Angiotensin II in experimental hyperdynamic sepsis

INTRODUCTION: Angiotensin II (Ang II) is a potential vasopressor treatment for hypotensive hyperdynamic sepsis. However, unlike other vasopressors, its systemic, regional blood flow and renal functional effects in hypotensive hyperdynamic sepsis have not been investigated. METHODS: We performed an experimental randomised placebo-controlled animal study. We induced hyperdynamic sepsis by the intravenous administration of live E. coli in conscious ewes after chronic instrumentation with flow probes around the aorta and the renal, mesenteric, coronary and iliac arteries. We allocated animals to either placebo or angiotensin II infusion titrated to maintain baseline blood pressure. RESULTS: Hyperdynamic sepsis was associated with increased renal blood flow (from 292 +/- 61 to 397 +/- 74 ml/min), oliguria and a decrease in creatinine clearance (from 88.7 +/- 19.6 to 47.7 +/- 21.0 ml/min, P < 0.0001). Compared to placebo, Ang II infusion restored arterial pressure but reduced renal blood flow (from 359 +/- 81 ml/min to 279 +/- 86 ml/min; P < 0.0001). However, despite the reduction in renal blood flow, Ang II increased urine output approximately 7-fold (364 +/- 272 ml/h vs. 48 +/- 18 ml/h; P < 0.0001), and creatinine clearance by 70% (to 80.6 +/- 20.7 ml/min vs.46.0 +/- 26 ml/min; P < 0.0001). There were no major effects of Ang II on other regional blood flows. CONCLUSIONS: In early experimental hypotensive hyperdynamic sepsis, intravenous angiotensin II infusion decreased renal blood while inducing a marked increase in urine output and normalizing creatinine clearance

The histopathology of septic acute kidney injury: a systematic review

INTRODUCTION: Sepsis is the most common trigger of acute kidney injury (AKI) in critically ill patients; understanding the structural changes associated with its occurrence is therefore important. Accordingly, we systematically reviewed the literature to assess current knowledge on the histopathology of septic AKI. METHODS: A systematic review of the MEDLINE, EMBASE and CINHAL databases and bibliographies of the retrieved articles was performed for all studies describing kidney histopathology in septic AKI. RESULTS: We found six studies reporting the histopathology of septic AKI for a total of only 184 patients. Among these patients, only 26 (22%) had features suggestive of acute tubular necrosis (ATN). We found four primate studies. In these, seven out of 19 (37%) cases showed features of ATN. We also found 13 rodent studies of septic AKI. In total, 23% showed evidence of ATN. In two additional studies performed in a dog model and a sheep model there was no evidence of ATN on histopathologic examination. Overall, when ATN was absent, studies reported a wide variety of kidney morphologic changes in septic AKI - ranging from normal (in most cases) to marked cortical tubular necrosis. CONCLUSION: There are no consistent renal histopathological changes in human or experimental septic AKI. The majority of studies reported normal histology or only mild, nonspecific changes. ATN was relatively uncommon

Systemic and renal hemodynamic effects of intra-arterial radiocontrast

Hydrogen in excess of solid solubility precipitates as hydride phase of plate shaped morphology in hcp α-Zr with the broad face of the hydride plate coinciding with certain crystallographic plane of α-Zr crystal called habit plane. The objective of the present investigation is to predict the habit plane of δ-hydride precipitating in α-Zr at 298 K using strain energy minimization technique. The δ-hydride phase is modeled to undergo isotropic elasto-plastic deformation. The α-Zr phase was modeled to undergo transverse isotropic elastic deformation but isotropic plastic deformation. Accommodation strain energy of δ-hydride forming in α-Zr crystal was computed using initial strain method as a function of hydride nuclei orientation. Hydride was modeled as disk with round edge. Contrary to several habit planes reported in literature for δ- hydrides precipitating in α-Zr crystal, the total accommodation energy minima at 298 K suggests only basal plane i.e. (0001) as the habit plane

Pulmonary Artery Catheter (PAC) Accuracy and Efficacy Compared with Flow Probe and Transcutaneous Doppler (USCOM): An Ovine Cardiac Output Validation

Background. The pulmonary artery catheter (PAC) is an accepted clinical method of measuring cardiac output (CO) despite no prior validation. The ultrasonic cardiac output monitor (USCOM) is a noninvasive alternative to PAC using Doppler ultrasound (CW). We compared PAC and USCOM CO measurements against a gold standard, the aortic flow probe (FP), in sheep at varying outputs. Methods. Ten conscious sheep, with implanted FPs, had measurements of CO by FP, USCOM, and PAC, at rest and during intervention with inotropes and vasopressors. Results. CO measurements by FP, PAC, and USCOM were 4.0 ± 1.2 L/min, 4.8 ± 1.5 L/min, and 4.0 ± 1.4 L/min, respectively, (n = 280, range 1.9 L/min to 11.7 L/min). Percentage bias and precision between FP and PAC, and FP and USCOM was −17 and 47%, and 1 and 36%, respectively. PAC under-measured Dobutamine-induced CO changes by 20% (relative 66%) compared with FP, while USCOM measures varied from FP by 3% (relative 10%). PAC reliably detected −30% but not +40% CO changes, as measured by receiver operating characteristic area under the curve (AUC), while USCOM reliably detected ±5% changes in CO (AUC > 0.70). Conclusions. PAC demonstrated poor accuracy and sensitivity as a measure of CO. USCOM provided equivalent measurements to FP across a sixfold range of outputs, reliably detecting ±5% changes

Recording sympathetic nerve activity in conscious humans and other mammals:guidelines and the road to standardization

Over the past several decades, studies of the sympathetic nervous system in humans, sheep, rabbits, rats, and mice have substantially increased mechanistic understanding of cardiovascular function and dysfunction. Recently, interest in sympathetic neural mechanisms contributing to blood pressure control has grown, in part because of the development of devices or surgical procedures that treat hypertension by manipulating sympathetic outflow. Studies in animal models have provided important insights into physiological and pathophysiological mechanisms that are not accessible in human studies. Across species and among laboratories, various approaches have been developed to record, quantify, analyze, and interpret sympathetic nerve activity (SNA). In general, SNA demonstrates “bursting” behavior, where groups of action potentials are synchronized and linked to the cardiac cycle via the arterial baroreflex. In humans, it is common to quantify SNA as bursts per minute or bursts per 100 heart beats. This type of quantification can be done in other species but is only commonly reported in sheep, which have heart rates similar to humans. In rabbits, rats, and mice, SNA is often recorded relative to a maximal level elicited in the laboratory to control for differences in electrode position among animals or on different study days. SNA in humans can also be presented as total activity, where normalization to the largest burst is a common approach. The goal of the present paper is to put together a summary of “best practices” in several of the most common experimental models and to discuss opportunities and challenges relative to the optimal measurement of SNA across species. Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/guidelines-for-measuring-sympathetic-nerve-activity/ </jats:p

A systematic review and meta-synthesis of the impact of low back pain on people's lives

Copyright @ 2014 Froud et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Background - Low back pain (LBP) is a common and costly problem that many interpret within a biopsychosocial model. There is renewed concern that core-sets of outcome measures do not capture what is important. To inform debate about the coverage of back pain outcome measure core-sets, and to suggest areas worthy of exploration within healthcare consultations, we have synthesised the qualitative literature on the impact of low back pain on people’s lives. Methods - Two reviewers searched CINAHL, Embase, PsycINFO, PEDro, and Medline, identifying qualitative studies of people’s experiences of non-specific LBP. Abstracted data were thematic coded and synthesised using a meta-ethnographic, and a meta-narrative approach. Results - We included 49 papers describing 42 studies. Patients are concerned with engagement in meaningful activities; but they also want to be believed and have their experiences and identity, as someone ‘doing battle’ with pain, validated. Patients seek diagnosis, treatment, and cure, but also reassurance of the absence of pathology. Some struggle to meet social expectations and obligations. When these are achieved, the credibility of their pain/disability claims can be jeopardised. Others withdraw, fearful of disapproval, or unable or unwilling to accommodate social demands. Patients generally seek to regain their pre-pain levels of health, and physical and emotional stability. After time, this can be perceived to become unrealistic and some adjust their expectations accordingly. Conclusions - The social component of the biopsychosocial model is not well represented in current core-sets of outcome measures. Clinicians should appreciate that the broader impact of low back pain includes social factors; this may be crucial to improving patients’ experiences of health care. Researchers should consider social factors to help develop a portfolio of more relevant outcome measures.Arthritis Research U

Renal Denervation Update From the International Sympathetic Nervous System Summit:JACC State-of-the-Art Review

Three recent renal denervation studies in both drug-naïve and drug-treated hypertensive patients demonstrated a significant reduction of ambulatory blood pressure compared with respective sham control groups. Improved trial design, selection of relevant patient cohorts, and optimized interventional procedures have likely contributed to these positive findings. However, substantial variability in the blood pressure response to renal denervation can still be observed and remains a challenging and important problem. The International Sympathetic Nervous System Summit was convened to bring together experts in both experimental and clinical medicine to discuss the current evidence base, novel developments in our understanding of neural interplay, procedural aspects, monitoring of technical success, and others. Identification of relevant trends in the field and initiation of tailored and combined experimental and clinical research efforts will help to address remaining questions and provide much-needed evidence to guide clinical use of renal denervation for hypertension treatment and other potential indications

Scalable production of large quantities of defect-free few-layer graphene by shear exfoliation in liquids

To progress from the laboratory to commercial applications, it will be necessary to develop industrially scalable methods to produce large quantities of defect-free graphene. Here we show that high-shear mixing of graphite in suitable stabilizing liquids results in large-scale exfoliation to give dispersions of graphene nanosheets. X-ray photoelectron spectroscopy and Raman spectroscopy show the exfoliated flakes to be unoxidized and free of basal-plane defects. We have developed a simple model that shows exfoliation to occur once the local shear rate exceeds 10(4) s(-1). By fully characterizing the scaling behaviour of the graphene production rate, we show that exfoliation can be achieved in liquid volumes from hundreds of millilitres up to hundreds of litres and beyond. The graphene produced by this method performs well in applications from composites to conductive coatings. This method can be applied to exfoliate BN, MoS2 and a range of other layered crystals

Conserved community structure and simultaneous divergence events in the fig wasps associated with Ficus benjamina in Australia and China

Localised patterns of species diversity can be influenced by many factors, including regional species pools, biogeographic features and interspecific interactions. Despite recognition of these issues, we still know surprisingly little about how invertebrate biodiversity is structured across geographic scales. In particular, there have been few studies of how insect communities vary geographically while using the same plant host. We compared the composition (species, genera) and functional structure (guilds) of the chalcid wasp communities associated with the widespread fig tree, Ficus benjamina, towards the northern (Hainan province, China) and southern (Queensland, Australia) edges of its natural range. Sequence data were generated for nuclear and mtDNA markers and used to delimit species, and Bayesian divergence analyses were used to test patterns of community cohesion through evolutionary time. Both communities host at least 14 fig wasp species, but no species are shared across continents. Community composition is similar at the genus level, with six genera shared although some differ in species diversity between China and Australia; a further three genera occur in only China or Australia. Community functional structure remains very similar in terms of numbers of species in each ecological guild despite community composition differing a little (genera) or a lot (species), depending on taxonomic level. Bayesian clustering analyses favour a single community divergence event across continents over multiple events for different ecological guilds. Molecular dating estimates of lineage splits between nearest inter-continental species pairs are broadly consistent with a scenario of synchronous community divergence from a shared "ancestral community". Fig wasp community structure and genus-level composition are largely conserved in a wide geographic comparison between China and Australia. Moreover, dating analyses suggest that the functional community structure has remained stable for long periods during historic range expansions. This suggests that ecological interactions between species may play a persistent role in shaping these communities, in contrast to findings in some comparable temperate systems

Effects of selective β1-adrenoceptor blockade on cardiovascular and renal function and circulating cytokines in ovine hyperdynamic sepsis

INTRODUCTION: Activation of the sympathetic nervous system has beneficial cardiovascular effects in sepsis, but there is also evidence that sympatholytics have beneficial actions in sepsis. We therefore determined the effect of selective β(1)-adrenoceptor blockade on cardiac and renal function and cytokine release in ovine hyperdynamic sepsis. METHODS: Hyperdynamic sepsis was induced by infusion of live E. coli for 24 hours in nine conscious sheep instrumented with flow probes on the pulmonary and left renal artery. Cardiovascular and renal function and levels of plasma cytokines were determined in a control group and during selective β1-adrenoceptor blockade with atenolol (10 mg intravenous bolus then 0.125 mg/kg/h) from 8 to 24 hours of sepsis. RESULTS: Hyperdynamic sepsis was characterized by hypotension with increases in cardiac output (CO), heart rate (HR) and renal blood flow (RBF), and acute kidney injury. Atenolol caused sustained reductions in HR (P <0.001) and CO (P <0.001). Despite the lower CO the sepsis-induced fall in mean arterial pressure (MAP) was similar in both groups. The sepsis-induced increase in RBF, decrease in renal function and increase in arterial lactate were unaffected by atenolol. Sepsis increased plasma levels of tumour necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and IL-10. Atenolol caused a further increase in IL-10, but did not affect levels of TNF-α or IL-6. CONCLUSIONS: In sepsis, selective β(1)-adrenoceptor blockade reduced CO, but not MAP. During sepsis, atenolol did not alter the development of acute kidney injury or the levels of pro-inflammatory cytokines, but enhanced the release of IL-10. Atenolol appears safe in sepsis, has no deleterious cardiovascular or renal effects, and has an anti-inflammatory effect