Mechanisms of nitrate accumulation in plasma during pacing-induced heart failure in conscious dogs
Mechanisms of nitrate accumulation in plasma during pacing-induced heart failure in conscious dogs
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DOI：
10.1006/niox.1997.0150
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发表时间：
1997-10-01
影响因子：
3.9
通讯作者：
Hintze, TH
中科院分区：
文献类型：
--
作者：
Bernstein, RD;Zhang, XP;Hintze, TH
本研究的目的是了解心力衰竭期间血浆氮氧化物变化背后的机制。心力衰竭与血浆硝酸盐水平升高有关，但大多数实验证据表明心力衰竭期间内皮一氧化氮的产生减少。狗长期接受仪器测量全身血流动力学和左心室（LV）尺寸。心脏起搏频率为 210 bpm，持续 3 周 (n = 14)，然后以 240 bpm 持续 1 周 (n = 7)。每周监测血流动力学、动脉血气、血浆氮氧化物和肌酐水平。心力衰竭表现为恶病质、腹水和血流动力学改变。静息心率上升（94 +/- 6 至 135 +/- 9 bpm），LV dP/dt 下降（2810 +/- 82 至 1471 +/- 99 mm Hg/s），而 LV 舒张末压增加四倍（5.8 +/- 0.7 至 25 +/- 0.8 mm Hg），舒张期壁应力增加四倍（11 +/- 0.8 mm Hg）。 1.3 至 43 +/- 6.0 g/cm(2)，所有 P < 0.05）。这些变化发生在血浆NOx倍增期间（5.5+/-1.5至10+/-1.6μM，P<0.05）。起搏 3 周后，血浆 NOx 没有变化。血浆肌酐水平增加 450%（从 0.27 +/- 0.32 至 1.21 +/- 0.63 mg%）。起搏 3 周后，筛选的冠状微血管中激动剂刺激的亚硝酸盐产生量没有变化，但在心力衰竭后减少。血浆 NOx 与 LV dP/dt 或收缩期壁应力无关，但与 LV EDP 或舒张期壁应力直接相关，与心脏做功成反比。血浆 NOx 升高与血浆肌酐水平直接相关（Y = 4.8X + 2.8，r(2) = 0.84），表明心力衰竭期间血浆 NOx 升高是由于肾功能下降而不是 NO 产生增加所致。 (C) 1997 年学术出版社。
The goal of this study was to understand the mechanisms behind the changes in plasma NOx during heart failure. Heart failure is associated with an increase in plasma nitrate levels, and yet most experimental evidence demonstrates a reduction in endothelial nitric oxide production during heart failure. Dogs were chronically instrumented for measurement of systemic hemodynamics and left ventricular (LV) dimensions. Hearts were paced at 210 bpm for 3 weeks (n = 14) and then 240 bpm for 1 week (n = 7). Hemodynamics, arterial blood gases, plasma NOx, and creatinine levels were monitored weekly. Heart failure was evidenced by cachexia, ascites, and hemodynamic alterations. Resting heart rate rose (94 +/- 6 to 135 +/- 9 bpm), and LV dP/dt fell (2810 +/- 82 to 1471 +/- 99 mm Hg/s), while LV end diastolic pressure quadrupled (5.8 +/- 0.7 to 25 +/- 0.8 mm Hg), and diastolic wall stress quadrupled (11 +/- 1.3 to 43 +/- 6.0 g/cm(2), all P < 0.05). These changes occurred during a doubling in plasma NOx (5.5 +/- 1.5 to 10 +/- 1.6 mu M, P < 0.05). There were no changes in plasma NOx through 3 weeks of pacing. Plasma creatinine levels increased 450% (from 0.27 +/- 0.32 to 1.21 +/- 0.63 mg%). Stimulated nitrite production by agonists in sieved coronary microvessels was unchanged after 3 weeks of pacing but was reduced after heart failure. Plasma NOx did not correlate with LV dP/dt or systolic wall stress but correlated directly with LV EDP or diastolic wall stress and inversely with cardiac work. Plasma NOx rose in direct relation to plasma creatinine levels (Y = 4.8X + 2.8, r(2) = 0.84), suggesting that the rise in plasma NOx during heart failure is due to decreased renal function not increased NO production. (C) 1997 Academic Press.