RESUMEN
Cardiovascular disease is the leading indirect cause of maternal morbidity and mortality, accounting for nearly one third of maternal deaths during pregnancy. The burden of cardiovascular disease in pregnancy is increasing, as are the incidence of maternal morbidity and mortality. Normal physiologic adaptations to pregnancy, including increased cardiac output and plasma volume, may unmask cardiac conditions, exacerbate previously existing conditions or create de novo complications. It is important for care providers to understand the normal physiologic changes of pregnancy and how they may impact the care of patients with cardiovascular disease. This review outlines the physiologic adaptions during pregnancy and their pathologic implications for some of the more common cardiovascular conditions in pregnancy.
RESUMEN
Limited views are often obtained in the setting of cardiac ultrasound, however, the likelihood of missing left ventricular (LV) dysfunction based on a single view is not known. We sought to determine the echo views that were least likely to miss LV systolic dysfunction in consecutive transthoracic echocardiograms (TTEs). Structured data from TTEs performed at 2 hospitals from September 25, 2017, to January 15, 2019, were screened. Studies of interest were those with reported LV dysfunction. Views evaluated were the parasternal long-axis (PLAX), parasternal-short axis at mitral (PSAX M), papillary muscle (PSAX PM), and apical (PSAX A) levels, apical 2 (AP2), apical 3 (AP3), and apical 4 (AP4) chamber views. The probability that a view contained at least 1 abnormal segment was determined and analyzed with McNemar's test for 21 adjusted pair-wise comparisons. There were 4102 TTE studies included for analysis. TTEs on males comprised 72.7% of studies with a mean LV ejection fraction of 42.8 ± 9.7%. The echo view with the greatest likelihood of encompassing an abnormal segment was the AP2 view with a prevalence of 93.4% (p < 0.001, compared to all other views). The PLAX view performed the worst with a prevalence of 82.5% (p < 0.015, compared to all other views). The best parasternal view for the detection of abnormality was the PSAX PM view at 90.4%. In conclusions, a single echo view will contain abnormal segments > 82% of the time in the setting of LV systolic dysfunction, with a prevalence of up to 93.4% in the apical windows.
RESUMEN
Oligodendroglial cell death and demyelination are hallmarks of neurotrauma and multiple sclerosis that cause axonal damage and functional impairments. Remyelination remains a challenge as the ability of endogenous precursor cells for oligodendrocyte replacement is hindered in the unfavorable milieu of demyelinating conditions. Here, in a rat model of lysolecithin lysophosphatidyl-choline (LPC)-induced focal demyelination, we report that Neuregulin-1 (Nrg-1), an important factor for oligodendrocytes and myelination, is dysregulated in demyelinating lesions and its bio-availability can promote oligodendrogenesis and remyelination. We delivered recombinant human Nrg-1ß1 (rhNrg-1ß1) intraspinally in the vicinity of LPC demyelinating lesion in a sustained manner using poly lactic-co-glycolic acid microcarriers. Availability of Nrg-1 promoted generation and maturation of new oligodendrocytes, and accelerated endogenous remyelination by both oligodendrocyte and Schwann cell populations in demyelinating foci. Importantly, Nrg-1 enhanced myelin thickness in newly remyelinated spinal cord axons. Our complementary in vitro studies also provided direct evidence that Nrg-1 significantly promotes maturation of new oligodendrocytes and facilitates their transition to a myelinating phenotype. Nrg-1 therapy remarkably attenuated the upregulated expression chondroitin sulfate proteoglycans (CSPGs) specific glycosaminoglycans in the extracellular matrix of demyelinating foci and promoted interleukin-10 (IL-10) production by immune cells. CSPGs and IL-10 are known to negatively and positively regulate remyelination, respectively. We found that Nrg-1 effects are mediated through ErbB2 and ErbB4 receptor activation. Our work provides novel evidence that dysregulated levels of Nrg-1 in demyelinating lesions of the spinal cord pose a challenge to endogenous remyelination, and appear to be an underlying cause of myelin thinning in newly remyelinated axons.
