. A role for platelet-derived growth factor ␤-receptor in a newborn rat model of endothelin-mediated pulmonary vascular remodeling. Am J Physiol Lung Cell Mol Physiol 288: L1162-L1170, 2005. First published February 18, 2005 doi:10.1152/ajplung.00180.2004.-Newborn rats exposed to 60% O 2 for 14 days develop endothelin (ET)-1-dependent pulmonary hypertension with vascular remodeling, characterized by increased smooth muscle cell (SMC) proliferation and medial thickening of pulmonary resistance arteries. Using immunohistochemistry and Western blot analyses, we examined the effect of exposure to 60% O 2 on expression in the lung of receptors for the platelet-derived growth factors (PDGF), which are implicated in the pathogenesis of arterial smooth muscle hyperplasia. We observed a marked O 2-induced upregulation of PDGF-␣ and -␤ receptors (PDGF-␣R and -␤R) on arterial smooth muscle. This led us to examine pulmonary vascular PDGF receptor expression in 60% O 2-exposed rats given SB-217242, a combined ET receptor antagonist, which we found prevented the O 2-induced upregulation of PDGF-␤R, but not PDGF-␣R, on arterial smooth muscle. PDGF-BB, a major PDGF-␤R ligand, was found to be a potent in vitro inducer of hyperplasia and DNA synthesis in cultured pulmonary artery SMC from infant rats. A critical role for PDGF-␤R ligands in arterial SMC proliferation was confirmed in vivo using a truncated soluble PDGF-␤R intervention, which attenuated SMC proliferation induced by exposure to 60% O 2 . Collectively, these data are consistent with a major role for PDGF-␤R-mediated SMC proliferation, acting downstream of increased ET-1 in a newborn rat model of 60% O 2-induced pulmonary hypertension. pulmonary oxygen toxicity; vascular smooth muscle; growth factors; soluble receptors PULMONARY HYPERTENSION IN THE NEWBORN is a common end result of a variety of perinatal and postnatal insults. Regardless of the initial etiology, several pathological events that account for the hallmark manifestation of raised pulmonary arterial pressure are consistently found. These are abnormal vasoconstriction and subsequent structural remodeling of the pulmonary vasculature, which render the pulmonary circulation less responsive to vasodilator therapies (19). Recent data from human infants with bronchopulmonary dysplasia (BPD), a chronic neonatal lung injury that affects preterm infants, have demonstrated structural remodeling of pulmonary resistance arteries as early as 2 wk after birth (30). These data provide a pathological correlate for recent echocardiographic studies demonstrating raised pulmonary arterial resistance in infants with BPD (27, 28), which together indicate that pulmonary hypertension remains a common manifestation of this condition.Newborn rats exposed to 60% O 2 for 14 days, a model for human BPD, develop pulmonary hypertension characterized by right ventricular hypertrophy and remodeling of pulmonary arteries with thickening of the medial layer due to increased smooth muscle mass (18,20). We have previously reported that exp...

No abstract

Background: There is no quality metric for emergency physicians' diagnostic time for acute coronary occlusion. Objective: We sought to quantify diagnostic time associated with automated interpretation, classic STelevation myocardial infarction (STEMI) criteria, STEMIequivalents, and subtle occlusions, using electrocardiogram (ECG)-to-activation of catheterization laboratory time. Methods: This multicenter retrospective study reviewed all code STEMI patients from the emergency department (ED) with confirmed culprit lesions from January 2016 to December 2018. We measured door-to-ECG (DTE) time and ECG-to-activation (ETA) time. We examined the first ED ECGs to determine whether automated interpretation labeled ''STEMI,'' and they met classic STEMI criteria, STEMI-equivalents, or rules for subtle occlusion. ECG analysis was performed by two emergency physicians blinded to clinical scenario, automated interpretation, and angiographic outcome. Results: There were 177 code STEMIs with culprit lesions, with a median DTE time of 9.0 min and a median ETA time of 16.0 min. Automated interpretation labeled 55.4% of first ECGs ''STEMI'' (ETA 6.5 min) and 44.6% not ''STEMI'' (ETA 66 min, p < 0.0001). Of first ECGs, 63.8% met classic STEMI criteria (ETA 8.0 min), 8.5% had STEMI-equivalents (ETA 32.0 min, p = 0.0026), 16.4% had subtle occlusions (ETA 89.0 min, p = 0.045), and 11.3% had no diagnostic sign of occlusion (ETA 68.0 min, p = 0.20). Conclusions: STEMI criteria missed more than one-third of occlusions on first ECG, but most had STEMI-equivalents or rules for subtle occlusion. ETA time can serve as a quality metric for emergency physicians to promote new ECG insights and assess quality improvement initiatives.

No abstract