Shekerdemian Lara S, Ravn Hanne B, Penny Daniel J
Paediatric Intensive Care Unit, Royal Children's Hospital, Flemington Road, Parkville, Victoria 3052, Australia.
Pediatr Res. 2004 Mar;55(3):413-8. doi: 10.1203/01.PDR.0000112033.81970.C2. Epub 2004 Jan 7.
There has been recent interest in the use of the phosphodiesterase-5 inhibitor sildenafil for treating pulmonary hypertension. We examined the interaction between inhaled nitric oxide (iNO) and i.v. sildenafil in 12 piglets with acute pulmonary hypertension and lung injury secondary to meconium aspiration. Six animals (controls) received no intervention after meconium instillation, and six received iNO (20 ppm) from 120 min, with the addition at 240 min of an i.v. sildenafil infusion (2 mg/kg over 2 h). Meconium instillation increased mean pulmonary artery (PA) pressure from 16.0 +/- 3.1 to 24.8 +/- 4.6 mm Hg (p < 0.01) and pulmonary vascular resistance (PVR) from 0.047 +/- 0.008 to 0.089 +/- 0.027 mm Hg. ml(-1). min(-1). kg(-1) (p < 0.01). Oxygenation index increased from 3 +/- 0.8 to 8.3 +/- 3.0 (p < 0.01). There were no further changes beyond 120 min in controls. iNO reduced PA pressure and PVR to baseline values, without influencing oxygenation. The addition of sildenafil further reduced PA pressure, tended to increase the cardiac output, and reduced PVR from 0.049 +/- 0.02 to 0.028 +/- 0.01 mm Hg. ml(-1). min(-1). kg(-1) (p < 0.05). Sildenafil lowered the systemic blood pressure and systemic vascular resistance and produced profound arterial hypoxemia, reducing arterial Po(2) from 69 +/- 23 mm Hg to 49 +/- 15 mm Hg, despite substantial increases first in inspired oxygen fraction and subsequently in mean airway pressures. Consequently, the oxygenation index increased by 13.9 +/- 4.8 (p = 0.01). When given in addition to iNO, sildenafil at a dose of >0.5 mg/kg produced profound pulmonary vasodilation, but this was coupled with an unacceptable deterioration in oxygenation and systemic vasodilation in this model of pulmonary hypertension with acute parenchymal lung disease.
最近，人们对使用磷酸二酯酶-5抑制剂西地那非治疗肺动脉高压产生了兴趣。我们研究了吸入一氧化氮（iNO）与静脉注射西地那非在12只因胎粪吸入继发急性肺动脉高压和肺损伤的仔猪中的相互作用。6只动物（对照组）在滴入胎粪后未接受干预，6只动物在120分钟后接受iNO（20 ppm），并在240分钟时加用静脉注射西地那非输注（2 mg/kg，持续2小时）。滴入胎粪使平均肺动脉（PA）压从16.0±3.1 mmHg升高至24.8±4.6 mmHg（p<0.01），肺血管阻力（PVR）从0.047±0.008 mmHg·ml-1·min-1·kg-1升高至0.089±0.027 mmHg·ml-1·min-1·kg-1（p<0.01）。氧合指数从3±0.8升高至8.3±3.0（p<0.01）。对照组在120分钟后无进一步变化。iNO将PA压和PVR降至基线值，而不影响氧合。加用西地那非进一步降低了PA压，倾向于增加心输出量，并将PVR从0.049±0.02 mmHg·ml-1·min-1·kg-1降至0.028±0.01 mmHg·ml-1·min-1·kg-1（p<0.05）。西地那非降低了体循环血压和体循环血管阻力，并导致严重的动脉低氧血症，尽管首先显著增加了吸入氧分数，随后又增加了平均气道压力，但动脉血氧分压（Po2）仍从69±23 mmHg降至49±15 mmHg。因此，氧合指数增加了13.9±4.8（p = 0.01）。在该急性实质性肺疾病的肺动脉高压模型中，当与iNO联合使用时，剂量>0.5 mg/kg的西地那非可产生显著的肺血管舒张作用，但这伴随着氧合的不可接受的恶化和体循环血管舒张。
