Ignite Creation Date:
2024-05-05 @ 5:16 PM
Last Modification Date:
2024-10-26 @ 9:30 AM
Study NCT ID:
NCT00423553
Status:
COMPLETED
Last Update Posted:
2017-07-02
First Post:
2007-01-17
Brief Title:
Collection of Heart Tissue Sample During Open Heart Surgery
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Modifying Tolerance to Ischemic Injury in Human Atrial Tissue
Status:
COMPLETED
Status Verified Date:
2007-12-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will collect heart tissue that is routinely removed and discarded during open-heart surgery The Cardiology Branch of the NHLBI is conducting a variety of laboratory experiments that require a sample of heart tissue A segment of tissue is routinely cut out of the right atrial appendage of the heart during open-heart surgery to allow the heart-lung bypass machine to be attached to the heart for protection during surgery This small tissue sample is not re-attached after the bypass machine is removed but usually destroyed as medical waste
People between 18 and 80 years of age who are scheduled to undergo coronary artery bypass surgery or aortic valve replacement surgery may be eligible for this study
Participants donate the right atrial appendage of the heart which would normally be destroyed after their open-heart surgery The tissue will be used by NHLBI investigators in studies directed at learning how to make the heart less sensitive to damage from a heart attack The samples may be used for example to evaluate the effectiveness of known therapies refine treatment approaches identify potential new therapies or explore opportunities for disease prevention
People between 18 and 80 years of age who are scheduled to undergo coronary artery bypass surgery or aortic valve replacement surgery may be eligible for this study
Participants donate the right atrial appendage of the heart which would normally be destroyed after their open-heart surgery The tissue will be used by NHLBI investigators in studies directed at learning how to make the heart less sensitive to damage from a heart attack The samples may be used for example to evaluate the effectiveness of known therapies refine treatment approaches identify potential new therapies or explore opportunities for disease prevention
Detailed Description:
Transient non-lethal ischemia followed by reperfusion activates a cell survival program resulting in increased tolerance to subsequent ischemic injury This biological phenomenon is termed ischemic preconditioning and is a powerful cell survival program that is operational in the human heart This program is triggered by signaling intermediates activated in response to the transient ischemiahypoxia and reperfusion of preconditioning Characterization of these signaling intermediates should enable us to identify therapeutic agents to augment tissue tolerance to ischemia
Interestingly nitrite which is an endogenous reservoir for nitric oxide NO undergoes bioconversion to NO via hypoxia-dependent signaling Whether nitrite accumulation and bioconversion are components of the ischemic preconditioning program is unknown Recently Dr Gladwin and colleagues in the Vascular Medicine Branch unequivocally demonstrated that exogenous nitrite administration is cytoprotective against ischemia-reperfusion injury in murine liver and heart and in the canine heart Establishing a mechanistic link between the ischemic preconditioning program and nitrite biology would promote nitrite as an attractive compound for future therapeutic interventions To evaluate this link we propose to use cardiac right atrial appendage tissue that is routinely excised to facilitate right atrial cannulation for heart-lung bypass This excised tissue is then usually discarded as medical waste
We hypothesize that nitrite administration to atrial tissue in an ex-vivo study will demonstrate increased tolerance to ischemic stress compared to atrial tissue not exposed to nitrite Furthermore we propose that this cytoprotective effect of nitrite administration will demonstrate equivalency to cytoprotection in response to ischemic preconditioning Finally we would employ this tissue to identify nitrite mediated genomic proteomic and metabolomic modifications in human myocardium thereby identifying the biological programs orchestrating the cytoprotective properties of nitrite in the human heart
Interestingly nitrite which is an endogenous reservoir for nitric oxide NO undergoes bioconversion to NO via hypoxia-dependent signaling Whether nitrite accumulation and bioconversion are components of the ischemic preconditioning program is unknown Recently Dr Gladwin and colleagues in the Vascular Medicine Branch unequivocally demonstrated that exogenous nitrite administration is cytoprotective against ischemia-reperfusion injury in murine liver and heart and in the canine heart Establishing a mechanistic link between the ischemic preconditioning program and nitrite biology would promote nitrite as an attractive compound for future therapeutic interventions To evaluate this link we propose to use cardiac right atrial appendage tissue that is routinely excised to facilitate right atrial cannulation for heart-lung bypass This excised tissue is then usually discarded as medical waste
We hypothesize that nitrite administration to atrial tissue in an ex-vivo study will demonstrate increased tolerance to ischemic stress compared to atrial tissue not exposed to nitrite Furthermore we propose that this cytoprotective effect of nitrite administration will demonstrate equivalency to cytoprotection in response to ischemic preconditioning Finally we would employ this tissue to identify nitrite mediated genomic proteomic and metabolomic modifications in human myocardium thereby identifying the biological programs orchestrating the cytoprotective properties of nitrite in the human heart
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 07-H-0057 | None | None | None |