A5046243793- Cardiac electrophysiology and arrhythmias
- Cardiovascular Function and Risk Factors
- Cardiac Ischemia and Reperfusion
- Mitochondrial Function and Pathology
- Connexins and lens biology
- Cardiac Arrest and Resuscitation
- Cardiac Valve Diseases and Treatments
- Metabolism, Diabetes, and Cancer
- Cardiac Structural Anomalies and Repair
- Adipose Tissue and Metabolism
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Pancreatic function and diabetes
- Cardiac Imaging and Diagnostics
- Atrial Fibrillation Management and Outcomes
- Caveolin-1 and cellular processes
- Diabetes Treatment and Management
- Autophagy in Disease and Therapy
- Cardiovascular Disease and Adiposity
- Heart Failure Treatment and Management
- Fuel Cells and Related Materials
- Cardiac Fibrosis and Remodeling
- Nutrition and Health in Aging
- RNA Research and Splicing
- Hemoglobinopathies and Related Disorders
- Ion Transport and Channel Regulation
University of Pittsburgh
2019-2024
Case Western Reserve University
2009-2023
University School
2023
University of Pittsburgh Medical Center
2023
Louis Stokes Cleveland VA Medical Center
2023
Providence College
2014-2016
Rhode Island Hospital
2014-2015
Brown University
2013-2014
Lifespan
2013-2014
University of Illinois Chicago
2012-2014
Previously, we showed that a mouse model (ACE8/8) of cardiac renin-angiotensin system activation has high rate spontaneous ventricular tachycardia and sudden death secondary to reduction in connexin43 level. Angiotensin-II increases reactive oxygen species (ROS) production, ACE8/8 mice show increased ROS. We sought determine the source ROS whether played role arrhythmogenesis.Wild-type with without 2 weeks treatment L-NIO (NO synthase inhibitor), sepiapterin (precursor tetrahydrobiopterin),...
Background— Genome-wide association studies have revealed significant of caveolin-1 (Cav1) gene variants with increased risk cardiac arrhythmias. Nevertheless, the mechanism for this linkage is unclear. Methods and Results— Using adult Cav1 -/- mice, we a marked reduction in left ventricular conduction velocity absence myocardial Cav1, which accompanied inducibility Further demonstrated that loss leads to activation cSrc tyrosine kinase, resulting downregulation connexin 43 subsequent...
Traditional preclinical echocardiography (ECHO) modalities, including 1-dimensional motion-mode (M-Mode) and 2-dimensional long axis (2D-US), rely on geometric temporal assumptions about the heart for volumetric measurements. Surgical animal models, such as mouse coronary artery ligation (CAL) model of myocardial infarction, result in morphologic changes that do not fit these assumptions. New ECHO technology, 4-dimensional ultrasound (4D-US), improves traditional models. This paper aims to...
Cardiac arrest (CA) causes high mortality due to multi-system organ damage attributable ischemia-reperfusion injury. Recent work in our group found that among diabetic patients who experienced cardiac arrest, those taking metformin had less evidence of and renal after when compared not metformin. Based on these observations, we hypothesized metformin's protective effects the heart were mediated by AMPK signaling, signaling could be targeted as a therapeutic strategy following resuscitation...
Aim Mouse models of sudden cardiac arrest are limited by challenges with surgical technique and obtaining reliable venous access. To overcome this limitation, we sought to develop a simplified method in the mouse that uses ultrasound-guided injection potassium chloride directly into heart. Methods Potassium was delivered left ventricular cavity under ultrasound guidance intubated mice, resulting immediate asystole. Mice were resuscitated epinephrine manual chest compressions evaluated for...
Abstract Background Traditional preclinical echocardiography (ECHO) modalities, including 1-dimensional motion-mode (M-Mode) and 2-dimensional long axis (2D-US), rely on geometric temporal assumptions about the heart for volumetric measurements. Surgical animal models, such as mouse coronary artery ligation (CAL) model of myocardial infarction, result in morphologic changes that do not fit these assumptions. New ECHO technology, 4-dimensional ultrasound (4D-US), improves traditional models....
Abstract Background It is increasingly recognized that inflammatory changes play a significant role in myocardial injury following cardiac arrest. However, the pathophysiological mechanisms responsible for functional myocardium event remain incompletely understood. Here, we characterize transcriptomic and immunological mouse model of arrest to explore roles epinephrine ischemia/reperfusion on inflammation. Methods Results Male female mice (C57BL/6J) were divided into three groups: (1) Naïve...
Human heart failure has been associated with reduced cardiac Nav1.5 Na+ channel current and SCN5A mRNA abundance. We hypothesized that stability would contribute to the reduction of mRNA. Hu proteins are known The 3’-untranslated region (UTR) contains two sets putative protein binding site. Over-expression HuR HuB in cardiomyocytes derived from primary human fetal ventricle increased wild-type 46.3% (P=0.004) 60.7% (P=0.008), respectively. Knocking down or by siRNA decreased 27.5% (P=0.000)...
The loss of skeletal muscle, also known as sarcopenia, is an aging-associated muscle disorder that disproportionately present in heart failure (HF) patients. HF patients with sarcopenia have poor outcomes compared to the overall patient population. prevalence only expected grow global population ages, and novel treatment strategies are needed improve this cohort. Multiple mechanistic pathways emerged may explain increased population, a better understanding these lead development therapies...
Abstract Aim Mouse models of sudden cardiac arrest are limited by challenges with surgical technique and reliable venous access. To overcome this limitation, we sought to develop a simplified method in the mouse that uses ultrasound-guided injection potassium chloride directly into heart. Methods Potassium was delivered left ventricular cavity under ultrasound guidance intubated mice, resulting immediate asystole. Mice were resuscitated epinephrine manual chest compressions evaluated for...
Objectives: The aim of this study was to investigate the effect ischemia on cardiac Na+ channel (Nav1.5) and possible treatments in a mouse model myocardial infarction (MI). Methods: MI induced 12-week old C57BL/6 mice by coronary artery occlusion. Sham-operated were used as controls. Two weeks following surgery, either given mitochondria-targeted antioxidant, mitoTEMPO (0.7 mg/kg/day, intraperitoneally), or left untreated for two weeks. Cardiomyocytes isolated from scar border ventricular...
Introduction: Sudden cardiac arrest (SCA) affects over 600,000 Americans yearly with substantial mortality. After resuscitation, multiple system organ damage is common. Metformin has previously demonstrated ischemic protection in and renal tissues. We retrospectively evaluated kidney function a cohort of diabetic SCA patients. also developed mouse model that replicates human pathology pretreated metformin to evaluate the molecular changes driving these outcomes. Methods: performed...
Abstract Purpose Diastolic dysfunction is an increasingly common cardiac pathology linked to heart failure with preserved ejection fraction. Previous studies have implicated glucagon-like peptide 1 (GLP-1) receptor agonists as potential therapies for improving diastolic dysfunction. In this study, we investigate the physiologic and metabolic changes in a mouse model of angiotensin II (AngII) mediated without GLP-1 agonist liraglutide (Lira). Methods Mice were divided into sham, AngII, or...
Background: Cardiac arrest (CA) affects over 600,000 Americans every year and is associated with overwhelming mortality. After CA, myocardial stunning a common occurrence leading to reduced cardiac output, nearly 25% of CA die from cardiogenic shock. This injury driven by ischemia-reperfusion injury. Mitochondria make up 30% the heart volume are highly prone damage. damage may impair mitochondrial DNA (mtDNA), which necessary for maintaining function. Mitochondrial transcription factor A...
Introduction: Mitochondria participate in Ca2+ homeostasis and oscillations are thought to be involved arrhythmogenesis. Nevertheless, the role of mitochondria arrhythmogenesis is unclear. We have reported spontaneous induced arrhythmias a mouse model nonischemic cardiomyopathy, so we investigated mitochondrial handling this model. Methods: Nonischemic cardiomyopathy was C57BL/6 mice by 6 weeks hypertension evoked after unilateral nephrectomy, deoxycorticosterone acetate (DOCA) pellet...
Background: Activation of the cardiac renin-angiotensin system (RAS) is associated with increased risk ventricular arrhythmia and sudden death. Increased RAS activity leads to conduction block spontaneous arrhythmias as a result connexin 43 (Cx43) degradation mediated by activation redox-sensitive tyrosine kinase c-Src signaling. The molecular mechanism downstream signaling remains elusive. Results: Using transgenic mouse model cardiac-specific overexpression angiotensin converting enzyme...