Introduction: Postoperative atrial fibrillation (POAF), characterized as AF that arises 1-3 days after surgery, occurs after 30%-40% of cardiac and 10%-20% of non-cardiac surgeries, and is thought to arise due to transient surgery-induced triggers acting on a preexisting vulnerable atrial substrate often associated with inflammation and autonomic nervous system dysfunction. Current experimental studies often rely on human atrial tissue samples, collected during surgery prior to arrhythmia development, or animal models such as sterile pericarditis and atriotomy, which have not been robustly characterized.

Aim: To characterize the demographic, electrophysiologic, and inflammatory properties of a POAF mouse model.

Methods and Results: A total of 131 wild-type C57BL/6J mice were included in this study. A total of 86 (65.6%) mice underwent cardiothoracic surgery (THOR), which consisted of bi-atrial pericardiectomy with 20 s of aortic cross-clamping; 45 (34.3%) mice underwent a sham procedure consisting of dissection down to but not into the thoracic cavity. Intracardiac pacing, performed 72 h after surgery, was used to assess AF inducibility. THOR mice showed greater AF inducibility (38.4%) compared to Sham mice (17.8%, P = 0.027). Stratifying the cohort by tertiles of age showed that the greatest risk of POAF after THOR compared to Sham occurred in the 12-19-week age group. Stratifying by sex showed that cardiothoracic (CT) surgery increased POAF risk in females but had no significant effect in males. Quantitative polymerase chain reaction of atrial samples revealed upregulation of transforming growth factor beta 1 (TGF-β1) and interleukin 6 (IL6) and 18 (IL18) expression in THOR compared to Sham mice.

Conclusion: Here, we demonstrate that the increased POAF risk associated with CT surgery is most pronounced in female and 12-19-week-old mice, and that the expression of inflammatory cytokines is upregulated in the atria of THOR mice prone to inducible AF.

One sentence summary: We developed a mouse model of POAF that replicates key features of this condition in humans in terms of incidence and inflammatory indices. We demonstrated that female mice have a greater POAF risk than males, highlighting the importance of considering biological sex in future POAF mouse studies.

The development of age-related cardiovascular (CV) dysfunction increases the risk of CV disease as well as other chronic age-associated disorders, including chronic kidney disease, and Alzheimer’s disease and related dementias. Major manifestations of age-associated CV dysfunction that increase disease risk are vascular dysfunction, primarily vascular endothelial dysfunction and arterial stiffening, and elevated systolic blood pressure. Declines in nitric oxide bioavailability secondary to increased oxidative stress and inflammation are established mechanisms of CV dysfunction with aging. Moreover, fundamental mechanisms of aging, termed the “hallmarks of aging” extend to the CV system and, as such, may be considered “hallmarks of CV aging”. These mechanisms represent viable therapeutic targets for treating CV dysfunction with aging. Healthy lifestyle behaviors, such as regular aerobic exercise and certain dietary patterns, are considered “first-line” strategies to prevent and/or treat age-associated CV dysfunction. Despite the well-established benefits of these strategies, many older adults do not meet the recommended guidelines for exercise or consume a healthy diet. Therefore, it is important to establish alternative and/or complementary evidence-based approaches to prevent or reverse age-related CV dysfunction. Targeting fundamental mechanisms of CV aging with interventions such as time-efficient exercise training, food-derived molecules, termed nutraceuticals, or select synthetic pharmacological agents represents a promising approach. In the present review, we will highlight emerging topics in the field of healthy CV aging with a specific focus on how exercise, nutrition/dietary patterns, nutraceuticals and select synthetic pharmacological compounds may promote healthy CV aging, in part, by targeting the hallmarks of CV aging.

Cardiac aging is accompanied by progressive loss of cellular function, leading to impaired heart function and heart failure. There is an urgent need for efficient strategies to combat this age-related cardiac dysfunction. A growing number of events suggest that age-related cardiac diseases are tightly related to metabolic imbalance. This review summarizes recent findings concerning metabolic changes during cardiac aging and highlights the therapeutic approaches that target metabolic pathways in cardiac aging.

Introduction: Low aerobic exercise capacity is an independent risk factor for cardiovascular disease (CVD) and a predictor of premature death. In combination with aging, low aerobic capacity lowers the threshold for CVD.

Aim: Since low aerobic capacity and aging have been linked to mitochondrial oxidative stress and dysfunction, we investigated whether aged Low-Capacity Runner (LCR) rats (27 months) had vascular dysfunction compared to High-Capacity Runner (HCR) rats.

Methods and Results: A significant decrease in aortic eNOS levels and vasodilation as well as an increase in aortic collagen and stiffness were observed in aged LCR rats compared to age and sex-matched HCR rats. There was a correlation between age-related vascular dysfunction and increased levels of ROS and DNA damage in aortas of LCR rats. Moreover, mitochondrial oxygen consumption, membrane potential, ATP levels, and mitophagy were lower in VSMCs of aged LCR rats. VSMCs from older LCR rats showed AIM2 inflammasome activation. VSMCs of young (4 months old) LCR rats treated with purified mitochondrial damage-associated molecular patterns (DAMP) recapitulated an inflammasome activation phenotype similar to that seen in aged rat VSMCs. Rapamycin, a potent immunosuppressant, induced mitophagy, stimulated electron transport chain activity, reduced inflammasome activity, mitochondrial ROS and DAMP levels in VSMCs from aged LCR rats. MitoTEMPO, a mitochondrial ROS scavenger, was similarly effective on VSMCs from aged rats.

Conclusion: The findings suggest that impaired mitophagy and inflammasome activation in the vasculature under conditions of low aerobic exercise capacity during aging results in arterial dysfunction and aortic stiffness. In older adults with reduced aerobic capacity, mitochondrial antioxidants, mitophagy induction, and inflammasome inhibition may be effective therapeutic strategies for enhancing vascular health.