Medicine and Health Sciences Commons^™

Effect Of Flecainide And Ibutilide Alone And In Combination To Terminate And Prevent Recurrence Of Atrial Fibrillation, Alexander Burashnikov, José M. Di Diego, Bence Patocskai, Debra S. Echt, Luiz Belardinelli, Charles Antzelevitch

Division of Cardiology Faculty Papers

BACKGROUND: There is a need for improved approaches to rhythm control therapy of atrial fibrillation (AF).

METHODS: The effectiveness of flecainide (1.5 µmol/L) and ibutilide (20 nmol/L), alone and in combination, to cardiovert and prevent AF recurrence was studied in canine-isolated coronary-perfused right atrioventricular preparations. We also examined the safety of the combination of flecainide (1.5 µmol/L) and ibutilide (50 nmol/L) using canine left ventricular wedge preparations.

RESULTS: Sustained AF (>1 hour) was inducible in 100%, 60%, 20%, and 0% of atria in the presence of acetylcholine alone, acetylcholine+ibutilide, acetylcholine+flecainide, and acetylcholine+ibutilide+flecainide, respectively. When used alone, flecainide and ibutilide …

Mechanisms Underlying The Antiarrhythmic Effect Of Arumenamide-787 In Experimental Models Of The J Wave Syndromes And Hypothermia, José M. Di Diego, Hector Barajas-Martinez, Robert Cox, Victoria M Robinson, Joseph Jung, Mohamed Fouda, Mena Abdelsayed, Peter C Ruben, Charles Antzelevitch

Department of Medicine Faculty Papers

BACKGROUND: Brugada (BrS) and early repolarization syndromes (ERS), the so-called J wave syndromes (JWS), are associated with life-threatening ventricular arrhythmias. Pharmacologic approaches to therapy are currently limited. In this study, we examine the effects of ARumenamide-787 (AR-787) to suppress the electrocardiographic and arrhythmic manifestations of JWS and hypothermia.

METHODS: We studied the effects of AR-787 on INa and IKr in HEK-293 cells stably expressing the α- and β1-subunits of the cardiac (NaV1.5) sodium channel and hERG channel, respectively. In addition, we studied its effect on Ito, INa and ICa in dissociated canine ventricular myocytes along with action potentials and ECG …

Effect Of Calcium Chloride And Isoflurane On Force Frequency Relationship In Canines, Harrison Patrizio, Lawrence Mulligan

Rowan-Virtua Research Day

Proper calcium cycling is critical for a optimally functioning heart.

Improper calcium cycling in humans can contribute to heart failure.

Human calcium cycling is difficult to study due to the risks of damaging the patient’s cardiac tissue.

Risk of further damaging cardiac tissue is substantially increased in a heart failure patient.

Past studies focus on studying the effects of changing calcium cycling in lab rats.

Current research shows limited alternative methods in studying relationships between calcium cycling and FFR in larger mammals.

This project analyzes data to determine the response of the canine force frequency relationship to calcium chloride and …

Early Gadolinium Enhancement For Area At Risk Determination: A Preclinical Validation Study, Sophia Hammer-Hansen, Steve W. Leung, Li-Yueh Hsu, Joel R. Wilson, Joni Taylor, Anders M. Greve, Jens Jakob Thune, Lars Køber, Peter Kellman, Andrew E. Arai

Internal Medicine Faculty Publications

Objectives—The aim of this study was to determine if early gadolinium enhancement (EGE) by cardiovascular magnetic resonance (CMR) imaging in a canine model of reperfused myocardial infarction depicts the area at risk (AAR) as determined by microsphere blood flow analysis.

Background—It remains controversial whether only the irreversibly injured myocardium enhances when performing CMR imaging in the setting of acute myocardial infarction. Recently, EGE has been proposed as a measure of the AAR in acute myocardial infarction as it correlates well with T2-weighted imaging of the AAR, but still requires pathological validation.

Methods—Eleven dogs underwent 2 hours of …

Mast Cell Stabilization Decreases Cardiomyocyte And Lv Function In Dogs With Isolated Mitral Regurgitation., Betty Pat, Cheryl Killingsworth, Yuanwen Chen, James D Gladden, Greg Walcott, Pamela C Powell, Thomas Denney, Himanshu Gupta, Ravi Desai, Michael Tillson, A Ray Dillon, Louis J Dell'italia

Ravi V Desai MD

BACKGROUND: Mast cells are increased in isolated mitral regurgitation (MR) in the dog and may mediate extracellular matrix loss and left ventricular (LV) dilatation. We tested the hypothesis that mast cell stabilization would attenuate LV remodeling and improve function in the MR dog.

METHODS AND RESULTS: MR was induced in adult dogs randomized to no treatment (MR, n = 5) or to the mast cell stabilizer, ketotifen (MR + MCS, n = 4) for 4 months. LV hemodynamics were obtained at baseline and after 4 months of MR and magnetic resonance imaging (MRI) was performed at sacrifice. MRI-derived, serial, short-axis …

Chymase Inhibition Prevents Fibronectin And Myofibrillar Loss And Improves Cardiomyocyte Function And Lv Torsion Angle In Dogs With Isolated Mitral Regurgitation., Betty Pat, Yuanwen Chen, Cheryl Killingsworth, James D Gladden, Ke Shi, Junying Zheng, Pamela C Powell, Greg Walcott, Mustafa I Ahmed, Himanshu Gupta, Ravi Desai, Chih-Chang Wei, Naoki Hase, Tsunefumi Kobayashi, Abdelkarim Sabri, Henk Granzier, Thomas Denney, Michael Tillson, A Ray Dillon, Ahsan Husain, Louis J Dell'italia

Ravi V Desai MD

BACKGROUND: The left ventricular (LV) dilatation of isolated mitral regurgitation (MR) is associated with an increase in chymase and a decrease in interstitial collagen and extracellular matrix. In addition to profibrotic effects, chymase has significant antifibrotic actions because it activates matrix metalloproteinases and kallikrein and degrades fibronectin. Thus, we hypothesize that chymase inhibitor (CI) will attenuate extracellular matrix loss and LV remodeling in MR.

METHODS AND RESULTS: We studied dogs with 4 months of untreated MR (MR; n=9) or MR treated with CI (MR+CI; n=8). Cine MRI demonstrated a >40% increase in LV end-diastolic volume in both groups, consistent with …

Heterogeneity Of Left Ventricular Signal Characteristics In Response To Acute Vagal Stimulation During Ventricular Fibrillation In Dogs, Alireza Nazeri, Macarthur A Elayda, Lubomir Dragnev, Christopher M Frank, Jihong Qu, Valtino X Afonso, Abdi Rasekh, Mohammad Saeed, Jie Cheng, Mossaab Shuraih, Ali Massumi, Mehdi Razavi

The Texas Heart Institute Journal

Studies have shown that long-term vagal stimulation is protective against ventricular fibrillation; however, the effects of acute vagal stimulation during ventricular fibrillation in the normal heart have not been investigated. We examined the effects of acute vagal stimulation on ventricular fibrillation in a canine model. In 4 dogs, we induced 30-second periods of ventricular fibrillation by means of intraventricular pacing. During 2 of the 4 periods of fibrillation that we analyzed, vagal stimulation was delivered through electrodes in the caudal ends of the vagus nerves. Noncontact unipolar electrograms were recorded from 3 ventricular regions: the basal septum, apical septum, and …