No abstract

Background-Recent data highlight a vital link between well-performed cardiopulmonary resuscitation (CPR) and survival after cardiac arrest; however, the quality of CPR as actually performed by trained healthcare providers is largely unknown. We sought to measure in-hospital chest compression rates and to determine compliance with published international guidelines. Methods and Results-We developed and validated a handheld recording device to measure chest compression rate as a surrogate for CPR quality. A prospective observational study of adult cardiac arrests was performed at 3 hospitals from April 2002 to October 2003. Resuscitations were witnessed by trained observers using a customized personal digital assistant programmed to store the exact time of each chest compression, allowing offline calculation of compression rates at serial time points. In 97 arrests, data from 813 minutes during which chest compressions were delivered were analyzed in 30-second time segments. In 36.9% of the total number of segments, compression rates were Ͻ80 compressions per minute (cpm), and 21.7% had rates Ͻ70 cpm. Higher chest compression rates were significantly correlated with initial return of spontaneous circulation (mean chest compression rates for initial survivors and nonsurvivors, 90Ϯ17 and 79Ϯ18 cpm, respectively; Pϭ0.0033). Conclusions-In-hospital chest compression rates were below published resuscitation recommendations, and suboptimal compression rates in our study correlated with poor return of spontaneous circulation. CPR quality is likely a critical determinant of survival after cardiac arrest, suggesting the need for routine measurement, monitoring, and feedback systems during actual resuscitation. (Circulation. 2005;111:428-434.)

Pdgfra-expressing (Pdgfra+) cells have been implicated as progenitors in many mesenchymal tissues. To determine lineage potential, we generated PdgfrartTA knockin mice using CRISPR/Cas9. During lung maturation, counter to a prior study reporting that Pdgfra+ cells give rise equally to myofibroblasts and lipofibroblasts, lineage tracing using PdgfrartTA;tetO-cre mice indicated that ~95% of the lineaged cells are myofibroblasts. Genetic ablation of Pdgfra+cells using PdgfrartTA-driven diphtheria toxin (DTA) led to alveolar simplification, demonstrating that these cells are essential for building the gas exchange surface area. In the adult bleomycin model of lung fibrosis, lineaged cells increased to contribute to pathological myofibroblasts. In contrast, in a neonatal hyperoxia model of bronchopulmonary dysplasia (BPD), lineaged cells decreased and do not substantially contribute to pathological myofibroblasts. Our findings revealed complexity in the behavior of the Pdgfra-lineaged cells as exemplified by their distinct contributions to myofibroblasts in normal maturation, BPD and adult fibrosis.

Myofibroblasts are modified fibroblasts, characterized by the presence of a well-developed contractile apparatus, and the formation of robust actin stress fibers. These mechanically active cells are thought to orchestrate extracellular matrix remodeling during normal wound healing in response to tissue injury, and in aberrant tissue remodeling found in fibrosing disorders. This review surveys the understanding of the role of actin stress fibers in myofibroblast biology. From its original description as a defining ultrastructural and morphologic feature, to well-accepted observations demonstrating its participation in contraction, focal adhesion maturation, and extracellular matrix reorganization, and finally to more recent observations demonstrating its role in transducing mechanical force into biochemical signals, transcriptional control of genes involved in locomotion, contraction, and matrix reorganization, and the localized regulation of mRNA translation. This breadth of functionality of the actin stress fiber serves to reinforce and amplify its mechanical function, via induced expression of proteins that themselves augment contraction, focal adhesion formation, and matrix remodeling. In composite, the functions of the actin cytoskeleton are most often aligned, allowing for the integration and amplification of signals promoting both myofibroblast differentiation and matrix remodeling during fibrogenesis.