Cardiorespiratory adjustments to chronic environmental warming improve hypoxia tolerance in European perch (Perca fluviatilis)

Aquatic hypoxia will become increasingly prevalent in the future due to eutrophication combined with climate warming. While short-term warming typically constrains fish hypoxia tolerance, many fishes cope with warming by adjusting physiological traits through thermal acclimation. Yet, little is known about how such adjustments affect tolerance to hypoxia.We examined European perch (Perca fluviatilis) from the Biotest enclosure (23°C, Biotest population), a unique ∼1 km2 ecosystem artificially warmed by cooling water from a nuclear power plant, and an adjacent reference site (16-18°C, Reference population). Specifically, we evaluated how acute and chronic warming affect routine oxygen consumption rate (MO2routine) and cardiovascular performance in acute hypoxia, alongside assessments of the thermal acclimation of the aerobic contribution to hypoxia tolerance (critical O2 tension for MO2routine; Pcrit) and absolute hypoxia tolerance (O2 tension at loss of equilibrium; PLOE).Chronic adjustments (possibly across lifetime or generations) alleviated energetic costs of warming in Biotest perch by depressing MO2routine and cardiac output, and by increasing blood O2 carrying capacity relative to reference perch acutely warmed to 23°C. These adjustments were associated with improved maintenance of cardiovascular function and MO2routine in hypoxia (i.e., reduced Pcrit). However, while Pcrit was only partially thermally compensated in Biotest perch, they had superior absolute hypoxia tolerance (i.e., lowest PLOE) relative to reference perch irrespective of temperature.We show that European perch can thermally adjust physiological traits to safeguard and even improve hypoxia tolerance during chronic environmental warming. This points to cautious optimism that eurythermal fish species may be resilient to the imposition of impaired hypoxia tolerance with climate warming.

Measures to improve environmental safety of vehicle transport. Part 2

In a trend with varying success, implemented within the framework of the global environmental warming prevention project coordinated by several relevant United Nations Committees at once, there are measures to improve the environmental safety of road vehicles. In this process, the main direction of solving the problem is dominated by an effective, according to energy and environmental experts in the automotive sector, a way of universal phased transition from internal combustion engines to power units of an electrified drive of wheeled vehicles. Keywords automotive wheeled vehicles, power plants, hybridization, electrification

Cardiac mitochondrial plasticity and thermal sensitivity in a fish inhabiting an artificially heated ecosystem

Some evidence suggests that cardiac mitochondrial functions might be involved in the resilience of ectotherms such as fish to environmental warming. Here, we investigated the effects of acute and chronic changes in thermal regimes on cardiac mitochondrial plasticity and thermal sensitivity in perch (Perca fluviatilis) from an artificially heated ecosystem; the “Biotest enclosure” (~25 °C), and from an adjacent area in the Baltic Sea with normal temperatures (reference, ~16 °C). We evaluated cardiac mitochondrial respiration at assay temperatures of 16 and 25 °C, as well as activities of lactate dehydrogenase (LDH) and citrate synthase (CS) in Biotest and reference perch following 8 months laboratory-acclimation to either 16 or 25 °C. While both populations exhibited higher acute mitochondrial thermal sensitivity when acclimated to their natural habitat temperatures, this sensitivity was lost when Biotest and reference fish were acclimated to 16 and 25 °C, respectively. Moreover, reference fish displayed patterns of metabolic thermal compensation when acclimated to 25 °C, whereas no changes were observed in Biotest perch acclimated to 16 °C, suggesting that cardiac mitochondrial metabolism of Biotest fish expresses local adaptation. This study highlights the adaptive responses of cardiac mitochondria to environmental warming, which can impact on fish survival and distribution in a warming climate.

Paroxysmal Cold Hemoglobinuria Successfully Treated with Complement Inhibition

Introduction: Paroxysmal cold hemoglobinuria (PCH) is a rare autoimmune hemolytic anemia (AIHA) that causes intravascular hemolysis and profound, sometimes life-threatening anemia. It most commonly occurs in children following viral infection, and presents with acute onset anemia, pallor, jaundice, and hemoglobinuria. PCH is caused by a biphasic immunoglobulin G (IgG) autoantibody that targets the P-antigen on red blood cells (RBCs) with complement fixation at low temperatures. Subsequent warming in the central circulation leads to complement activation and intravascular hemolysis. Management of PCH has been primarily supportive, with environmental warming to prevent autoantibody binding and transfusion with warmed packed red blood cells (PRBCs) as clinically indicated. Efficacy of corticosteroids has not been demonstrated. We report on successful treatment of PCH by complement blockade using a single dose of eculizumab. Case Description: We treated a previously healthy 4-year-old boy who presented with 5-day history of transient maculopapular rash, 3-day history of fatigue, thigh and abdominal pain, 2-day history of cough, chills, vomiting, diarrhea and high-grade fevers, and on the day of presentation, developed jaundice and dark urine. Hemoglobin (Hgb) level was 6.4 g/dL at a primary care visit. On admission, he was febrile, tachycardic, with scleral icterus and pallor, worsening anemia (Hgb 5.6 g/dL) which 1 hour later dropped to 4.5 g/dL, with reticulocytopenia, spherocytosis, and positive direct antiglobulin test (DAT). Initially he received methylprednisolone as empiric treatment for AIHA. Monospecific DAT was positive for C3d and negative for IgG, leading to suspicion of cold-antibody mediated AIHA (cAIHA). Due to hemoglobinuria consistent with intravascular hemolysis, PCH was suspected and a Donath-Landsteiner (DL) test was ordered. Despite environmental warming and azithromycin for potential Mycoplasma pneumoniae induced cold agglutinin syndrome, he developed worsening anemia (nadir Hgb 3.0 g/dL) with signs of shock including altered mental status, tachycardia, lactic acidosis, and high oxygen extraction, and continued transfusion requirement. On hospital day 4, we decided to treat him with eculizumab 600 mg intravenously. That afternoon, definitive testing for PCH with the DL test returned positive, confirming PCH diagnosis. Markers of hemolysis, including lactate dehydrogenase and bilirubin, decreased immediately following eculizumab administration. No further transfusion was required. Hgb levels stabilized, and reticulocyte counts increased daily. Steroids were discontinued on hospital day 6. Complete complement blockade following a single dose of eculizumab was confirmed on hospital day 7, with total complement level (CH50) reported as <13.8 U/mL. The patient continued to improve and was discharged home on hospital day 15 with Hgb 6.6 g/dL, improving to 9.1 g/dL 6 days later. Diagnostic tests for infectious and toxin-mediated causes of PCH remained negative. He was given prophylaxis for encapsulated bacterial infections with penicillin VK, given increased risk of infection from ongoing complement blockade and his unvaccinated status. This was discontinued when CH50 levels normalized, 42 days after eculizumab administration. Discussion: To our knowledge, this is the first published observation of successful complement blockade for the treatment of PCH. Complement is a key effector of intravascular hemolysis in PCH. Eculizumab, an anti-C5 monoclonal antibody that blocks the terminal complement pathway, resulted in an efficient, complete, and sustained clinical improvement following a single dose. We observed no adverse effects. This case suggests a need for further investigation of complement-blockade, either at the terminal pathway or classical pathway level, in the treatment of this disease. Figure Disclosures Berentsen: Apellis: Consultancy, Honoraria; Alexion: Honoraria; Bioverativ, a Sanofi company: Consultancy, Honoraria; Janssen-Cilag: Honoraria; Mundipharma: Research Funding; True North Therapeutics: Consultancy, Honoraria. OffLabel Disclosure: Eculizumab for paroxysmal cold hemoglobinuria