Cohen R I, Shapir Y, Chen L, Scharf S M
Division of Pulmonary and Critical Care Medicine, The Long Island Jewish Medical Center, New Hyde Park, NY 11040-1433, USA.
Crit Care Med. 1998 Apr;26(4):738-47. doi: 10.1097/00003246-199804000-00026.
To determine whether the decrease in cardiac output after nitric oxide synthase inhibition in endotoxemia is due to increased left ventricular afterload or right ventricular afterload.
Prospective, randomized, unblinded study.
Research laboratory at an academic, university medical center.
Nonanesthetized, sedated, mechanically ventilated pigs.
Pigs were infused with 250 microg/kg of endotoxin over 30 mins. Normal saline was infused to maintain pulmonary artery occlusion pressure (PAOP) at a value not exceeding 1.5 times the baseline value. Left ventricular dimensions and function were studied using echocardiography. Right ventricular volumes and ejection fraction were determined via a rapid thermistor pulmonary artery catheter. We also measured mean arterial pressure (MAP), cardiac output, pulmonary arterial pressure, and calculated pulmonary and systemic resistances. Gastric tonometry was used as an index of gastric mucosal oxygenation and peripheral oxygenation. When MAP had decreased to < or =60 mm Hg or had decreased 30 mm Hg from baseline, nine animals received NG-nitro-L-arginine methyl ester (L-NAME) at 15 mg/kg to restore MAP to baseline. A second group of animals (n = 6) continued to receive normal saline, ensuring that PAOP did not exceed 1.5 times its baseline value. A third group of pigs (n = 5) did not receive endotoxin and served as the time control. In this group, a balloon was used to occlude the descending thoracic aorta and to increase MAP by approximately the same amount as in the L-NAME group.
Endotoxin caused an increase in pulmonary arterial pressure and right ventricular volumes, and a decrease in gastric mucosal pH. Cardiac output was maintained in the animals receiving the saline infusion. By 2 hrs, pulmonary arterial pressure had decreased but was still notably higher than baseline. However, by this time, MAP had decreased to < or =60 mm Hg. L-NAME administration restored MAP to its baseline value but resulted in worsening pulmonary hypertension, increased right ventricular volumes, and decreased cardiac output, compared with the saline group. Three animals that received L-NAME died of right ventricular failure. We did not observe any evidence of left ventricular dysfunction with increased left ventricular afterload. Moreover, the restoration of MAP with L-NAME infusion did not correct gastric mucosal acidosis. No changes were noted in the time-control group. Occlusion of the thoracic aorta increased MAP but did not change cardiac output. This finding demonstrates that increases in left ventricular afterload of the magnitude seen with the infusion of L-NAME do not lead to decreases in cardiac output.
The decrease in cardiac output after nitric oxide synthase inhibition in endotoxemia is due to increased right ventricular afterload and not to left ventricular afterload.
确定内毒素血症中一氧化氮合酶抑制后心输出量的降低是由于左心室后负荷增加还是右心室后负荷增加所致。
前瞻性、随机、非盲研究。
一所学术性大学医学中心的研究实验室。
未麻醉、镇静、机械通气的猪。
猪在30分钟内输注250微克/千克内毒素。输注生理盐水以维持肺动脉闭塞压(PAOP)不超过基线值的1.5倍。使用超声心动图研究左心室大小和功能。通过快速热敏电阻肺动脉导管测定右心室容积和射血分数。我们还测量了平均动脉压(MAP)、心输出量、肺动脉压,并计算了肺和全身阻力。胃张力测定法用作胃黏膜氧合和外周氧合的指标。当MAP降至≤60毫米汞柱或较基线值降低30毫米汞柱时,9只动物接受15毫克/千克的NG-硝基-L-精氨酸甲酯(L-NAME)以将MAP恢复至基线值。第二组动物(n = 6)继续接受生理盐水,确保PAOP不超过其基线值的1.5倍。第三组猪(n = 5)未接受内毒素,作为时间对照组。在该组中,使用球囊阻塞胸降主动脉,使MAP升高的幅度与L-NAME组大致相同。
内毒素导致肺动脉压升高和右心室容积增加,胃黏膜pH值降低。接受生理盐水输注的动物心输出量得以维持。到2小时时,肺动脉压有所下降,但仍明显高于基线。然而,此时MAP已降至≤60毫米汞柱。与生理盐水组相比,给予L-NAME可使MAP恢复至基线值,但导致肺动脉高压加重、右心室容积增加和心输出量降低。3只接受L-NAME的动物死于右心室衰竭。我们未观察到左心室后负荷增加导致左心室功能障碍的任何证据。此外,输注L-NAME恢复MAP并未纠正胃黏膜酸中毒。时间对照组未观察到任何变化。阻塞胸主动脉可使MAP升高,但不改变心输出量。这一发现表明,输注L-NAME时所见程度的左心室后负荷增加不会导致心输出量降低。
内毒素血症中一氧化氮合酶抑制后心输出量的降低是由于右心室后负荷增加而非左心室后负荷增加所致。