Alkaline phosphatase for the prevention of acute lung injury in a piglet model of deep hypothermic circulatory arrest

Doctor's Name: 
Jesse Davidson
University of Colorado Denver

Collaboratively awarded through the CHF and AHA Congenital Heart Defect Research Awards

(Total Grant Amount $149,998; CHF portion = $80,998.92)

Children with heart defects often require use of a heart-lung machine to provide blood to their body during heart surgery. In more complex surgeries, sometimes blood flow to the body must be stopped completely in order to perform key parts of the surgery (circulatory arrest). During these times, the lungs do not receive enough blood and may be injured. Doctors currently have no treatment for this injury. We are interested in a naturally occurring protein called alkaline phosphatase that may help protect the lungs. However, before we treat children with it, we want to learn more about how well it works and how safe it is. So we are planning to test it in animals that will be placed on the heart-lung machine and then have their blood flow stopped for a period of time. Our Theory: Giving alkaline phosphatase to piglets during the heart-lung machine and prior to stopping all blood flow will help protect the lungs from injury.

1) If we give medicine to stop alkaline phosphatase from working, do the piglets have more injury to their lungs, showing that their own alkaline phosphatase is important for their protection? 2) If we treat with extra alkaline phosphatase do the piglet have less injury to their lungs, showing that alkaline phosphatase might serve as a treatment to prevent lung injury in babies having heart surgery? 3) What dose of alkaline phosphatase is necessary to protect the lungs? 4) Does alkaline phosphatase work by increasing a molecule called adenosine?

We plan to use the results of this research to decide if it will be safe and helpful in future research studies to give alkaline phosphatase as a medicine to prevent lung injury in children having open heart surgery to repair heart defects. Preventing lung injury would help children heal their lungs faster, get off the mechanical ventilator sooner, and get out of the hospital faster. It might also help their hearts function better, providing more oxygen for the heart muscle and making it easier for the heart to pump blood through the lungs.

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