A5000573670- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Heart Rate Variability and Autonomic Control
- Neuroscience and Neural Engineering
- Atrial Fibrillation Management and Outcomes
- Vagus Nerve Stimulation Research
- Urinary Bladder and Prostate Research
- Cardiac Arrhythmias and Treatments
- Pelvic floor disorders treatments
- Cardiac pacing and defibrillation studies
- Pluripotent Stem Cells Research
- Cardiovascular Effects of Exercise
- Cardiovascular Function and Risk Factors
- Cardiomyopathy and Myosin Studies
- Neuroscience of respiration and sleep
- Blood Pressure and Hypertension Studies
- Nicotinic Acetylcholine Receptors Study
- Receptor Mechanisms and Signaling
- Cardiac Ischemia and Reperfusion
- Urological Disorders and Treatments
- Nitric Oxide and Endothelin Effects
- Ovarian function and disorders
- ECG Monitoring and Analysis
- Urinary Tract Infections Management
- Biochemical and Molecular Research
Norwegian University of Science and Technology
2025
St Olav's University Hospital
2025
University of Madras
2025
British Heart Foundation
2024
Linköping University
2024
Roswell Park Comprehensive Cancer Center
2023
University of Washington
2023
University of Hertfordshire
2015-2021
BioElectronics (United States)
2021
GlaxoSmithKline (United Kingdom)
2009-2017
Abnormal cardiac ryanodine receptor (RyR2) function is recognized as an important factor in the pathogenesis of heart failure (HF). However, specific molecular causes underlying RyR2 defects HF remain poorly understood. In present study, we used a canine model chronic to test hypothesis that HF-related alterations are caused by posttranslational modification reactive oxygen species generated failing heart. Experimental approaches included imaging cytosolic ([Ca(2+)](c)) and sarcoplasmic...
The antimalarial drug DSM265 displays activity against blood and liver stages of Plasmodium falciparum has a long predicted half-life in humans.
Human-induced pluripotent stem cell cardiomyocytes (hiPSC-CMs) are a potential source to develop assays for predictive electrophysiological safety screening. Published studies show that the relevant physiology and pharmacology exist but does not translation between cardiomyocyte other preclinical screening assays, which is crucial drug discovery scientists regulators. Our first of ion channel blockade compare them with existing functional cardiac electrophysiology studies. Ten compounds (a...
Diminished Ca release from the sarcoplasmic reticulum (SR) is an important contributor to impaired contractility of failing heart. Despite extensive effort, underlying causes abnormal SR in heart failure (HF) remain unknown. We used a combination simultaneous imaging cytosolic and intraluminal [Ca] isolated cardiomyocytes recordings single-ryanodine receptor (RyR) channels reconstituted into lipid bilayers investigate alterations intracellular handling experimental model chronic HF. found...
Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) have been widely proposed as in vitro models of myocardial physiology and disease. A significant obstacle, however, is their immature phenotype. We hypothesised that Ca2+ cycling iPSC-CM influenced by culture conditions can be manipulated to obtain a more mature cellular behaviour. To test this hypothesis we seeded onto fibronectin coated microgrooved polydimethylsiloxane (PDMS) scaffolds fabricated using photolithography, or...
AimsAlthough cardiac alternans is a known predictor of lethal arrhythmias, its underlying causes remain largely undefined in disease settings. The potential role of, and mechanisms responsible for, beat-to-beat alternations the amplitude systolic Ca2+ transients (Ca2+ alternans) was investigated canine post-myocardial infarction (MI) model sudden death (SCD).
In heart failure (HF), abnormal myocyte Ca2+ handling has been implicated in cardiac arrhythmias and contractile dysfunction. the present study, we investigated relationships between handling, reduced contractility, enhanced arrhythmogenesis during HF progression a canine model of non-ischaemic HF. Key parameters were determined by measuring cytosolic intra-sarcoplasmic reticulum (SR) [Ca2+] isolated ventricular myocytes at different stages The was associated with an early continuous...
The sympathetic autonomic nervous system plays a major role in arrhythmia development and maintenance. Historical preclinical studies describe preferential increases cardiac tone upon selective stimulation of the subclavian ansae (SA), nerve cord encircling artery. This study sought to define, for first time, functional anatomy physiology SA humans using percutaneous approach. authors prospectively recruited patients undergoing catheter ablation paroxysmal atrial fibrillation (AF) under...
Restoration of the intestinal epithelial barrier is crucial for achieving mucosal healing, therapeutic goal inflammatory bowel disease (IBD). During homeostasis, renewal maintained by crypt stem cells and progenitors that cease to divide as they differentiate into mature colonocytes. Inflammation a major effector damage in IBD has been found affect stemness, regeneration cellular functions. However, impact immune cell-modulating drugs on homeostasis repair poorly understood. It likely these...
Isolated diastolic dysfunction is found in almost half of asymptomatic patients with well-controlled diabetes and may precede heart failure. However, mechanisms that underlie during are not well understood. We tested the hypothesis isolated associated impaired myocardial Ca(2+) handling type 1 diabetes. Streptozotocin-induced diabetic rats were compared age-matched placebo-treated rats. Global left ventricular performance systolic function preserved animals. Diabetes-induced was evident on...
The autonomic nervous system innervates all lymphoid tissues including the spleen therefore providing a link between central and immune system. only known mechanism of neural inhibition inflammation in relies on production norepinephrine by splenic catecholaminergic fibers which binds to β2-adrenergic receptors (β 2-ARs) CD4+ T cells. These cells trigger release acetylcholine that inhibits secretion inflammatory cytokines macrophages through α7 nicotinic receptor (α7nAchRs) signaling. While...
The magnitude of innate inflammatory immune responses is dependent on interactions between peripheral neural and cells. In particular, a cholinergic anti-inflammatory pathway (CAP) has been identified in the spleen whereby noradrenaline (NA) released by splenic nerves binds to ß2-adrenergic receptors (β2-AR) CD4+ T cells which, turn, release acetylcholine (ACh). binding ACh α7 (α7-AChR) expressed macrophages inhibits production cytokines, including tumor necrosis factor (TNF). However, role...
Heart failure is a common antecedent to atrial fibrillation; both heart and fibrillation are associated with increased myocardial oxidative stress. Chronic canine reduces action potential duration refractoriness. We hypothesized that inducible nitric oxide synthase 2 (NOS2) contributes stress electrophysiologic alterations. A 16-week tachypacing model of was used (n= 21). At 10 weeks, dogs were randomized either placebo (n = 12) or active treatment 9) NOS cofactor, tetrahydrobiopterin (BH4,...
AimsWe sought to define the underlying mechanisms for atrial fibrillation (AF) during chronic heart failure (HF).
Abstract Background Vagus nerve stimulation is currently clinically evaluated as a treatment for inflammatory bowel disease. However, the mechanism by which this therapeutic intervention can have an immune‐regulatory effect in colitis remains unclear. We determined of intestine‐specific vagotomy or sympathectomy superior mesenteric ( SMN ) on dextran sodium sulfate DSS )‐induced mice. Furthermore, we tested efficacy to treat ‐induced rats. Methods Vagal and fibers were surgically dissected...
Neurostimulation is an emerging treatment for conditions like hypertension. The renal nerves, comprising sensory afferent and sympathetic efferent fibers, are crucial blood pressure (BP) regulation. inhibitory reno-renal reflex, where central integration of input reduces outflow systemic BP, presents a promising target neurostimulation interventions. We therefore investigated nerve stimulation (RNS) as potential hypertension therapy. Anesthetized male spontaneously hypertensive rats (SHRs)...
Oxidative stress has been implicated in the pathogenesis of atrial fibrillation. There are multiple systems myocardium which contribute to redox homeostasis, and loss homeostasis can result oxidative stress. Potential sources oxidants include nitric oxide synthases (NOS), normally produce heart. Two NOS isoforms (1 3) expressed During pathologies such as heart failure, there is induction 2 cell types myocardium. In certain conditions, enzymes may become uncoupled, shifting from production...
Pudendal nerve stimulation is a promising treatment approach for lower urinary tract dysfunction, including symptoms of overactive bladder. Despite some clinical studies, there remain many unknowns as to how best stimulate the pudendal maximize therapeutic efficacy. We quantified changes in bladder capacity and voiding efficiency during single-fill cystometry response electrical sensory branch urethane-anesthetized female Wistar rats. Increases were dependent on both amplitude rate....
I(Kur) (Ultra-rapid delayed rectifier current) has microM sensitivity to 4-aminopyridine (4-AP) and is an important modulator of the plateau amplitude action potential duration in canine atria. Kv1.5 encodes present both atria ventricles canines humans. We hypothesized that a similar outward current with 4-AP ventricle.We used established voltage clamp protocols (50 100 microM) measure normal myocytes isolated from left ventricular mid-myocardium.Action recordings presence showed significant...
Neuroendocrine chromaffin cells of the adrenal medulla in rat receive excitatory synaptic input through anterior and posterior divisions sympathetic splanchnic nerve. Upon stimulation, releases catecholamines, epinephrine, norepinephrine into suprarenal vein for circulation throughout body. Under tone, catecholamine release is modest. However, upon activation sympathoadrenal stress reflex, increased firing, output increases dramatically. Moreover, specific stressors can preferentially...
Many cardiac interventional procedures, such as coronary angioplasty, stenting, and thrombolysis, attempt to reintroduce blood flow (reperfusion) an ischemic region of myocardium. However, the reperfusion is accompanied by a complex cascade cellular molecular events resulting in oxidative damage, termed myocardial ischemia-reperfusion (I/R) injury. In this study, we evaluated ability HO-4038, N-hydroxypiperidine derivative verapamil, on modulation tissue oxygenation (Po 2 ), I/R injury, key...