Cohen R I, Chen L, Scharf S M
Division of Pulmonary and Critical Care Medicine, Long Island Jewish Medical Center, Albert Einstein College of Medicine, New Hyde Park, NY 11040, USA.
J Crit Care. 1996 Dec;11(4):206-13. doi: 10.1016/s0883-9441(96)90032-5.
Nitric oxide (NO) synthase inhibition has been reported to cause elevation in mean arterial pressure (MAP) and a decrease in cardiac index (CI), the cause of which is not completely understood. It has been shown that increased concentrations of NO synthase inhibitors cause a further drop in cardiac output without a corresponding increase in arterial pressure, prompting the conclusion that NO inhibition results in direct myocardial depression. However, myocardial ischemia was not completely ruled out as a cause for myocardial dysfunction in these studies. The purpose of this study was to examine the effects of 30 mg/kg of the NO synthase inhibitor NG-nitro-L-arginine-methyl ester (L-NAME) to those of 300 mg/kg and assess the effects on coronary ischemia and myocardial function.
Eight anesthetized dogs underwent median sternotomy and pericardiectomy. L-NAME 30 mg/kg was administered and the effects were recorded at 5, 15, and 30 minutes. Thereafter, 300 mg/kg was administered and the effects were observed for 5, 15, and 30 minutes. We measured MAP, heart rate (HR), CI, left ventricle (LV) and systolic and diastolic pressures, the first derivative of LV pressure (dP/dt), left anterior descending artery blood flow, regional LV contraction, gas tensions, and lactates. A coronary sinus catheter allowed for measurements of coronary sinus pressure, lactate, and gas tensions. Stroke volume, percent myocardial shortening (dL/dt) myocardial oxygen consumption, and net lactate myocardial production were calculated.
Whereas 30 mg/kg had minimal effects on coronary blood flow and LV function, 300 mg/kg resulted in profound hypotension, drop in CI, and acidocsis.
L-NAME at 30 mg/kg caused a rise in MAP and systemic vascular resistance; however, it had no effect on ventricular function. High dose NO synthase inhibition causes myocardial depression not related to increased afterload, coronary vasoconstriction, or myocardial ischemia.
据报道，一氧化氮（NO）合酶抑制可导致平均动脉压（MAP）升高和心脏指数（CI）降低，其原因尚未完全明确。研究表明，NO合酶抑制剂浓度增加会导致心输出量进一步下降，而动脉压却没有相应升高，这提示NO抑制会导致直接的心肌抑制。然而，在这些研究中，心肌缺血作为心肌功能障碍的一个原因并未被完全排除。本研究的目的是检验30mg/kg的NO合酶抑制剂NG-硝基-L-精氨酸甲酯（L-NAME）与300mg/kg的L-NAME的作用，并评估其对冠状动脉缺血和心肌功能的影响。
八只麻醉犬接受正中胸骨切开术和心包切除术。给予30mg/kg的L-NAME，并在5、15和30分钟记录其效果。此后，给予300mg/kg，并观察5、15和30分钟的效果。我们测量了MAP、心率（HR）、CI、左心室（LV）及收缩压和舒张压、LV压力的一阶导数（dP/dt）、左前降支动脉血流量、局部LV收缩、气体张力和乳酸。一根冠状窦导管用于测量冠状窦压力、乳酸和气体张力。计算每搏输出量、心肌缩短百分比（dL/dt）、心肌耗氧量和心肌净乳酸生成量。
30mg/kg对冠状动脉血流量和LV功能影响极小，而300mg/kg则导致严重低血压、CI下降和酸中毒。
30mg/kg的L-NAME可使MAP和全身血管阻力升高；然而，对心室功能无影响。高剂量的NO合酶抑制会导致心肌抑制，这与后负荷增加、冠状动脉收缩或心肌缺血无关。
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