Pathobiology of cardiac dyssynchrony &resynchronization

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Project Title: Pathobiology of cardiac dyssynchrony &resynchronization
Principal Investigators (PI): KASS DAVID ALAN
Project Number: 1P01HL077180-01
Organization: JOHNS HOPKINS UNIVERSITY
 
Project Description:
Cardiac intraventricular conduction delay results in mechanical dyssynchrony, dividing the heart into early and late contracting regions and worsening overall chamber function and mechanical efficiency. The clinical impact of this problem is large, affecting 15-30% of the millions of patients with dilated cardiomyopathy. Biventricular or left-ventricular stimulation can resynchronize the heart (cardiac resynchronization therapy, CRT), and this benefits cardiac function, clinical symptoms, and morbidity/mortality endpoints. However, many questions remain regarding optimal identification of responsive candidates and how to best implement and assess the therapy. There is virtually no existing data regarding basic molecular and cellular mechanisms by which dyssynchrony (and CRT) impact the failing or normal myocardium. Our Program Project aims to critically address this lack of knowledge. The proposed studies draw from our recent discoveries that marked molecular and electrophysiologic abnormalities are induced in the late-contracting lateral endocardium, and that mechanical/electrical dyssynchrony are far from synonymous. We developed a novel large animal model that combines cardiac failure with contractile dyssynchrony and can also examine either feature alone. The three projects in the Program are highly integrated making use of the common model and informing each other with respect to mechanisms and data interpretation. Project by Van Eyk focuses on molecular signaling affected by dyssynchrony and CRT, examining targeted pathways associated with hypertrophy/stress response, broader sub-proteomes, and gene-transcription using a custom-canine array. We also test the consequences of dyssynchrony on regional myocyte function. Project by Halperin focuses on electrophysiological abnormalities, utilizing optical mapping of myocardial wedge preparations to study transmural heterogeneity, and conducting electrophysiology and molecular analyses. Project by Tomaselli is performed at the chamber level and addresses central questions of CRT targeting, its implementation, and optimized dyssynchrony measurements. This Project utilizes our novel methods to combine 3-D magnetic resonance strain analysis with full chamber electrophysiology mapping. The Program will greatly expand our understanding of dyssynchrony and CRT providing important new and clinically relevant information. More broadly, this research should yield fundamental new insights into myocardial stress-signaling and heart failure pathophysiology.
 
Project Terms:
cardiovascular disorder therapy electronic pacemaker heart contraction heart electrical activity heart failure heart disorder heart conduction system pathologic process dogs
Project Title: Pathobiology of cardiac dyssynchrony &resynchronization
Principal Investigators (PI): KASS DAVID ALAN
Project Number: 1P01HL077180-01
Organization: JOHNS HOPKINS UNIVERSITY
 
Project Categories:
• Natural Sciences > Aging Diseases and Pathology, Experimental techniques > Cardiovascular and cerebrovascular diseases, in vitro methods > Heart failure, Proteomic analys > Immunoelectrophoresis
 
Other Information:
Fiscal Year: 2004
Project Start Date: 15 September 2004
Project End Date: 31 August 2009
Administering Institute Or Center: HL
 
Project Funding Information:
Total Funding: $2,261,167
Year Funding Organization Total Funding, $
2004 NATIONAL HEART, LUNG, AND BLOOD INSTITUTE $2,261,167
Project Title: Pathobiology of cardiac dyssynchrony &resynchronization
Principal Investigators (PI): KASS DAVID ALAN
Project Number: 1P01HL077180-01
Organization: JOHNS HOPKINS UNIVERSITY
 
Project_number Title Year FY Total Cost
1P01HL077180-01-9003 Core a--administrative core 2004 $98821
1P01HL077180-01-9002 Core--cell /molecular /microscopy 2004 $268687
1P01HL077180-01-9001 Core--animal core 2004 $203090
1P01HL077180-01-0003 Optimizing electromechanical resynchronization (crt) 2004 $312650
1P01HL077180-01-0002 Electrophysiology of cardiac dyssynchrony and crt 2004 $252084
1P01HL077180-01-0001 Molecular polarization in dyssynchronous hearts and crt 2004 $259296
Project Title: Pathobiology of cardiac dyssynchrony &resynchronization
Principal Investigators (PI): KASS DAVID ALAN
Project Number: 1P01HL077180-01
Organization: JOHNS HOPKINS UNIVERSITY
 
Project number Project title Organization FY Funding Organization FY Total Cost
5T32HL007227-29Pathophysiology of Myocardial DiseaseJOHNS HOPKINS UNIVERSITY2004NATIONAL HEART
$440,636
5R01HL047511-11Role of Stretch to Endothelial Pulse-Perfusion ResponseJOHNS HOPKINS UNIVERSITY2004NATIONAL HEART
$367,875
1P01HL077180-01-9003CORE A--ADMINISTRATIVE COREJOHNS HOPKINS UNIVERSITY2004NATIONAL HEART
$98,821
1P01HL077180-01-9001CORE--ANIMAL COREJOHNS HOPKINS UNIVERSITY2004NATIONAL HEART
$203,090
1P01HL077180-01Pathobiology of Cardiac Dyssynchrony &ResynchronizationJOHNS HOPKINS UNIVERSITY2004NATIONAL HEART
$2,261,167
5T32HL007227-28Pathophysiology of Myocardial DiseaseJOHNS HOPKINS UNIVERSITY2003NATIONAL HEART
$745,173
5R01HL047511-10Role of Stretch to Endothelial Pulse-Perfusion ResponseJOHNS HOPKINS UNIVERSITY2003NATIONAL HEART
$367,875
2T32HL007227-26Pathophysiology of Myocardial DiseaseJOHNS HOPKINS UNIVERSITY2001NATIONAL HEART
$658,948
5T32HL007227-27Pathophysiology of Myocardial DiseaseJOHNS HOPKINS UNIVERSITY2002NATIONAL HEART
$663,508
2R01HL047511-09Role of Stretch to Endothelial Pulse-Perfusion ResponseJOHNS HOPKINS UNIVERSITY2002NATIONAL HEART
$367,875
5P50HL052307-08-9002Core--animal model and cellJOHNS HOPKINS UNIVERSITY2002NATIONAL HEART
$209,733
3P50HL052307-08S1-9002Core--animal model and cellJOHNS HOPKINS UNIVERSITY2002NATIONAL HEART
$209,733
5P50HL052307-08-0007Mechanism of neurohumoral modulation of cardiac remodelingJOHNS HOPKINS UNIVERSITY2002NATIONAL HEART
$209,733
3P50HL052307-08S1-0007Mechanism of neurohumoral modulation of cardiac remodelingJOHNS HOPKINS UNIVERSITY2002NATIONAL HEART
$209,733
5P50HL052307-07-9002Core--animal model and cellJOHNS HOPKINS UNIVERSITY2001NATIONAL HEART
$209,733
5P50HL052307-07-0007Mechanism of neurohumoral modulation of cardiac remodelingJOHNS HOPKINS UNIVERSITY2001NATIONAL HEART
$209,733
5T32HL007227-25PATHOPHYSIOLOGY OF MYOCARDIAL DISEASEJOHNS HOPKINS UNIVERSITY2000NATIONAL HEART
$499,272
5R01HL047511-08PATHOPHYSIOLOGY OF VENTRICULAR-VASCULAR INTERACTIONJOHNS HOPKINS UNIVERSITY2000NATIONAL HEART
$297,855
2P50HL052307-06-9002Core--animal model and cellJOHNS HOPKINS UNIVERSITY2000NATIONAL HEART
$209,733
2P50HL052307-06-0007Mechanism of neurohumoral modulation of cardiac remodelingJOHNS HOPKINS UNIVERSITY2000NATIONAL HEART
$209,733
Project Title: Pathobiology of cardiac dyssynchrony &resynchronization
Principal Investigators (PI): KASS DAVID ALAN
Project Number: 1P01HL077180-01
Organization: JOHNS HOPKINS UNIVERSITY
 
Project number Project title Principal investigator
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Project Title: Pathobiology of cardiac dyssynchrony &resynchronization
Principal Investigators (PI): KASS DAVID ALAN
Project Number: 1P01HL077180-01
Organization: JOHNS HOPKINS UNIVERSITY
 
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