Division of Thoracic & Cardiovascular Surgery

NIH R01 Grant Awarded to PI Sufan Chien, M.D. and his Team." More info...

In Focus: Tissue Ischemia and Energy Metabolism Sufan Chien, MD Professor Division of Thoracic & Cardiovascular Surgery

A Novel Way to Deliver ATP to Normal and Ischemic Cells
Tissue ischemia due to reduced blood flow or disturbed oxygen supply is a universal event in various forms of trauma and diseases. The cessation of blood flow not only halts the influx of oxygen and nutrients, but also stops the carrying away of toxic wastes. While many of these changes are poorly understood, several important inter-related events are involved, including:

		The decline of high-energy phosphates
		Accumulation of metabolic intermediates
		Cell swelling
		Intracellular acidosis
		Accumulation of oxygen free radicals
		Structural changes.

Damage Control
Among these changes, depletion of high-energy phosphates is the fundamental cause of ischemic tissue damage. Direct infusion of high-energy phosphates such as adenosine triphosphate (ATP) would be a simple solution to block this effect, and administration of ATP has been reported to improve tissue protection during ischemia in many models and species, including heart, kidney, liver, and various forms of shock.

Restoring Energy
Molecules like ATP normally cannot pass the cell membrane in quantities large enough to satisfy tissue metabolic requirements. Further, the half-life of free ATP in the blood is less than 40 seconds -- limiting its efficacy as a bioenergetic substrate. For this reason, ATP therapy has yet to translate into a clinically useful technique.

We have developed a new ATP-encapsulation technique to deliver high-energy phosphate directly into the cytosol of normal or ischemic cells. It will substantially enhance our understanding of ischemia and tissue protection, and provide a totally new therapeutic approach to various clinical ischemic conditions, such as shock, stroke, heart attack, coronary artery disease, spinal cord injury, cardiopulmonary bypass surgery, organ transplantation, severe trauma, and whole-body poisoning.

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