Long-Term Right Ventricular Adaptation to Postnatal Hyperoxia: Too Much of a Good Thing?
Long-Term Right Ventricular Adaptation to Postnatal Hyperoxia: Too Much of a Good Thing?
复制标题
右心室对产后高氧的长期适应：好事太多了？
DOI：
10.1165/rcmb.2016-0429ed
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发表时间：
2017
影响因子：
6.4
通讯作者：
Perez,VinicioAdeJesus
中科院分区：
文献类型：
--
作者：
Perez,VinicioAdeJesus
Over the past 30 years, the rate of premature births (defined as, 37 weeks of gestation) in the developed world has risen, resulting in more premature babies requiring intensive care in neonatal centers to acutely manage and prevent the complications associated with immature organ function (1). More recently, there has been growing awareness that adults with a history of premature birth are at a high risk of suffering from learning disabilities, metabolic disorders, and chronic cardiopulmonary problems (2). Bronchopulmonary dysplasia (BPD) is a cardiopulmonary disease of premature children that is characterized by severe postnatal respiratory distress requiring implementation of mechanical ventilation and supplemental oxygen therapy to maintain tissue oxygenation and ensure survival (3). However, long-term exposure to high oxygen concentrations can impair lung development via disruption of pulmonary vasculogenesis and alveolar hypoplasia, resulting in BPD. Patients with BPD are at a high risk of pulmonary arterial hypertension (PAH), a chronic life-threatening cardiopulmonary disorder associated with progressive elevation in pulmonary pressures, obliterative vasculopathy, and right heart failure (4). The right ventricle (RV) adapts to increased afterload by hypertrophy and an increase in size, but, as the pressures continue to rise, the RV fails to compensate, as evidenced by reduction in cardiac output, progressive dilation, and impaired venous return. Patients with decompensated RV have reduced survival and limited quality of life (5). Because of our incomplete understanding of the molecular mechanisms associated with RV failure in BPD-PAH, therapeutic options for these patients are limited, and clinical outcomes remain poor. Compared with patients with sporadic PAH, patients with BPD-PAH may be at a higher risk of decompensated RV failure caused by abnormal RV development, as evidenced by a smaller RV size and increased mass (6). Ventricular tissue demonstrates increased fibrosis and hypertrophic cardiomyocytes similar to those seen in hearts before the switch from high-pressure placental circulation to low-pressure postnatal circulation. These cardiomyocytes appear to follow a fetal program and demonstrate a switch toward an anaerobic metabolism characterized by reduced mitochondria activity and dependence on glycolysis for energy production (7). Although initially beneficial, this switch is inadequate to meet the energy demands of the RV to maintain proper function, leading to impaired function and heart failure. Addressing this state would provide a window of opportunity for developing strategies that could help turn this phenotype toward an aerobic metabolism that dominates postnatal life and normalizes cardiomyocyte structure and function. As a step toward this goal, it is imperative to find animal models that closely recapitulate the phenotype of BPD-PAH to dissect the molecular mechanisms behind maladaptive RV function during postnatal life and allow testing of therapeutic approaches. Neonatal mice exposed to hyperoxia are a well-established model for the study of BPD and early RV adaption responses (8). However, the model does not address the long-term consequences of hyperoxia, in particular the adaptive mechanisms used by the RV to compensate for persistent pulmonary hypertension and increased afterload. In this issue of the Journal, Goss and colleagues (pp. 609-619) attempt to bridge this gap by using rats exposed to postnatal hyperoxia to study adaptive and maladaptive RV responses during the first year of life (ie, the equivalent of age 30 years in humans)(9). Through the combination of …
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影响因子：
9.6
作者：
Jacobs, Wouter;van de Veerdonk, Marielle C.;Noordegraaf, Anton Vonk
通讯作者：
Noordegraaf, Anton Vonk
影响因子：
37.8
作者：
Reddy S;Bernstein D
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DOI：
10.1016/j.jtcvs.2008.01.040
发表时间：
2008-07-01
影响因子：
6
作者：
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影响因子：
37.8
作者：
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通讯作者：
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