Cynthia Carnes, PharmD, PhD

Professor

Pharmaceutics and Pharmacology

Research Areas: Cardiovascular Disorders, The Division of Pharmaceutics & Pharmacology

217A Parks Hall

Professional Interests

My research is focused on cardiac arrhythmias (abnormal heart rhythms), particularly in heart failure. We use an integrated approach from proteins to cells to tissues to the intact organism to study the causes, and potential treatments of cardiac arrhythmias. My clinical practice is at the Ambulatory Care Center at the Ross Heart Hospital, where I provide patient care in antiarrhythmic medication monitoring.

Education

1996, PhD, The Ohio State University, Pharmacy and Veterinary Clinical Sciences
1988, PharmD, University of Utah, Pharmacy
1983, BS, University of Texas, Pharmacy

Publications

MATE1 Deficiency Exacerbates Dofetilide-Induced Proarrhythmia., International journal of molecular sciences. 2022 Aug | journal-article. doi: 10.3390/ijms23158607.
Ero1α-Dependent ERp44 Dissociation From RyR2 Contributes to Cardiac Arrhythmia., Circulation research. 2022 Jan | journal-article. doi: 10.1161/circresaha.121.320531.
Pyridostigmine improves cardiac function and rhythmicity through RyR2 stabilization and inhibition of STIM1‐mediated calcium entry in heart failure, Journal of Cellular and Molecular Medicine. 2021 May | journal-article. doi: 10.1111/jcmm.16356.
Targeting OCT3 attenuates doxorubicin-induced cardiac injury., Proceedings of the National Academy of Sciences of the United States of America. 2021 Feb | journal-article. doi: 10.1073/pnas.2020168118.
Muscarinic-dependent phosphorylation of the cardiac ryanodine receptor by protein kinase G is mediated by PI3K–AKT–nNOS signaling, Journal of Biological Chemistry. 2020 Aug | journal-article. doi: 10.1074/jbc.RA120.014054.
Tetrodotoxin-Sensitive Neuronal-Type Na⁺ Channels: A Novel and Druggable Target for Prevention of Atrial Fibrillation., Journal of the American Heart Association. 2020 May | journal-article. doi: 10.1161/jaha.119.015119.
Chronic heart failure increases negative chronotropic effects of adenosine in canine sinoatrial cells via A1R stimulation and GIRK-mediated I_Kado., Life sciences. 2019 Nov | journal-article. doi: 10.1016/j.lfs.2019.117068.
Exercise does not ameliorate cardiac dysfunction in obese mice exposed to fine particulate matter., Life sciences. 2019 Oct | journal-article. doi: 10.1016/j.lfs.2019.116885.
Enhancement of Cardiac Store Operated Calcium Entry (SOCE) within Novel Intercalated Disk Microdomains in Arrhythmic Disease., Scientific reports. 2019 Jul | journal-article. doi: 10.1038/s41598-019-46427-x.
Development and validation of a UPLC-MS/MS analytical method for dofetilide in mouse plasma and urine, and its application to pharmacokinetic study., Journal of pharmaceutical and biomedical analysis. 2019 Apr | journal-article. doi: 10.1016/j.jpba.2019.04.041.
The role of luminal Ca regulation in Ca signaling refractoriness and cardiac arrhythmogenesis., The Journal of general physiology. 2017 Aug | journal-article. doi: 10.1085/jgp.201711808.
The role of spatial organization of Ca²⁺ release sites in the generation of arrhythmogenic diastolic Ca²⁺ release in myocytes from failing hearts., Basic research in cardiology. 2017 Jun | journal-article. doi: 10.1007/s00395-017-0633-2.
Evaluation of a pharmacist-managed electrolyte protocol in outpatients on antiarrhythmic medications., Journal of the American Pharmacists Association : JAPhA. 2017 Jun | journal-article. doi: 10.1016/j.japh.2017.05.001.
In Utero Particulate Matter Exposure Produces Heart Failure, Electrical Remodeling, and Epigenetic Changes at Adulthood., Journal of the American Heart Association. 2017 Apr | journal-article. doi: 10.1161/jaha.117.005796.
Muscarinic Stimulation Facilitates Sarcoplasmic Reticulum Ca Release by Modulating Ryanodine Receptor 2 Phosphorylation Through Protein Kinase G and Ca/Calmodulin-Dependent Protein Kinase II., Hypertension (Dallas, Tex. : 1979). 2016 Sep | journal-article. doi: 10.1161/hypertensionaha.116.07666.
Chronic Omega-3 Polyunsaturated Fatty Acid Treatment Variably Affects Cellular Repolarization in a Healed Post-MI Arrhythmia Model., Frontiers in physiology. 2016 Jun | journal-article. doi: 10.3389/fphys.2016.00225.
Dysfunction of the β2-spectrin-based pathway in human heart failure., American journal of physiology. Heart and circulatory physiology. 2016 Apr | journal-article. doi: 10.1152/ajpheart.00875.2015.
Protein phosphatase 2A regulatory subunit B56α limits phosphatase activity in the heart., Science signaling. 2015 Jul | journal-article. doi: 10.1126/scisignal.aaa5876.
Use of whole exome sequencing for the identification of Ito-based arrhythmia mechanism and therapy., Journal of the American Heart Association. 2015 May | journal-article. doi: 10.1161/jaha.114.001762.
Dysfunction in the βII spectrin-dependent cytoskeleton underlies human arrhythmia., Circulation. 2015 Jan | journal-article. doi: 10.1161/circulationaha.114.013708.
Heart failure duration progressively modulates the arrhythmia substrate through structural and electrical remodeling., Life sciences. 2015 Jan | journal-article. doi: 10.1016/j.lfs.2014.12.024.
Treating cocaine cardiotoxicity: Does receptor subtype matter?, Trends in cardiovascular medicine. 2015 Jan | journal-article. doi: 10.1016/j.tcm.2015.01.001.
What is the role of pharmacogenetics in optimization of warfarin dosing?, Trends in cardiovascular medicine. 2014 Oct | journal-article. doi: 10.1016/j.tcm.2014.10.003.
Calcium-activated potassium current modulates ventricular repolarization in chronic heart failure., PloS one. 2014 Oct | journal-article. doi: 10.1371/journal.pone.0108824.
Upregulation of adenosine A1 receptors facilitates sinoatrial node dysfunction in chronic canine heart failure by exacerbating nodal conduction abnormalities revealed by novel dual-sided intramural optical mapping., Circulation. 2014 May | journal-article. doi: 10.1161/circulationaha.113.007086.
Ibandronate and ventricular arrhythmia risk., Journal of cardiovascular electrophysiology. 2013 Dec | journal-article. doi: 10.1111/jce.12327.
Shortened Ca2+ Signaling Refractoriness Underlies Cellular Arrhythmogenesis in a Postinfarction Model of Sudden Cardiac Death, Circulation Research. 2012 Jan | journal-article. doi: 10.1161/CIRCRESAHA.111.260455.
Arrhythmogenic adverse effects of cardiac glycosides are mediated by redox modification of ryanodine receptors, Journal of Physiology-London. 2011 Jan | journal-article. doi: 10.1113/jphysiol.2011.210005.
Chronic heart failure selectively induces regional heterogeneity of insulin-responsive glucose transporters, American Journal of Physiology-Regulatory Integrative and Comparative Physiology. 2011 Jan | journal-article. doi: 10.1152/ajpregu.00822.2010.
Is NOS uncoupling the missing link between atrial fibrillation and chronic non-ischaemic cardiomyopathy? Reply, Cardiovascular Research. 2011 Jan | journal-article. doi: 10.1093/cvr/cvr178.
MicroRNA-1 and-133 Increase Arrhythmogenesis in Heart Failure by Dissociating Phosphatase Activity from RyR2 Complex, Plos One. 2011 Jan | journal-article. doi: 10.1371/journal.pone.0028324.
Pharmacokinetics of oral ivabradine in healthy cats, Journal of Veterinary Pharmacology and Therapeutics. 2011 Jan | journal-article. doi: 10.1111/j.1365-2885.2010.01253.x.
Tetrahydrobiopterin depletion and NOS2 uncoupling contribute to heart failure-induced alterations in atrial electrophysiology, Cardiovascular Research. 2011 Jan | journal-article. doi: 10.1093/cvr/cvr087.
The relationship between arrhythmogenesis and impaired contractility in heart failure: role of altered ryanodine receptor function, Cardiovascular Research. 2011 Jan | journal-article. doi: 10.1093/cvr/cvr025.
Effects of dietary omega-3 fatty acids on ventricular function in dogs with healed myocardial infarctions: in vivo and in vitro studies, American Journal of Physiology-Heart and Circulatory Physiology. 2010 Jan | journal-article. doi: 10.1152/ajpheart.01065.2009.
Renewing Vision and Strategic Priorities for an Academic Unit, American Journal of Pharmaceutical Education. 2010 Jan | journal-article. .
Uni- or hi-ventricular hypertrophy and susceptibility to drug-induced torsades de pointes, Journal of Pharmacological and Toxicological Methods. 2010 Jan | journal-article. doi: 10.1016/j.vascn.2010.04.007.
Cardioprotection by HO-4038, a novel verapamil derivative, targeted against ischemia and reperfusion-mediated acute myocardial infarction, American Journal of Physiology-Heart and Circulatory Physiology. 2009 Jan | journal-article. doi: 10.1152/ajpheart.00687.2008.
Chronic heart failure and the substrate for atrial fibrillation, Cardiovascular Research. 2009 Jan | journal-article. doi: 10.1093/cvr/cvp216.
Redox modification of ryanodine receptors underlies calcium alternans in a canine model of sudden cardiac death, Cardiovascular Research. 2009 Jan | journal-article. doi: 10.1093/cvr/cvp246.
Dysregulated sarcoplasmic reticulum calcium release: Potential pharmacological target in cardiac disease, Pharmacology & Therapeutics. 2008 Jan | journal-article. doi: 10.1016/j.pharmthera.2008.06.002.
Redox Modification of Ryanodine Receptors Contributes to Sarcoplasmic Reticulum Ca2+ Leak in Chronic Heart Failure, Circulation Research. 2008 Jan | journal-article. doi: 10.1161/CIRCRESAHA.108.184457.
Repolarization abnormalities and afterdepolarizations in a canine model of sudden cardiac death, American Journal of Physiology-Regulatory Integrative and Comparative Physiology. 2008 Jan | journal-article. doi: 10.1152/ajpregu.90583.2008.
Atrial glutathione content, calcium current, and contractility, Journal of Biological Chemistry. 2007 Jan | journal-article. doi: 10.1074/jbc.M704893200.
Chronic cardiac resynchronization therapy and reverse ventricular remodeling in a model of nonischemic cardiomyopathy, Life Sciences. 2007 Jan | journal-article. doi: 10.1016/j.1fs.2007.08.022.
Differential expression of sarcolipin protein during muscle development and cardiac pathophysiology, Journal of Molecular and Cellular Cardiology. 2007 Jan | journal-article. doi: 10.1016/j.yjmcc.2007.05.009.
Enhanced ryanodine receptor-mediated calcium leak determines reduced sarcoplasmic reticulum calcium content in chronic canine heart failure, Biophysical Journal. 2007 Jan | journal-article. doi: 10.1529/biophysj.107.114546.
Exercise training normalizes beta-adrenoceptor expression in dogs susceptible to ventricular fibrillation, American Journal of Physiology-Heart and Circulatory Physiology. 2007 Jan | journal-article. doi: 10.1152/ajpheart.00763.2007.
Mechanisms of impaired calcium handling underlying subclinical diastolic dysfunction in diabetes, American Journal of Physiology-Regulatory Integrative and Comparative Physiology. 2007 Jan | journal-article. doi: 10.1152/ajpregu.00059.2007.
N-hydroxy-pyrroline modification of verapamil exhibits antioxidant protection of the heart against ischemia/reperfusion-induced cardiac dysfunction without compromising its calcium antagonistic activity, Journal of Pharmacology and Experimental Therapeutics. 2007 Jan | journal-article. doi: 10.1124/jpet.107.127167.
The plateau outward current in canine ventricle, sensitive to 4-aminopyridine, is a constitutive contributor to ventricular repolarization, British Journal of Pharmacology. 2007 Jan | journal-article. doi: 10.1038/sj.bjp.0707403.
n-3 (omega-3) polyunsaturated fatty acids prevent acute atrial electrophysiological remodeling, British Journal of Pharmacology. 2007 Jan | journal-article. doi: 10.1038/sj.njp.0706977.
Abnormal diastolic currents in ventricular myocytes from spontaneous hypertensive heart failure rats, American Journal of Physiology-Heart and Circulatory Physiology. 2006 Jan | journal-article. doi: 10.1152/ajpheart.01146.2005.
Atrial, SA nodal, and AV nodal electrophysiology in standing horses: Normal findings and electrophysiologic effects of quinidine and diltiazem, . 2006 Jan | conference-paper. .
Chronic cardiac resynchronization reverses abnormal calcium handling in failing ventricular myocytes, . 2006 Jan | other. .
Potassium current abnormalities in a canine model of post-infarction ventricular fibrillation, . 2006 Jan | other. .
Reduced rapid delayed rectifier (I-xr) and inward rectifier current (I-x1) contribute action potential prolongation and diastolic depolarization in a chronic canine heart failure model, . 2006 Jan | other. .
Abnormal intrastore calcium signaling in chronic heart failure, Proceedings of the National Academy of Sciences of the United States of America. 2005 Jan | journal-article. doi: 10.1073/pnas.0504298102.
Canine nonischemic left ventricular dysfunction: A model of chronic human cardiomyopathy, Journal of Cardiac Failure. 2005 Jan | journal-article. doi: 10.1016/j.cardfail.2005.05.006.
Mechanisms of Disease: beta-adrenergic receptors - alterations in signal transduction and pharmacogenomics in heart failure, Nature Clinical Practice Cardiovascular Medicine. 2005 Jan | journal-article. doi: 10.1038/ncpcardio0309.
Age-dependent changes in contraction and regional myocardial myosin heavy chain isoform expression in rats, Journal of Applied Physiology. 2004 Jan | journal-article. doi: 10.1152/japplphysiol.00439.2003.
Elevated defibrillation threshold with venlafaxine therapy, Pharmacotherapy. 2004 Jan | journal-article. .
Lack of efficacy of N-acetylcysteine in attenuating contrast induced nephropathy in patients with severe systolic heart failure, . 2004 Jan | other. .
Left ventricular dysfunction and impaired exercise tolerance in a chronic canine model, . 2004 Jan | other. .
Age and anesthetic effects on murine electrocardiography, Life Sciences. 2003 Jan | journal-article. doi: 10.1016/S0024-3205(03)00137-1.
Chronic mitral regurgitation modulates atrial K+ currents, . 2003 Jan | other. .
Effects of changing heart rate on electrophysiological and hemodynamic function in the dog, Life Sciences. 2003 Jan | journal-article. doi: 10.1016/S0024-3205(03)00015-8.
Effects of dihydrotestosterone on cardiac inward rectifier K+ current, International Journal of Andrology. 2002 Jan | journal-article. .
Systemic inflammation, atrial fibrillation, and cancer - Response, Circulation. 2002 Jan | journal-article. .
Ascorbate attenuates atrial pacing-induced peroxynitrite formation and electrical remodeling and decreases the incidence of postoperative atrial fibrillation, Circulation Research. 2001 Jan | journal-article. .
C-reactive protein elevation in patients with atrial arrhythmias - Inflammatory mechanisms and persistence of atrial fibrillation, Circulation. 2001 Jan | journal-article. .
Electrophysiologic and hemodynamic effects of apomorphine in dogs, Toxicology and Applied Pharmacology. 2001 Jan | journal-article. doi: 10.1006/taap.2001.9297.
Impaired myofibrillar energetics and oxidative injury during human atrial fibrillation, Circulation. 2001 Jan | journal-article. .
Transgenic mice with cardiac-specific expression of activating transcription factor 3, a stress-inducible gene, have conduction abnormalities and contractile dysfunction, American Journal of Pathology. 2001 Jan | journal-article. .
Atrial, SA nodal, and AV nodal electrophysiology in standing horses: Reference values and electrophysiologic effects of quinidine and diltiazem., . 1 Jan | other. .
ELECTROPHYSIOLOGIC INTERACTIONS OF PROCAINAMIDE AND N-ACETYLPROCAINAMIDE - EFFECTS ON DEPOLARIZATION, . 1 Jan | other. .
Electromechanical restitution in thapsigargin-treated rat ventricular cardiomyocytes, . 1 Jan | other. .
Impact of hydrogen peroxide on human and canine atrial calcium current and action potentials: Implications for postoperative atrial fibrillation, . 1 Jan | other. .
Impaired myofibrillar energetics and oxidative injury during human atrial fibrillation, . 1 Jan | other. .
Myosin isoform expression in rat myocardium: Conductile and contractile regional differences., . 1 Jan | other. .
Oxidative pathways in chronic human atrial fibrillation: Xanthine oxidase induction and peroxynitrite formation, . 1 Jan | other. .
Pacemaker current in the ventricle of spontaneous hypertensive heart failure rats, . 1 Jan | other. .
Redox changes may underlie the earliest electrical remodelling in human atrial fibrillation, . 1 Jan | other. .