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

Background In patients with aortic valve stenosis (AS), the pathophysiological abnormalities involved in the transition to heart failure are unclear. As chronic heart failure progresses, the ratio between myocardial stroke work and oxygen consumption, i.e. myocardial external efficiency (MEE), steadily deteriorates. However, in patients with AS, it is unknown whether changes in MEE are involved in disease progression. Purpose We investigated changes in MEE and if MEE was associated with long-term prognosis in patients with AS. Methods Ten healthy controls and 38 patients with moderate-severe AS and preserved left ventricular ejection fraction ≥50% were included in the study. To evaluate MEE, we used serial 11C-acetate positron emission tomography, cardiovascular magnetic resonance imaging and echocardiography, with a median follow-up period of 2.8 years. Furthermore, we conducted a long-term follow-up for a median of 5.2 years to detect cardiac events and related them to MEE. Results In patients with AS, MEE increased during follow-up from 25.2% (95% CI: 24.0 to 26.5%) to 29.5% (95% CI: 27.3 to 31.8%; p=0.001) and was higher than in healthy volunteers, 19.9% (18.1 to 21.8; p<0.001). Patients who experienced a cardiac event during long-term follow-up (n=24, 63%) had higher baseline MEE, 26.5% (95% CI: 24.6 to 28.4%), than event-free patients, 23.3% (95% CI: 22.2 to 24.3%; p=0.004). Conclusion In asymptomatic patients with AS, MEE increased over time and high baseline MEE predicted a poor prognosis. Thus, the myocardium displayed an inherent capacity to improve the coupling between oxidative metabolism and contractile function in response to pressure overload.

Background: Electronic cigarette adoption has transformed nicotine delivery patterns globally, with 15% prevalence among youth aged 13-15 years. The cardiovascular implications of combined electronic cigarette and combustible tobacco use remain incompletely characterized. We examined the associations of combined smoking and/or vaping versus no nicotine exposure with elevated blood pressure (BP) and hypertension prevalence using nationally representative United States data from 2021-2023. Methods: Data from the US National Health and Nutrition Examination Survey (NHANES) 2021-2023 cycle, which included 6,262 individuals aged ≥12 years old with complete smoking/vaping status: any smoking and/or vaping (n=1,190) versus no smoking or vaping (n=5,072) were used. Elevated BP was classified as ≥120/70mmHg and hypertension as ≥140/90mmHg, and history of smoking and/or vaping were collected with questionnaire. Multivariable logistic regression and mediation path analysis were conducted. Results: Among 6,262 participants (mean age 42.2 years [SD 21], 63.3% female), smokers/vapers had significantly higher prevalence of elevated BP compared to non-smokers/non-vapers (54.4% vs 39.2%, p<0.001) and hypertension (15.4% vs 11.8%, p<0.001). In fully adjusted models, smoking/vaping was associated with increased odds of elevated BP (aOR: 1.34, 95%CI: 1.12-1.60, p=0.001) and hypertension (aOR: 1.46, 95% CI: 1.06-1.99, p<0.001). Smoking/vaping was associated with a 1.05 mmHg higher diastolic BP (p<0.001) but had no association with systolic BP. Mediation analysis revealed that higher total cholesterol partly mediated (6.7% mediation effect) the relationship between smoking/vaping and diastolic BP. Conclusions: Combined smoking and/or vaping exposure was associated with higher odds of elevated BP and hypertension compared to no nicotine use. The selective diastolic BP elevation suggests an increased peripheral vascular resistance as the primary mechanism; however, longitudinal studies examining these direct vascular mechanisms are warranted.

There are numerous differences in arrhythmia propensity and cardiac electrophysiology between women and men. One proposed reason is differences in the autonomic nervous system (ANS) activity. We therefore compared the sympathetic and parasympathetic influence (sympatho-vagal balance) on the sinoatrial node (SAN) at rest in healthy young women (n=15) and men (n=15) with a mean age of 24 years. Pharmacological blockade of the ANS activity on the SAN was induced by sequential bolus injections of atropine (0.04 mg per kg b.w) and propranolol (0.2mg per kg b.w.) during continuous electrocardiographic recordings. The heart rate (HR) at baseline, after atropine, and the intrinsic HR (IHR) after adding propranolol were used to calculate the accelerator "m" which is ≥1.00 and decelerator "n" which is ≤1.00 according to the Rosenblueth & Simeone concept and equation: HR=m*n*IHR. On the group level IHR was median (IQR) 93.3 (88.4-98.8) beats per min, m was 1.16 (1.13-1.22), n was 0.58 (0.55-0.64), and the sympatho-vagal balance m*n was 0.70 (0.65-0.76), confirming dominant parasympathetic influence at rest. There were no significant differences between women and men in any of these measures, and thus no fundamental difference in the ANS influence on the main impulse generator of the heart at rest. This result contrasts to the significant differences in electrophysiological measures at rest and their responses to stress tests, as well as to the differences in arrhythmia propensity between women and men on both the atrial and ventricular level of the heart.

Cardiac glycosides (CG) like ouabain exert positive inotropic effects by inhibiting the Na⁺-K⁺-ATPase. CGs wide spread use is limited by CGs narrow therapeutic window. Mis- or overdosing with CGs may cause cardiac arrhythmias, resulting from electrolyte disturbances. To study the ethically challenging topic of CG overdosing, we here optimized the in ovo platform to test, if treatment with the selective ouabain antagonist rostafuroxin prevents CG-mediated electrophysiological derangements and arrhythmia by restoring electrolyte homeostasis. We employed incubated chicken eggs (iCEs), a 3R-compliant model, for which we established Electrocardiograms (ECGs). ECGs were recorded under i) baseline conditions, ii) after treatment with ouabain and iii) after co-treatment with rostafuroxin. Underlying mechanisms of ouabain and rostafuroxin effects were studied using blood gas analysis and fluorescence microscopy. Isolated murine and human cardiomyocytes served as an independent model to confirm in ovo results. Ouabain treatment resulted in increased heart rate variability (HRV), transient sinus arrest, and atrio-ventricular dyssynchrony, accompanied by plasma hyperkalemia and cardiomyocyte Na⁺ overload. Co-treatment of ouabain and rostafuroxin led to reduced HRV and ameliorated the frequency and duration of transient sinus arrest, while plasma K⁺ levels remained unchanged. In isolated cardiomyocytes, ouabain treatment induced intracellular Na⁺ overload which was abolished by additional rostafuroxin treatment. Our work demonstrates the in ovo platform and corresponding readouts as a suitable tool to study cardiac electrophysiology in a 3R compliant manner. We found, that rostafuroxin treatment ameliorated ouabain-induced electrophysiological disturbances, suggesting rostafuroxin as a potential therapeutic intervention for ouabain mis- or overdosing.

Childhood obesity is associated with gut microbiome dysbiosis, inflammation, and early cardiac autonomic dysfunction. Lifestyle interventions integrating physical activity and dietary modification represent a primary strategy to mitigate cardiometabolic risk during childhood. This longitudinal intervention study investigated cardiovascular, autonomic, inflammatory, metabolic, and gut microbiome-related outcomes before and after a 4-month program combining structured physical exercise with food and nutrition education in 51 children with obesity aged 7 to 10 years. The intervention promoted favorable dietary changes, including reduced intake of saturated fatty acids (SFA), sodium, and total energy. These modifications were accompanied by a reduction in body fat percentage and systemic inflammation, evidenced by lower circulating interleukin-17A (IL-17A) and tumor necrosis factor-alpha (TNF-α) levels. Improvements in biochemical profiles were observed, including increased albumin and high-density lipoprotein cholesterol (HDL-c), and reduced serum triglyceride and urea levels. Metabolomic analyses revealed beneficial shifts in circulating phosphatidylethanolamines, phosphatidylglycerols, choline, and branched-chain amino acids (BCAA). Cardiovascular assessments demonstrated significant reductions in systolic and diastolic blood pressure and improvements in heart rate variability, indicating enhanced cardiac autonomic modulation. Gut microbiota analyses showed no differences in alpha or beta diversity; however, Bray-Curtis volatility analyses identified significant within-subject compositional shifts. Exploratory multivariate analyses suggested potential associations between specific gut taxa (e.g., Ligilactobacillus, Streptococcus, Roseburia), circulating metabolites, and cardiovascular autonomic indices, supporting the existence of microbiota-metabolite-heart interactions. In summary, a 4-month multicomponent lifestyle intervention improved cardiovascular autonomic function, inflammatory status, and cardiometabolic profiles in children with obesity. These findings highlight the cardiovascular benefits of early lifestyle modification and support integrative approaches targeting autonomic and metabolic pathways in pediatric obesity.

Ossabaw minipigs differ from other (mini)pig strains by their genetic predisposition to develop full metabolic syndrome and their non-responsiveness to cardioprotective interventions, even before developing the diseased phenotype. Previous DNA sequencing data revealed differences in a cluster of mitochondrial protein-coding genes between Ossabaw and Göttingen minipigs - a large animal model without such a genetic predisposition and a responsiveness to cardioprotection. Alterations in mitochondrial protein composition affect mitochondrial function, and mitochondria play a crucial role in the development of metabolic syndrome, and for cardioprotection. Therefore, we aimed to compare the cardiac mitochondrial proteome between lean Ossabaw minipigs with a healthy phenotype and Göttingen minipigs to gain initial insights into potential differences in mitochondrial protein composition and function. Cardiac mitochondria (left ventricular tissue) of both minipig strains (male/female pigs) were isolated and the proteome was analyzed by liquid chromatography-tandem mass spectrometry. An unbiased, non-hypothesis-driven proteome analysis, identified 97% overlap in the proteome. Among the 3% of differentially expressed proteins, 19 were related to mitochondrial metabolism, eight to transcription and translation, three to small molecule transport, two to oxidative phosphorylation, and one to dynamics and surveillance. These small differences in protein composition, were associated with an altered mitochondrial energy turnover - ATP production was reduced by 49% in Ossabaw compared to Göttingen minipig mitochondria. This proteome analysis provides a broader basis to understand how genetic alterations result in changes of the mitochondrial proteome and function, which might be relevant for the development and progression of metabolic syndrome and/or the primordial non-responsiveness to cardioprotection in Ossabaw minipigs.

Neuregulin-1β (NRG1) improves cardiac output in heart failure patients, yet concerns remain that ErbB activation may promote maladaptive hypertrophy, particularly during hemodynamic stress. We investigated how NRG1 influences structural, functional, and molecular remodeling during pressure overload. Male and female C57BL/6NRj mice underwent transverse aortic constriction (TAC) or sham surgery and received saline or recombinant NRG1 via osmotic minipumps or daily injection. In male mice, NRG1 increased ejection fraction at 1 and 4 weeks after TAC. NRG1 accentuated TAC-induced concentric remodeling without increasing left ventricular weight or cardiomyocyte cross-sectional area. It markedly reduced fibrosis and macrophage infiltration and prevented progression toward early cardiac decompensation. NRG1 amplified TAC-induced Myh7 and Nppa expression and also shifted Glut1/Glut4 toward their fetal profile. Transcriptomic analysis identified two novel NRG1-regulated genes: NRG1 reversed TAC-induced upregulation of the skeletal muscle gene Mybpc2 and induced the expression of Popdc2. Furthermore, NRG1 increased expression of Gja1 and localization of connexin 43 at the intercalated disc, consistent with enhanced electrical coupling. In female mice, NRG1 increased systolic function and regulated similar molecular targets yet did not reduce the modest increase in fibrosis that was observed. In conclusion, our findings show that NRG1 promotes adaptive molecular and structural remodeling under pressure overload and enhances contractile performance without exacerbating hypertrophy. The identification of NRG1-responsive genes linked to contraction and conduction highlights potential mechanisms and supports further exploration of NRG1-based strategies for cardiac disease.