Cohen R I, Huberfeld S, Genovese J, Steinberg H N, Scharf S M
Division of Pulmonary and Critical Care Medicine, The Long Island Jewish Medical Center, New Hyde Park, New York 11040, USA.
J Crit Care. 1996 Mar;11(1):27-36. doi: 10.1016/s0883-9441(96)90017-9.
Nitric oxide (NO) synthase inhibitors increase mean arterial pressure (MAP) and systemic vascular resistance (SVR) in animal models of sepsis and in humans with septic shock. However, NO synthase inhibitors may cause coronary vessel constriction leading to myocardial ischemia and increased mortality in endotoxemic animals. This study was designed to test the acute effect of NG-nitro-L-arginine (L-NAME) on left ventricular (LV) function and coronary blood flow in a dog model of endotoxemia.
In open chest, anesthetized dogs endotoxemia was induced intravenously (IV) by Escherichia coli lipopolysaccharide at 2 mg/kg for 60 minutes. This resulted in hypotension, acidosis, and decreased SVR while cardiac index (CI) was maintained. When MAP was < or = 60 mm Hg, animals were resuscitated with either dextran (group I), or L-NAME 30 mg/kg IV bolus (group II). Group III received L-NAME only. A fourth group of dogs was given endotoxin and not resuscitated. Animals were followed up for 30 minutes after intervention. Animals in the fourth group were followed up until the MAP was approximately 30 mm Hg. Heart rate, CI, MAP, LV end systolic and diastolic pressures, dP/dt at a pressure of 40 mm Hg, left anterior descending artery coronary blood flow, regional LV contraction (sonomicrometer crystals), coronary pressures, gas tension, and lactates were continuously recorded. A catheter placed in the coronary sinus allowed measurement of coronary sinus pressure, as well as coronary sinus lactate and gas tensions. Stroke volume index, stroke work index, systemic vascular resistance index (SVRI), coronary vascular resistance, percent myocardial shortening, myocardial oxygen consumption (Mvo2) and net myocardial lactate production were calculated.
In Group I, fluid administration increased MAP, stroke work index, coronary blood flow, percent myocardial shortening, and Mvo2. In Group II, L-NAME increased MAP to the same extent as fluid administration without evidence of coronary ischemia or myocardial dysfunction. L-NAME did not alter Mvo2 in either endotoxemic or nonendotoxemic animals. In group III, L-NAME alone resulted in a significant increase in MAP and SVRI, but its effects on coronary blood flow and LV function were not significant. We did not observe net lactate production in any of the groups. Coronary blood flow increased out of proportion to Mvo2 in group I animals.
We conclude that although L-NAME at 30 mg/kg causes vasoconstriction, its effects on coronary blood flow and LV function were not significant.
在脓毒症动物模型和感染性休克患者中，一氧化氮（NO）合酶抑制剂可增加平均动脉压（MAP）和全身血管阻力（SVR）。然而，NO合酶抑制剂可能导致冠状动脉收缩，进而引起心肌缺血，并增加内毒素血症动物的死亡率。本研究旨在测试NG-硝基-L-精氨酸（L-NAME）对内毒素血症犬模型左心室（LV）功能和冠状动脉血流的急性影响。
在开胸、麻醉的犬中，通过静脉注射（IV）2mg/kg大肠杆菌脂多糖诱导内毒素血症60分钟。这导致低血压、酸中毒和SVR降低，而心脏指数（CI）保持不变。当MAP≤60mmHg时，动物用右旋糖酐（I组）或30mg/kg L-NAME静脉推注（II组）进行复苏。III组仅接受L-NAME。第四组犬给予内毒素但未进行复苏。干预后对动物随访30分钟。第四组动物随访至MAP约为30mmHg。持续记录心率、CI、MAP、左心室收缩末期和舒张末期压力、40mmHg压力下的dP/dt、左前降支冠状动脉血流、局部左心室收缩（超声微测晶体）、冠状动脉压力、气体张力和乳酸。置于冠状窦的导管用于测量冠状窦压力以及冠状窦乳酸和气体张力。计算每搏量指数、每搏功指数、全身血管阻力指数（SVRI）、冠状动脉血管阻力、心肌缩短百分比、心肌耗氧量（Mvo2）和心肌乳酸净生成量。
在I组中，补液增加了MAP、每搏功指数、冠状动脉血流、心肌缩短百分比和Mvo2。在II组中，L-NAME使MAP升高的程度与补液相同，且无冠状动脉缺血或心肌功能障碍的证据。L-NAME对内毒素血症或非内毒素血症动物的Mvo2均无影响。在III组中，单独使用L-NAME导致MAP和SVRI显著升高，但其对冠状动脉血流和左心室功能的影响不显著。我们在任何一组中均未观察到乳酸净生成。I组动物的冠状动脉血流增加与Mvo2不成比例。
我们得出结论，尽管30mg/kg的L-NAME会引起血管收缩，但其对冠状动脉血流和左心室功能的影响并不显著。
