Effect of propofol and etomidate on normoxic and chronically hypoxic pulmonary artery

BACKGROUND: Chronic alveolar hypoxia results in sustained arterial constriction, and increase in pulmonary vascular resistance leading to pulmonary artery hypertension (PAHT). The aim of this study was to investigate the effect of propofol and etomidate on pulmonary artery (PA) reactivity in chronically hypoxic (CH) rats, a model of pulmonary arterial hypertension (PAHT), in normoxic animals, and human PA. METHODS: CH rats were maintained 14 days at 380 mmHg pressure in a hypobaric chamber. Human tissue was retrieved from histological lung pieces from patients undergoing resection for carcinoma. Cumulative concentrations of anaesthetics were tested on isolated vascular rings precontracted with phenylephrine (PHE) or 100 mM KCl. Statistical comparisons were done by ANOVA, followed, when needed, by Student t tests with Bonferroni correction as post-hoc tests. RESULTS: In normoxic rat PA, maximal relaxation (R(max)) induced by etomidate and propofol was 101.3 ± 0.8% and 94.0 ± 2.3%, respectively, in KCl-precontracted rings, and 63.3 ± 9.7% and 46.1 ± 9.1%, respectively, in PHE-precontracted rings (n = 7). In KCl-precontracted human PA, R(max )was 84.7 ± 8.6 % and 66.5 ± 11.8%, for etomidate and propofol, respectively, and 154.2 ± 22.4 % and 51.6 ± 15.1 %, respectively, in PHE-precontracted human PA (n = 7). In CH rat PA, the relaxant effect of both anaesthetics was increased in PHE-precontracted and, for etomidate only, in KCl-precontracted PA. In aorta, CH induced no change in the relaxant effect of anaesthetics. CONCLUSION: Propofol and etomidate have relaxant properties in PA from human and normoxic rat. The relaxant effect is specifically accentuated in PA from CH rat, mainly via an effect on the pharmacomechanical coupling. Etomidate appears to be more efficient than propofol at identical concentration, but, taking into account clinical concentrations, etomidate is less potent than propofol, which effect was in the range of clinical doses. Although these findings provide experimental support for the preferential use of etomidate for haemodynamic stability in patients suffering from PAHT, the clinical relevance of the observations requires further investigation

The role of sex in the pathophysiology of pulmonary hypertension

Pulmonary arterial hypertension (PAH) is a progressive disease characterised by increased pulmonary vascular resistance and pulmonary artery remodelling as result of increased vascular tone and vascular cell proliferation, respectively. Eventually, this leads to right heart failure. Heritable PAH is caused by a mutation in the bone morphogenetic protein receptor-II (BMPR-II). Female susceptibility to PAH has been known for some time, and most recent figures show a female-to-male ratio of 4:1. Variations in the female sex hormone estrogen and estrogen metabolism modify FPAH risk, and penetrance of the disease in BMPR-II mutation carriers is increased in females. Several lines of evidence point towards estrogen being pathogenic in the pulmonary circulation, and thus increasing the risk of females developing PAH. Recent studies have also suggested that estrogen metabolism may be crucial in the development and progression of PAH with studies indicating that downstream metabolites such as 16α-hydroxyestrone are upregulated in several forms of experimental pulmonary hypertension (PH) and can cause pulmonary artery smooth muscle cell proliferation and subsequent vascular remodelling. Conversely, other estrogen metabolites such as 2-methoxyestradiol have been shown to be protective in the context of PAH. Estrogen may also upregulate the signalling pathways of other key mediators of PAH such as serotonin

Altered Gene Expression in Pulmonary Tissue of Tryptophan Hydroxylase-1 Knockout Mice: Implications for Pulmonary Arterial Hypertension

The use of fenfluramines can increase the risk of developing pulmonary arterial hypertension (PAH) in humans, but the mechanisms responsible are unresolved. A recent study reported that female mice lacking the gene for tryptophan hydroxylase-1 (Tph1(−/−) mice) were protected from PAH caused by chronic dexfenfluramine, suggesting a pivotal role for peripheral serotonin (5-HT) in the disease process. Here we tested two alternative hypotheses which might explain the lack of dexfenfluramine-induced PAH in Tph1(−/−) mice. We postulated that: 1) Tph1(−/−) mice express lower levels of pulmonary 5-HT transporter (SERT) when compared to wild-type controls, and 2) Tph1(−/−) mice display adaptive changes in the expression of non-serotonergic pulmonary genes which are implicated in PAH. SERT was measured using radioligand binding methods, whereas gene expression was measured using microarrays followed by quantitative real time PCR (qRT-PCR). Contrary to our first hypothesis, the number of pulmonary SERT sites was modestly up-regulated in female Tph1(−/−) mice. The expression of 51 distinct genes was significantly altered in the lungs of female Tph1(−/−) mice. Consistent with our second hypothesis, qRT-PCR confirmed that at least three genes implicated in the pathogenesis of PAH were markedly up-regulated: Has2, Hapln3 and Retlna. The finding that female Tph1(−/−) mice are protected from dexfenfluramine-induced PAH could be related to compensatory changes in pulmonary gene expression, in addition to reductions in peripheral 5-HT. These observations emphasize the intrinsic limitation of interpreting data from studies conducted in transgenic mice that are not fully characterized

Woodland Recovery after Suppression of Deer: Cascade effects for Small Mammals, Wood Mice (Apodemus sylvaticus) and Bank Voles (Myodes glareolus)

Over the past century, increases in both density and distribution of deer species in the Northern Hemisphere have resulted in major changes in ground flora and undergrowth vegetation of woodland habitats, and consequentially the animal communities that inhabit them. In this study, we tested whether recovery in the vegetative habitat of a woodland due to effective deer management (from a peak of 0.4–1.5 to <0.17 deer per ha) had translated to the small mammal community as an example of a higher order cascade effect. We compared deer-free exclosures with neighboring open woodland using capture-mark-recapture (CMR) methods to see if the significant difference in bank vole (Myodes glareolus) and wood mouse (Apodemus sylvaticus) numbers between these environments from 2001–2003 persisted in 2010. Using the multi-state Robust Design method in program MARK we found survival and abundance of both voles and mice to be equivalent between the open woodland and the experimental exclosures with no differences in various metrics of population structure (age structure, sex composition, reproductive activity) and individual fitness (weight), although the vole population showed variation both locally and temporally. This suggests that the vegetative habitat - having passed some threshold of complexity due to lowered deer density - has allowed recovery of the small mammal community, although patch dynamics associated with vegetation complexity still remain. We conclude that the response of small mammal communities to environmental disturbance such as intense browsing pressure can be rapidly reversed once the disturbing agent has been removed and the vegetative habitat is allowed to increase in density and complexity, although we encourage caution, as a source/sink dynamic may emerge between old growth patches and the recently disturbed habitat under harsh conditions

Selective Serotonin Reuptake Inhibitor Use Is Associated with Right Ventricular Structure and Function: The MESA-Right Ventricle Study

PURPOSE:Serotonin and the serotonin transporter have been implicated in the development of pulmonary hypertension (PH). Selective serotonin reuptake inhibitors (SSRIs) may have a role in PH treatment, but the effects of SSRI use on right ventricular (RV) structure and function are unknown. We hypothesized that SSRI use would be associated with RV morphology in a large cohort without cardiovascular disease (N = 4114). METHODS:SSRI use was determined by medication inventory during the Multi-Ethnic Study of Atherosclerosis baseline examination. RV measures were assessed via cardiac magnetic resonance imaging. The cross-sectional relationship between SSRI use and each RV measure was assessed using multivariable linear regression; analyses for RV mass and end-diastolic volume (RVEDV) were stratified by sex. RESULTS:After adjustment for multiple covariates including depression and left ventricular measures, SSRI use was associated with larger RV stroke volume (RVSV) (2.75 mL, 95% confidence interval [CI] 0.48-5.02 mL, p = 0.02). Among men only, SSRI use was associated with greater RV mass (1.08 g, 95% CI 0.19-1.97 g, p = 0.02) and larger RVEDV (7.71 mL, 95% 3.02-12.40 mL, p = 0.001). SSRI use may have been associated with larger RVEDV among women and larger RV end-systolic volume in both sexes. CONCLUSIONS:SSRI use was associated with higher RVSV in cardiovascular disease-free individuals and, among men, greater RV mass and larger RVEDV. The effects of SSRI use in patients with (or at risk for) RV dysfunction and the role of sex in modifying this relationship warrant further study

Temporal dynamics of the shrub and herbaceous layer of an area of moist grassland in Alto Paraíso de Goiás, Brazil

Este trabalho avaliou a dinâmica estrutural e fl orística de uma comunidade de espécies herbáceo-arbustivas de uma área de campo limpo úmido em Alto Paraíso de Goiás, o primeiro inventário realizado em 2000 (T0) e o segundo em 2007 (T1). A diversidade de Shannon entre os períodos foi comparada pelo teste-t de Hutcheson e a similaridade fl orística, pelo índice de similaridade de Chao-Sørensen. As relações fl orísticas e a cobertura, entre os períodos e as linhas, foram avaliadas por meio de análises de correspondência retifi cada (DCA). Foram amostradas 98 espécies, 88 no T0 e 67 no T1, sendo 31 exclusivas do T0 e 10 do T1. A diversidade fl orística na comunidade foi elevada nos dois períodos, porém diferente entre esses (t = 7,12; p < 0,001), devido a variação no número e cobertura das espécies. A similaridade entre os dois inventários foi alta (Chao-Sørensen ± IC = 0,841 ± 0,074). A ordenação por DCA indicou relações entre a composição fl orística e a cobertura com o gradiente de umidade e de matéria orgânica no solo identifi cados em T0. Houve modifi cações nas linhas em zonas sazonais, as quais se tornaram mais semelhantes às linhas constantemente saturadas por água. Em um intervalo de sete anos o campo limpo úmido apresentou mudanças na composição fl orística e, principalmente na estrutura devido o aumento da cobertura de espécies perenes, cespitosas e entouceiradas, que foram favorecidas pela maior umidade no solo em resposta à elevação da pluviosidade da região. __________________________________________________________________________________________ ABSTRACTTh is study evaluated the fl oristic and structural dynamics of a community of herbaceous-shrub species in an area of moist grassland in Alto Paraíso de Goiás. Th e fi rst inventory was undertaken in 2000 (T0) and the second in 2007 (T1). Shannon’s diversity between the periods was compared by Hutchesons´s t-test, and the fl oristic similarity by the Chao-Sørensen similarity index. Floristic composition and cover, between periods and lines, were evaluated by detrended correspondence analysis (DCA). We sampled 98 species, 88 at T0 and 67 at T1; 31 were unique to T0 and 10 to T1. Floristic diversity in the community was high in both periods, but diff erent between them (t = 7.12, p <0.001), due to variation in species number and coverage. Similarity between the two surveys was high (Chao-Sørensen CI = ± 0.841 ± 0.074). Th e DCA ordination indicated relationships between the fl oristic composition and cover with a gradient of moisture and organic matter in the soil identifi ed in T0. Th ere were changes in the lines in the seasonal zones, which became more similar in those constantly saturated with water. During an interval of seven years the moist grassland showed changes in fl oristic composition and mainly in structure due to increased cover of the clumped tussock perennial species, which were favored by higher soil moisture due to high rainfall in the region

Beyond climate envelopes: effects of weather on regional population trends in butterflies

Although the effects of climate change on biodiversity are increasingly evident by the shifts in species ranges across taxonomical groups, the underlying mechanisms affecting individual species are still poorly understood. The power of climate envelopes to predict future ranges has been seriously questioned in recent studies. Amongst others, an improved understanding of the effects of current weather on population trends is required. We analysed the relation between butterfly abundance and the weather experienced during the life cycle for successive years using data collected within the framework of the Dutch Butterfly Monitoring Scheme for 40 species over a 15-year period and corresponding climate data. Both average and extreme temperature and precipitation events were identified, and multiple regression was applied to explain annual changes in population indices. Significant weather effects were obtained for 39 species, with the most frequent effects associated with temperature. However, positive density-dependence suggested climatic independent trends in at least 12 species. Validation of the short-term predictions revealed a good potential for climate-based predictions of population trends in 20 species. Nevertheless, data from the warm and dry year of 2003 indicate that negative effects of climatic extremes are generally underestimated for habitat specialists in drought-susceptible habitats, whereas generalists remain unaffected. Further climatic warming is expected to influence the trends of 13 species, leading to an improvement for nine species, but a continued decline in the majority of species. Expectations from climate envelope models overestimate the positive effects of climate change in northwestern Europe. Our results underline the challenge to include population trends in predicting range shifts in response to climate change

Operational Research: methods and applications

This is the final version. Available on open access from Taylor & Francis via the DOI in this recordThroughout its history, Operational Research has evolved to include methods, models and algorithms that have been applied to a wide range of contexts. This encyclopedic article consists of two main sections: methods and applications. The first summarises the up-to-date knowledge and provides an overview of the state-of-the-art methods and key developments in the various subdomains of the field. The second offers a wide-ranging list of areas where Operational Research has been applied. The article is meant to be read in a nonlinear fashion and used as a point of reference by a diverse pool of readers: academics, researchers, students, and practitioners. The entries within the methods and applications sections are presented in alphabetical order. The authors dedicate this paper to the 2023 Turkey/Syria earthquake victims. We sincerely hope that advances in OR will play a role towards minimising the pain and suffering caused by this and future catastrophes