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Advancing respiratory-cardiovascular physiology with the working heart-brainstem preparation over 25 years.

ABSTRACT: Twenty-five years ago, a new physiological preparation called the working heart-brainstem preparation (WHBP) was introduced with the claim it would provide a new platform allowing studies not possible before in cardiovascular, neuroendocrine, autonomic and respiratory research. Herein, we review some of the progress made with the WHBP, some advantages and disadvantages along with potential future applications, and provide photographs and technical drawings of all the customised equipment used for the preparation. Using mice or rats, the WHBP is an in situ experimental model that is perfused via an extracorporeal circuit benefitting from unprecedented surgical access, mechanical stability of the brain for whole cell recording and an uncompromised use of pharmacological agents akin to in vitro approaches. The preparation has revealed novel mechanistic insights into, for example, the generation of distinct respiratory rhythms, the neurogenesis of sympathetic activity, coupling between respiration and the heart and circulation, hypothalamic and spinal control mechanisms, and peripheral and central chemoreceptor mechanisms. Insights have been gleaned into diseases such as hypertension, heart failure and sleep apnoea. Findings from the in situ preparation have been ratified in conscious in vivo animals and when tested have translated to humans. We conclude by discussing potential future applications of the WHBP including two-photon imaging of peripheral and central nervous systems and adoption of pharmacogenetic tools that will improve our understanding of physiological mechanisms and reveal novel mechanisms that may guide new treatment strategies for cardiorespiratory diseases.

SUBMITTER: Paton JFR

PROVIDER: S-EPMC9322470 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Advancing respiratory-cardiovascular physiology with the working heart-brainstem preparation over 25 years.

Paton Julian F R JFR Machado Benedito H BH Moraes Davi J A DJA Zoccal Daniel B DB Abdala Ana P AP Smith Jeffrey C JC Antunes Vagner R VR Murphy David D Dutschmann Mathias M Dhingra Rishi R RR McAllen Robin R Pickering Anthony E AE Wilson Richard J A RJA Day Trevor A TA Barioni Nicole O NO Allen Andrew M AM Menuet Clément C Donnelly Joseph J Felippe Igor I St-John Walter M WM

The Journal of physiology 20220407 9

Twenty-five years ago, a new physiological preparation called the working heart-brainstem preparation (WHBP) was introduced with the claim it would provide a new platform allowing studies not possible before in cardiovascular, neuroendocrine, autonomic and respiratory research. Herein, we review some of the progress made with the WHBP, some advantages and disadvantages along with potential future applications, and provide photographs and technical drawings of all the customised equipment used fo ...[more]

PMID: 35294064

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Project description:Background:Physiology is a foundation for studying medicine. Student-centred learning methods are needed for a better understanding of the subject. Preparation of working models by students in Physiology is expected to provide better understanding of the subject since they learn by doing these themselves. The present study was designed to understand the effectiveness of a working model making activity for first-year undergraduate medical students. Methods:The participants were 97 first-year medical undergraduate students. These students were divided into teams. The topics to prepare working models were chosen by the students according to their interests. The models were prepared by using clay, thermocol, batteries, motors, etc. by the students. These models were displayed in an exhibition organized by the department and marks were awarded to the students according to their performance. A feedback questionnaire form was provided to the students, which they had to complete individually. The questionnaires were analyzed to understand the perception of students regarding the activity. Results:Of the students, 35% strongly agreed and 52% agreed that model making was a useful exercise and helped them in understanding Physiology. Of the students, 27% strongly agreed and 50% agreed that their understanding improved with this assignment and 32% of students strongly agreed and 58% agreed that this activity allowed them to analyze the topic and think logically. Of the students, 36% strongly agreed and 50% agreed that they gained confidence in the topic while they were preparing the model and seeing it functioning. Of the students, 37% strongly agreed and 46% agreed that they had the opportunity to work in a team. Of the students, 39% strongly agreed and 47% agreed that faculty had supported them appropriately. Most of the students agreed that they would recommend such activities to their friends studying in medical colleges elsewhere. Conclusion:The students found the activity not only interesting but useful and would encourage their friends studying elsewhere to participate in such activities.

Project description:BackgroundRespiratory morbidity and mortality during childhood remains a major challenge for global health. Due to the rapid economic development in Chongqing, we expect substantial temporal changes in respiratory health status and environmental risk factors in children. By leveraging a historical dataset, this study aims to assess the changes in prevalence of respiratory symptoms and diseases, residential exposure factors, and their associations in school-age children over a period of 25 years.MethodsThis study involved two cross-sectional surveys conducted in Chongqing with a 25-year interval (2017 vs. 1993). Purpose sampling was used to conduct questionnaire surveys on school-age children in both surveys. Information collected include children's respiratory health outcomes, family residential exposures, demographic information, and parental respiratory disease history. The changes of residential exposures as well as demographics were determined by chi-square test. Odds ratios were calculated to compare the prevalence of children's respiratory symptoms and diseases between the two periods. Associations between children's respiratory outcomes and exposure indicators were assessed using multivariate logistic regressions.ResultsThe majority of residential exposure indicators improved in 2017, including sleep in shared room, cooking with coal, poor kitchen ventilation, cooking frequency, and parental smoking. Compared to the 1993 study, the adjusted risk for children's wheezing was lower (OR: 0.38, 95% CI: 0.29, 0.49), but the risk for bronchitis was higher (OR: 1.89, 95% CI: 1.54, 2.31) in the 2017 study. Poor kitchen ventilation and parental smoking were linked to an increased risk of children's wheezing (OR: 1.39, 95% CI: 1.02, 1.90) and bronchitis (OR: 1.51, 95% CI: 1.02, 2.21), respectively, while heating in winter was linked to an increased risk of phlegm (OR: 1.40, 95% CI: 1.03, 1.90) and wheezing (OR: 1.47, 95% CI: 1.07, 2.01) in the 1993 study. However, these residential exposure factors were no longer associated with the children's respiratory diseases in the 2017 study.ConclusionsOur study found improvement of residential exposures in Chongqing, a decline of prevalence of children's wheezing but an increase of that of bronchitis from 1993 to 2017. Poor kitchen ventilation, heating in winter, and parental smoking were significant risk factors in the 1993 survey but, with significantly reduced prevalence in 2017, were not significantly associated with children's respiratory morbidity in the latter survey.

Project description:BackgroundOver the recent decades, residential lifestyle and household environment have changed substantially with rapid development of industrialization and urbanization in China. Whether the prevalence of respiratory diseases changed is still lack of evidence. The objective of this study is to assess potential changes in children's respiratory disease prevalence and associated household environmental factors in Wuhan over a 25-year time interval.MethodsTwo cross-sectional studies in the Period 1 (1993 to 1996) and Period 2 (2017 to 2018) were compared in this research. Elementary school children in period 1 (N=2,517) and in period 2 (N=3,152) were recruited in Wuhan, China. The respiratory health condition, home environmental factors, and family socioeconomic status of each subject were acquired through questionnaire survey using the same protocols in both periods. We used the Chi-square test to analyze the difference of household environmental factors (focused on three indoor air quality determinants) and children's respiratory health condition between two periods. Logistic regression models were used to assess the impacts of household environmental determinants on children's respiratory diseases and symptoms between the two studies, by adjusting a set of covariates.ResultsThe three indoor air quality determinants have reduced substantially in prevalence from period 1 to period 2: environment tobacco smoke (ETS) from 86.6% to 45.9%, household coal use from 47.6% to 4.9%, and kitchen smoke from 58.9% to 7.3%. The prevalence of certain respiratory symptoms in children significantly decreased, such as cough with colds (51.1% to 41.6%) and phlegm with colds (22.3% to 17.7%). The prevalence of asthma was 2.5% and 2.4% and that of bronchitis was 27.1% and 29.8% in both periods. Coal use was a risk factor for asthma in period 1 (OR =2.34, 95% CI: 1.30-4.23), while it was not significantly associated with prevalence of asthma in period 2 (OR =0.60, 95% CI: 0.08-4.51).ConclusionsHousehold indoor air quality determinants and respiratory health condition of children in Wuhan has been improved over the last 25 years. At present, kitchen smoke is an important factor affecting the prevalence of wheeze whatever child has a cold or not and reducing exposure to ETS could be beneficial to protect children to be less likely to develop bronchitis.

Project description:This study aimed to review and evaluate our experience in 750 patients, who underwent transhiatal esophagectomy (THE) and analyze our data. Special attention was paid to some strategies, which we developed in the course of time, regarding the postoperative management of these patients and formulation of improved guidelines.This is a retrospective analysis of all THE operations performed between January 1981 until May 2007 in 750 patients: 60 patients (8%) had benign lesions, while 690 (92%) had malignant ones (5.2% of malignancies were located in the upper esophagus, 7.4% in the middle esophagus, 19% in the lower esophagus, and 68.4% at the cardioesophageal junction). THE and esophageal reconstruction were performed at the same operation in all patients. The stomach was our esophageal substitute of first choice with the colon and jejunum being acceptable alternatives in patients with prior gastric surgery and those necessitating synchronous gastrectomy for cancer invasion. A gastric tube was used as an esophageal substitute in 624 patients (83.2%), the whole stomach in 70 (9.4%), the colon in 43 (5.73%), and a jejunal loop in 13 (1.73%).The overall in-hospital mortality rate was 2.93% (22 patients). There was no intraoperative death. Major complications included atelectasis or pneumonia (4.8%), pleural effusion (22.7%), myocardial infarction (0.5%), recurrent laryngeal nerve paralysis (1.33%), and three tracheal lacerations (0.4%). The anastomotic leak rate decreased gradually over time from 29.4% to 11.1% in the last 6 years. The average intraoperative blood loss was 315 ml and 82% of the patients did not receive any blood transfusion. Late functional results were good or excellent in 93%. The average length of hospital stay was 11 days and intensive care unit stay was 2.3 days. The actuarial 5-year survival rate after THE for carcinoma was 21%.THE is a safe and effective method of esophageal resection with low morbidity and mortality rates and good functional results when performed by experienced surgeons. We believe that our strategies concerning the way of dissecting the cervical esophagus, avoidance of performing pyloromyotomy, the delayed removal of the cervical drain and the delayed advance to oral feeding have reduced, noticeably, morbidity and mortality in our series.

Project description:ImportanceWith rapid aging of the US population, understanding trends over time in dementia occurrence is essential to public health planning and intervention; this understanding includes trends in neuropathologies underlying clinical dementia.ObjectiveTo characterize trends in pathways underlying dementia by examining prevalence of postmortem neuropathologies in birth cohorts across 25 years.Design, setting, and participantsTwo longitudinal cohorts, the Religious Orders Study and the Rush Memory and Aging Project, with autopsy data from 1997 to 2022 with up to 27 years follow-up were analyzed. Deceased individuals with complete postmortem neuropathology evaluations were included, and 177 individuals with most distant (<1905) or recent (>1930) years of birth were excluded.ExposuresFour categories of year of birth: 1905-1914, 1915-1919, 1920-1924, and 1925-1930.Main outcomes and measuresOutcomes included pathologic diagnosis of Alzheimer disease (AD), global AD pathology, amyloid load, tau tangles, neocortical Lewy bodies, limbic-predominant age-related TDP-43 encephalopathy neuropathological change, atherosclerosis, arteriolosclerosis, gross chronic infarcts, and chronic microinfarcts. For comparison, pathologies in each birth epoch were age-standardized to age distribution of the cohorts. χ2 Tests were used for categorical outcomes, and analysis of variance was used to compare means across birth epochs.ResultsOverall, 1554 participants were examined (510 [33%] male; median [range] age at death, 90 [66-108] years). Participants were distributed fairly evenly across birth epochs (1905-1914: n = 374; 1915-1919: n = 360; 1920-1924: n = 466; 1925-1930: n = 354). Across year of birth groups, no differences were found in prevalence of pathologic AD diagnosis; age-standardized prevalence fluctuated between 62% and 68% in the birth cohorts (χ2 test: P = .76 across birth epochs). Similarly, no differences were found in mean levels of global AD pathology, although there was greater density specifically of tau tangles in later birth cohorts (eg, age-standardized mean [SD], 1.53 [1.20] years for the 1905-1914 cohort and 1.87 [1.47] years for the 1925-1930 cohort; analysis of variance test: P = .01 across birth cohorts). There were no differences over time in other neurodegenerative pathologies. In contrast, atherosclerosis and arteriosclerosis were dramatically lower over time; for example, age-standardized prevalence of moderate to severe atherosclerosis ranged from 54% among those born from 1905-1914 to 22% for 1925-1930 (χ2 test: P < .001 across birth epochs).Conclusion and relevanceIn this study, few differences in neurodegenerative pathologies were found, but there may be worse levels of tau tangles across birth cohorts over 25 years. This indicates that any improvements over time in clinical dementia observed by cohorts are likely in part associated with improved resilience to pathology rather than reduced AD pathology. Finally, vessel pathologies were markedly lower over birth cohorts, indicating the assocation with brain health of populationwide improvements in several vascular risk factors.

Dataset Information

Advancing respiratory-cardiovascular physiology with the working heart-brainstem preparation over 25 years.

Publications

Advancing respiratory-cardiovascular physiology with the working heart-brainstem preparation over 25 years.

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