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Despite the growing evidence supporting the existence of CNS involvement in acute and chronic graft-versus-host disease (CNS-GvHD), the characteristics and course of the disease are still largely unknown. In this multicenter retrospective study, we analyzed the clinical, biological, radiological, and histopathological characteristics, as well as the clinical course of 66 patients diagnosed with possible CNS-GvHD (pCNS-GvHD), selected by predetermined diagnostic criteria. Results were then contrasted depending on whether pCNS-GvHD occurred before or after day 100 following allogeneic hematopoietic stem cell transplantation. Median time between hematopoietic stem cell transplantation and pCNS-GvHD onset was 149 days (IQ25-75 48-321), and pCNS-GvHD onset occurred before day 100 following transplantation in 44% of patients. The most frequent findings at presentation were cognitive impairment (41%), paresis (21%), altered consciousness (20%), sensory impairment (18%), and headache (15%). Clinical presentation did not significantly differ between patients with pCNS-GvHD occurring before or after day 100 following transplantation. Brain MRI found abnormalities compatible with the clinical picture in 57% of patients, while CT detected abnormalities in only 7%. Seven patients had documented spinal cord MRI abnormalities, all of them with pCNS-GvHD occurring after day 100 following transplantation. In the cerebrospinal fluid, white blood cell count was increased in 56% of the population (median 18 cells/μL). Histopathological analyses were performed on 12 specimens and were suggestive of pCNS-GvHD in 10. All compatible specimens showed parenchymal and perivascular infiltration by CD3+ and CD163+ cells. Immunosuppressive therapy was prescribed in 97% of patients, achieving complete clinical response in 27%, partial improvement in 47% and stable disease in 6%. Response to immunosuppressive therapy did not significantly differ between patients with pCNS-GvHD occurring before or after day 100 following transplantation. Clinical relapse was observed in 31% of patients who initially responded to treatment. One-year overall survival following pCNS-GvHD onset was 41%. Onset before day 100 following hematopoietic stem cell transplantation (HR [95%CI]: 2.1 [1.0-4.5]; P=0.041) and altered consciousness at initial presentation (HR [95%CI]: 3.0 [1.3-6.7]; P=0.0077) were associated with a reduced one-year overall survival probability. Among surviving patients, 61% had neurological sequelae. This study supports that immune-mediated CNS manifestations may occur following allo-HSCT. These can be associated with both acute and chronic GvHD and carry a grim prognosis. The clinical presentation as well as the radiological and biological findings appear variable., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Introduction: Large B-cell lymphomas (LBCL) are the most frequently aggressive B-cell non-Hodgkin lymphomas. Anti-CD19 chimeric antigen receptor (CAR)-T cell therapy has emerged as a new, powerful treatment for relapsed or refractory (R/R) disease. Two CAR-T cell products, tisagenlecleucel (tisa-cel,) and axicabtagene ciloleucel (axi-cel), are reimbursed in Belgium for R/R LBCL beyond second line., Objectives and Methods: We conducted a retrospective cohort study to report the outcome with tisa-cel and axi-cel for R/R LBCL beyond second line in the years 2019-2023 at the University Hospitals Leuven for 79 patients selected for apheresis and CAR-T infusion., Results: Eleven patients (14%) did not proceed to CAR-T cell infusion. For infused patients ( n  = 68), the best overall response rate (ORR)/complete response (CR) rate was 64%/49% for tisa-cel and 88%/66% for axi-cel ( p  = 0.04 for ORR). After a median follow-up of 13.8 months, progression-free survival (PFS) and overall survival (OS) at 1 year were 30% and 43% for tisa-cel and 48% and 62% for axi-cel. Cytokine release syndrome (CRS) (all grades/grade ≥3) occurred in 82%/9% after tisa-cel and in 97%/0% after axi-cel. Immune effector cell-associated neurotoxicity syndrome (ICANS) (all grades/grade ≥3) occurred in 24%/18% after tisa-cel and in 54%/40% after axi-cel. The non-relapse mortality in the infusion cohort was 13%., Conclusion: Our real-world data show high and durable response rates, with a non-significant trend towards a higher efficacy and higher toxicity for axi-cel compared to tisa-cel. Our results are in line with other real-world registries except for a shorter median OS and more high-grade ICANS.

Species invasions are a global problem of increasing concern, especially in highly connected aquatic environments. Despite this, salinity conditions can pose physiological barriers to their spread, and understanding them is important for management. In Scandinavia's largest cargo port, the invasive round goby ( Neogobius melanostomus ) is established across a steep salinity gradient. We used 12,937 SNPs to identify the genetic origin and diversity of three sites along the salinity gradient and round goby from western, central and northern Baltic Sea, as well as north European rivers. Fish from two sites from the extreme ends of the gradient were also acclimated to freshwater and seawater, and tested for respiratory and osmoregulatory physiology. Fish from the high-salinity environment in the outer port showed higher genetic diversity, and closer relatedness to the other regions, compared to fish from lower salinity upstream the river. Fish from the high-salinity site also had higher maximum metabolic rate, fewer blood cells and lower blood Ca 2+ . Despite these genotypic and phenotypic differences, salinity acclimation affected fish from both sites in the same way: seawater increased the blood osmolality and Na + levels, and freshwater increased the levels of the stress hormone cortisol. Our results show genotypic and phenotypic differences over short spatial scales across this steep salinity gradient. These patterns of the physiologically robust round goby are likely driven by multiple introductions into the high-salinity site, and a process of sorting, likely based on behaviour or selection, along the gradient. This euryhaline fish risks spreading from this area, and seascape genomics and phenotypic characterization can inform management strategies even within an area as small as a coastal harbour inlet., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Evolutionary Applications published by John Wiley & Sons Ltd.)

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 [Ca 2+ ] 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.

Bio-logging devices can provide unique insights on the life of freely moving animals. However, implanting these devices often requires invasive surgery that causes stress and physiological side-effects. While certain medications in connection to surgeries have therapeutic capacity, others may have aversive effects. Here, we hypothesized that the commonly prescribed prophylactic treatment with enrofloxacin would increase the physiological recovery rate and reduce the presence of systemic inflammation following the intraperitoneal implantation of a heart rate bio-logger in rainbow trout (Oncorhynchus mykiss). To assess post-surgical recovery, heart rate was recorded for 21 days in trout with or without enrofloxacin treatment. Contrary to our hypothesis, treated trout exhibited a prolonged recovery time and elevated resting heart rates during the first week of post-surgical recovery compared to untreated trout. In addition, an upregulated mRNA expression of TNFα in treated trout indicate a possible inflammatory response 21 days post-surgery. Interestingly, the experience level of the surgeon was observed to have a long-lasting impact on heart rate. In conclusion, our study showed no favorable effects of enrofloxacin treatment. Our findings highlight the importance of adequate post-surgical recovery times and surgical training with regards to improving the welfare of experimental animals and reliability of research outcomes.

Blood doping, the practice of boosting the oxygen carrying capacity of blood, is an illegal strategy used by human athletes to enhance aerobic capacity and athletic performance. Interestingly, the practice of boosting blood oxygen carrying capacity is also naturally prevalent in the animal kingdom via the splenic release of stored erythrocytes. Here, we demonstrate that an Antarctic notothenioid fish, the bald notothen ( Pagothenia borchgrevinki ), is a master of this practice. Because of the sub-zero environment these fish inhabit, they sequester a large proportion of erythrocytes in the spleen during times of inactivity to reduce the energetic and physiological costs associated with continuously pumping highly viscous blood around the body. However, in response to metabolically demanding situations (i.e. exercise and feeding), these fish contract the spleen to eject stored erythrocytes into circulation, which boosts blood oxygen carrying capacity by up to 207% (cf. exercise-induced increases of ∼40-60% in a range of other vertebrates and ∼5-25% in blood-doping athletes). By evaluating cardiorespiratory differences between splenectomized (unable to release erythrocytes from the spleen) and sham-operated individuals, we demonstrate the metabolic benefits (i.e. aerobic scope increase of 103%) and the cardiovascular trade-offs (i.e. ventral aortic blood pressure and cardiac workload increase of 12% and 30%, respectively) associated with the splenic blood-boosting strategy. In conclusion, this strategy provides bald notothens with an extraordinary facultative aerobic scope that enables an active lifestyle in the extreme Antarctic marine environment, while minimizing the energetic and physiological costs of transporting highly viscous blood during times of reduced energetic demand., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Investigating the mechanisms that fish employ to maintain homeostasis in their everyday life requires measurements of physiological and behavioural responses in the field. With multivariate bio-loggers, we continuously measured gastrointestinal blood flow (GBF), heart rate, activity and body temperature in rainbow trout (Oncorhynchus mykiss) swimming freely amongst ~5000 conspecifics in a sea cage. Our findings clearly demonstrate that while both acute aquaculture-related stress and spontaneous activity resulted in transient reductions in GBF (i.e. reductions of up to 65%), recovery from stressful handling practices subsequently involved a substantial and prolonged gastrointestinal hyperemia far beyond the level observed prior to the stressor. The gastrointestinal hyperemia may be necessary to repair the damage to the gastrointestinal tract caused by acute stress. Furthermore, heart rate responses to acute stress or voluntary activity differed depending on the individual's physiological state. Stressed fish (i.e. mean heart rates >70 beats min -1 ) exhibited a bradycardic response to acute stress or activity, whereas fish with mean heart rates <60 beats min -1 instead demonstrated strong tachycardic responses. Remote monitoring of physiological and behavioural variables using bio-loggers can provide unique insights into 'real-life' responses of animals, which can largely differ from the responses observed in confined laboratory settings.

Background: Treatment adherence is an important medical and pharmaco-economical phenomenon, influenced by multiple variables. Treatment adherence in systemic sclerosis (SSc) has been poorly studied., Objective: The aim of the present study was to assess treatment adherence in SSc patients and to identify factors associated with good and poor adherence., Methods: We conducted a monocentric, cross-sectional, observational study. Treatment adherence was evaluated by the Compliance Questionnaire of Rheumatology (CQR). The necessity of treatment and concerns about treatment were investigated using the Beliefs about Medicines Questionnaire-Specific (BMQ-S). The Illness Perception Questionnaire-Revised (IPQ-R) assessed illness perceptions. Disease-related characteristics were collected retrospectively., Results: A total of 66 patients were enrolled in this study. Of these, 47 (71.2%) had a weighted CQR score of ≤80% ("poor adherence") and 19 (28.8%) had a weighted CQR score of >80% ("good adherence"). No significant relationship between demographic, clinical or psychological factors and overall adherence could be found, except with the IPQ subscale "timeline acute/chronic" (p = 0.042). Our patient population estimated the necessity of their medication high (mean necessity score 20.5), with moderate concern beliefs (mean concern score 15.1). Subjective adherence, as self-reported by patients, was high., Conclusions: This study demonstrated low treatment adherence rates in SSc patients. We could not identify demographic, clinical or psychological factors associated with treatment adherence, except with the IPQ subscale "timeline acute/chronic". This suggests a correlation between poor adherence and the belief that the disease will be chronic without improvement over time. Symptom relief was an important motivating factor for taking medication. The treatment necessity was scored higher than treatment concerns, but the necessity beliefs were not associated with adherence., (© 2018 John Wiley & Sons, Ltd.)

Greater salinity variations resulting from ongoing climate change requires consideration in conservation management as this may impact on the performance of aquatic organisms. Euryhaline fish exhibit osmoregulatory flexibility and can exploit a wide range of salinities. In seawater (SW), they drink and absorb water in the intestine, which is associated with increased gastrointestinal blood flow. Yet, detailed information on other cardiovascular changes and their control across salinities is scant. Such knowledge is fundamental to understand how fish are affected during migrations between environments with different salinities, as well as by increased future salinity variability. We used rainbow trout ( Oncorhynchus mykiss ) as a euryhaline model species and determined dorsal aortic blood pressure, cardiac output and systemic vascular resistance in vivo after chronic freshwater-or SW-acclimation. We also assessed α-adrenergic control of blood pressure using pharmacological tools. Dorsal aortic blood pressure and systemic vascular resistance were reduced, whereas cardiac output increased in SW. α-Adrenergic stimulation with phenylephrine caused similar dose-dependent increases in resistance and pressure across salinities, indicating unaltered α-adrenoceptor sensitivity. α-Adrenergic blockade with prazosin decreased resistance and pressure across salinities, but the absolute reduction in resistance was smaller in SW. Yet, both pressure and resistance after prazosin remained consistently lower in SW. This shows that SW-acclimation lowers systemic resistance through reduced vascular α-adrenergic tone, along with other unknown vasodilating factors. The marked changes in adrenergic regulation of the vasculature across salinities discovered here may have implications for cardiovascular and aerobic performance of fishes, with possible impacts on fitness-related traits like digestion and exercise capacity. Moreover, the evolution of more complex circulatory control systems in teleost fishes compared with elasmobranchs and cyclostomes may have been an important factor in the evolution of euryhalinity, and may provide euryhaline teleosts with competitive advantages in more variable salinity environments of the future.

The aim of the current work was to elucidate if there is a connection between stress-induced decrease in coeliacomesenteric artery blood flow (i.e. gastrointestinal blood flow; GBF) and disruption of the intestinal primary barrier in rainbow trout Oncorhynchus mykiss. Upon initiation of a 15 min acute chasing stress, the GBF decreased instantly by c. 92%. The GBF then slowly increased and reached c. 28% of resting values at the end of the stress protocol. After the stress was ceased, the GBF slowly increased and returned to resting values within c. 45 min. Intestinal permeability assessment in an Ussing-chambers set-up revealed impaired intestinal barrier function 24 h after stress. When the stress-induced GBF reduction was mimicked by an experimental occlusion of the coeliacomesenteric artery for 15 min followed by 24 h recovery, no effect on intestinal barrier function was observed. These results suggest that no direct causal relationship can be found between the GBF reduction and development of intestinal barrier dysfunction following periods of acute stress in this species of fish., (© 2018 The Fisheries Society of the British Isles.)

The fish gut is responsible for numerous potentially energetically costly processes, yet little is known about its metabolism. Here, we provide the first in vivo measurements of aerobic metabolism of the gut in a teleost fish by measuring gut blood flow, as well as arterial and portal venous oxygen content. At 10°C, gut oxygen uptake rate was 4.3±0.5 ml O 2  h -1  kg -1 (∼11% of whole-animal oxygen uptake). Following acute warming to 15°C, gut blood flow increased ∼3.4-fold and gut oxygen uptake rate increased ∼3.7-fold (16.0±3.3 ml O 2  h -1  kg -1 ), now representing ∼25% of whole-animal oxygen uptake. Although gut blood flow decreased following an acute stress event at 15°C, gut oxygen uptake remained unchanged as a result of a ∼2-fold increase in oxygen extraction. The high metabolic thermal sensitivity of the gut could have important implications for the overall aerobic capacity and performance of fish in a warming world and warrants further investigation., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

Cardiac oxygenation is achieved via both coronary arterial and luminal venous oxygen supply routes in many fish species. However, the relative importance of these supplies for cardiac and aerobic metabolic performance is not fully understood. Here, we investigated how coronary artery ligation in rainbow trout ( Oncorhynchus mykiss ), implanted with heart rate loggers, affected cardiorespiratory performance in vivo While coronary ligation significantly elevated resting heart rate, the standard metabolic rate was unchanged compared to sham-treated controls. However, coronary ligation reduced the maximum metabolic rate while heart rate remained unchanged following enforced exercise. Thus, coronary ligation reduced metabolic and heart rate scopes by 29% and 74%, respectively. Our findings highlight the importance of coronary oxygen supply for overall cardiorespiratory performance in salmonid fish, and suggest that pathological conditions that impair coronary flow (e.g. coronary arteriosclerosis) constrain the ability of fish to cope with metabolically demanding challenges such as spawning migrations and environmental warming., (© 2018 The Author(s).)

Upon exposure to seawater, euryhaline teleosts need to imbibe and desalinate seawater to allow for intestinal ion and water absorption, as this is essential for maintaining osmotic homeostasis. Despite the potential benefits of increased mixing and transport of imbibed water for increasing the efficiency of absorptive processes, the effect of water salinity on intestinal motility in teleosts remains unexplored. By qualitatively and quantitatively describing in vivo intestinal motility of euryhaline rainbow trout ( Oncorhynchus mykiss ), this study demonstrates that, in freshwater, the most common motility pattern consisted of clusters of rhythmic, posteriorly propagating contractions that lasted ∼1-2 min followed by a period of quiescence lasting ∼4-5 min. This pattern closely resembles mammalian migrating motor complexes (MMCs). Following a transition to seawater, imbibed seawater resulted in a significant distension of the intestine and the frequency of MMCs increased twofold to threefold with a concomitant reduction in the periods of quiescence. The increased frequency of MMCs was also accompanied by ripple-type contractions occurring every 12-60 s. These findings demonstrate that intestinal contractile activity of euryhaline teleosts is dramatically increased upon exposure to seawater, which is likely part of the overall response for maintaining osmotic homeostasis as increased drinking and mechanical perturbation of fluids is necessary to optimise intestinal ion and water absorption. Finally, the temporal response of intestinal motility in rainbow trout transitioning from freshwater to seawater coincides with previously documented physiological modifications associated with osmoregulation and may provide further insight into the underlying reasons shaping the migration patterns of salmonids., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2017. Published by The Company of Biologists Ltd.)

Gill parasites on fish are likely to negatively influence their host by inhibiting respiration, oxygen transport capacity and overall fitness. The glochidia larvae of the endangered freshwater pearl mussel (FPM, Margaritifera margaritifera (Linnaeus, 1758)) are obligate parasites on the gills of juvenile salmonid fish. We investigated the effects of FPM glochidia encystment on the metabolism and haematology of brown trout (Salmo trutta Linnaeus, 1758). Specifically, we measured whole-animal oxygen uptake rates at rest and following an exhaustive exercise protocol using intermittent flow-through respirometry, as well as haematocrit, in infested and uninfested trout. Glochidia encystment significantly affected whole-animal metabolic rate, as infested trout exhibited higher standard and maximum metabolic rates. Furthermore, glochidia-infested trout also had elevated levels of haematocrit. The combination of an increased metabolism and haematocrit in infested fish indicates that glochidia encystment has a physiological effect on the trout, perhaps as a compensatory response to the potential respiratory stress caused by the glochidia. When relating glochidia load to metabolism and haematocrit, fish with low numbers of encysted glochidia were the ones with particularly elevated metabolism and haematocrit. Standard metabolic rate decreased with substantial glochidia loads towards levels similar to those of uninfested fish. This suggests that initial effects visible at low levels of encystment may be countered by additional physiological effects at high loads, e.g. potential changes in energy utilization, and also that high numbers of glochidia may restrict oxygen uptake by the gills.

Thermal tolerance in fish may be related to an oxygen limitation of cardiac function. While the hearts of some fish species receive oxygenated blood via a coronary circulation, the influence of this oxygen supply on thermal tolerance and cardiac performance during warming remain unexplored. Here, we analyzed the effect in vivo of acute warming on coronary blood flow in adult sexually mature rainbow trout ( Onchorhynchus mykiss ) and the consequences of chronic coronary ligation on cardiac function and thermal tolerance in juvenile trout. Coronary blood flow at 10°C was higher in females than males (0.56 ± 0.08 vs. 0.30 ± 0.08 ml·min -1 ·g ventricle -1 ), and averaged 0.47 ± 0.07 ml·min -1 ·g ventricle -1 across sexes. Warming increased coronary flow in both sexes until 14°C, at which it peaked and plateaued at 0.78 ± 0.1 and 0.61 ± 0.1 ml·min -1 ·g ventricle -1 in females and males, respectively. Thus, the scope for increasing coronary flow was 101% in males, but only 39% in females. Coronary-ligated juvenile trout exhibited elevated heart rate across temperatures, reduced Arrhenius breakpoint temperature for heart rate (23.0 vs. 24.6°C), and reduced upper critical thermal maximum (25.3 vs. 26.3°C). To further analyze the effects of coronary flow restriction on cardiac rhythmicity, electrocardiogram characteristics were determined before and after coronary occlusion in anesthetized trout. Occlusion resulted in reduced R-wave amplitude and an elevated S-T segment, indicating myocardial ischemia, while heart rate was unaffected. This suggests that the tachycardia in ligated trout across temperatures in vivo was mainly to compensate for reduced cardiac contractility to maintain cardiac output. Moreover, our findings show that coronary flow increases with warming in a sex-specific manner. This may improve whole animal thermal tolerance, presumably by sustaining cardiac oxygenation and contractility at high temperatures., (Copyright © 2017 the American Physiological Society.)

Anadromy is a distinctive life-history strategy in fishes that has evolved independently many times. In an evolutionary context, the benefits of anadromy for a species or population must outweigh the costs and risks associated with the habitat switch. The migration of fish across the freshwater-ocean boundary coincides with potentially energetically costly osmoregulatory modifications occurring at numerous levels of biological organization. By integrating whole animal and sub-cellular metabolic measurements, this study presents significant findings demonstrating how an anadromous salmonid (i.e. rainbow trout, Oncorhynchus mykiss) is able to transform from a hyper- to hypo-osmoregulatory state without incurring significant increases in whole animal oxygen consumption rate. Instead, underlying metabolic mechanisms that fuel the osmoregulatory machinery at the organ level (i.e. intestine) are modulated, as mitochondrial coupling and anaerobic metabolism are increased to satisfy the elevated energetic demands. This may have positive implications for the relative fitness of the migrating individual, as aerobic capacity may be maintained for locomotion (i.e. foraging and predator avoidance) and growth. Furthermore, the ability to modulate mitochondrial metabolism in order to maintain osmotic balance suggests that mitochondria of anadromous fish may have been a key target for natural selection, driving species adaptations to different aquatic environments.

Cellular and mitochondrial metabolic capacity of the heart has been suggested to limit performance of fish at warm temperatures. We investigated this hypothesis by studying the effects of acute temperature increases (16, 23, 30, 32.5 and 36°C) on the thermal sensitivity of 10 key enzymes governing cardiac oxidative and glycolytic metabolism in two populations of European perch (Perca fluviatilis) field-acclimated to 15.5 and 22.5°C, as well as the effects of acclimation on cardiac lipid composition. In both populations of perch, the activity of glycolytic (pyruvate kinase and lactate dehydrogenase) and tricarboxylic acid cycle (pyruvate dehydrogenase and citrate synthase) enzymes increased with acute warming. However, at temperatures exceeding 30°C, a drastic thermally induced decline in citrate synthase activity was observed in the cold- and warm-acclimated populations, respectively, indicating a bottleneck for producing the reducing equivalents required for oxidative phosphorylation. Yet, the increase in aspartate aminotransferase and malate dehydrogenase activities occurring in both populations at temperatures exceeding 30°C suggests that the malate-aspartate shuttle may help to maintain cardiac oxidative capacities at high temperatures. Warm acclimation resulted in a reorganization of the lipid profile, a general depression of enzymatic activity and an increased fatty acid metabolism and oxidative capacity. Although these compensatory mechanisms may help to maintain cardiac energy production at high temperatures, the activity of the electron transport system enzymes, such as complexes I and IV, declined at 36°C in both populations, indicating a thermal limit of oxidative phosphorylation capacity in the heart of European perch., (© 2017. Published by The Company of Biologists Ltd.)

Rhythmic contractions of the mammalian gastrointestinal tract can occur in the absence of neuronal or hormonal stimulation owing to the generation of spontaneous electrical activity by interstitial cells of Cajal (ICC) that are electrically coupled to smooth muscle cells. The myogenically driven component of gastrointestinal motility patterns in fish probably also involves ICC; however, little is known of their presence, distribution and function in any fish species. In the present study, we combined immunohistochemistry and in vivo recordings of intestinal motility to investigate the involvement of ICC in the motility of the proximal intestine in adult shorthorn sculpin (Myoxocephalus scorpius). Antibodies against anoctamin 1 (Ano1, a Ca 2+ -activated Cl - channel), revealed a dense network of multipolar, repeatedly branching cells in the myenteric region of the proximal intestine, similar in many regards to the mammalian ICC-MY network. The addition of benzbromarone, a potent blocker of Ano1, altered the motility patterns seen in vivo after neural blockade with TTX. The results indicate that ICC are integral for the generation and propagation of the majority of rhythmic contractile patterns in fish, although their frequency and amplitude can be modulated via neural activity., (© 2017. Published by The Company of Biologists Ltd.)

Substantial increases in cardiac output (CO), stroke volume (SV), and gastrointestinal blood flow are essential for euryhaline rainbow trout (Oncorhyncus mykiss) osmoregulation in seawater. However, the underlying hemodynamic mechanisms responsible for these changes are unknown. By examining a range of circulatory and cardiac morphological variables of seawater- and freshwater-acclimated rainbow trout, the present study revealed a significantly higher central venous pressure (CVP) in seawater-acclimated trout (~0.09 vs. -0.02 kPa). This serves to increase cardiac end-diastolic volume in seawater and explains the elevations in SV (~0.41 vs. 0.27 ml/kg) and CO (~21.5 vs. 14.2 ml·min -1 ·kg -1 ) when compared with trout in freshwater. Furthermore, these hemodynamic modifications coincided with a significant increase in the proportion of compact myocardium, which may be necessary to compensate for the increased wall tension associated with a larger stroke volume. Following a temperature increase from 10 to 16.5°C, both acclimation groups exhibited similar increases in heart rate (Q 10 of ~2), but SV tended to decrease in seawater-acclimated trout despite the fact that CVP was maintained in both groups. This resulted in CO of seawater- and freshwater-acclimated trout stabilizing at a similar level after warming (~26 ml·min -1 ·kg -1 ). The consistently higher CVP of seawater-acclimated trout suggests that factors other than compromised cardiac filling constrained the SV and CO of these individuals at high temperatures. The present study highlights, for the first time, the complex interacting effects of temperature and water salinity on cardiovascular responses in a euryhaline fish species., (Copyright © 2017 the American Physiological Society.)

Oxygen supply to the heart has been hypothesized to limit cardiac performance and whole animal acute thermal tolerance (CTmax) in fish. We tested these hypotheses by continuously measuring venous oxygen tension (Pvo2) and cardiovascular variables in vivo during acute warming in European perch (Perca fluviatilis) from a reference area during summer (18°C) and a chronically heated area (Biotest enclosure) that receives warm effluent water from a nuclear power plant and is normally 5-10°C above ambient (24°C at the time of experiments). While CTmax was 2.2°C higher in Biotest compared with reference perch, the peaks in cardiac output and heart rate prior to CTmax occurred at statistically similar Pvo2 values (2.3-4.0 kPa), suggesting that cardiac failure occurred at a common critical Pvo2 threshold. Environmental hyperoxia (200% air saturation) increased Pvo2 across temperatures in reference fish, but heart rate still declined at a similar temperature. CTmax of reference fish increased slightly (by 0.9°C) in hyperoxia, but remained significantly lower than in Biotest fish despite an improved cardiac output due to an elevated stroke volume. Thus, while cardiac oxygen supply appears critical to elevate stroke volume at high temperatures, oxygen limitation may not explain the bradycardia and arrhythmia that occur prior to CTmax Acute thermal tolerance and its thermal plasticity can, therefore, only be partially attributed to cardiac failure from myocardial oxygen limitations, and likely involves limiting factors on multiple organizational levels., (Copyright © 2016 the American Physiological Society.)

Understanding the resilience of aquatic ectothermic animals to climate warming has been hindered by the absence of experimental systems experiencing warming across relevant timescales (for example, decades). Here, we examine European perch (Perca fluviatilis, L.) from the Biotest enclosure, a unique coastal ecosystem that maintains natural thermal fluctuations but has been warmed by 5-10 °C by a nuclear power plant for over three decades. We show that Biotest perch grow faster and display thermally compensated resting cardiorespiratory functions compared with reference perch living at natural temperatures in adjacent waters. However, maximum cardiorespiratory capacities and heat tolerance limits exhibit limited or no thermal compensation when compared with acutely heated reference perch. We propose that while basal energy requirements and resting cardiorespiratory functions (floors) are thermally plastic, maximum capacities and upper critical heat limits (ceilings) are much less flexible and thus will limit the adaptive capacity of fishes in a warming climate.

Increased gastrointestinal blood flow is essential for euryhaline fishes to maintain osmotic homeostasis during the initial phase of a transition from freshwater to seawater. However, the cardiorespiratory responses and hemodynamic changes required for a successful long-term transition to seawater remain largely unknown. In the present study, we simultaneously measured oxygen consumption rate (ṀO2), cardiac output (CO), heart rate (HR), and gastrointestinal blood flow (GBF) in rainbow trout (Oncorhynchus mykiss) acclimated to either freshwater or seawater for at least 6 wk. Seawater-acclimated trout displayed significantly elevated ṀO2 (day: 18%, night: 19%), CO (day: 22%, night: 48%), and GBF (day: 96%, night: 147%), demonstrating that an overall cardiorespiratory upregulation occurs during seawater acclimation. The elevated GBF was achieved via a combination of increased CO, mediated through elevated stroke volume (SV), and a redistribution of blood flow to the gastrointestinal tract. Interestingly, virtually all of the increase in CO of seawater-acclimated trout was directed to the gastrointestinal tract. Although unfed seawater-acclimated trout displayed substantially elevated cardiorespiratory activity, the ingestion of a meal resulted in a similar specific dynamic action (SDA) and postprandial GBF response as in freshwater-acclimated fish. This indicates that the capacity for the transportation of absorbed nutrients, gastrointestinal tissue oxygen delivery, and acid-base regulation is maintained during digestion in seawater. The novel findings presented in this study clearly demonstrate that euryhaline fish upregulate cardiovascular function when in seawater, while retaining sufficient capacity for the metabolic and cardiovascular changes associated with the postprandial response., (Copyright © 2016 the American Physiological Society.)

A progressive inability of the cardiorespiratory system to maintain systemic oxygen supply at elevated temperatures has been suggested to reduce aerobic scope and the upper thermal limit of aquatic ectotherms. However, few studies have directly investigated the dependence of thermal limits on oxygen transport capacity. By manipulating oxygen availability (via environmental hyperoxia) and blood oxygen carrying capacity (via experimentally induced anaemia) in European perch (Perca fluviatilis Linneaus), we investigated the effects of oxygen transport capacity on aerobic scope and the critical thermal maximum (CT(max)). Hyperoxia resulted in a twofold increase in aerobic scope at the control temperature of 23°C, but this did not translate to an elevated CT(max) in comparison with control fish (34.6±0.1 versus 34.0±0.5°C, respectively). Anaemia (∼43% reduction in haemoglobin concentration) did not cause a reduction in aerobic scope or CT(max) (33.8±0.3°C) compared with control fish. Additionally, oxygen consumption rates of anaemic perch during thermal ramping increased in a similar exponential manner to that in control fish, highlighting that perch have an impressive capacity to compensate for a substantial reduction in blood oxygen carrying capacity. Taken together, these results indicate that oxygen limitation is not a universal mechanism determining the CT(max) of fishes., (© 2015. Published by The Company of Biologists Ltd.)

The large-scale migrations of anadromous fish species from freshwater to seawater have long been considered particularly enigmatic, as this life history necessitates potentially energetically costly changes in behaviour and physiology. A significant knowledge gap concerns the integral role of cardiovascular responses, which directly link many of the well-documented adaptations (i.e. through oxygen delivery, water and ion transport) allowing fish to maintain osmotic homeostasis in the sea. Using long-term recordings of cardiorespiratory variables and a novel method for examining drinking dynamics, we show that euryhaline rainbow trout (Oncorhynchus mykiss) initiate drinking long before the surrounding environment reaches full seawater salinity (30-33 ppt), suggesting the presence of an external osmo-sensing mechanism. Onset of drinking was followed by a delayed, yet substantial increase in gastrointestinal blood flow through increased pulse volume exclusively, as heart rate remained unchanged. While seawater entry did not affect whole animal energy expenditure, enhanced gastrointestinal perfusion represents a mechanism crucial for ion and water absorption, as well as possibly increasing local gastrointestinal oxygen supply. Collectively, these modifications are essential for anadromous fish to maintain homeostasis at sea, whilst conserving cardiac and metabolic scope for activities directly contributing to fitness and reproductive success.

This is the first study to catalogue the diverse array of in vivo motility patterns in a teleost fish and how they are affected by feeding. Video recordings of exteriorised proximal intestine from fasted and fed shorthorn sculpin (Myoxocephalus scorpius) were used to generate spatio-temporal maps to portray and quantify motility patterns. Propagating and non-propagating contractions were observed to occur at different frequencies and durations. The most apparent difference between the feeding states was that bands of relatively high amplitude contractions propagating slowly in the anal direction were observed in all fasted fish (N=10) but in only 35% of fed fish (N=11). Additionally, fed fish displayed a reduced frequency (0.21±0.03 versus 0.32±0.06 contractions min(-1)) and rhythmicity of these contractions compared with fasted fish. Although the underlying mechanisms of these slow anally propagating contractions differ from those of mammalian migrating motor complexes, we believe that they may play a similar role in shorthorn sculpin during the interdigestive period, to potentially remove food remnants and prevent the establishment of pathogens. 'Ripples' were the most prevalent contraction type in shorthorn sculpin and may be important during mixing and absorption. The persistence of shallow ripples and pendular movements of longitudinal muscle after tetrodotoxin (1 μmol l(-1)) treatment suggests these contractions were myogenic in origin. The present study highlights both similarities and differences in motility patterns between shorthorn sculpin and other vertebrates, as well as providing a platform to examine other aspects of gastrointestinal functions in fish, including the impact of environmental changes., (© 2014. Published by The Company of Biologists Ltd.)