衡标记，绘制缺血后有氧灌注或再灌注（左前降支冠状动脉血流减少60%，持续30分钟）期间冠状动脉流出物中所含放射性脂肪酸产物的摄取和洗脱曲线。有氧心脏中的左前降支对照血流略微过度灌注（比缺血/复流心脏高18%）;除此之外，两组之间的回旋支和右冠状动脉血流、左心室压力、血清脂肪酸和血糖水平相当。正如在缺血/再流心脏中所预期的，再灌注时局部收缩期缩短和心肌耗氧量的恢复仅受到中度损害（分别为-20%和-19%，与缺血前值相比不显著，p <0.011，有氧心脏不显著）。在任一组中，标记脂肪酸利用释放的唯一显著代谢产物是14 CO2。还测量了较小的脂肪酸池，并由冠状动脉血管内容积中所含的脂肪酸池解释。我们可以确定没有显着的反向扩散的脂肪酸从心肌在任何灌注条件。两组中14 CO2产生早期的摄取时间常数也几乎相同（需氧和缺血/复流心脏分别为19.9 +/- 3.2和16.7 +/- 3.2分钟），并且与心率所述的血流动力学密切相关。在洗脱研究中，两个研究组中水溶性和脂肪酸合并液中的组织放射性均下降，复合脂质和胆固醇/胆固醇酯的计数保持稳定，而三酰甘油的计数变化。两组中的14 CO2洗脱在停止向灌注液中注入同位素后40分钟的采样中从未达到背景放射性，这表明捕获的底物从细胞内池缓慢释放，然后进行脂肪酸氧化。总之，这些实验表明，有氧和再灌注心肌之间的脂肪酸摄取，储存和释放特性非常相似的结果。我们发现，可逆性缺血后再流在首选底物利用和氧化方面没有差异。
Twenty-nine intact, working pig hearts were extracorporeally perfused and divided into two study groups (16 Aerobic and 13 Ischemic/Reflow hearts). Step function, equilibrium labeling with [14C]palmitate was used to develop uptake and washout curves of radioactive fatty acid products contained in coronary effluent during either aerobic perfusion or reperfusion after ischemia (60% reduction in left anterior descending coronary flow for 30 minutes). Left anterior descending control flows were slightly overperfused in Aerobic hearts (18% higher than in Ischemic/Reflow hearts); otherwise, circumflex and right coronary flows, left ventricular pressure, and serum fatty acids and blood sugar levels were comparable between groups. As expected in Ischemic/Reflow hearts, recovery of regional systolic shortening and myocardial oxygen consumption in reperfusion was only modestly impaired (-20% and -19%, respectively, not significant and p less than 0.011 compared with preischemic values, not significant from Aerobic hearts). The only significant metabolized product to be released from labeled fatty acid utilization in either group was 14CO2. A smaller fatty acid pool also was measured and accounted for by that contained in the coronary intravascular volume. We could determine no significant back diffusion of fatty acids from myocardium in either perfusion condition. Uptake time constants of the early phase of 14CO2 production also were virtually identical in both groups (19.9 +/- 3.2 versus 16.7 +/- 3.2 minutes in Aerobic and Ischemic/Reflow hearts, respectively) and strongly correlated with hemodynamics as described by heart rate. In washout studies, tissue radioactivity in the aqueous soluble and fatty acid pools declined in both study groups, and counts in complex lipids and cholesterol/cholesteryl esters remained steady, whereas those in triacylglycerols varied. Washout of 14CO2 in both groups never reached background radioactivity over a 40-minute sampling after cessation of isotope infusion into the perfusate, suggesting slow release of trapped substrate from intracellular pools, which then proceeded to fatty acid oxidation. In conclusion, these experiments have demonstrated very similar findings with respect to fatty acid uptake, storage, and release characteristics between aerobic and reperfused myocardium. We found no differences in preferred substrate utilization and oxidation as a result of reversible ischemia followed by reflow.