Publications by authors named "Robert Lakin"

Atrial fibrillation (AF) is a supraventricular tachyarrhythmia that is strongly associated with cardiovascular (CV) disease and sedentary lifestyles. Despite the benefits of exercise on overall health, AF incidence in high-level endurance athletes rivals that of CV disease patients, suggesting a J-shaped relationship with AF. To investigate the dependence of AF vulnerability on exercise, we varied daily swim durations (120, 180 or 240 min day ) in 7-week-old male CD1 mice.

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Aims: Endurance exercise is associated with an increased risk of atrial fibrillation (AF). We previously established that adverse atrial remodelling and AF susceptibility induced by intense exercise in mice require the mechanosensitive and pro-inflammatory cytokine tumour necrosis factor (TNF). The cellular and mechanistic basis for these TNF-mediated effects is unknown.

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The prognosis and treatment outcomes of heart failure (HF) patients rely heavily on disease etiology, yet the majority of underlying signaling mechanisms are complex and not fully elucidated. Phosphorylation is a major point of protein regulation with rapid and profound effects on the function and activity of protein networks. Currently, there is a lack of comprehensive proteomic and phosphoproteomic studies examining cardiac tissue from HF patients with either dilated dilated cardiomyopathy (DCM) or ischemic cardiomyopathy (ICM).

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The intercalated disc (ICD) is a unique membrane structure that is indispensable to normal heart function, yet its structural organization is not completely understood. Previously, we showed that the ICD-bound transmembrane protein 65 (Tmem65) was required for connexin43 (Cx43) localization and function in cultured mouse neonatal cardiomyocytes. Here, we investigate the functional and cellular effects of Tmem65 reductions on the myocardium in a mouse model by injecting CD1 mouse pups (3-7 days after birth) with recombinant adeno-associated virus 9 (rAAV9) harboring Tmem65 shRNA, which reduces Tmem65 expression by 90% in mouse ventricles compared to scrambled shRNA injection.

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Heart rate (HR) and blood pressure as well as adverse cardiovascular events show clear circadian patterns, which are linked to interdependent daily variations in physical activity and cardiac autonomic nerve system (ANS) activity. We set out to assess the relative contributions of the ANS (alone) and physical activity to circadian HR fluctuations. To do so, we measured HR (beats per minute, bpm) in mice that were either immobilized using isoflurane anesthesia or free-moving.

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Atrial Fibrillation (AF) is the most common supraventricular tachyarrhythmia that is typically associated with cardiovascular disease (CVD) and poor cardiovascular health. Paradoxically, endurance athletes are also at risk for AF. While it is well-established that persistent AF is associated with atrial fibrosis, hypertrophy and inflammation, intensely exercised mice showed similar adverse atrial changes and increased AF vulnerability, which required tumor necrosis factor (TNF) signaling, even though ventricular structure and function improved.

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Acute exhaustive endurance exercise can differentially impact the right ventricle (RV) versus the left ventricle (LV). However, the hemodynamic basis for these differences and its impact on postexercise recovery remain unclear. Therefore, we assessed cardiac structure and function along with hemodynamic properties of mice subjected to single bouts (216 ± 8 min) of exhaustive swimming (ES).

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Previous studies have shown an association between elevated atrial NADPH-dependent oxidative stress and decreased plasma apelin in patients with atrial fibrillation (AF), though the basis for this relationship is unclear. In the current study, RT-PCR and immunofluorescence studies of human right atrial appendages (RAAs) showed expression of the apelin receptor, APJ, and reduced apelin content in the atria, but not in plasma, of patients with AF versus normal sinus rhythm. Disruption of the apelin gene in mice increased (2.

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Background: Variability in the anatomy and orientation of the triangle of Koch (TK) complicates ablation procedures involving the atrioventricular (AV) node. We used CT angiography (CTA) to assess the anatomical TK orientation, the CS ostium direction, and the relationship between the two, and we validated an individualized CS-guided projection during ablation procedures.

Methods: In 104 patients without structural heart disease undergoing computed tomography (CT) angiography, TK orientations were determined in relation to the coronary sinus ostium (CSo) as well as two standard right anterior oblique (RAO) projection angles (30 and 45) commonly used in ablation procedures.

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Phosphodiesterase type 3 (PDE3) inhibitors block the cAMP hydrolyzing activity of both PDE3 isoforms, PDE3A and PDE3B, which have distinct roles in the heart. Although PDE3 inhibitors improve cardiac function in heart disease patients, they also increase mortality. Nevertheless, PDE3 inhibitors can provide benefit to non-ischemic heart disease patients and are used extensively to treat heart failure in dogs.

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Intense endurance exercise is linked to atrial fibrillation (AF). We established previously that interventions that simultaneously interfere with TNFα signaling, mediated via both the enzymatically liberated soluble and membrane-bound forms of TNFα, prevent atrial remodeling and AF vulnerability in exercised mice. To investigate which signaling modality underlies this protection, we treated exercised mice with XPRO®1595, a selective dominant-negative inhibitor of solTNFα.

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Rationale: Anti-thrombosis therapy for atrial fibrillation (AF) management and stroke prevention is an important aspect of disease management. Novel oral anticoagulants (NOACs) are recommended by guidelines for AF management. However, if one can switch one NOAC to another when the former showed a poor effect has not been fully determined.

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Unlabelled: Most exercise studies in mice have relied on forced training which can introduce psychological stress. Consequently, the utility of mouse models for understanding exercise-mediated effects in humans, particularly autonomic nervous system (ANS) remodeling, have been challenged. We compared the effects of voluntary free-wheel running vs.

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Rationale: Left ventricular non-compaction cardiomyopathy (LVNC) is a rare heart disorder related to thrombosis. Anticoagulant therapy is suggested for the treatment of this disease. The success of the novel oral anticoagulant rivaroxaban as a treatment option for this disorder is unclear.

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Aerobic exercises such as running, walking and cycling are known to elicit a PEH (post-exercise hypotensive) response in both trained and UT (untrained) subjects. However, it is not known whether swim exercise produces a similar effect in normotensive individuals. The complex acute physiological responses to water immersion suggest swimming may affect BP (blood pressure) differently than other forms of aerobic exercises.

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