Sehgal Arvind, Krishnamurthy Mohan B, Clark Megan, Menahem Samuel
Monash Newborn, Monash Children's Hospital, Melbourne, Victoria, Australia.
Department of Pediatrics, Monash University, Melbourne, Victoria, Australia.
Physiol Rep. 2018 Sep;6(17):e13821. doi: 10.14814/phy2.13821.
Premature infants have a high incidence of bronchopulmonary dysplasia (BPD). Systemic hypertension, arterial thickness and stiffness, and increased systemic afterload may all contribute to BPD pathophysiology by altering left ventricular (LV) function and increasing pulmonary venous congestion by lowering end-diastolic compliance. This case series studied the usefulness of angiotensin-converting enzyme (ACE) inhibition by measuring clinical and echocardiographic improvements in six consecutive infants with "severe" BPD unresponsive to conventional therapy. The range of gestation and birthweight were 23-29 weeks and 505-814 g, respectively. All required mechanical ventilation (including high-frequency oscillation) and all but one were administered postnatal corticosteroids. Other treatments including sildenafil and diuretics made no clinical improvements. Captopril was started for systemic hypertension after cardiac and vascular ultrasounds which were repeated 5 weeks later. A significant reduction in oxygen (55 ± 25 to 29 ± 3%, two-tailed P = 0.03) and ventilator requirements, and improved cardiovascular parameters were noted. This included a trend toward reduction in aorta intima media thickness [840 ± 94 to 740 ± 83 μm, P = 0.07] and an increased pulsatile diameter [36 ± 14 to 63 ± 25 μm, P = 0.04]). Improvements were observed for both systolic (increased LV output, 188 ± 13 to 208 ± 13 mL/kg/min, P = 0.046 and mean velocity of circumferential fiber shortening, 1.6 ± 0.2 to 2.5 ± 0.3 [circ/sec], P = 0.0004) and diastolic (decreased isovolumic relaxation time, 69.6 ± 8.2 to 59.4 ± 5 msec, P = 0.044) function which was accompanied by increased pulmonary vein flow. Right ventricular output increased accompanied by a significant lowering of pulmonary vascular resistance. These findings suggest that improving respiratory and cardiac indices (especially diastolic function) warrants further exploration of ACE inhibition in BPD infants unresponsive to conventional therapy.
早产儿支气管肺发育不良（BPD）的发病率很高。系统性高血压、动脉厚度和僵硬度增加以及全身后负荷增加，都可能通过改变左心室（LV）功能并降低舒张末期顺应性来增加肺静脉充血，从而导致BPD的病理生理过程。本病例系列研究了血管紧张素转换酶（ACE）抑制的作用，通过测量连续6例对传统治疗无反应的“重度”BPD婴儿的临床和超声心动图改善情况进行评估。胎龄范围为23 - 29周，出生体重范围为505 - 814克。所有婴儿均需要机械通气（包括高频振荡通气），除1例之外，所有婴儿均接受了产后皮质类固醇治疗。包括西地那非和利尿剂在内的其他治疗均未带来临床改善。在进行心脏和血管超声检查后，因系统性高血压开始使用卡托普利，5周后重复超声检查。结果显示，氧需求（从55±25%降至29±3%，双侧P = 0.03）和呼吸机需求显著降低，心血管参数得到改善。这包括主动脉内膜中层厚度有降低趋势[从840±94μm降至740±83μm，P = 0.07]，搏动直径增加[从36±14μm增至63±25μm，P = 0.04]。收缩功能（左心室输出增加，从188±13增至208±13 mL/kg/min，P = 0.046；圆周纤维缩短平均速度，从1.6±0.2增至2.5±0.3[circ/sec]，P = 0.0004）和舒张功能（等容舒张时间缩短，从69.6±8.2降至59.4±5毫秒，P = 0.044）均有改善，同时肺静脉血流增加。右心室输出增加，同时肺血管阻力显著降低。这些发现表明，改善呼吸和心脏指标（尤其是舒张功能）值得对传统治疗无反应的BPD婴儿进一步探索ACE抑制治疗。
