Fish in coastal ecosystems can be exposed to acute variations in CO2 of between 0.2 and 1 kPa CO2 (2000-10,000 µatm). Coping with this environmental challenge will depend on the ability to rapidly ...compensate for the internal acid-base disturbance caused by sudden exposure to high environmental CO2 (blood and tissue acidosis); however, studies about the speed of acid-base regulatory responses in marine fish are scarce. We observed that upon sudden exposure to ∼1 kPa CO2, European sea bass (Dicentrarchus labrax) completely regulate erythrocyte intracellular pH within ∼40 min, thus restoring haemoglobin-O2 affinity to pre-exposure levels. Moreover, blood pH returned to normal levels within ∼2 h, which is one of the fastest acid-base recoveries documented in any fish. This was achieved via a large upregulation of net acid excretion and accumulation of HCO3- in blood, which increased from ∼4 to ∼22 mmol l-1. While the abundance and intracellular localisation of gill Na+/K+-ATPase (NKA) and Na+/H+ exchanger 3 (NHE3) remained unchanged, the apical surface area of acid-excreting gill ionocytes doubled. This constitutes a novel mechanism for rapidly increasing acid excretion during sudden blood acidosis. Rapid acid-base regulation was completely prevented when the same high CO2 exposure occurred in seawater with experimentally reduced HCO3- and pH, probably because reduced environmental pH inhibited gill H+ excretion via NHE3. The rapid and robust acid-base regulatory responses identified will enable European sea bass to maintain physiological performance during large and sudden CO2 fluctuations that naturally occur in coastal environments.
Guidelines recommend ambulatory or home blood pressure monitoring to improve hypertension diagnosis and monitoring. Both these methods are ascribed the same threshold values, but whether they produce ...similar results has not been established in certain patient groups.
Adults with mild/moderate stroke or transient ischemic attack (N = 80) completed 2 sets of ambulatory and home blood pressure monitoring. Systolic and diastolic blood pressure values from contemporaneous measurements were compared, and the limits of agreement were assessed. Exploratory analyses for predictive factors of any difference were conducted.
Daytime ambulatory blood pressure values were consistently lower than home values, the mean difference in systolic blood pressure for initial ambulatory versus first home monitoring was −6.6 ± 13.5 mm Hg (P≤.001), and final ambulatory versus second home monitoring was −7.1 ± 11.0mm Hg (P≤.001). Mean diastolic blood pressure differences were −2.1 ± 8.5mm Hg (P=.03) and −2.0 ± 7.2mm Hg (P=.02). Limits of agreement for systolic blood pressure were −33.0 to 19.9mm Hg and −28.7 to 14.5mm Hg for the 2 comparisons and for DBP were −18.8 to 14.5mm Hg and −16.1 to 12.2mm Hg, respectively. The individual mean change in systolic blood pressure difference was 11.0 ± 8.3mm Hg across the 2 comparisons. No predictive factors for these differences were identified.
Daytime ambulatory systolic and diastolic blood pressure values were significantly lower than home monitored values at both time points. Differences between the 2 methods were not reproducible for individuals. Using the same threshold value for both out-of-office measurement methods may not be appropriate in patients with cerebrovascular disease.
The therapeutic benefit of self-monitoring blood pressure in stroke patients is uncertain. We investigated the effect of self-monitoring with or without guided antihypertensive management compared ...with usual care in patients with a recent cerebrovascular event. No between-group differences in blood pressure at outcome were found, but blood pressure self-monitoring and management was well tolerated.
Trials of lowering blood pressure in patients with acute ischaemic stroke not undergoing thrombolysis have not demonstrated improved outcomes with intervention. Rather than absolute levels, it may be ...that blood pressure variability is important. However, there are no prospective randomised trials investigating the benefit of reducing blood pressure variability in this patient group.
The primary aim of this trial was to determine the feasibility of recruitment to a randomised trial investigating the effect of different antihypertensive medications on blood pressure variability.
CAARBS was a multi-centre, open-label, randomised parallel group controlled feasibility trial. Adults with a first mild-moderate ischaemic stroke or transient ischaemic attack, requiring antihypertensive therapy for secondary prevention, were randomised to a calcium channel blocker or angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. Blood pressure and variability were measured at baseline, three weeks, and three months. Compliance with measurements and treatment was monitored.
Fourteen patients were recruited to the trial (0.6% of those screened), nine of whom completed follow-up. The majority of patients screened (98.1%) were ineligible. Compliance with the intervention was good, as were measurement completion rates (88.9% or higher in all cases except ambulatory measurements). No major adverse events were recorded.
Recruitment to the trial was difficult due to patient ineligibility, suggesting that the current protocol is unlikely to be successful if scaled for a definitive trial. However, the intervention was safe, and compliance was good, suggesting a future trial with modified eligibility criteria could be successful.
Trial registration: ISRCTN10853487.
•Lowering blood pressure variability (BPV) after ischaemic stroke may be beneficial.•This feasibility trial investigating BPV reduction did not meet recruitment targets.•Potential changes to eligibility criteria for possible future trials were identified.•Measuring change in BPV over a follow-up period of three months was possible.•Intervention to reduce BPV in the subacute phase of ischaemic stroke was safe.
Hydrogels are increasingly being used to control mass transport in the analytical determination of trace elements. Quantitative use of the techniques of diffusive gradients in thin-films (DGT) and ...voltammetry at gel covered microelectrodes relies on precise knowledge of the diffusion coefficients in the gels. Two simple procedures, one relying on establishing pseudo steady state (Fick’s first law) and the other on a dynamic response (Fick’s second law), have been used to measure the diffusion coefficients of trace metals and fulvic and humic substances in five different hydrogels. To obtain consistent results it was essential to treat gels with an electrolyte prior to measurement. The different procedures agreed to within 5% with each other and with measurements made by DGT. For polyacrylamide gels cross-linked with an agarose derivative (APA) and with Bis acrylamide at 5% monomer concentration (BPA2) and for pure agarose gel (AGE), there was no significant difference between the diffusion coefficients of trace metals measured in the gels and those reported for water. Bis cross-linked gels containing 15% monomer (BPA1) and the constrained gel (CGa) impeded the diffusion of metal ions compared to water. There was little evidence for the AGE gel impeding the diffusion of fulvic substances, but it appeared to increasingly restrict the diffusion of humic substances as molecular weight increased. There was clear restriction of fulvic and humic substances by the APA gel and much greater restriction by the constrained gel (CGa). The results are consistent with the known open structures of AGE and APA gels and the dependence of the structure of BPA gels on monomer concentration. The much greater retardation of humic and fulvic substances in the constrained gels compared to trace metals opens up the possibility of using gel techniques to discriminate organically and inorganically complexed metals in natural waters.
Cognitive impairment and dementia following cerebrovascular disease are increasingly common in the UK. One potential strategy to prevent post-stroke cognitive decline is multimodal vascular risk ...factor management. However, its efficacy remains uncertain and its application in vulnerable patients with incident cerebrovascular disease and early cognitive impairment has not been assessed. The primary aim of this study was to assess the feasibility of recruitment and retention of patients with early cognitive impairment post-stroke or transient ischaemic attack (TIA) to a trial of enhanced vascular risk factor management combining primary and secondary care.
In this single centre, open label trial adults with a recent stroke or TIA and mild cognitive impairment (MCI) were randomised 1:1 to a three-monthly multimodal vascular risk factor intervention jointly delivered by the trial team and General Practitioner (GP), or control (defined as usual care from the GP). Chosen risk factors were blood pressure (BP), total cholesterol, blood glucose (HbA1C) in those with diabetes, and heart rate and adequacy of anticoagulation in those with atrial fibrillation (AF). Similar patients with normal cognition were enrolled in an embedded observational cohort and also received usual care from the GP. Repeat cognitive screening was undertaken in all participants after 12 months.
Seventy three participants were recruited to the randomised trial and 94 to the observational cohort (21.8% of those screened). From the randomised trial 35/73 (47.9%) dropped out before final follow-up. In all groups guideline based rates of risk factor control were mostly poor at baseline and did not significantly improve during follow-up. The observational cohort demonstrated greater decline in cognitive test scores at 12 months, with no difference between the randomised groups.
Recruitment to such a study was feasible, but retention of participants was difficult and generally poor rates of risk factor control suggested insufficient application of the intervention. Consequently, successful scaling up of the trial would require protocol changes with less reliance on primary care services. Any future trial should include participants with normal cognition post-stroke as they may be at greatest risk of cognitive decline.
ISRCTN, ISRCTN42688361 . Registered 16 April 2015.
Gaining meaningful blood samples from water-breathing fish is a significant challenge. Two main methods typically used are grab 'n' stab and surgical cannulation. Both methods have benefits, but also ...significant limitations under various scenarios. Here we present a method of blood sampling laboratory fish involving gradual induction of anaesthesia within their home tank, avoiding physical struggling associated with capture, followed by rapid transfer to a gill irrigation system to maintain artificial ventilation via adequate gill water flow and then followed by sampling the caudal vasculature. This method negates many blood chemistry disturbances associated with grab 'n' stab (i.e., low pH and oxygen, elevated lactate, CO
and stress hormones) and generates results that are directly comparable to cannulated fish under a wide range of experimentally-induced acid-base scenarios (acidosis and alkalosis). Crucially this method was successful in achieving accurate acid-base blood measurements from fish ten times smaller than are typically suitable for cannulation. This opens opportunities not previously possible for studies that relate to basic physiology, sustainable aquaculture, ecotoxicology, conservation, and climate change.
The Mekong Delta is host to a large number of freshwater species, including a unique group of facultative air‐breathing Anabantiforms. Of these, the striped snakehead (Channa striata), the climbing ...perch (Anabas testudineus), the giant gourami (Osphronemus goramy) and the snakeskin gourami (Trichogaster pectoralis) are major contributors to aquaculture production in Vietnam. The gastrointestinal responses to feeding in these four species are detailed here. Relative intestinal length was lowest in the snakehead, indicating carnivory, and 5.5‐fold greater in the snakeskin, indicating herbivory; climbing perch and giant gourami were intermediate, indicating omnivory. N‐waste excretion (ammonia‐N + urea‐N) was greatest in the carnivorous snakehead and least in the herbivorous snakeskin, whereas the opposite trend was observed for net K+ excretion. Similarly, the more carnivorous species had a greater stomach acidity than the more herbivorous species. Measurements of acid–base flux to water indicated that the greatest postprandial alkaline tide occurred in the snakehead and a potential acidic tide in the snakeskin. Additional findings of interest were high levels of both PCO2 (up to 40 mmHg) and HCO3− (up to 33 mM) in the intestinal chyme of all four of these air‐breathing species. Using in vitro gut sac preparations of the climbing perch, it was shown that the intestinal net absorption of fluid, Na+ and HCO3− was upregulated by feeding but not net Cl− uptake, glucose uptake or K+ secretion. Upregulated net absorption of HCO3− suggests that the high chyme (HCO3−) does not result from secretion by the intestinal epithelium. The possibility of ventilatory control of PCO2 to regulate postprandial acid–base balance in these air‐breathing fish is discussed.
IntroductionRaised blood pressure (BP) is common after stroke and is associated with a poor prognosis, yet trials of BP lowering in the immediate poststroke period have not demonstrated a benefit. ...One possible explanation for this may be that BP variability (BPV) rather than absolute levels predicts outcome, as BPV is increased after stroke and is associated with poor outcomes. Furthermore, there is evidence of distinct antihypertensive class effects on BPV despite similar BP-lowering effects. However, whether BPV in the immediate poststroke period is a therapeutic target has not been prospectively investigated.The objectives of this trial are to assess the feasibility and safety of recruiting patients following an acute ischaemic stroke or transient ischaemic attack (TIA) to an interventional randomised controlled trial comparing the effects of two different antihypertensive drug classes on BPV. Secondary exploratory objectives are to assess if different therapeutic strategies have diverse effects on levels of BPV and if this has an impact on outcomes.Methods150 adult patients with first-ever ischaemic stroke or TIA who require antihypertensive therapy for secondary prevention will be recruited within 7 days of the event from stroke services across three sites. After baseline assessments they will be randomly assigned to treatment with a calcium channel blocker or ACE inhibitor/angiotensin receptor blocker-based regimen and followed up for a period of three months.Ethics and disseminationEthical and regulatory approvals have been granted. Dissemination is planned via publication in peer-reviewed medical journals and presentation at relevant conferences.Trial registration numberISRCTN10853487.
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