Hypoxia induces dilated cardiomyopathy in the chick embryo: mechanism, intervention, and long-term consequences

Background: Intrauterine growth restriction is associated with an increased future risk for developing cardiovascular diseases. Hypoxia in utero is a common clinical cause of fetal growth restriction. We have previously shown that chronic hypoxia alters cardiovascular development in chick embryos. The aim of this study was to further characterize cardiac disease in hypoxic chick embryos. Methods: Chick embryos were exposed to hypoxia and cardiac structure was examined by histological methods one day prior to hatching (E20) and at adulthood. Cardiac function was assessed in vivo by echocardiography and ex vivo by contractility measurements in isolated heart muscle bundles and isolated cardiomyocytes. Chick embryos were exposed to vascular endothelial growth factor (VEGF) and its scavenger soluble VEGF receptor-1 (sFlt-1) to investigate the potential role of this hypoxia-regulated cytokine. Principal Findings: Growth restricted hypoxic chick embryos showed cardiomyopathy as evidenced by left ventricular (LV) dilatation, reduced ventricular wall mass and increased apoptosis. Hypoxic hearts displayed pump dysfunction with decreased LV ejection fractions, accompanied by signs of diastolic dysfunction. Cardiomyopathy caused by hypoxia persisted into adulthood. Hypoxic embryonic hearts showed increases in VEGF expression. Systemic administration of rhVEGF165 to normoxic chick embryos resulted in LV dilatation and a dose-dependent loss of LV wall mass. Lowering VEGF levels in hypoxic embryonic chick hearts by systemic administration of sFlt-1 yielded an almost complete normalization of the phenotype. Conclusions/Significance: Our data show that hypoxia causes a decreased cardiac performance and cardiomyopathy in chick embryos, involving a significant VEGF-mediated component. This cardiomyopathy persists into adulthood

Failure Mode and Effects Analysis (FMEA) at the preanalytical phase for POCT blood gas analysis: proposal for a shared proactive risk analysis model.

Objectives Proposal of a risk analysis model to diminish negative impact on patient care by preanalytical errors in blood gas analysis (BGA). Methods Here we designed a Failure Mode and Effects Analysis (FMEA) risk assessment template for BGA, based on literature references and expertise of an international team of laboratory and clinical health care professionals. Results The FMEA identifies pre-analytical process steps, errors that may occur whilst performing BGA (potential failure mode), possible consequences (potential failure effect) and preventive/corrective actions (current controls). Probability of failure occurrence (OCC), severity of failure (SEV) and probability of failure detection (DET) are scored per potential failure mode. OCC and DET depend on test setting and patient population e.g., they differ in primary community health centres as compared to secondary community hospitals and third line university or specialized hospitals. OCC and DET also differ between stand-alone and networked instruments, manual and automated patient identification, and whether results are automatically transmitted to the patient’s electronic health record. The risk priority number (RPN = SEV × OCC × DET) can be applied to determine the sequence in which risks are addressed. RPN can be recalculated after implementing changes to decrease OCC and/or increase DET. Key performance indicators are also proposed to evaluate changes. Conclusions This FMEA model will help health care professionals manage and minimize the risk of preanalytical errors in BGA