Fukahara K, Murakami A, Watanabe G, Kotoh K, Misaki T
Department of Surgery, Toyama Medical and Pharmaceutical University, Japan.
Eur J Cardiothorac Surg. 1997 Feb;11(2):343-9. doi: 10.1016/s1010-7940(96)01027-5.
Pulmonary hypertension and transient graft dysfunction may complicate the postoperative course of patients undergoing lung transplantation. Recent studies have suggested that ischemia followed by reperfusion impairs release of endothelium-derived nitric oxide (NO). We investigated the acute effect of inhaled NO on hemodynamics and the oxygen free radical scavenger system after reperfusion following lung ischemia.
Fourteen anesthetized mongrel dogs were ventilated mechanically. After median sternotomy the left lung was rendered ischemic by totally clamping the left pulmonary hilum. After 90 min, the left lung was reperfused for 150 min by unclamping of the left hilum and clamping the right pulmonary hilum so that all pulmonary blood flow was directed to the left lung. Seven dogs inhaled 30 parts per million (ppm) NO during reperfusion (NO group); the other seven dogs were ventilated without NO inhalation (control group). Hemodynamics, gas exchange, superoxide dismutase activity and lipid peroxide of pulmonary venous blood, and wet/dry ratio of reperfused lung were measured.
Neither of the two groups showed any change in systemic blood pressure prior to or following reperfusion. Immediately after reperfusion, mean pulmonary arterial pressure was significantly less (23.2 +/- 4.2 mmHg) in the NO group than in the control group (32.7 +/- 5.8 mmHg), as had been throughout reperfusion. Pulmonary vascular resistance and right ventricular end diastolic pressure were lower after reperfusion in the NO group. Superoxide dismutase activity after reperfusion in the control group significantly decreased to 41% of preischemic value. In the NO group, however, no decrease was seen and a significantly higher value was observed. The wet/dry ratio of reperfused lung was 5.47 +/- 0.52 in the control group and 4.72 +/- 0.36 in the NO group, with decreased pulmonary moisture noted in the NO group. There was no difference in lipid peroxide between the two groups.
NO inhalation suppressed pulmonary hypertension after reperfusion following lung ischemia without affecting systemic arterial pressure. As superoxide dismutase activity was not depressed in the NO group, NO inhalation might enhance suppression of oxygen free radicals. These findings suggest that NO inhalation may be therapeutically useful after lung transplantation.
肺动脉高压和短暂性移植肺功能障碍可能使肺移植患者术后病程复杂化。最近的研究表明，缺血再灌注会损害内皮源性一氧化氮（NO）的释放。我们研究了吸入NO对肺缺血再灌注后血流动力学和氧自由基清除系统的急性影响。
14只麻醉的杂种犬进行机械通气。经正中胸骨切开术后，通过完全夹闭左肺门使左肺缺血。90分钟后，松开左肺门并夹闭右肺门，使所有肺血流都流向左肺，对左肺进行150分钟的再灌注。7只犬在再灌注期间吸入百万分之30（ppm）的NO（NO组）；另外7只犬在无NO吸入的情况下进行通气（对照组）。测量血流动力学、气体交换、肺静脉血中超氧化物歧化酶活性和脂质过氧化物，以及再灌注肺的湿/干比。
两组在再灌注前后全身血压均无变化。再灌注后即刻，NO组的平均肺动脉压（23.2±4.2 mmHg）明显低于对照组（32.7±5.8 mmHg），整个再灌注过程中均如此。NO组再灌注后肺血管阻力和右心室舒张末期压力较低。对照组再灌注后的超氧化物歧化酶活性显著下降至缺血前值的41%。然而，NO组未见下降，且观察到显著更高的值。对照组再灌注肺的湿/干比为5.47±0.52，NO组为4.72±0.36，NO组肺含水量降低。两组脂质过氧化物无差异。
吸入NO可抑制肺缺血再灌注后的肺动脉高压，而不影响体动脉压。由于NO组中超氧化物歧化酶活性未降低，吸入NO可能增强对氧自由基的抑制作用。这些发现表明，吸入NO在肺移植后可能具有治疗作用。
