Reduced nitric oxide production and altered myocardial metabolism during the decompensation of pacing-induced heart failure in the conscious dog.
Reduced nitric oxide production and altered myocardial metabolism during the decompensation of pacing-induced heart failure in the conscious dog.
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DOI：
10.1161/01.res.83.10.969
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发表时间：
1998-11
影响因子：
20.1
通讯作者：
F. Recchia;P. McConnell;R. Bernstein;T. Vogel;Xiaobin Xu;T. Hintze
中科院分区：
文献类型：
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作者：
F. Recchia;P. McConnell;R. Bernstein;T. Vogel;Xiaobin Xu;T. Hintze
本研究的目的是确定心脏一氧化氮（NO）的产生是否在起搏引起的心力衰竭的进展过程中发生变化，以及这种变化是否与心肌代谢的改变有关。对犬（n=8）进行仪器化，心脏起搏，直至左心室舒张末期压达到25 mm Hg，严重衰竭的临床体征明显。每周记录血流动力学测量结果，并从主动脉和冠状窦抽取血样，用于测量NO代谢产物、O2含量、游离脂肪酸（FFA）、乳酸和葡萄糖浓度。心脏产生的NO代谢物或消耗的O2或底物的利用率计算为冠状窦动脉差乘以冠状动脉流量。在终末期衰竭中，发生在29+/-1.6天，左心室舒张末期压为25+/-1 mm Hg，左心室收缩压为92+/-3 mm Hg，平均动脉压为75+/-2.5 mm Hg，dP/dtmax为1219+/-73 mm Hg/s（均P<0.05）。这些血流动力学的变化与心脏NO代谢产物的产生从0.37+/-0.16下降到-0.28+/-0.13 nmol/beat（P<0.05）有关。与对照组相比，O2消耗量和乳酸摄取量没有显著变化，而FFA摄取量从0.16+/-0.03降至0.05+/-0.01 microEq/beat，葡萄糖摄取量从-2.3+/-7.0增至41+/-10 microEq/beat（P<0.05）。心脏呼吸商也显著增加了28%。在14只正常狗中，在对照组和注射30 mg/kg硝基-L-精氨酸（一种NO合酶的竞争性抑制剂）后1小时进行了相同的测量。O2消耗量从对照组的0.05+/-0.002 mL/次增加到硝基-L-精氨酸后的0.071+/-0.003 mL/次，而FFA摄取从0.1+/-0.01微当量/拍减少到0.06+/-0.01微当量/拍，乳酸摄取从0.15+/-0.04微摩尔/拍增加到0.31+/-0.03微摩尔/拍，葡萄糖摄取从8.2+/-5.0微摩尔/拍增加到35.4+/-9.5微摩尔/拍，RQ增加23%（P均<0.05）。我们的研究结果表明，在心脏失代偿过程中，基础心脏产生的NO福尔斯低于正常水平，并且底物利用率发生变化。这种心肌底物利用的转换也发生在急性药理学阻断正常犬的NO产生后。
The aim of the present study was to determine whether cardiac nitric oxide (NO) production changes during the progression of pacing-induced heart failure and whether this occurs in association with alterations in myocardial metabolism. Dogs (n=8) were instrumented and the heart paced until left ventricular end-diastolic pressure reached 25 mm Hg and clinical signs of severe failure were evident. Every week, hemodynamic measurements were recorded and blood samples were withdrawn from the aorta and the coronary sinus for measurement of NO metabolites, O2 content, free fatty acids (FFAs), and lactate and glucose concentrations. Cardiac production of NO metabolites or consumption of O2 or utilization of substrates was calculated as coronary sinus-arterial difference times coronary flow. In end-stage failure, occurring at 29+/-1.6 days, left ventricular end-diastolic pressure was 25+/-1 mm Hg, left ventricular systolic pressure was 92+/-3 mm Hg, mean arterial pressure was 75+/-2.5 mm Hg, and dP/dtmax was 1219+/-73 mm Hg/s (all P<0.05). These changes in hemodynamics were associated with a fall of cardiac NO metabolite production from 0.37+/-0.16 to -0.28+/-0.13 nmol/beat (P<0.05). O2 consumption and lactate uptake did not change significantly from control, while FFA uptake decreased from 0.16+/-0.03 to 0.05+/-0.01 microEq/beat and glucose uptake increased from -2.3+/-7.0 to 41+/-10 microgram/beat (P<0.05). The cardiac respiratory quotient also increased significantly by 28%. In 14 normal dogs the same measurements were performed at control and 1 hour after we injected 30 mg/kg of nitro-L-arginine, a competitive inhibitor of NO synthase .O2 consumption increased from 0.05+/-0.002 mL/beat at control to 0.071+/-0.003 mL/beat after nitro-L-arginine, while FFA uptake decreased from 0.1+/-0.01 to 0.06+/-0.01 microEq/beat, lactate uptake increased from 0.15+/-0.04 to 0.31+/-0.03 micromol/beat, glucose uptake increased from 8.2+/-5.0 to 35.4+/-9.5 microgram/beat, and RQ increased by 23% (all P<0.05). Our results indicate that basal cardiac production of NO falls below normal levels during cardiac decompensation and that there are shifts in substrate utilization. This switch in myocardial substrate utilization also occurs after acute pharmacological blockade of NO production in normal dogs.