Bland R D, Albertine K H, Carlton D P, Kullama L, Davis P, Cho S C, Kim B I, Dahl M, Tabatabaei N
Department of Pediatrics, University of Utah, Salt Lake City 84132, USA.
Pediatr Res. 2000 Jul;48(1):64-74. doi: 10.1203/00006450-200007000-00013.
Chronic lung disease of early infancy, or bronchopulmonary dysplasia, is a frequent complication of prolonged mechanical ventilation after premature birth. Pulmonary hypertension and edema are common features of this condition, which is often attributed to long-term, repetitive overinflation of incompletely developed lungs. The overall objective of this work was to examine the effects on the pulmonary circulation and lung fluid balance of different ventilation strategies using large versus small inflation volumes in an animal model of bronchopulmonary dysplasia. We studied 16 newborn lambs that were delivered prematurely (124+/-3 d gestation, term = 147 d) by cesarean section and mechanically ventilated for 3 to 4 wk. Ten lambs were ventilated at 20 breaths/min, yielding a tidal volume of 15+/-5 mL/kg, and six lambs were ventilated at 60 breaths/min, yielding a tidal volume of 6+/-2 mL/kg. All lambs received surfactant at birth and had subsequent surgery for closure of the ductus arteriosus and catheter placement to allow serial measurements of pulmonary vascular resistance and lung lymph flow. Chronic lung injury, documented by serial chest radiographs and postmortem pathologic examination, developed in all lambs irrespective of the pattern of assisted ventilation. Pulmonary vascular resistance, which normally decreases during the month after birth at term, did not change significantly from the first to the last week of study. Lung lymph flow, an index of net transvascular fluid filtration, increased with time in lambs that were ventilated at 20 breaths/min, but not in lambs ventilated at 60 breaths/min. Lymph protein concentration decreased with time, indicative of increased fluid filtration pressure, without evidence of a change in lung vascular protein permeability. Postmortem studies showed interstitial lung edema, increased pulmonary arteriolar smooth muscle and elastin, decreased numbers of small pulmonary arteries and veins, and decreased capillary surface density in distal lung of chronically ventilated lambs compared with control lambs that were killed either 1 d (same postconceptional age) or 3 wk (same postnatal age) after birth at term. Thus, chronic lung injury from prolonged mechanical ventilation after premature birth inhibits the normal postnatal decrease in pulmonary vascular resistance and leads to lung edema from increased fluid filtration pressure. These abnormalities of the pulmonary circulation may contribute to the abnormal respiratory gas exchange that often exists in infants with bronchopulmonary dysplasia.
婴儿早期慢性肺部疾病，即支气管肺发育不良，是早产之后长时间机械通气常见的并发症。肺动脉高压和肺水肿是这种病症的常见特征，通常归因于未完全发育的肺脏长期反复过度充气。这项研究的总体目标是，在支气管肺发育不良动物模型中，研究采用大通气量与小通气量的不同通气策略对肺循环和肺液平衡的影响。我们研究了16只早产（妊娠124±3天，足月为147天）的新生羔羊，通过剖宫产分娩，并进行3至4周的机械通气。10只羔羊以每分钟20次呼吸进行通气，潮气量为15±5毫升/千克，6只羔羊以每分钟60次呼吸进行通气，潮气量为6±2毫升/千克。所有羔羊出生时均接受了表面活性剂治疗，并随后接受手术关闭动脉导管并放置导管，以便连续测量肺血管阻力和肺淋巴流量。所有羔羊无论辅助通气模式如何，均出现了慢性肺损伤，通过连续胸部X光片和死后病理检查得以证实。肺血管阻力在足月出生后的第一个月通常会下降，但在研究的第一周和最后一周之间没有显著变化。肺淋巴流量是血管内液体净滤过的指标，在以每分钟20次呼吸通气的羔羊中随时间增加，但在以每分钟60次呼吸通气的羔羊中则没有增加。淋巴蛋白浓度随时间下降，表明滤过压力增加，且没有肺血管蛋白通透性变化的证据。死后研究显示，与足月出生后1天（相同受孕后年龄）或3周（相同出生后年龄）处死的对照羔羊相比，长期通气的羔羊肺间质水肿、肺小动脉平滑肌和弹性蛋白增加、肺小动脉和小静脉数量减少以及远端肺脏毛细血管表面密度降低。因此，早产之后长时间机械通气导致的慢性肺损伤会抑制出生后肺血管阻力的正常下降，并因滤过压力增加导致肺水肿。肺循环的这些异常可能导致支气管肺发育不良婴儿中常常存在的异常呼吸气体交换。
