Failure of physiological transformation and spiral artery atherosis: their roles in preeclampsia.

Physiological transformation with remodeling of the uteroplacental spiral arteries is key to a successful placentation and normal placental function. It is an intricate process that involves, but is not restricted to, complex interactions between maternal decidual immune cells and invasive trophoblasts in the uterine wall. In normal pregnancy, the smooth muscle cells of the arterial tunica media of uteroplacental spiral arteries are replaced by invading trophoblasts and fibrinoid, and the arterial diameter increases 5- to 10-fold. Poor remodeling of the uteroplacental spiral arteries is linked to early-onset preeclampsia and several other major obstetrical syndromes, including fetal growth restriction, placental abruption, and spontaneous preterm premature rupture of membranes. Extravillous endoglandular and endovenous trophoblast invasions have recently been put forth as potential contributors to these syndromes as well. The well-acknowledged disturbed extravillous invasion of maternal spiral arteries in preeclampsia is summarized, as are briefly novel concepts of disturbed extravillous endoglandular and endovenous trophoblast invasions. Acute atherosis is a foam cell lesion of the uteroplacental spiral arteries associated with poor remodeling. It shares some morphologic features with early stages of atherosclerosis, but several molecular differences between these lesions have also recently been revealed. Acute atherosis is most prevalent at the maternal-fetal interface, at the tip of the spiral arteries. The localization of acute atherosis downstream of poorly remodeled arteries suggests that alterations in blood flow may trigger inflammation and foam cell development. Acute atherosis within the decidua basalis is not, however, confined to unremodeled areas of spiral arteries or to hypertensive disorders of pregnancy and may even be present in some clinically uneventful pregnancies. Given that foam cells of atherosclerotic lesions are known to arise from smooth muscle cells or macrophages activated by multiple types of inflammatory stimulation, we have proposed that multiple forms of decidual vascular inflammation may cause acute atherosis, with or without poor remodeling and/or preeclampsia. Furthermore, we propose that acute atherosis may develop at different gestational ages, depending on the type and degree of the inflammatory insult. This review summarizes the current knowledge of spiral artery remodeling defects and acute atherosis in preeclampsia. Some controversies will be presented, including endovascular and interstitial trophoblast invasion depths, the concept of 2-stage trophoblast invasion, and whether the replacement of maternal spiral artery endothelium by fetal endovascular trophoblasts is permanent. We will discuss the role of acute atherosis in the pathophysiology of preeclampsia and short- and long-term health correlates. Finally, we suggest future opportunities for research on this intriguing uteroplacental interface between the mother and fetus.

Acute Atherosis Lesions at the Fetal-Maternal Border: Current Knowledge and Implications for Maternal Cardiovascular Health.

Decidua basalis, the endometrium of pregnancy, is an important interface between maternal and fetal tissues, made up of both maternal and fetal cells. Acute atherosis is a uteroplacental spiral artery lesion. These patchy arterial wall lesions containing foam cells are predominantly found in the decidua basalis, at the tips of the maternal arteries, where they feed into the placental intervillous space. Acute atherosis is prevalent in preeclampsia and other obstetric syndromes such as fetal growth restriction. Causal factors and effects of acute atherosis remain uncertain. This is in part because decidua basalis is challenging to sample systematically and in large amounts following delivery. We summarize our decidua basalis vacuum suction method, which facilitates tissue-based studies of acute atherosis. We also describe our evidence-based research definition of acute atherosis. Here, we comprehensively review the existing literature on acute atherosis, its underlying mechanisms and possible short- and long-term effects. We propose that multiple pathways leading to decidual vascular inflammation may promote acute atherosis formation, with or without poor spiral artery remodeling and/or preeclampsia. These include maternal alloreactivity, ischemia-reperfusion injury, preexisting systemic inflammation, and microbial infection. The concept of acute atherosis as an inflammatory lesion is not novel. The lesions themselves have an inflammatory phenotype and resemble other arterial lesions of more extensively studied etiology. We discuss findings of concurrently dysregulated proteins involved in immune regulation and cardiovascular function in women with acute atherosis. We also propose a novel hypothesis linking cellular fetal microchimerism, which is prevalent in women with preeclampsia, with acute atherosis in pregnancy and future cardiovascular and neurovascular disease. Finally, women with a history of preeclampsia have an increased risk of premature cardiovascular disease. We review whether presence of acute atherosis may identify women at especially high risk for premature cardiovascular disease.

A young woman who did not awake after extensive surgery. / En ung kvinne som ikke våknet etter omfattende operasjon.

BACKGROUND: Cystic echinococcosis (CE) caused by Echinococcus granulosus, significantly impacts health globally, but is a rare disease in Norway. CE is treated with a combination of anthelmintics and surgery, or percutaneous drainage. CASE PRESENTATION: A woman in her thirties underwent extensive surgery due to disseminated CE in the abdominal cavity and liver. Due to intraoperative cyst rupture with contamination of the abdominal cavity, peritoneal lavage with hypertonic saline (20 % NaCl), a scolicidal agent, was performed for ten minutes before irrigation with physiological saline. Immediately after surgery, the patient was haemodynamically unstable and did not awake. Blood level of sodium was found to be severely increased at 188 mmol/L (ref 137−144 mmol/L). Hypotonic fluids (5 % glucose) were immediately administered intravenously to correct the acute hypernatraemia. CT scan of the head did not show signs of bleeding or oedema. The sodium level was normalised on postoperative day three and the patient was discharged without any neurological sequelae. INTERPRETATION: Our patient developed iatrogenic acute severe hypernatraemia following abdominal lavage with hypertonic saline. Acute severe hypernatraemia is potentially lethal. Hypertonic saline must be used intraoperatively with great caution. Regular blood tests to detect hypernatraemia and monitor other electrolyte disturbances should be mandatory.

Acute atherosis of decidua basalis; characterization of spiral arteries, endothelial status and activation.

INTRODUCTION: Acute atherosis (AA) is a lesion affecting uteroplacental spiral arteries during pregnancy, most frequently in preeclampsia but occasionally in normal pregnancy. It is commonly observed in untransformed spiral arteries (intact smooth muscle cell layer, lacking intramural trophoblasts). The mechanism causing lesion development is unknown. AA shares some morphological similarities with atherosclerosis, in which endothelial activation occurs early. Here we histologically characterize decidua basalis spiral arteries with and without AA, focusing on endothelial status and activation. METHODS: Formalin-fixed and paraffin-embedded decidua basalis tissue sections from 32 patients (16 normotensive, 5 with AA, 16 preeclampsia, 7 with AA) were stained with H + E, PAS, MSB (Martius Scarlet Blue), desmin, CK7, CD68, CD31, vWF and ICAM-1. We logged remodeling status, presence of AA, endothelial morphology, endothelial CD31 intensity and activation (ICAM-1-positive cells). RESULTS: We observed fully or partially transformed spiral arteries in most decidua basalis samples, and no untransformed arteries. AA arteries were also observed, characterized by intramural CD68-positive vacuolated cells and fibrinoid necrosis. They lacked a smooth muscle cell layer and intramural trophoblasts. The fibrinoid necrosis in AA lesions stained red with MSB. AA arteries were associated with lower CD31 staining intensity of endothelial cells. More arteries had an abnormal or destroyed endothelium relative to arteries without AA. Endothelial activation was not observed in the majority of AA arteries. DISCUSSION: Our results indicate an altered endothelial phenotype as important in the development of AA, supporting previous observations. The histology of AA differs from that of atherosclerosis.