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ACE inhibition for severe bronchopulmonary dysplasia - an approach based on physiology
Arvind Sehgal1,2, Mohan B Krishnamurthy1, Megan Clark3
1Monash Newborn, Monash Children's Hospital, Melbourne, Victoria, Australia.
Insights
Angiotensin-converting enzyme (ACE) inhibition with captopril improved respiratory and cardiovascular function in premature infants with severe bronchopulmonary dysplasia (BPD). This treatment reduced oxygen and ventilator needs, suggesting ACE inhibitors as a potential therapy for severe BPD.
Area of Science:
- Neonatal Medicine
- Pediatric Cardiology
- Pulmonology
Background:
- Bronchopulmonary dysplasia (BPD) is common in premature infants and can be exacerbated by systemic hypertension, arterial stiffness, and increased afterload, impacting left ventricular function and pulmonary venous congestion.
- Conventional therapies, including postnatal corticosteroids and sildenafil, were ineffective in improving clinical outcomes for infants with severe BPD in this cohort.
Purpose of the Study:
- To evaluate the efficacy of angiotensin-converting enzyme (ACE) inhibition using captopril in improving clinical and echocardiographic parameters in premature infants suffering from severe BPD unresponsive to standard treatments.
Main Methods:
- A case series involving six premature infants (23-29 weeks gestation, 505-814 g birthweight) with severe BPD requiring mechanical ventilation.
- Captopril was administered for systemic hypertension, with cardiac and vascular ultrasounds repeated after 5 weeks to assess changes.
- Clinical assessments included oxygen and ventilator requirements, alongside echocardiographic measurements of cardiac function (systolic and diastolic), aortic intima-media thickness, and pulmonary vascular resistance.
Main Results:
- Significant reductions in oxygen requirements (55% to 29%, P=0.03) and ventilator support were observed.
- Echocardiographic findings showed improved systolic function (increased left ventricular output and velocity of circumferential fiber shortening) and diastolic function (decreased isovolumic relaxation time, P=0.044).
- A trend towards reduced aorta intima-media thickness (P=0.07) and increased pulsatile diameter (P=0.04) was noted, along with increased pulmonary vein flow and lowered pulmonary vascular resistance.
Conclusions:
- Angiotensin-converting enzyme (ACE) inhibition with captopril demonstrated significant clinical and echocardiographic benefits in premature infants with severe BPD.
- Improvements in respiratory support, cardiac function (particularly diastolic function), and vascular parameters suggest ACE inhibition warrants further investigation as a therapeutic option for refractory severe BPD.
Abstract:
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.
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