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Biomedical subjects

Steven H Abman

Publications and source records attributed to Steven H Abman.

43 records · Page 3Linked to original sources
PubMed2002

Interactive effects of high-frequency oscillatory ventilation and inhaled nitric oxide in acute hypoxemic respiratory failure in pediatrics.

OBJECTIVE: High-frequency oscillatory ventilation (HFOV) and inhaled nitric oxide (iNO) have been reported to improve oxygenation in children with acute hypoxemic respiratory failure (AHRF), but their roles in the treatment of AHRF remains unknown. The use of HFOV improves oxygenation by increasing lung recruitment. iNO can improve oxygenation in AHRF, but it may have limited efficacy in patients with poor lung inflation. Based on these findings, we hypothesized that the combined treatment of HFOV and inhalation of low-dose NO would improve oxygenation and survival in children with severe AHRF compared with children treated with conventional mechanical ventilation (CMV) or either treatment alone. SETTING: Tertiary pediatric intensive care units at seven academic centers. DESIGN: Post hoc analysis of data from children enrolled in a multicenter, randomized, masked study of the use of iNO in the treatment of AHRF. PATIENTS: A total of 108 pediatric patients with AHRF defined as an oxygenation index of >15 twice within 6 hrs. Mode of ventilation (HFOV or CMV) was determined by the patient's physician based on guidelines to maximize oxygenation. The patient was then randomized to treatment with or without iNO. Comparisons were made between patients who were treated with HFOV plus iNO (n = 14), HFOV alone (n = 12), CMV plus iNO (n = 35), and CMV alone (n = 38). INTERVENTIONS: Ventilation with CMV or HFOV with or without iNO. MEASUREMENTS AND MAIN RESULTS: We found that the change in Pao /Fio ratio was greatest in the HFOV plus iNO group compared with the other treatment groups at 4 hrs (p =.02) and 12 hrs (p =.01). After 24 hrs of treatment, both HFOV plus iNO and HFOV alone resulted in greater improvement in Pao2/Fio2 ratio than either CMV alone or CMV plus iNO (p =.005). After 72 hrs, treatment with HFOV alone resulted in a greater improvement in Pao2/Fio2 ratio than either CMV alone or CMV plus iNO (p =.03). There was no difference in predefined treatment failures between treatment groups. CONCLUSIONS: We conclude that the combination of HFOV with iNO causes a greater improvement in oxygenation than either treatment strategy alone in children with severe AHRF. We speculate that the enhanced lung recruitment by HFOV enhances the effects of low dose iNO on gas exchange.

Administration, Inhalation↗
PubMed2002

Treatment of newborn rats with a VEGF receptor inhibitor causes pulmonary hypertension and abnormal lung structure.

To determine whether disruption of vascular endothelial growth factor (VEGF)-VEGF receptor (VEGFR) signaling in the newborn has long-term effects on lung structure and function, we injected 1-day-old newborn rat pups with a single dose of Su-5416, a VEGFR inhibitor, or vehicle (controls). Lungs from infant (3-wk-old) and adult (3- to 4-mo-old) rats treated with Su-5416 as newborns showed reductions in arterial density (82 and 31%, respectively) and alveolar counts (45 and 29%) compared with controls. Neonatal treatment with Su-5416 increased right ventricle weight to body wt ratios (4.2-fold and 2.0-fold) and pulmonary arterial wall thickness measurements (2.7-fold and 1.6-fold) in infant and adult rats, respectively, indicating marked pulmonary hypertension. We conclude that treatment of newborn rats with the VEGFR inhibitor Su-5416 impaired pulmonary vascular growth and postnatal alveolarization and caused pulmonary hypertension and that these effects were long term, persisting well into adulthood.

Angiography↗
PubMed2002

Chronic hypertension impairs flow-induced vasodilation and augments the myogenic response in fetal lung.

We hypothesized that altered vasoreactivity in perinatal pulmonary hypertension (PH) is characterized by abnormal responses to hemodynamic stress, including the loss of flow-induced vasodilation and an augmented myogenic response. Therefore, we studied the acute hemodynamic effects of brief compression of the ductus arteriosus (DA) in control fetal lambs and in lambs during exposure to chronic PH. In both groups, acute DA compression decreased pulmonary vascular resistance (PVR) by 20% at baseline (day 0). After 2 days of hypertension, acute DA compression paradoxically increased PVR by 50% in PH lambs, whereas PVR decreased by 25% in controls. During the 8-day study period, PVR increased during acute DA compression in PH lambs, whereas acute DA compression continued to cause vasodilation in controls. Brief treatment with the nitric oxide (NO) synthase inhibitor nitro-L-arginine (L-NA) increased basal PVR in control but not PH lambs, suggesting decreased NO production in PH lambs. Chronic hypertension increased the myogenic response after L-NA in PH lambs, whereas the myogenic response remained unchanged in controls. The myogenic response was inhibited by nifedipine in PH lambs, suggesting that the myogenic response is dependent upon the influx of extracellular calcium. We conclude that chronic PH impairs flow-induced vasodilation and increases the myogenic response in fetal lung. We speculate that decreased NO signaling and an augmented myogenic response contributes to abnormal vasoreactivity in PH.

Animals↗
PubMed2002

Ontogeny of endothelin-converting enzyme gene expression and protein content in the ovine fetal lung.

Endothelin 1 (ET-1) is a potent vasoconstrictor and smooth muscle comitogen that is produced by endothelin-converting enzyme 1 (ECE-1) in endothelium and smooth muscle of the vascular wall in adult pulmonary arteries. However, little is known about the role of ECE-1 in the fetal pulmonary circulation. The ET-1 protein content falls just prior to birth in the fetal lamb lung. We hypothesized that the expression of ECE-1 is developmentally regulated and that ECE-1 levels fall prior to birth. To test this hypothesis, we measured lung ECE-1 mRNA levels and protein content and determined the cellular localization of ECE-1 expression in lung tissues from fetal lambs between 70 and 140 days of gestation (term = 145 days), newborn lambs, and ewes. We found that ECE-1 mRNA expression and protein content were lower in the fetal lamb lung just prior to birth in comparison with the newborn lamb lung. Immunolocalization of ECE-1 protein showed expression of ECE-1 in the vascular endothelium but not in the vascular smooth muscle at all gestational ages. We conclude that ECE-1 is developmentally regulated and that ECE-1 is expressed in the vascular endothelium but not in the smooth muscle of the fetal pulmonary vasculature. We speculate that alterations in ECE-1 contribute to the changes in ET-1 levels during the perinatal period and that the majority of ET-1 produced in the fetal lamb pulmonary vasculature is produced by the vascular endothelium.

Animals↗
PubMed2002

Vascular endothelial growth factor causes pulmonary vasodilation through activation of the phosphatidylinositol-3-kinase-nitric oxide pathway in the late-gestation ovine fetus.

Vascular endothelial growth factor (VEGF) causes vasodilation in adult models of peripheral vascular disease and myocardial ischemia through the acute release of nitric oxide (NO). However, the hemodynamic effects of VEGF and its effects on NO production have not been studied in the developing lung circulation. We hypothesized that VEGF causes fetal pulmonary vasodilation, and that its actions are mediated through the release of endogenous NO. We performed surgery in 16 fetal lambs (125-135 d gestation; term = 147 d), and placed catheters in the main pulmonary artery, aorta, and left atrium to measure pressures. An ultrasonic flow transducer was placed on the left pulmonary artery (LPA) to measure blood flow, and a catheter was placed in the LPA for local drug infusion. Pulmonary vascular resistance in the left lung was calculated as pulmonary artery pressure minus left atrial pressure divided by LPA flow. Fetal lambs were treated with brief infusions of recombinant human VEGF (dose, 0.5-2.0 micro g) into the LPA. Recombinant human VEGF infusions acutely increased LPA flow by up to 3-fold (p < 0.02) and decreased pulmonary vascular resistance by 65% (p < 0.05) in a dose-related fashion, without affecting aortic pressure or heart rate. To determine the mechanism of VEGF-induced vasodilation, we studied the effects of nitro-L-arginine, an NO synthase inhibitor, and LY294002, a phosphatidylinositol-3-kinase inhibitor, on the response to VEGF. We found that pretreatment with either nitro-L-arginine or LY294002 completely inhibited the vasodilator response to recombinant human VEGF (p < 0.005). These findings suggest that recombinant human VEGF causes fetal pulmonary vasodilation, and that this response is likely mediated by the release of NO through activation of phosphatidylinositol-3-kinase.

Animals↗