Continuous gastric saline perfusion elicits cardiovascular responses in freshwater rainbow trout (Oncorhynchus mykiss)

When in seawater, rainbow trout (Oncorhynchus mykiss) drink to avoid dehydration and display stroke volume (SV) mediated elevations in cardiac output (CO) and an increased proportion of CO is diverted to the gastrointestinal tract as compared to when in freshwater. These cardiovascular alterations are associated with distinct reductions in systemic and gastrointestinal vascular resistance (R-Sys and R-GI, respectively). Although increased gastrointestinal blood flow (GBF) is likely essential for osmoregulation in seawater, the sensory functions and mechanisms driving the vascular resistance changes and other associated cardiovascular changes in euryhaline fishes remain poorly understood. Here, we examined whether internal gastrointestinal mechanisms responsive to osmotic changes mediate the cardiovascular changes typically observed in seawater, by comparing the cardiovascular responses of freshwater-acclimated rainbow trout receiving continuous (for 4 days) gastric perfusion with half-strength seawater (1/2 SW, similar to 17 ppt) to control fish (i.e., no perfusion). We show that perfusion with 1/2 SW causes significantly larger increases in CO, SV and GBF, as well as reductions in R-Sys and R-GI, compared with the control, whilst there were no significant differences in blood composition between treatments. Taken together, our data suggest that increased gastrointestinal luminal osmolality is sensed directly in the gut, and at least partly, mediates cardiovascular responses previously observed in SW acclimated rainbow trout. Even though a potential role of mechano-receptor stimulation from gastrointestinal volume loading in eliciting these cardiovascular responses cannot be excluded, our study indicates the presence of internal gastrointestinal milieu-sensing mechanisms that affect cardiovascular responses when environmental salinity changes

Energetic savings and cardiovascular dynamics of a marine euryhaline fish (Myoxocephalus scorpius) in reduced salinity

Few studies have addressed how reduced water salinity affects cardiovascular and metabolic function in marine euryhaline fishes, despite its relevance for predicting impacts of natural salinity variations and ongoing climate change on marine fish populations. Here, shorthorn sculpin (Myoxocephalus scorpius) were subjected to different durations of reduced water salinity from 33 to 15 ppt. Routine metabolic rate decreased after short-term acclimation (4-9 days) to 15 ppt, which corresponded with similar reductions in cardiac output. Likewise, standard metabolic rate decreased after acute transition (3 h) from 33 to 15 ppt, suggesting a reduced energetic cost of osmoregulation at 15 ppt. Interestingly, gut blood flow remained unchanged across salinities, which contrasts with previous findings in freshwater euryhaline teleosts (e.g., rainbow trout) exposed to different salinities. Although plasma osmolality, [Na+], [Cl-] and [Ca2+] decreased in 15 ppt, there were no signs of cellular osmotic stress as plasma [K+], [hemoglobin] and hematocrit remained unchanged. Taken together, our data suggest that shorthorn sculpin are relatively weak plasma osmoregulators that apply a strategy whereby epithelial ion transport mechanisms are partially maintained across salinities, while plasma composition is allowed to fluctuate within certain ranges. This may have energetic benefits in environments where salinity naturally fluctuates, and could provide shorthorn sculpin with competitive advantages if salinity fluctuations intensify with climate change in the future

Increased reliance on coronary perfusion for cardiorespiratory performance in seawater-acclimated rainbow trout

Salmonid ventricles are composed of spongy and compact myocardium, the latter being perfused via a coronary circulation. Rainbow trout (Oncorhynchus mykiss) acclimated to sea water have higher proportions of compact myocardium and display stroke volume-mediated elevations in resting cardiac output relative to freshwater-acclimated trout, probably to meet the higher metabolic needs of osmoregulatory functions. Here, we tested the hypothesis that cardiorespiratory performance of rainbow trout in sea water is more dependent on coronary perfusion by assessing the effects of coronary ligation on cardiorespiratory function in resting and exhaustively exercised trout acclimated to fresh water or sea water. While ligation only had minor effects on resting cardiorespiratory function across salinities, cardiac function after chasing to exhaustion was impaired, presumably as a consequence of atrioventricular block. Ligation reduced maximum O2 consumption rate by 33% and 17% in fish acclimated to sea water and fresh water, respectively, which caused corresponding 41% and 17% reductions in aerobic scope. This was partly explained by different effects on cardiac performance, as maximum stroke volume was only significantly impaired by ligation in sea water, resulting in 38% lower maximum cardiac output in seawater compared with 28% in fresh water. The more pronounced effect on respiratory performance in sea water was presumably also explained by lower blood O2 carrying capacity, with ligated seawater-acclimated trout having 16% and 17% lower haemoglobin concentration and haematocrit, respectively, relative to ligated freshwater trout. In conclusion, we show that the coronary circulation allows seawater-acclimated trout to maintain aerobic scope at a level comparable to that in fresh water

Healthy eating index and diet diversity score as determinants of serum perfluoroalkyl acid (PFAA) concentrations in a national survey of Swedish adolescents

Food is an important source of perfluoroalkyl acid (PFAA) exposure for the general adult population, but few data exist for adolescents. Healthy food habits established during adolescence may positively influence health later in life. Associations between serum PFAA concentrations and a healthy eating index (SHEIA15), as well as a diet diversity score (RADDS), were determined in a nationally representative adolescent population from Sweden (Riksmaten Adolescents 2016–2017, RMA). Using consumption data from food registrations and frequency questionnaires, we additionally analyzed associations with commonly consumed food groups. Associations were analyzed by fitting a cumulative probability model using ordinal regression. Among the seven PFAAs detected in ≥70% of the 1098 participants (age 10–21 years), median concentrations ranged fro

Demographic, life-style and physiological determinants of serum per- and polyfluoroalkyl substance (PFAS) concentrations in a national cross-sectional survey of Swedish adolescents

Per: and polyfluoroalkyl substances (PFAS) may affect adolescent health, yet factors related to PFAS concentrations in serum are poorly understood. We studied demographic, life-style and physiological determinants of serum PFAS concentrations in Swedish adolescents from a nation-wide survey, Riksmaten Adolescents 2016-17 (RMA, age 10-21 years, n = 1098). Serum samples were analyzed for 42 PFAS, using liquid chromatography-tandem mass spectrometry. The cumulative probability model was used to estimate associations between serum PFAS and determinants, using ordinal logistic regression. Legacy linear (lin-) perfluorooctanoic acid (PFOA), perfluorononaoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), lin-perfluorohexanesulfonic acid (PFHxS) and lin-/branched (br-) perfluorooctanesulfonic acid (PFOS) were quantifiable in >= 70% of the samples. The emerging PFAS 9-chlorohexanedecafluoro-3-oxanone-1-sulfonic acid (9Cl-PF3ONS) was quantified in 5.4% of the samples, suggesting initiation of long-range transport far from production sites. Median concentrations of all legacy PFAS were 100 ng/g serum) lin-PFHxS and lin-/br-PFOS concentrations due to previous high exposure from PFAS-contaminated drinking water. Legacy PFAS exposure was strongly associated with birth country of the participants and their mothers. 2-fold higher estimated adjusted mean (EAM) concentrations were seen among high income country participants with mothers from high income countries than among low/lower-middle income country participants with mothers from the same category. Menstruating females had lower lin-PFOA and br-PFOS EAM concentrations than those who were not. Iron status (plasma ferritin) among females may be a marker of intensity of menstrual bleeding, but it was not significantly associated with legacy PFAS concentrations among females. Further studies are needed to determine how physiological changes occurring around menstruation affect the toxicokinetics of PFAS in females. In conclusion, PFAS are pollutants of the industrialized world and some of the identified determinants may be overlooked confounders/effect modifiers that should be included in future PFAS/health studies among adolescents

177 Lu-octreotate therapy for neuroendocrine tumours is enhanced by Hsp90 inhibition

Lu-177-octreotate is an FDA-approved radionuclide therapy for patients with gastroenteropancreatic neuroendocrine tumours (NETs) expressing somatostatin receptors. The Lu-177-octreotate therapy has shown promising results in clinical trials by prolonging progression-free survival, but complete responses are still uncommon. The aim of this study was to improve the Lu-177-octreotate therapy by means of combination therapy. To identify radiosensitising inhibitors, two cell lines, GOT1 and P-STS, derived from small intestinal neuroendocrine tumours (SINETs), were screened with 1224 inhibitors alone or in combination with external radiation. The screening revealed that inhibitors of Hsp90 can potentiate the tumour cell-killing effect of radiation in a synergistic fashion (GOT1; false discovery rate < 3.2 x 10(-11)). The potential for Hsp90 inhibitor ganetespib to enhance the anti-tumour effect of Lu-177-octreotate in an in vivo setting was studied in the somatostatin receptor-expressing GOT1 xenograft model. The combination led to a larger decrease in tumour volume relative to monotherapies and the tumour-reducing effect was shown to be synergistic. Using patient-derived tumour cells from eight metastatic SINETs, we could show that ganetespib enhanced the effect of Lu-177-octreotate therapy for all investigated patient tumours. Levels of Hsp90 protein expression were evaluated in 767 SINETs from 379 patients. We found that Hsp90 expression was upregulated in tumour cells relative to tumour stroma in the vast majority of SINETs. We conclude that Hsp90 inhibitors enhance the tumour-killing effect of Lu-177-octreotate therapy synergistically in SINET tumour models and suggest that this potentially promising combination should be further evaluated

Bigger is not better: cortisol-induced cardiac growth and dysfunction in salmonids

acceptedVersio

Socially induced stress and behavioural inhibition in response to angling exposure in rainbow trout

It is well known that fish can learn to avoid angling gear after experiencing a catch‐and‐release event, that is, after a private hooking experience. However, the possible importance of social information cues and their influence on an individual's vulnerability to angling remains largely unexplored, that is, social experience of a conspecific capture. The effects of private and social experience of hooking on the stress response of fish and subsequent catch rates were examined. Hatchery‐reared rainbow trout, Oncorhynchus mykiss (Walbaum), were implanted with heart rate loggers and experimentally subjected to private or social experience of hooking. Private and social experience of angling induced an increased heart rate in fish compared with naïve control fish. While private experience of hooking explained most of the reduced vulnerability to capture, no clear evidence was found that social experience of hooking affected angling vulnerability in fish that had never been hooked before. While both private and social experiences of angling constitute significant physiological stressors for rainbow trout, only the private experience reduces an individual's vulnerability to angling and in turn affecting population‐level catchability

Cold Physiology: Postprandial Blood Flow Dynamics and Metabolism in the Antarctic Fish Pagothenia borchgrevinki

Previous studies on metabolic responses to feeding (i.e. the specific dynamic action, SDA) in Antarctic fishes living at temperatures below zero have reported long-lasting increases and small peak responses. We therefore hypothesized that the postprandial hyperemia also would be limited in the Antarctic fish Pagothenia borchgrevinki. The proportion of cardiac output directed to the splanchnic circulation in unfed fish was 18%, which is similar to temperate fish species. Contrary to our prediction, however, gastrointestinal blood flow had increased by 88% at twenty four hours after feeding due to a significant increase in cardiac output and a significant decrease in gastrointestinal vascular resistance. While gastric evacuation time appeared to be longer than in comparable temperate species, digestion had clearly commenced twenty four hours after feeding as judged by a reduction in mass of the administered feed. Even so, oxygen consumption did not increase suggesting an unusually slowly developing SDA. Adrenaline and angiotensin II was injected into unfed fish to investigate neuro-humoral control mechanisms of gastrointestinal blood flow. Both agonists increased gastrointestinal vascular resistance and arterial blood pressure, while systemic vascular resistance was largely unaffected. The hypertension was mainly due to increased cardiac output revealing that the heart and the gastrointestinal vasculature, but not the somatic vasculature, are important targets for these agonists. It is suggested that the apparently reduced SDA in P. borchgrevinki is due to a depressant effect of the low temperature on protein assimilation processes occurring outside of the gastrointestinal tract, while the gastrointestinal blood flow responses to feeding and vasoactive substances resemble those previously observed in temperate species

Postoperative Analgesia after Radical Retropubic Prostatectomy

Background: Postoperative pain after radical retropubic prostatectomy can be severe unless adequately treated. Low thoracic epidural analgesia and patient-controlled intravenous analgesia were compared in this double-blind, randomized study. Methods: Sixty patients were randomly assigned to receive either low thoracic epidural analgesia (group E) or patientcontrolled intravenous analgesia (group P) for postoperative pain relief. All patients had general anesthesia combined with thoracic epidural analgesia during the operation. Postoperatively, patients in group E received an infusion of 1 mg/ml ropivacaine, 2 g/ml fentanyl, and 2 g/ml adrenaline, 10 ml/h during 48 h epidurally, and a placebo patient-controlled intravenous analgesia pump intravenously. Patients in group P received a patient-controlled intravenous analgesia pump with morphine intravenously and 10 ml/h placebo epidurally. Pain, the primary outcome variable, was measured using the numeric rating scale at rest (incision pain and "deep" visceral pain) and on coughing. Secondary outcome variables included gastrointestinal function, respiratory function, mobilization, and full recovery. Health-related quality of life was measured using the Short Form-36 questionnaire, and plasma concentration of fentanyl was measured in five patients to exclude a systemic effect of fentanyl. Results: Incisional pain and pain on coughing were lower in group E compared with group P at 2-24 h, as was deep pain between 3 and 24 h postoperatively (P < 0.05). Maximum expiratory pressure was greater in group E at 4 and 24 h (P < 0.05) compared with group P. No difference in time to home discharge was found between the groups. The mean plasma fentanyl concentration varied from 0.2 to 0.3 ng/ml during 0 -48 h postoperatively. At 1 month, the scores on emotional role, physical functioning, and general health of the Short Form-36 were higher in group E compared with group P. However, no group ؋ time interaction was found in the Short Form-36. Conclusions: The authors found evidence for better pain relief and improved expiratory muscle function in patients receiving low thoracic epidural analgesia compared with patient