The Role of Nitrite in Preconditioning Mediated Tolerance to Ischemic Stress
Condition: Ischemic Stress; Transient Non-Lethal Ischemia
MeSH terms: Ischemia
Study type: Interventional
Phase: Phase 1

Summary: 
      Many studies have shown that if the human body is stressed by a lack of blood flow for a
      short period of time, the body develops defenses to make the body more resistant to a future
      stress from lack of blood flow. This natural defense system is called preconditioning.
      Finding medications that have a preconditioning effect to protect against damage from loss of
      blood flow would be of great help in the treatment of diseases such as heart attacks and
      stroke that occur because of blockages of blood flow.

      Predicting future heart attacks or strokes is very difficult and makes it difficult to study
      medications that could have a preconditioning effect. However, it has recently been
      recognized that we can mimic the preconditioning effect in the human arm, by blocking blood
      flow using a blood pressure cuff under pressure. Here, blowing up the cuff for 5 minutes and
      then letting the pressure out for 5 minutes and repeating this process twice more (a way to
      precondition the arm), has been shown to improve blood vessel function in response to a
      longer period of blood pressure cuff inflation (20 minutes).

      As nitrite, a naturally occurring blood substance, has biological effects suggesting that it
      may mimic preconditioning. The main objective of this study is to assess whether nitrite is
      equivalent to preconditioning in its capacity to protect the forearm blood flow in response
      to a 20 minute blockage of blood flow by blood pressure cuff inflation of the forearm.

      We hypothesize that in human subjects the ischemic preconditioning program works through
      activation of the pool of nitrite in the blood stream. Moreover, we propose that nitrite
      treatment will improve (1) blood vessel recovery (2) skeletal muscle blood flow and (3)
      skeletal muscle mitochondrial function and (4) reduce the activation of inflammation in
      response to the 20 minute stress of blood pressure cuff inflation.
    

Detailed description: 
      Many studies have shown that if the human body is stressed by a lack of blood flow for a
      short period of time, the body develops defenses to make the body more resistant to a future
      stress from lack of blood flow. This natural defense system is called preconditioning.
      Finding medications that have a preconditioning effect to protect against damage from loss of
      blood flow would be of great help in the treatment of diseases such as heart attacks and
      stroke that occur because of blockages of blood flow.

      Predicting future heart attacks or strokes is very difficult and makes it difficult to study
      medications that could have a preconditioning effect. However, it has recently been
      recognized that we can mimic the preconditioning effect in the human arm, by blocking blood
      flow using a blood pressure cuff under pressure. Here, blowing up the cuff for 5 minutes and
      then letting the pressure out for 5 minutes and repeating this process twice more (a way to
      precondition the arm), has been shown to improve blood vessel function in response to a
      longer period of blood pressure cuff inflation (20 minutes).

      As nitrite, a naturally occurring blood substance, has biological effects suggesting that it
      may mimic preconditioning. The main objective of this study is to assess whether nitrite is
      equivalent to preconditioning in its capacity to protect the forearm blood flow in response
      to a 20 minute blockage of blood flow by blood pressure cuff inflation of the forearm.

      We hypothesize that in human subjects the ischemic preconditioning program works through
      activation of the pool of nitrite in the blood stream. Moreover, we propose that nitrite
      treatment will improve (1) blood vessel recovery (2) skeletal muscle blood flow and (3)
      skeletal muscle mitochondrial function and (4) reduce the activation of inflammation in
      response to the 20 minute stress of blood pressure cuff inflation.
    

Intervention name(s): Sodium Nitrate; Acetylcholine
Intervention type(s): Drug; Drug
Intervention MeSH terms: Acetylcholine
Primary purpose: Treatment
Keywords: Ischemia Tolerance; Endothelial Function; Forearm Blood Flow; Muscle Recovery; Inflammation; Healthy Volunteer; HV