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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.
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 ischemia/hypoxia 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.
National Institutes of Health Clinical Center (CC)
Published on BioPortfolio: 2014-08-26T22:40:39-0400
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A disorder characterized by a reduction of oxygen in the blood combined with reduced blood flow (ISCHEMIA) to the brain from a localized obstruction of a cerebral artery or from systemic hypoperfusion. Prolonged hypoxia-ischemia is associated with ISCHEMIC ATTACK, TRANSIENT; BRAIN INFARCTION; BRAIN EDEMA; COMA; and other conditions.
The chilling of a tissue or organ during decreased BLOOD perfusion or in the absence of blood supply. Cold ischemia time during ORGAN TRANSPLANTATION begins when the organ is cooled with a cold perfusion solution after ORGAN PROCUREMENT surgery, and ends after the tissue reaches physiological temperature during implantation procedures. WARM ISCHEMIA TIME starts then and ends with completion of SURGICAL ANASTOMOSIS.
Localized reduction of blood flow to brain tissue due to arterial obstruction or systemic hypoperfusion. This frequently occurs in conjunction with brain hypoxia (HYPOXIA, BRAIN). Prolonged ischemia is associated with BRAIN INFARCTION.
Reduced blood flow to the spinal cord which is supplied by the anterior spinal artery and the paired posterior spinal arteries. This condition may be associated with ARTERIOSCLEROSIS, trauma, emboli, diseases of the aorta, and other disorders. Prolonged ischemia may lead to INFARCTION of spinal cord tissue.
Exposure of myocardial tissue to brief, repeated periods of vascular occlusion in order to render the myocardium resistant to the deleterious effects of ISCHEMIA or REPERFUSION. The period of pre-exposure and the number of times the tissue is exposed to ischemia and reperfusion vary, the average being 3 to 5 minutes.
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