Collection of Heart Tissue Sample During Open Heart Surgery
Condition: Ischemia
MeSH terms: Ischemia
Study type: Observational

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.
    

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 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.
    

Keywords: Nitrite and Cytoprotection; Ischemic Preconditioning; Atrial Trabeculae Contractile Function; Ischemia