Objective— Angiotensin II (AII) has been shown to increase endothelial NAD(P)H oxidase activity, which is a source of superoxide anion that in turn may induce the formation of peroxynitrite. Estrogen (E 2 ) has been reported to have vascular protective effects. In this study, we hypothesized that E 2 reduces the AII-induced expression of NAD(P)H oxidase and peroxynitrite in endothelial cells. Methods and Results— Endothelial cells were cultured and stimulated with AII in the absence or presence of E 2 . Western blots were used to assess nitric oxide synthase (NOS) and NAD(P)H oxidase expression. Immunofluorescence of nitrotyrosine provided evidence of peroxynitrite formation. Our data indicate that AII increased the expression of endothelial NOS, inducible NOS, and NAD(P)H oxidase in a dose-dependent manner, which was attenuated by incubation with either E 2 , superoxide dismutase, or the AII type 1 receptor (AT 1 R) inhibitor candesartan. Estrogen as well as superoxide dismutase also inhibited AII-induced AT 1 R expression and nitrotyrosine staining. The effects of E 2 on the AII responses were not inhibited by the E 2 receptor antagonist ICI-182,780. Conclusions— AII stimulation of endothelial cells increases expression of NAD(P)H oxidase and NOS, which may contribute to oxidative stress, as evidenced by peroxynitrite formation. E 2 inhibits these AII effects, possibly through reduced AT 1 R expression.
We tested whether propofol or Intralipid inoculated with Staphylococcus epidermidis would promote bacterial growth within an intravenous (IV) injection hub, a site prone to bacterial contamination. In tubes incubated under optimal conditions, S epidermidis exhibited growth in Intralipid, but not in propofol. In contrast, within the IV hub incubated with either propofol or intralipid at room temperature, S epidermidis bacterial numbers declined with time, and virtually no contamination remained after 12 hours. These data suggest that certain IV lines are inhospitable for S epidermidis.
Prenatal iron deficiency alters fetal developmental trajectories, which results in persistent changes in organ function. Here, we studied the effects of prenatal iron deficiency on fetal kidney and liver mitochondrial function. Pregnant Sprague-Dawley rats were fed partially or fully iron-restricted diets to induce a state of moderate or severe iron deficiency alongside iron-replete control rats. We assessed mitochondrial function via high-resolution respirometry and reactive oxygen species generation via fluorescence microscopy on gestational d 21. Hemoglobin levels were reduced in dams in the moderate (−31%) and severe groups (−54%) compared with controls, which was accompanied by 55% reductions in fetal hemoglobin levels in both moderate and severe groups versus controls. Male iron-deficient kidneys exhibited globally reduced mitochondrial content and respiration, as well as increased cytosolic superoxide and decreased NO. Female iron-deficient kidneys exhibited complex II down-regulation and increased mitochondrial oxidative stress. Male iron-deficient livers exhibited reduced complex IV respiration and increased cytosolic superoxide, whereas female liver tissues exhibited no alteration in oxidant levels or mitochondrial function. These findings indicate that prenatal iron deficiency causes changes in mitochondrial content and function as well as oxidant status in a sex- and organ-dependent manner, which may be an important mechanism that underlies the programming of cardiovascular disease.—Woodman, A. G., Mah, R., Keddie, D., Noble, R. M. N., Panahi, S., Gragasin, F. S., Lemieux, H., Bourque, S. L. Prenatal iron deficiency causes sex-dependent mitochondrial dysfunction and oxidative stress in fetal rat kidneys and liver. FASEB J. 32, 3254–3263 (2018). www.fasebj.org
Poor reporting quality may contribute to irreproducibility of results and failed ‘bench-to-bedside’ translation. Consequently, guidelines have been developed to improve the complete and transparent reporting of in vivo preclinical studies. To examine the impact of such guidelines on core methodological and analytical reporting items in the preclinical anesthesiology literature, we sampled a cohort of studies. Preclinical in vivo studies published in Anesthesiology, Anesthesia & Analgesia, Anaesthesia, and the British Journal of Anaesthesia (2008–2009, 2014–2016) were identified. Data was extracted independently and in duplicate. Reporting completeness was assessed using the National Institutes of Health Principles and Guidelines for Reporting Preclinical Research. Risk ratios were used for comparative analyses. Of 7615 screened articles, 604 met our inclusion criteria and included experiments reporting on 52 490 animals. The most common topic of investigation was pain and analgesia (30%), rodents were most frequently used (77%), and studies were most commonly conducted in the United States (36%). Use of preclinical reporting guidelines was listed in 10% of applicable articles. A minority of studies fully reported on replicates (0.3%), randomization (10%), blinding (12%), sample-size estimation (3%), and inclusion/exclusion criteria (5%). Statistics were well reported (81%). Comparative analysis demonstrated few differences in reporting rigor between journals, including those that endorsed reporting guidelines. Principal items of study design were infrequently reported, with few differences between journals. Methods to improve implementation and adherence to community-based reporting guidelines may be necessary to increase transparent and consistent reporting in the preclinical anesthesiology literature.
Introduction Fetal exposure to an adverse intrauterine environment can lead to altered growth and developmental trajectories, thereby increasing susceptibility to chronic disease in later life. Iron deficiency (ID) is the most common nutritional disorder in the world, and pregnant women are the most susceptible subgroup. We have shown that prenatal ID programs offspring metabolic function, characterized by an increased propensity for fat accumulation in later life; however, the mechanisms underlying this metabolic function are unknown. Brown adipose tissue (BAT) is highly metabolically active tissue which generates large quantities of heat to maintain core body temperature. The capacity of BAT to burn calories as heat makes it an attractive therapeutic target for obesity. We sought to determine whether prenatal ID predisposes offspring to obesity by chronically altering the thermogenic capacity of BAT, and thus whole body metabolism. Methods Female Sprague Dawley rats were fed either a control or an iron‐restricted (3–10 ppm iron) diet prior to and throughout gestation. At birth, dams were fed a normal rat chow, and pups were subsequently fed a high‐fat/high‐sucrose diet at weaning (postnatal day 21). At 4wk of age, one male and female offspring from each litter were subjected to a chronic cold exposure protocol (4°C, 12h/day, 5wk) to stimulate brown fat, and one male and female littermate were maintained at room temperature (22°C). Metabolic parameters were analyzed in vivo via open‐circuit indirect calorimetry. Maximal thermogenic capacity from BAT was assessed following pharmacological stimulation with the β3 agonist CL316,243. Results Prenatal ID caused lower body weights in offspring from birth until 4wk of age, but both male and female offspring exhibited catch‐up growth when fed the high‐fat/high‐sucrose diet. Cold exposure increased BAT mass in all offspring (P<0.001), and this correlated with increased thermogenic capacity in all offspring (P<0.001). Whereas cold exposure had minimal effects on control offspring body weight and body composition, cold exposure prevented body weight and fat mass gain in male PID offspring (P<0.001), but not in female PID offspring. Conclusions Prenatal ID causes sex‐specific programming of body composition and BAT function in the offspring. BAT may therefore represent an attractive target for therapeutic intervention to prevent the obesity and metabolic function caused by early stressors such as prenatal ID. Support or Funding Information This research has been facilitated by the Women and Children's Health Research Institute through the generosity of the Stollery Children's Hospital Foundation and supporters of the Lois Hole Hospital for Women, and the Canadian Institutes of Health Research.
( A A Case Rep . 2016;6:160–162) In this case report, a 32-year-old primigravida woman with a history of idiopathic intracranial hypertension (IIH) presented to the labor and delivery suite at 40 weeks gestation in active labor and with pseudotumor cerebri syndrome (PTCS). PTCS, which includes IIH, is a rare disorder mainly of obese women of childbearing age, characterized by increased intracranial pressure in the absence of a space-occupying lesion, ventriculomegaly, or abnormal cerebrospinal fluid (CSF) composition. Symptoms include headache, pulsatile tinnitus, back pain, dizziness, photophobia, neck pain, cognitive dysfunction, radicular pain, diplopia, and in some cases, permanent vision loss. This patient was diagnosed with IIH at age 14 and was treated with multiple lumbar punctures and diuretics until age 18 years. She was then asymptomatic until 23 years of age, at which time she had a recurrence and resumed diuretic therapy until her pregnancy.
The proportion of elderly people in the population is steadily increasing, and the inevitable consequence is that this subpopulation is more frequently represented in common medical procedures and surgeries. Understanding the circulatory changes that accompany the aging process is therefore becoming increasingly timely and relevant. In this short review, we discuss aspects of vascular control in aging that are particularly relevant in the maintenance of intraoperative hemodynamic stability. We subsequently review the effects of certain notable anesthetic agents with respect to the aging vasculature.
Sepsis is associated with circulatory dysfunction contributing to disturbed blood flow and organ injury. Decreased organ perfusion in sepsis is attributed, in part, to the loss of vasoregulatory mechanisms. Identifying which vascular beds are most susceptible to dysfunction is important for monitoring the recovery of organ function and guiding interventions. This study aimed to investigate the development of vascular dysfunction as sepsis progressed to septic shock. Anesthetized C57Bl/6 mice were instrumented with a fiberoptic pressure sensor in the carotid artery for blood pressure measurements. In subgroups of mice, regional blood flow measurements were taken by positioning a perivascular flow probe around either the left carotid, left renal, or superior mesenteric arteries. Hemodynamic parameters and their responsiveness to bolus doses of vasoactive drugs were recorded prior to and continuously after injection of fecal slurry (1.3 mg/g body weight) for 4 h. Fecal slurry-induced peritonitis reduced mean arterial pressure (62.7 ± 2.4 mmHg vs. 37.5 ± 3.2 mmHg in vehicle and septic mice, respectively), impaired cardiac function, and eventually reduced organ blood flow (71.9%, 66.8%, and 65.1% in the superior mesenteric, renal, and carotid arteries, respectively). The mesenteric vasculature exhibited dysregulation before the renal and carotid arteries, and this underlying dysfunction preceded the blood pressure decline and impaired organ blood flow.
