American Journal of Physiology - Heart and Circulatory Physiology最新文献

{"title":"Activation of the non-neuronal cholinergic cardiac system by hypoxic preconditioning protects isolated adult cardiomyocytes from hypoxia/reoxygenation injury","authors":"Felix Braczko, Sara Romina Fischl, Jörg Reinders, Helmut Raphael Lieder, Petra Kleinbongard","doi":"10.1152/ajpheart.00211.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00211.2024","url":null,"abstract":"Background: Activation of the vagus nerve mediates cardioprotection and attenuates myocardial ischemia/reperfusion (I/R) injury. In response to vagal activation, acetylcholine (ACh) is released from the intracardiac nervous system (ICNS) and activates intracellular cardioprotective signaling cascades. Recently, however, a non-neuronal cholinergic cardiac system (NNCCS) in cardiomyocytes has been described as an additional source of ACh. Aim: To investigate whether the NNCCS mediates cardioprotection in absence of vagal and ICNS activation. For that, we used a reductionist approach of isolated adult rat ventricular cardiomyocytes in absence of neuronal cells with hypoxic preconditioning (HPC) as protective stimulus. Methods: Adult rat ventricular cardiomyocytes were isolated, absence of neuronal cells was confirmed, HPC was induced by 10/20 min hypoxia/reoxygenation (H/R) before subjection to 30/5 min H/R to simulate I/R injury. Cardiomyocyte viability was assessed by trypan blue staining. Intra- and extracellular ACh was quantified using liquid chromatography-coupled mass spectrometry at baseline, after HPC, after hypoxia, and after reoxygenation, respectively. In a subset of experiments, muscarinic/nicotinic ACh receptor (mAChR/nAChR) antagonists were added during HPC or during H/R. Results: Cardiomyocyte viability at baseline (69±4%) was reduced by H/R (10±3%). With HPC cardiomyocyte viability was preserved after H/R (25±6%). Intra- and extracellular ACh increased during hypoxia, HPC further increased both intra- and extracellular ACh (from 0.9±0.7 to 1.5±1.0 nmol/mg; from 0.7±0.6 to 1.1±0.7 nmol/mg). Addition of mAChR and nAChR antagonists during HPC had no impact on HPC´s protection, however protection was abrogated when antagonists were added during H/R (cardiomyocyte viability after H/R: 23±5%; 13±4%). Conclusion: Activation of the NNCCS is involved in cardiomyocyte protection: HPC increases intra- and extracellular ACh during H/R, and m-/nAChRs are causally involved in HPC´s cardiomyocyte protection during H/R. The interplay between upstream ICNS activation and the NNCCS activation to myocardial cholinergic metabolism and cardioprotection needs to be investigated in future studies.","PeriodicalId":7640,"journal":{"name":"American Journal of Physiology - Heart and Circulatory Physiology","volume":"85 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140831193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sensitivity and activation of endoplasmic reticulum stress response and apoptosis in the perinatal sheep heart","authors":"Karthikeyan Bose, Herbert M. Espinoza, Samantha Louey, Sonnet S. Jonker","doi":"10.1152/ajpheart.00043.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00043.2024","url":null,"abstract":"American Journal of Physiology-Heart and Circulatory Physiology, Ahead of Print. <br/>","PeriodicalId":7640,"journal":{"name":"American Journal of Physiology - Heart and Circulatory Physiology","volume":"279 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140830963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isoproterenol Improves Hemodynamics And Right Ventricle-Pulmonary Artery Coupling After Heart Transplantation","authors":"David Levy, Ouriel Saura, Manuela Lucenteforte, Elena Collado Lledó, Pierre Demondion, Nadjib Hammoudi, Benjamin Assouline, Matthieu Petit, Melchior Gautier, Lucie Le Fevre, Marc Pineton de Chambrun, Guillaume Coutance, Elodie Berg, Juliette Chommeloux, Matthieu Schmidt, Charles-Edouard Luyt, Guillaume Lebreton, Pascal Leprince, Guillaume Hekimian, Alain Combes","doi":"10.1152/ajpheart.00200.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00200.2024","url":null,"abstract":"American Journal of Physiology-Heart and Circulatory Physiology, Ahead of Print. <br/>","PeriodicalId":7640,"journal":{"name":"American Journal of Physiology - Heart and Circulatory Physiology","volume":"85 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140831313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perspective on statistical power and equivalences tests","authors":"Markus Neuhäuser, Graeme D. Ruxton","doi":"10.1152/ajpheart.00746.2023","DOIUrl":"https://doi.org/10.1152/ajpheart.00746.2023","url":null,"abstract":"American Journal of Physiology-Heart and Circulatory Physiology, Ahead of Print. <br/>","PeriodicalId":7640,"journal":{"name":"American Journal of Physiology - Heart and Circulatory Physiology","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140830964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood pressure responses to handgrip exercise but not apnea or mental stress are enhanced in women with a recent history of preeclampsia","authors":"Danielle E. Berbrier, Tessa E. Adler, Cheryl A. Leone, Michael J. Paidas, Nina S. Stachenfeld, Charlotte W. Usselman","doi":"10.1152/ajpheart.00020.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00020.2024","url":null,"abstract":"Preeclampsia is a risk factor for future cardiovascular diseases. However, the mechanisms underlying this association remain unclear, limiting effective prevention strategies. Blood pressure responses to acute stimuli may reveal cardiovascular dysfunction not apparent at rest, identifying individuals at elevated cardiovascular risk. Therefore, we compared blood pressure responsiveness to acute stimuli between previously preeclamptic (PPE) women (34±5yr, 13±6 months postpartum) and women following healthy pregnancies (CTRL; 29±3yr, 15±4 months postpartum). Blood pressure (finger photoplethysmography calibrated to manual sphygmomanometry-derived values; PPE: n=12, CTRL: n=12) was assessed during end-expiratory apnea, mental stress, and isometric handgrip exercise protocols. Integrated muscle sympathetic nerve activity (MSNA) was assessed in a subset of participants (peroneal nerve microneurography; PPE: n=6, CTRL: n=8). Across all protocols, systolic blood pressure (SBP) was higher in PPE than CTRL (main effects of group all <i>P&lt;0.05</i>). Peak changes in SBP were stressor-specific: peak increases in SBP were not different between PPE and CTRL during apnea (+8±6 <i>vs.</i> +6±5mmHg, <i>P=0.32</i>) or mental stress (+9±5 <i>vs.</i> +4±7mmHg, <i>P=0.06</i>). However, peak exercise-induced increases in SBP were greater in PPE than CTRL (+11±5 <i>vs.</i> +7±7mmHg, <i>P=0.04</i>). MSNA was higher in PPE than CTRL across all protocols (main effects of group all <i>P&lt;0.05</i>), and increases in peak MSNA were greater in PPE than CTRL during apnea (+44±6 <i>vs.</i> +27±14burst/100hb, <i>P=0.04</i>) and exercise (+25±8 <i>vs.</i> +13±11burst/100hb, <i>P=0.01</i>) but not different between groups during mental stress (+2±3 <i>vs.</i> 0±5burst/100hb, <i>P=0.41</i>). Exaggerated pressor and sympathetic responses to certain stimuli may contribute to the elevated long-term risk for cardiovascular disease in PPE.","PeriodicalId":7640,"journal":{"name":"American Journal of Physiology - Heart and Circulatory Physiology","volume":"279 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140830909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Acute Hyperoxia on Autonomic Function and Coronary Tone in Patients with Peripheral Artery Disease","authors":"Mami Hamaoka, Urs A. Leuenberger, Zhaohui Gao, Faisal Aziz, Danielle Jin-Kwang Kim, Jonathan Carter Luck, Cheryl Blaha, Aimee E. Cauffman, Lawrence I. Sinoway, Jian Cui","doi":"10.1152/ajpheart.00225.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00225.2024","url":null,"abstract":"American Journal of Physiology-Heart and Circulatory Physiology, Ahead of Print. <br/>","PeriodicalId":7640,"journal":{"name":"American Journal of Physiology - Heart and Circulatory Physiology","volume":"63 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140831104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reflex sympathetic activation to inspiratory muscle loading is attenuated in females relative to males","authors":"Michael G Leahy, Stephen A. Busch, Scott F. Thrall, Sam J. Hillen, A. William Sheel, Glen E. Foster","doi":"10.1152/ajpheart.00133.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00133.2024","url":null,"abstract":"American Journal of Physiology-Heart and Circulatory Physiology, Ahead of Print. <br/>","PeriodicalId":7640,"journal":{"name":"American Journal of Physiology - Heart and Circulatory Physiology","volume":"117 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140830912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phosphorylation of Cardiac Sodium Channel at Ser571 Anticipates Manifestations of the Aging Myopathy","authors":"Emanuele Pizzo, Daniel O. Cervantes, Harshada Ketkar, Valentina Ripa, Drew M. Nassal, Benjamin Buck, Sreema P. Parambath, Valeria Di Stefano, Kanwardeep Singh, Carl I. Thompson, Peter J. Mohler, Thomas J. Hund, Jason T. Jacobson, Sudhir Jain, Marcello Rota","doi":"10.1152/ajpheart.00325.2023","DOIUrl":"https://doi.org/10.1152/ajpheart.00325.2023","url":null,"abstract":"Diastolic dysfunction and delayed ventricular repolarization are typically observed in the elderly, but whether these defects are intimately associated in the progressive manifestation of the aging myopathy remains to be determined. In this regard, aging in experimental animals is coupled with increased late Na⁺ current (I_NaL) in cardiomyocytes, raising the possibility that I_NaL conditions the modality of electrical recovery and myocardial relaxation of the aged heart. For this purpose, aging male and female wild-type (WT) C57Bl/6 mice were studied together with genetically engineered mice with phosphomimetic (gain-of-function, GoF) or ablated (loss-of-function, LoF) mutations of the sodium channel Nav1.5 at Ser571 associated with, respectively, increased and stabilized I_NaL. At ~18 months (m) of age, WT mice developed prolonged duration of the QT interval of the electrocardiogram and impaired diastolic left ventricular (LV) filling, defects that were reversed by I_NaL inhibition. Prolonged repolarization and impaired LV filling occurred prematurely in adult (~5 m) GoF mutant mice, whereas these alterations were largely attenuated in aging LoF mutant animals. Ca²⁺ transient decay and kinetics of myocyte shortening/relengthening were delayed in aged (~24 m) WT myocytes, with respect to adult cells. In contrast, delayed Ca²⁺ transients and contractile dynamics occurred at adult stage in GoF myocytes and further deteriorated at old age. Conversely, myocyte mechanics were minimally affected in aging LoF cells. Collectively, these results document that Nav1.5 phosphorylation at Ser571 and the late Na⁺ current modulates the modality of myocyte relaxation, constituting the mechanism linking delayed ventricular repolarization and diastolic dysfunction.","PeriodicalId":7640,"journal":{"name":"American Journal of Physiology - Heart and Circulatory Physiology","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140627309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Insights into the Pathobiology of Pulmonary Hypertension in Heart Failure with Preserved Ejection Fraction","authors":"Vaishnavi Aradhyula, Rohit Vyas, Prabhatchandra Dube, Steven T. Haller, Rajesh Gupta, Krishna Rao Maddipati, David J. Kennedy, Samer J. Khouri","doi":"10.1152/ajpheart.00068.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00068.2024","url":null,"abstract":"American Journal of Physiology-Heart and Circulatory Physiology, Ahead of Print. <br/>","PeriodicalId":7640,"journal":{"name":"American Journal of Physiology - Heart and Circulatory Physiology","volume":"98 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140627476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapy-naïve malignancy causes cardiovascular disease: A state-of-the-art cardio-oncology perspective","authors":"Leslie M. Ogilvie, Bridget Coyle-Asbil, Keith R. Brunt, Jim Petrik, Jeremy A. Simpson","doi":"10.1152/ajpheart.00795.2023","DOIUrl":"https://doi.org/10.1152/ajpheart.00795.2023","url":null,"abstract":"Cardiovascular disease (CVD) and cancer are the leading causes of mortality worldwide. Although generally thought of as distinct diseases, the intersectional overlap between CVD and cancer is increasingly evident in both causal and mechanistic relationships. The field of cardio-oncology is largely focused on cardiotoxic effects of cancer therapies (e.g., chemotherapy, radiation). Further, the cumulative effects of cardiotoxic therapy exposure and the prevalence of CVD risk factors in cancer patients leads to long-term morbidity and poor quality of life in this patient population-even when patients are cancer-free. Evidence from cancer patients and animal models demonstrates that the presence of malignancy itself, independent of cardiotoxic therapy exposure or CVD risk factors, negatively impacts cardiac structure and function. As such, the primary focus of this review is the cardiac pathophysiologic and molecular features of therapy-naïve cancer. We also summarize the strengths and limitations of preclinical cancer models for cardio-oncology research and discuss therapeutic strategies that have been tested experimentally for the treatment of cancer-induced cardiac atrophy and dysfunction. Finally, we explore an adjacent area of interest, called 'reverse cardio-oncology', where the sequelae of heart failure augment cancer progression. Here, we emphasize the cross-disease communication between malignancy and the injured heart, and discuss the importance of chronic low-grade inflammation and endocrine factors in the progression of both diseases.","PeriodicalId":7640,"journal":{"name":"American Journal of Physiology - Heart and Circulatory Physiology","volume":"103 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140627304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}