The animal and tissue procurement core is responsible for generating the canine model of cardiac dyssynchrony and/or tachypacing-induced dilated cardiomyopathy. Adult mongrel dogs weighing approximately 25 kg are employed in this study. Dyssynchrony is generated by radiofrequency ablation of the left bundle (or right bundle in a sub-set of studies). In addition, dyssynchrony can be induced by single-point pacing of the RV or LV free-wall - and this variant can also be utilized for some of the molecular/cellular analyses. Cardiac failure is induced by tachycardia pacing over a period of 3-6 weeks depending on the protocol. Cardiac resynchronization is achieved by converting 3-weeks of rapid atrial pacing in the setting of an established conduction delay - with 3-4 weeks of bi-ventricular pacing of left ventricular free wall and right ventricles. The primary aims of this Core are to 1) Perform the surgical and electrophysiologic procedures required to induce dyssynchrony with and without cardiac failure. Provide chronic instrumentation for mechanical and energetic analyses as required by the individual projects. 2) Maintain all chronic care of the animal, providing serial physiologic assessment as required, including coordinating echocardiographic analysis, intermittent pressure measurements, etc.. 3) Coordinate veterinary support on a per-need basis to assure optimal care and maintenance of the animals, catheters, repairing fractured or damaged pacing leads, etc.. 4) Perform terminal study - including rapid procurement of myocardial tissues used to wedge and cellular preparations, and rapid processing of frozen materials required for molecular and histochemistry analyses.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL077180-02
Application #
7118578
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2005-09-01
Budget End
2006-08-31
Support Year
2
Fiscal Year
2005
Total Cost
$209,092
Indirect Cost
Name
Johns Hopkins University
Department
Type
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Wang, Sheng-Bing; Venkatraman, Vidya; Crowgey, Erin L et al. (2018) Protein S-Nitrosylation Controls Glycogen Synthase Kinase 3? Function Independent of Its Phosphorylation State. Circ Res 122:1517-1531
Barth, Andreas S; Tomaselli, Gordon F (2016) Gene scanning and heart attack risk. Trends Cardiovasc Med 26:260-5
O'Rourke, Brian; Liu, Ting; Foster, D Brian (2016) Seeing the Forest for the Trees. Circ Res 119:1170-1172
Barth, Andreas S; Kumordzie, Ami; Tomaselli, Gordon F (2016) Orchestrated regulation of energy supply and energy expenditure: Transcriptional coexpression of metabolism, ion homeostasis, and sarcomeric genes in mammalian myocardium. Heart Rhythm 13:1131-1139
DeMazumder, Deeptankar; Kass, David A; O'Rourke, Brian et al. (2015) Cardiac resynchronization therapy restores sympathovagal balance in the failing heart by differential remodeling of cholinergic signaling. Circ Res 116:1691-9
Chung, Heaseung Sophia; Murray, Christopher I; Venkatraman, Vidya et al. (2015) Dual Labeling Biotin Switch Assay to Reduce Bias Derived From Different Cysteine Subpopulations: A Method to Maximize S-Nitrosylation Detection. Circ Res 117:846-57
Kirk, Jonathan A; Kass, David A (2015) Cellular and Molecular Aspects of Dyssynchrony and Resynchronization. Card Electrophysiol Clin 7:585-97
Kaushik, Gaurav; Spenlehauer, Alice; Sessions, Ayla O et al. (2015) Vinculin network-mediated cytoskeletal remodeling regulates contractile function in the aging heart. Sci Transl Med 7:292ra99
Kwon, Chulan; Tomaselli, Gordon F (2015) Coins of the realm in atrioventricular junction development. Circ Res 116:386-8
Tomaselli, Gordon F (2015) Introduction to a compendium on sudden cardiac death: epidemiology, mechanisms, and management. Circ Res 116:1883-6

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