American journal of physiology. Heart and circulatory physiology最新文献

{"title":"Establishment of a reproducible porcine myocardial infarction model using a minithoracotomy approach.","authors":"Ying-Sheng Lin, Pao-Hsien Chu, Wan-Chun Ho, Jeng-Yu Jan, Mei-Chun Chen, Kai-Jen Cheng, Ya-Ching Hsu, Chai-Yi Shen, Chen-Yi Li, Lun-De Liao, Yu-Sheng Lin","doi":"10.1152/ajpheart.00140.2026","DOIUrl":"10.1152/ajpheart.00140.2026","url":null,"abstract":"<p><p>Preclinical porcine models of myocardial infarction (MI) are essential for cardiovascular research but often require lengthy surgeries with variable outcomes. We developed a minimally invasive mini-thoracotomy approach to maximize procedural success, minimize operative time, and ensure reproducible infarct induction. Eleven Lanyu miniature pigs (25-30 kg) were assigned to an MI group (<i>n</i> = 7) or sham control group (<i>n</i> = 4). MI was induced by permanent left anterior descending (LAD) coronary artery ligation via mini-thoracotomy. Six of seven MI pigs (85.7%) survived, with a mean skin-to-skin operative time of 35.83 ± 2.86 min, whereas all sham controls survived without complications. Infarction was confirmed by postligation ST-segment elevation and pathological Q waves. Serial echocardiography and speckle-tracking strain analysis at baseline, 1 wk, and 3 mo revealed consistent regional systolic dysfunction in the MI group, though interanimal variability was observed in certain functional parameters. Cross-sectional area-based ejection fraction was significantly reduced at the papillary muscle and apical levels by 1 wk, persisting through 3 mo. Speckle tracking showed corresponding reductions in radial strain, particularly apically. Progressive ventricular remodeling was evident from an increased left ventricular mass index, and Masson's trichrome staining confirmed extensive myocardial fibrosis distal to the ligation sites (mean fibrotic area = 25.6 ± 4.3%). Sham controls retained preserved structure and function throughout. In conclusion, this minimally invasive porcine MI model provides a highly feasible, rapid, and reproducible translational platform, integrating surgical accessibility with robust functional and histological validation for investigating postinfarction remodeling and evaluating cardiovascular therapeutics.<b>NEW & NOTEWORTHY</b> We present a minimally invasive minithoracotomy porcine myocardial infarction model that achieves reproducible anterior infarction via permanent LAD ligation, with a mean operative time under 36 min and 85.7% survival. Serial echocardiography with speckle-tracking strain shows significant regional ejection fraction and radial strain reductions by 1 wk, persisting through 3 mo, alongside progressive remodeling and confirmed fibrosis. This efficient, reproducible model offers a practical translational platform for evaluating emerging cardiovascular therapeutics and devices.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1447-H1458"},"PeriodicalIF":3.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148878765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ejection fraction's shocking inability to uncouple contractility from loading conditions.","authors":"Stephen P Wright","doi":"10.1152/ajpheart.90035.2026","DOIUrl":"10.1152/ajpheart.90035.2026","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1509-H1511"},"PeriodicalIF":3.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A chronic pig model for comprehensive longitudinal studies of ventricular arrhythmias after ischemia and reperfusion.","authors":"Semra Oztemel Sari, Kristine Mørk Kindberg, Andreas Romaine, Las Hardy, Athiramol Sasi, Imran J Iversen, Emil Espe, Morten Eriksen, Kristin Ø Jenssen, Anders Opdahl, Erik Kongsgaard, Godfrey L Smith, Mathis K Stokke","doi":"10.1152/ajpheart.00353.2026","DOIUrl":"10.1152/ajpheart.00353.2026","url":null,"abstract":"<p><p>Ventricular arrhythmias (VAs) after myocardial infarction (MI) remain the leading cause of sudden cardiac death and a significant challenge in clinical cardiology. Animal studies play an important role for advances in the field providing mechanistic insights. Pig models are especially important for translational and preclinical studies due to their similarity to human coronary anatomy and cardiac electrophysiology. We have established a model and protocol, which allows comprehensive in vivo phenotyping as well as ex vivo characterization of the tissue level substrate for arrhythmias in longitudinal studies. The objective of this paper is to provide detailed practical descriptions of the procedures, contextualized by existing literature, with an aim to advance standardization and reproducibility of preclinical studies with pigs and appropriate adaptations of similar models in other studies. Such efforts will be key to translate fundamental insights to humans.<b>NEW & NOTEWORTHY</b> We present a chronic pig model of ischemia and reperfusion for longitudinal studies of ventricular arrhythmias, and a protocol for comprehensive data collection for in vivo, ex vivo, and histological studies. Detailed descriptions of procedures and comparison with previously published models are provided to facilitate standardization and reproducibility, and comparisons with key parameters in humans are included to clarify the translational value.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1549-H1572"},"PeriodicalIF":3.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148987809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transient hypertension, lasting consequences: repeated pressure overload reveals mechanisms of myocardial stiffness.","authors":"Payel Sen, Daphne Merkus, Oana Sorop","doi":"10.1152/ajpheart.00629.2026","DOIUrl":"https://doi.org/10.1152/ajpheart.00629.2026","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":"331 5","pages":"H1546-H1548"},"PeriodicalIF":3.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hemodynamic phenotyping in ME/CFS and ANOCA: complementary insights from coronary function testing and invasive cardiopulmonary exercise testing.","authors":"Zoë Mackay, Samit Shah, Jose Gomez Villalobos, Nida Latif, Adith Arun, Phillip Joseph, Paul Heerdt, Inderjit Singh","doi":"10.1152/ajpheart.90080.2026","DOIUrl":"10.1152/ajpheart.90080.2026","url":null,"abstract":"<p><p>This single-center cohort study sought to evaluate the association between myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and angina with nonobstructive coronary arteries (ANOCA), by determining the observed frequency of ME/CFS among patients with ANOCA diagnosed by coronary function testing (CFT). In addition, we performed an exploratory analysis of the diagnostic utility of invasive cardiopulmonary exercise testing (iCPET) in ME/CFS patients with CFT-confirmed ANOCA, with the aim of identifying the predominant physiological mechanism responsible for exertional limitation in this population. Systematic medical record review of 261 patients with CFT-confirmed ANOCA was performed using standardized diagnostic criteria to identify concurrent ME/CFS diagnosis. ME/CFS was identified in 47 patients, representing an observed frequency of 18%. The only statistically significant difference between ANOCA patients with and without ME/CFS was a higher frequency of connective tissue disease in the ME/CFS group (<i>P</i> = 0.0221). In a separate cohort of 27 patients with ME/CFS who underwent iCPET, 24 patients (89%) had CFT-confirmed ANOCA. The diagnosis of ANOCA by CFT prompted a change in medical management in 81% of patients in this cohort. iCPET revealed a primary peripheral limitation to exercise, characterized by impaired peak systemic oxygen extraction despite normal peak oxygen delivery. This study demonstrates a clinically significant association between ME/CFS and ANOCA. These findings underscore the clinical value of CFT in patients with ME/CFS and exertional chest pain and highlight iCPET as a complementary tool for hemodynamic phenotyping in this population. Prospective studies incorporating simultaneous CFT and iCPET with molecular phenotyping are warranted.<b>NEW & NOTEWORTHY</b> This study demonstrates a clinically significant association between myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and angina with nonobstructive coronary arteries (ANOCA), with 18% of patients with coronary function testing-confirmed ANOCA meeting diagnostic criteria for ME/CFS. Invasive cardiopulmonary exercise testing (iCPET) in patients with concurrent ME/CFS and ANOCA reveals a primary peripheral, not cardiac, limitation to exercise. These findings highlight the complementary roles of coronary function testing and iCPET for hemodynamic phenotyping in this underrecognized patient population.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1485-H1494"},"PeriodicalIF":3.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic molecular hydrogen exposure is governed by pulmonary clearance: insights from an arterioarterial shunt approach.","authors":"Victor Pascal-Moussellard, Cordélia Salomez-Ihl, Théo Ziegelmeyer, Jean-Pierre Alcaraz, Stéphane Tanguy, Philippe Cinquin, François Boucher","doi":"10.1152/ajpheart.00421.2026","DOIUrl":"https://doi.org/10.1152/ajpheart.00421.2026","url":null,"abstract":"<p><p>The beneficial effects of molecular hydrogen (H₂) have been reported in a wide range of pathological conditions, including cardiovascular and neurodegenerative diseases and cancer. However, its biodistribution is highly dependent on the route of administration, and H₂ concentration appears markedly reduced in arterial blood when not delivered by inhalation. In this study, we quantified H₂ concentrations in the liver, brain, and left ventricular cavity of male anesthetized rats during H₂ inhalation and following intragastric administration of hydrogen-rich water (HRW). Inhalation was the most effective route, producing high and homogeneous H₂ concentrations in all organs at steady state. In contrast, HRW administration resulted in increased H₂ levels in the liver only, with no detectable elevation in the brain or left ventricle, suggesting complete pulmonary clearance of H₂. To further test this hypothesis, we developed an experimental arterioarterial shunt model coupled to a gas exchanger, enabling the delivery of high H₂ concentrations downstream of the left ventricle ([Formula: see text] = 65.75 ± 30.86 µmol/L at the hepatic level). Despite considerable variability, no bypassing of the pulmonary clearance was observed, and H₂ concentrations in the left ventricular cavity remained unchanged, confirming the dominant role of the lungs in H₂ elimination. Together, these findings demonstrate that inhalation is the only route allowing complete systemic distribution of H₂, whereas administration downstream of the lungs limits exposure to organs located distal to the point of delivery. These results challenge current assumptions regarding nonpulmonary H₂ administration and open new avenues for optimizing H₂-based therapeutic strategies.<b>NEW & NOTEWORTHY</b> This study establishes a quantitative framework for hydrogen (H₂) pharmacokinetics, demonstrating that inhalation is the only way to achieve rapid and homogeneous systemic exposure, whereas hydrogen-rich water delivers H₂ only to downstream organs. Using complementary physiological, intragastric, and high-dose systemic approaches, we validate a nonsaturable pulmonary clearance model across clinically relevant and supraphysiological concentrations. These findings resolve inconsistencies in the literature and redefine how hydrogen-based therapies should be interpreted and optimized.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":"331 5","pages":"H1465-H1477"},"PeriodicalIF":3.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting systemic inflammation to save (micro-) vascular function: game changer or vascular martyrdom?","authors":"Chantal Eickelmann, Aaron J Trask","doi":"10.1152/ajpheart.90034.2026","DOIUrl":"10.1152/ajpheart.90034.2026","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1495-H1497"},"PeriodicalIF":3.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The pathophysiology of wild-type transthyretin amyloidosis: implications for exercise intolerance.","authors":"Jarred J Iacovelli, Spencer J Carter, D Walter Wray","doi":"10.1152/ajpheart.00430.2026","DOIUrl":"10.1152/ajpheart.00430.2026","url":null,"abstract":"<p><p>Wild-type transthyretin amyloidosis (ATTRwt) is an age-associated protein misfolding disorder marked by extracellular deposition of transthyretin fibrils within the myocardium, peripheral nerves, lungs, blood vessels, and musculoskeletal tissues. ATTRwt typically presents as a restrictive cardiomyopathy with preserved left ventricular ejection fraction that contributes to the development of hallmark symptoms such as exercise intolerance. Amyloid infiltration severely impairs ventricular compliance and diastolic reserve, limiting stroke volume and cardiac output augmentation during exercise, and is frequently accompanied by coronary microvascular dysfunction. These central limitations are compounded by autonomic dysfunction, including chronotropic incompetence and impaired sympathetic vasomotor control, which blunt heart rate responses and disrupt appropriate blood flow responses. Pulmonary hypertension, right ventricular-pulmonary artery uncoupling, and ventilatory inefficiency further constrain oxygen transport and contribute to exertional dyspnea and early fatigue. Other peripheral factors such as amyloid-related derangements in vascular endothelial function and musculoskeletal pathologies likely result in impaired hyperemic responses to exercise and accelerated cardiovascular deconditioning, further limiting physical capacity. Together, these integrated cardiac, pulmonary, autonomic, and peripheral abnormalities convergently impair exercise performance in ATTRwt. Considering the universal presentation of exercise intolerance in ATTRwt, therapies that may have favorable effects on physical capacity are of great interest to patients, physicians, and scientists alike. This review seeks to synthesize current evidence describing the central and peripheral pathophysiological mechanisms underlying exercise intolerance in ATTRwt and discuss the potential of pharmacologic and exercise-based interventions that may improve physical capacity in this population.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":"331 5","pages":"H1530-H1545"},"PeriodicalIF":3.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reawakening ApoB-specific immunity in atherosclerotic cardiovascular disease: P210-conjugated nanoparticles restore impaired CD4⁺ T cell responses.","authors":"Randa Salah Gomaa Mahmoud","doi":"10.1152/ajpheart.90037.2026","DOIUrl":"10.1152/ajpheart.90037.2026","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1483-H1484"},"PeriodicalIF":3.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Turtle power: α₂-adrenoceptors take the lead in resistance arteries.","authors":"Young Deanna Choi, Brant E Isakson","doi":"10.1152/ajpheart.90232.2026","DOIUrl":"10.1152/ajpheart.90232.2026","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1512-H1514"},"PeriodicalIF":3.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}