Prendergast B D, Sagach V F, Shah A M
Department of Cardiology, University of Wales College of Medicine, Cardiff, UK.
Circulation. 1997 Aug 19;96(4):1320-9. doi: 10.1161/01.cir.96.4.1320.
The Frank-Starling response contributes to the regulation of cardiac output. The major underlying subcellular mechanism is a length-dependent change in myofilament responsiveness to Ca2+. Recent studies indicate that nitric oxide decreases myofilament responsiveness to Ca2+ and modulates myocardial relaxation and left ventricular (LV) diastolic function. We therefore investigated the interaction between nitric oxide and the Frank-Starling response.
Isolated ejecting guinea pig hearts (constant afterload and heart rate) were studied before and after interventions. Elevation of filling pressure from 10 to 20 cm H2O increased cardiac output, LV end-diastolic pressure (LVEDP), and peak LV pressure (LVPmax). In the presence of N(G)-monomethyl-L-arginine (L-NMMA, 10 micromol/L; n=10) or free hemoglobin (1 micromol/L; n=8), preload-induced increases in cardiac output were significantly attenuated but baseline cardiac output was unaffected. The effects of L-NMMA were inhibited in the presence of excess L-arginine (100 micromol/L; n=6). These changes were not attributable to alterations in coronary flow. Prostaglandin F2alpha (0.01 micromol/L; n=6), which reduced coronary flow, failed to alter the cardiac output response to preload elevation. The exogenous nitric oxide donor sodium nitroprusside (1 micromol/L; n=6) reduced cardiac output at the lowest preload but not at higher preloads. LVEDP was elevated after L-NMMA and hemoglobin but reduced after sodium nitroprusside.
Basal intracardiac production of nitric oxide significantly augments preload-induced rises in cardiac output in the isolated ejecting guinea pig heart. The mechanism appears to be unrelated to changes in coronary flow and may involve direct effects of nitric oxide on myocardial diastolic and/or systolic function.
Frank-Starling 反应有助于心输出量的调节。其主要潜在的亚细胞机制是肌丝对 Ca2+反应性的长度依赖性变化。最近的研究表明，一氧化氮可降低肌丝对 Ca2+的反应性，并调节心肌舒张和左心室（LV）舒张功能。因此，我们研究了一氧化氮与 Frank-Starling 反应之间的相互作用。
对离体射血豚鼠心脏（后负荷和心率恒定）在干预前后进行研究。充盈压从 10 cm H2O 升高至 20 cm H2O 可增加心输出量、左心室舒张末期压力（LVEDP）和左心室峰值压力（LVPmax）。在存在 N(G)-单甲基-L-精氨酸（L-NMMA，10 μmol/L；n = 10）或游离血红蛋白（1 μmol/L；n = 8）的情况下，预负荷诱导的心输出量增加显著减弱，但基础心输出量未受影响。在存在过量 L-精氨酸（100 μmol/L；n = 6）时，L-NMMA 的作用受到抑制。这些变化并非归因于冠状动脉血流的改变。前列腺素 F2α（0.01 μmol/L；n = 6）可减少冠状动脉血流，但未能改变心输出量对预负荷升高的反应。外源性一氧化氮供体硝普钠（1 μmol/L；n = 6）在最低预负荷时降低心输出量，但在较高预负荷时则不然。L-NMMA 和血红蛋白处理后 LVEDP 升高，而硝普钠处理后则降低。
在离体射血豚鼠心脏中，心脏内一氧化氮的基础产生显著增强了预负荷诱导的心输出量增加。其机制似乎与冠状动脉血流的变化无关，可能涉及一氧化氮对心肌舒张和/或收缩功能的直接作用。
