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Background: Post-acute COVID-19 syndrome (PACS) has been linked to microvascular endothelial dysfunction as a potential underlying pathomechanism and can manifest even following a mild course of the initial infection. Prevalence of microvascular endothelial dysfunction and circulating natriuretic peptides in such PACS patients remains unknown., Methods: This prospective, cross-sectional cohort study enrolled 92 patients (82% females, median age 48 years) with PACS. Reactive hyperemia index (RHI) was evaluated with peripheral arterial tonometry, where <1.67 was defined as microvascular endothelial dysfunction, 1.67-2.0 as impaired function, and >2 normal endothelial function, on average 31 months after the acute infection. N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were collected at 2 different time points within over a 1-year span., Results: In total, 41% of PACS subjects had microvascular endothelial dysfunction and 20% had impaired RHI. No major differences in clinical characteristics, routine chemistry laboratory testing, or symptom burden were observed across the groups. Only subjects with microvascular endothelial dysfunction and impaired endothelial function had a significant increase in NT-proBNP levels over time, and those with larger increase in NT-proBNP had significantly lower RHI. There was a significant correlation between relative or absolute increase in NT-proBNP and RHI, which remained significant in a multivariable adjusted linear regression., Conclusions: Peripheral microvascular endothelial dysfunction was prevalent in a symptomatic PACS population long after recovery from a mild acute infection. Increases in NT-proBNP levels were associated with microvascular endothelial dysfunction, suggesting a link between, and providing a foundation for, future studies on post viral microvascular endothelial dysfunction in PACS., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Long-term oxygen supplementation for at least 15 hours per day prolongs survival among patients with severe hypoxemia. On the basis of a nonrandomized comparison, long-term oxygen therapy has been recommended to be used for 24 hours per day, a more burdensome regimen., Methods: To test the hypothesis that long-term oxygen therapy used for 24 hours per day does not result in a lower risk of hospitalization or death at 1 year than therapy for 15 hours per day, we conducted a multicenter, registry-based, randomized, controlled trial involving patients who were starting oxygen therapy for chronic, severe hypoxemia at rest. The patients were randomly assigned to receive long-term oxygen therapy for 24 or 15 hours per day. The primary outcome, assessed in a time-to-event analysis, was a composite of hospitalization or death from any cause within 1 year. Secondary outcomes included the individual components of the primary outcome assessed at 3 and 12 months., Results: Between May 18, 2018, and April 4, 2022, a total of 241 patients were randomly assigned to receive long-term oxygen therapy for 24 hours per day (117 patients) or 15 hours per day (124 patients). No patient was lost to follow-up. At 12 months, the median patient-reported daily duration of oxygen therapy was 24.0 hours (interquartile range, 21.0 to 24.0) in the 24-hour group and 15.0 hours (interquartile range, 15.0 to 16.0) in the 15-hour group. The risk of hospitalization or death within 1 year in the 24-hour group was not lower than that in the 15-hour group (mean rate, 124.7 and 124.5 events per 100 person-years, respectively; hazard ratio, 0.99; 95% confidence interval [CI], 0.72 to 1.36; 90% CI, 0.76 to 1.29; P = 0.007 for nonsuperiority). The groups did not differ substantially in the incidence of hospitalization for any cause, death from any cause, or adverse events., Conclusions: Among patients with severe hypoxemia, long-term oxygen therapy used for 24 hours per day did not result in a lower risk of hospitalization or death within 1 year than therapy for 15 hours per day. (Funded by the Crafoord Foundation and others; REDOX ClinicalTrials.gov number, NCT03441204.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: During the COVID-19 pandemic a need to process large volumes of publications emerged. As the pandemic is winding down, the clinicians encountered a novel syndrome - Post-acute Sequelae of COVID-19 (PASC) - that affects over 10 % of those who contract SARS-CoV-2 and presents a significant challenge in the medical field. The continuous influx of publications underscores a need for efficient tools for navigating the literature., Objectives: We aimed to develop an application which will allow monitoring and categorizing COVID-19-related literature through building publication networks and medical subject headings (MeSH) maps to identify key publications and networks., Methods: We introduce CORACLE (COVID-19 liteRAture CompiLEr), an innovative web application designed to analyse COVID-19-related scientific articles and to identify research trends. CORACLE features three primary interfaces: The "Search" interface, which displays research trends and citation links; the "Citation Map" interface, allowing users to create tailored citation networks from PubMed Identifiers (PMIDs) to uncover common references among selected articles; and the "MeSH" interface, highlighting current MeSH trends and their associations., Results: CORACLE leverages PubMed data to categorize literature on COVID-19 and PASC, aiding in the identification of relevant research publication hubs. Using lung function in PASC patients as a search example, we demonstrate how to identify and visualize the interactions between the relevant publications., Conclusion: CORACLE is an effective tool for the extraction and analysis of literature. Its functionalities, including the MeSH trends and customizable citation mapping, facilitate the discovery of emerging trends in COVID-19 and PASC research., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.)

Background: Few studies consider both radiological and functional outcomes in COVID-19 survivors treated in the intensive care unit (ICU). We investigated clinical findings and pulmonary abnormalities on chest computed tomography (CT) and compared outcomes of severe versus mild-moderate acute respiratory distress syndrome (ARDS) on long-term follow-up., Methods: This longitudinal cohort study included 118 COVID-19 patients (median age, 58 years; 79% men). Thoracic CT scans were performed 4, 10, and 22 months after hospital discharge. Two independent blinded radiologists analyzed the 10 months scans and scored the radiology findings semi-quantitatively, as no/minor versus widespread opacities [low-radiology opacity grade (ROG) versus high-ROG]. ARDS severity was based on the PaO2/FiO2 ratio. The 6 min walk test (6MWT) was performed after 3 and 9 months, and lung diffusion capacity for carbon monoxide (DLCO) and lung volume measurement after 9 and 15 months. Dynamic spirometry was done at all time points. Residual symptoms and health-related quality-of-life (HRQL) were evaluated using validated questionnaires., Results: At 10 months, most patients (81/118; 69%) were classified as high-ROG, of which 70% had severe ARDS during hospitalisation; 69% of those with mild-moderate ARDS also had high-ROG. Patients with high-ROG had longer ICU stay and lower PaO2/FiO2 during hospitalisation ( p  < 0.01). At 9 months follow-up, patients with high-ROG had smaller lung volumes as % of predicted values [mean (±CI): 80 (77-84) vs. 93 (88-98) ( p  < 0.001)], lower DLCO as % of predicted values [74 (70-78) vs. 87 (82-92) ( p  < 0.001)], lower oxygen saturation during 6MWT ( p  = 0.02), and a tendency to more severe dyspnoea ( p  = 0.07), but no difference was found in HRQL compared with no/minor ROG ( p  = 0.92). A higher opacity score was related to lower DLCO at follow-up ( r  = -0.48, p  < 0.001, Spearman rank test). Severe ARDS patients had slightly more severe fatigue at 9 months compared to mild-moderate, but no differences in dyspnoea or lung function at follow-up. Fibrotic-like changes were found in 93% of patients examined with CT scans at 2 years (55/118; 47%). Severe ARDS could predict widespread opacities (ROG > 25%) in most patients at follow-up at 10 months (AUC 0.74)., Conclusion: Residual radiological abnormalities in ICU-treated COVID-19 patients, evaluated for up to 2 years, relate to persisting symptoms and impaired lung function, demanding careful follow-up regardless of ARDS severity at hospitalisation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer MC declared a shared affiliation with the authors to the handling editor at the time of review., (Copyright © 2024 Björnson, Svensson, He, Sköld, Nyrén, Nygren-Bonnier, Bruchfeld, Runold, Jalde and Kistner.)

Background: Home oxygen therapy (HOT) improves survival in patients with hypoxaemic chronic respiratory disease. Most patients evaluated for HOT are former or active smokers. Oxygen accelerates combustion and smoking may increase the risk of burn injuries and fire hazards; therefore, it is considered a contraindication for HOT in many countries. However, there is variability in the practices and policies regarding this matter. This multidisciplinary Swedish taskforce aimed to review the potential benefits and risks of smoking in relation to HOT, including medical, practical, legal and ethical considerations., Methods: The taskforce of the Swedish Respiratory Society comprises 15 members across respiratory medicine, nursing, medical law and ethics. HOT effectiveness and adverse risks related to smoking, as well as practical, legal and ethical considerations, were reviewed, resulting in five general questions and four PICO (population-intervention-comparator-outcome) questions. The strength of each recommendation was rated according to the GRADE (grading of recommendation assessment, development and evaluation) methodology., Results: General questions about the practical, legal and ethical aspects of HOT were discussed and summarised in the document. The PICO questions resulted in recommendations about assessment, management and follow-up of smoking when considering HOT, if HOT should be offered to people that meet the eligibility criteria but who continue to smoke, if a specific length of time of smoking cessation should be considered before assessing eligibility for HOT, and identification of areas for further research., Conclusions: Multiple factors need to be considered in the benefit/risk evaluation of HOT in active smokers. A systematic approach is suggested to guide healthcare professionals in evaluating HOT in relation to smoking., Competing Interests: Conflict of interest: The authors have no conflict of interest relevant for this study to declare., (Copyright ©The authors 2024.)

Post-acute COVID-19 (PACS) are associated with cardiovascular dysfunction, especially postural orthostatic tachycardia syndrome (POTS). Patients with PACS, both in the absence or presence of POTS, exhibit a wide range of persisting symptoms long after the acute infection. Some of these symptoms may stem from alterations in cardiovascular homeostasis, but the exact mechanisms are poorly understood. The aim of this study was to provide a broad molecular characterization of patients with PACS with (PACS + POTS) and without (PACS-POTS) POTS compared to healthy subjects, including a broad proteomic characterization with a focus on plasma cardiometabolic proteins, quantification of cytokines/chemokines and determination of plasma sphingolipid levels. Twenty-one healthy subjects without a prior COVID-19 infection (mean age 43 years, 95% females), 20 non-hospitalized patients with PACS + POTS (mean age 39 years, 95% females) and 22 non-hospitalized patients with PACS-POTS (mean age 44 years, 100% females) were studied. PACS patients were non-hospitalized and recruited ≈18 months after the acute infection. Cardiometabolic proteomic analyses revealed a dysregulation of ≈200 out of 700 analyzed proteins in both PACS groups vs. healthy subjects with the majority (> 90%) being upregulated. There was a large overlap (> 90%) with no major differences between the PACS groups. Gene ontology enrichment analysis revealed alterations in hemostasis/coagulation, metabolism, immune responses, and angiogenesis in PACS vs. healthy controls. Furthermore, 11 out of 33 cytokines/chemokines were significantly upregulated both in PACS + POTS and PACS-POTS vs. healthy controls and none of the cytokines were downregulated. There were no differences in between the PACS groups in the cytokine levels. Lastly, 16 and 19 out of 88 sphingolipids were significantly dysregulated in PACS + POTS and PACS-POTS, respectively, compared to controls with no differences between the groups. Collectively, these observations suggest a clear and distinct dysregulation in the proteome, cytokines/chemokines, and sphingolipid levels in PACS patients compared to healthy subjects without any clear signature associated with POTS. This enhances our understanding and might pave the way for future experimental and clinical investigations to elucidate and/or target resolution of inflammation and micro-clots and restore the hemostasis and immunity in PACS., (© 2023. The Author(s).)

Competing Interests: Disclosures None.

Background: The Mycobacterium abscessus complex (MABC) is a difficult to treat mycobacterium with two distinct morphologies: smooth and rough. As the clinical implications are unclear, we explored the morphology of MABC in relation to disease and outcome., Methods: We performed a retrospective multicenter cohort study including patients with confirmed MABC in Sweden, 2009-2020, with treatment outcome as the primary outcome. MABC colony morphology was determined by light microscopy on Middlebrook 7H10 agar plates., Results: Of the 71 MABC isolates, a defined morphology could be determined for 63 isolates, of which 40 were smooth (56%) and 23 were rough (32%). Immunosuppression, pulmonary disease, and cavitary lesion on chest radiographs were significantly associated with a rough isolate morphology. Participants with smooth isolates had more favorable treatment outcomes (12/14, 86%) compared to those with rough isolates (3/10, 30%). In an age-adjusted logistic regression, rough morphology of MABC was associated to lower odds of clinical cure compared to smooth morphology (adjusted odds ratio, 0.12; P = .049)., Conclusions: Study participants with rough MABC colony morphology of isolates had a worse clinical outcome compared to those with smooth isolates. The biological mechanisms should be further characterized and colony morphology of MABC taken into account during clinical management., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Severe Covid-19 may cause a cascade of cardiovascular complications beyond viral pneumonia. The severe inflammation may affect the microcirculation which can be assessed by cardiovascular magnetic resonance (CMR) imaging using quantitative perfusion mapping and calculation of myocardial perfusion reserve (MPR). Furthermore, native T1 and T2 mapping have previously been shown to identify changes in myocardial perfusion by the change in native T1 and T2 during adenosine stress. However, the relationship between native T1, native T2, ΔT1 and ΔT2 with myocardial perfusion and MPR during long-term follow-up in severe Covid-19 is currently unknown. Therefore, patients with severe Covid-19 (n = 37, median age 57 years, 24% females) underwent 1.5 T CMR median 292 days following discharge. Quantitative myocardial perfusion (ml/min/g), and native T1 and T2 maps were acquired during adenosine stress, and rest, respectively. Both native T1 (R 2  = 0.35, p < 0.001) and native T2 (R 2  = 0.28, p < 0.001) correlated with myocardial perfusion. However, there was no correlation with ΔT1 or ΔT2 with MPR, respectively (p > 0.05 for both). Native T1 and native T2 correlate with myocardial perfusion during adenosine stress, reflecting the coronary circulation in patients during long-term follow-up of severe Covid-19. Neither ΔT1 nor ΔT2 can be used to assess MPR in patients with severe Covid-19., (© 2023. The Author(s).)

Background: With ~ 50 million individuals suffering from post-COVID condition (PCC), low health related quality of life (HRQoL) is a vast problem. Common symptoms of PCC, that persists 3 months from the onset of COVID-19 are fatigue, shortness of breath and cognitive dysfunction. No effective treatment options have been widely adopted in clinical practice. Hyperbaric oxygen (HBO 2 ) is a candidate drug., Methods: The objective of this interim analysis is to describe our cohort and evaluate the safety of HBO 2 for post covid condition. In an ongoing randomised, placebo-controlled, double blind, clinical trial, 20 previously healthy subjects with PCC were assigned to HBO 2 or placebo. Primary endpoints are physical domains in RAND-36; Physical functioning (PF) and Role Physical (RP) at 13 weeks. Secondary endpoints include objective physical tests. Safety endpoints are occurrence, frequency, and seriousness of Adverse Events (AEs). An independent data safety monitoring board (DSMB) reviewed unblinded data. The trial complies with Good Clinical Practice. Safety endpoints are evaluated descriptively. Comparisons against norm data was done using t-test., Results: Twenty subjects were randomised, they had very low HRQoL compared to norm data. Mean (SD) PF 31.75 (19.55) (95% Confidence interval; 22.60-40.90) vs 83.5 (23.9) p < 0.001 in Rand-36 PF and mean 0.00 (0.00) in RP. Very low physical performance compared to norm data. 6MWT 442 (180) (95% CI 358-525) vs 662 (18) meters p < 0.001. 31 AEs occurred in 60% of subjects. In 20 AEs, there were at least a possible relationship with the study drug, most commonly cough and chest pain/discomfort., Conclusions: An (unexpectedly) high frequency of AEs was observed but the DSMB assessed HBO 2 to have a favourable safety profile. Our data may help other researchers in designing trials. Trial Registration ClinicalTrials.gov: NCT04842448. Registered 13 April 2021, https://clinicaltrials.gov/ct2/show/NCT04842448 . EudraCT: 2021-000764-30. Registered 21 May 2021, https://www.clinicaltrialsregister.eu/ctr-search/trial/2021-000764-30/SE., (© 2023. The Author(s).)

Introduction: Long COVID-19, where symptoms persist 12 weeks after the initial SARS-CoV-2-infection, is a substantial problem for individuals and society in the surge of the pandemic. Common symptoms are fatigue, postexertional malaise and cognitive dysfunction. There is currently no effective treatment and the underlying mechanisms are unknown, although several hypotheses exist, with chronic inflammation as a common denominator. In prospective studies, hyperbaric oxygen therapy (HBOT) has been suggested to be effective for the treatment of similar syndromes such as chronic fatigue syndrome and fibromyalgia. A case series has suggested positive effects of HBOT in long COVID-19. This randomised, placebo-controlled clinical trial will explore HBOT as a potential treatment for long COVID-19. The primary objective is to evaluate if HBOT improves health-related quality of life (HRQoL) for patients with long COVID-19 compared with placebo/sham. The main secondary objective is to evaluate whether HBOT improves endothelial function, objective physical performance and short-term HRQoL., Methods and Analysis: A randomised, placebo-controlled, double-blind, phase II clinical trial in 80 previously healthy subjects debilitated due to long COVID-19, with low HRQoL. Clinical data, HRQoL questionnaires, blood samples, objective tests and activity metre data will be collected at baseline. Subjects will be randomised to a maximum of 10 treatments with hyperbaric oxygen or sham treatment over 6 weeks. Assessments for safety and efficacy will be performed at 6, 13, 26 and 52 weeks, with the primary endpoint (physical domains in RAND 36-Item Health Survey) and main secondary endpoints defined at 13 weeks after baseline. Data will be reviewed by an independent data safety monitoring board., Ethics and Dissemination: The trial is approved by the Swedish National Institutional Review Board (2021-02634) and the Swedish Medical Products Agency (5.1-2020-36673). Positive, negative and inconclusive results will be published in peer-reviewed scientific journals with open access., Trial Registration Number: NCT04842448., Competing Interests: Competing interests: AK and PL disclose funding from Swedish Heart-Lung Foundation (HLF) and Stockholm Health Council for the present trial. AK disclose funding from Oura Health Oy with complimentary hardware and software for the Oura rings. MS discloses funding from Swedish Research Council and Dysautonomia International during the trial and previously from HLF. MS also disclose consulting fees from the Swedish Agency for Health Technology Assessment of Social Services, speaker honoraria from Orion Pharma, Werfen, and has filed a patent for pharmacological treatment in post-COVID postural orthostatic tachycardia syndrome. JK declares consulting fee for statistical work in this trial. LA-H, AH, SEG, SA-E, EB, CJS, JP, KM, KRW, XZ, SBC, MR, JB and MN-B declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Covid-19 can cause chronic hypoxic respiratory failure, but the impact on the need for long-term oxygen therapy (LTOT) is unknown. The aim was to investigate change in incidence and characteristics of patients starting LTOT in Sweden 2020 after the outbreak of the pandemic., Material and Methods: Population-based observational study using data from the National Registry for Respiratory Failure (Swedevox) and from a survey to all centres prescribing LTOT in Sweden. Swedevox data provided information on incidence of LTOT and characteristics of patients starting LTOT during 2015-2020., Results: Between March-Dec 2020, 131 patients started LTOT due to covid-19, corresponding to 20.5% of incident LTOT in Sweden. Compared with 2015-19, the total number of patients starting LTOT did not increase. No significant differences in patient characteristics or underlying causes of hypoxemia were found between patients starting LTOT during 2020 compared 2015-2019. The majority of the LTOT centres estimated that, since the start of the pandemic, the incidence of LTOT was unchanged and the time devoted for LTOT work was the same or slightly less., Conclusions: Covid-19 caused one fifth of all LTOT starts during the pandemic in 2020. The LTOT incidence overall did not increase possibly due to reduction in other infections., Competing Interests: The authors have no conflicts of interest related to the study.

Technology developments and demand for flexibility in health care and in contact with the health care system are two factors leading to increased use of eHealth solutions. The use of eHealth has been shown to have positive effects in people with chronic obstructive pulmonary disease, but the full potential for this group needs to be explored. Therefore, the aim was to evaluate the feasibility of an eHealth tool used for exercise training and online contacts for people with severe chronic obstructive pulmonary disease. The 10-week intervention included an eHealth tool for exercise training in home environment and regular online contacts, as well as weekly e-rounds for health care professionals. Seven of the nine participants completed the study. The eHealth tool was found to be feasible for e-rounds, exercise training and online contacts. Participants could manage the tool and adhere to training; positive effects were shown, and no adverse events occurred. Technical functions need to be improved.

Objective: To investigate the diagnostic and therapeutic potential of plain abdominal radiographs and contrast radiography in patients with suspected small intestinal obstruction., Design: Retrospective study., Setting: General hospital, Sweden., Material: 2357 sets of plain abdominal radiographic casenotes., Main Outcome Measures: Analysis of plain abdominal radiographs for small intestinal obstruction. Establishment of the time that subsequent contrast radiography medium took to reach the caecum, and its success rate., Results: Of the 2357 plain abdominal films 1599 (68%) did not show small intestinal obstruction, 425 (18%) showed intermediate obstruction, and 333 (14%) showed small intestinal obstruction. The water-soluble contrast medium reached the colon in 394/591 (67%) of the cases with intermediate or complete small intestinal obstruction. Although the contrast medium passed to the colon there was remaining abnormality with dilated small intestine in 71/212 (33%) of the cases with intermediate obstruction and in 95/143 (66%) of the small intestinal obstruction group. The time for the contrast medium to reach the colon was 3.4 hours in the normal group, 5.5 hours in the intermediate group and 8.9 hours in the obstruction group., Conclusion: The plain abdominal radiographs seem to predict the success of follow-through examinations. Contrast radiography is safe and may have a therapeutic potential in small intestinal obstruction.

The purpose of the present study was to evaluate the role of adrenergic receptors in the cascade leading to hypoxic-ischaemic brain injury in neonatal rats. The effect of adrenergic agents (prazosin, yohimbine, idazoxan and clonidine) administered before or after hypoxia-ischaemia was evaluated with respect to mortality and brain injury. Rat pups of either 7 or 8 days of age were subjected to unilateral carotid artery ligation combined with hypoxia (6% or 8% O2 in N2). The mortality was higher in hypoxic-ischaemic groups pre-treated with the alpha-adrenergic receptor antagonists prazosin (48%) or yohimbine (53%) than in saline controls (7%). After 2 weeks the severity of the brain injury was evaluated in the surviving rats. Unilateral brain injury, evaluated by brain weight deficit of the injured ipsilateral hemisphere compared with the contralateral hemisphere, was 17.8 +/- 4.9% and 27.1 +/- 4.0% in pre- and post-treated saline groups, respectively. Post-treatment with clonidine, an alpha2-adrenergic agonist, reduced brain injury by 45% (p < 0.05) compared with saline controls. Pre-treatment with the same drug was not effective. Idazoxan had no effect on brain injury in this animal model. The results indicate that activation of central alpha2-adrenergic or imidazole receptors provides neuroprotection during reperfusion after hypoxic-ischaemic brain injury in neonatal rats.

The aim of this study was to test the effects of glucose on the gasping ability and survival in a rat pup model during acute anoxia. Newborn rat pups of both 1 and 8 days of age were given glucose (30 and 60 mg/animal) or saline intraperitoneally and subsequently subjected to anoxia (100% N2). Glucose supplement induced hyperglycemia. Respiration was recorded by barometric plethysmography. The rat pups responded to acute anoxia with a robust sequence of respiratory pattern: hyperpnea, primary apnea, hypoxic gasping and secondary apnea. During anoxia the 1-day-old rats gasped much longer than the 8-day-old rats (23.4 +/- 1.0 vs. 6.1 +/- 0.5 min, p < 0.001). No difference was found in gasping duration between the saline control and the glucose-supplemented 1-day-old rat pups. The 8-day-old supplemented rats gasped much longer (9.3 +/- 0.5 min) than the control rats (6.1 +/- 0.5 min, p < 0.01). The animals autoresuscitated when they received oxygen (100%) during the gasping period. When oxygen was given after the gasping period, the survival rate was 33.3% in control and 0% in supplemented 1-day-old rats, and 100% in control and 50% in glucose-supplemented 8-day-old rats (p < 0.02). Further controlled experiments for a fixed period of anoxia to 13.5 min resulted in survival rates of 50.0% for controls and 28.6% for supplemented animals, respectively. The overall survival rate was then 85.2% in control and 52.9% in supplemented 8-day-old rats (p < 0.05). Lactate concentration in blood rapidly increased in the first 6 min of anoxia and thereafter gradually increased to 22.1 mmol/l around the last gasp in the 1-day-old rats. Hyperglycemia did not cause further accumulation of lactate despite a transient elevation over the control rats at 6 min of anoxia. In the 8-day-old supplemented animals the lactate level was only modestly increased, probably due to the prolonged gasping period. In conclusion, we found that gasping performance was well preserved in the 8-day-old glucose-supplemented rats, whereas the autoresuscitation mechanism after the last gasp might be altered due to hyperglycemia. In addition, the accumulation of lactate in the blood did not affect the gasping performance and the mechanisms of autoresuscitation.

In the adult, pentobarbitone-anaesthetized rabbit, the in vivo release of substance P-like immunoreactivity was measured in the nucleus tractus solitarii using microdialysis and radioimmunoassay. Increased 160 +/- 16%) extracellular concentrations of substance P-like immunoreactivity were observed during hypoxic provocations of 9% O2 in N2 which also resulted in an increase in phrenic nerve activity. In bilateral carotid sinus nerve-denervated animals no enhanced release of substance P was seen in response to hypoxic challenges (105 +/- 6%) and the phrenic nerve activity was not significantly affected. Perfusion of the nucleus tractus solitarii region with the dopamine agonist, apomorphine (10(-5) M) resulted in a significant decrease in the extracellular level of substance P. These results provide further evidence that substance P is involved in the mediation of the hypoxic drive inputs from the peripheral chemoreceptors. The interactions of apomorphine with substance P release might also suggest a presynaptic modulation of substance Pergic neurons by dopamine in the nucleus tractus solitarii.

Substance P (SP) belongs to a group of peptides called tachykinins. Biological effects of SP are mediated by tachykinin receptors that have been classified as neurokinin-1 (NK-1), NK-2 and NK-3 subtypes. The aim of the present study is to elucidate the tachykinin receptor subtype(s) that mediate the excitatory effects of SP in the carotid body. For this purpose, we compared the carotid body responses elicited by SP with that of physalaemin and eledoisin. In other tissues, physalaemin exhibits equi or greater potency at NK-1 receptors and eledoisin exerts its effects more on NK-2 and NK-3 subtypes compared to SP. Experiments were performed on eight cats that were anaesthetized, paralyzed and artificially ventilated with room air. Close carotid body administration of SP and physalaemin produced dose-dependent augmentation of the chemoreceptor afferent activity. Chemoreceptor discharge, however, was unaffected by eledoisin. Compared to that by SP, the magnitude of excitation produced by physalaemin was the same at lower doses but significantly greater with the highest dose (100 nmol). The time course of the response induced by physalaemin, however, was the same as that by SP. The present results demonstrate that in the carotid body physalaemin is also either equi or relatively more potent than SP, whereas eledoisin has no effect on the chemoreceptor discharge. It is suggested that stimulation of the carotid body by SP is mediated by NK-1 but not NK-2 or NK-3 receptors.

Adenosine is known to increase carotid chemoreceptor discharge in vivo. Since adenosine has powerful vascular effects it is possible that this chemoexcitation is indirectly caused by changes in carotid body blood flow. To evaluate this possibility the effect of adenosine (0.02-2.0 mumol) was assessed on the chemoreceptor activity of the cat carotid bodies in vitro. All three doses of adenosine produced an increase in chemoreceptor discharge which reached its maximum within 10-20 s and subsequently returned to preinjection controls within 1 min. The chemoreceptor excitation caused by adenosine was dose-dependent. These results suggest that adenosine induces chemoexcitation without changes in blood pressure and blood flow.

Adenosine, which is released during hypoxia, increases carotid chemoreceptor discharge. It is not known if adenosine also may stimulate the aortic chemoreceptors. The purpose of this study was to investigate if adenosine also can stimulate aortic chemoreceptors. The effect of adenosine (0.01, 0.1 and 1.0 mumol/kg) on aortic chemoreceptor discharge was studied in seven anesthetized, paralyzed and artificially ventilated adult cats. Intra-aortic injections of adenosine produced an increase in chemoreceptor discharge, which reached its peak between 10 and 20 s. The chemoreceptor augmentation increased with higher doses of adenosine. Adenosine also caused a fall in blood pressure. The increase of chemoreceptor discharge was not related to fall in arterial blood pressure. Since adenosine is released during hypoxia, it is suggested that part of the cardiovascular changes induced by hypoxia is due to stimulation of aortic chemoreceptors by adenosine.

Substance P (SP), a member of the tachykinin group of peptides, has been shown to augment the sensory discharge of the carotid body, an oxygen sensing chemoreceptor. In this study we present evidence that the excitatory effect of SP, in part, could arise from a direct effect of the peptide on mitochondrial oxidative phosphorylation. Measurement of the partition coefficient of SP showed that the peptide has a relatively high apolar partition, which could be consistent with its distribution across lipid bilayers and in intracellular organelles. In addition, the effects of three concentrations of SP were tested on oxygen consumption of mitochondria isolated from rat hearts. The results showed that while the lower concentration of the peptide (0.5 microM) did not affect O2 consumption, higher concentrations, i.e., 1 and 2 microM, enhanced the rate of state 4 respiration by 52 and 64%, respectively. The rate of state 3 respiration, on the other hand, was unaltered with 0.5 and 1 microM, and was only slightly decreased with 2 microM of the peptide. The ADP:O ratio was unaffected by any concentrations of SP tested. The peptide-induced effect on state 4 respiration was even more pronounced with glutamate as a respiratory substrate and in presence of K+ in the medium. These results indicate that SP, in addition to its more accepted role as a neurotransmitter or modulator in the carotid body, may elicit intracellular response by interfering directly with oxidative phosphorylation.