ANAHEIM — Rabbit hearts lose two protective enzymes when deprived of oxygen, a finding that could lead to new drugs to preserve donated human hearts and prevent cardiac damage during surgery, a researcher has found.
"The objective of our work is to identify drugs that will improve the preservation of the heart," said University of Michigan pharmacologist Marshal Shlafer.
"In order to do that, we're looking at some of the major biochemical changes in the heart after it has been deprived of (blood and oxygen) flow" during surgery or after it is removed from a donor, he added. "The bottom line is that if we are going to administer drugs to protect the heart, we need to have drugs that will restore a (protective) process that is known to have been damaged."
During open-heart operations, surgeons halt the oxygen-rich blood flow to the heart. The heart is cooled and its beating stopped to prevent the oxygen deprivation from causing injury. Yet when blood and oxygen flow is restored after surgery, toxic chemicals can be created that damage the heart.
The possibility of such injury also means a heart removed from a donor can be preserved only a few hours before it must be implanted in a transplant recipient, Shlafer said at the annual meeting of the Federation of American Societies for Experimental Biology.
Shlafer and other Michigan researchers created such damage in rabbit hearts to study its biochemical causes. They removed hearts from rabbits and used pumps to keep them beating. They then cooled the hearts and deprived them of oxygen for two hours before restoring blood and oxygen flow.
They found the activity of two enzymes was significantly reduced in specific parts of heart muscle cells. The enzymes normally protect the heart by converting the toxic chemicals to water, Shlafer said. Enzymes are proteins which promote chemical changes in cells.
Determining Which Parts
Shlafer said his study pinpointed for the first time exactly what parts of heart cells were robbed of the protective enzymes. That told them where at least part of the process of heart damage occurs--knowledge necessary for targeting drugs to prevent such injury.
"If the findings in this study apply to the human situation, we may be able to develop new drug therapies to protect the heart during open-heart surgery" by providing a protective effect similar to that normally afforded by the enzymes, Shlafer said.
"We feel the same biochemical changes and drug treatments that relate to the preservation of the heart in the operating room can be applied to prolonging the viability of a (donated) heart for many hours so it could be transported across the country," he added.
Oxygen deprivation of the heart caused by clogged or blocked arteries can cause heart attacks. But Shlafer said he hasn't seen oxygen deprivation under those circumstances, so he can't say whether drugs aimed at protecting donated hearts or open-heart surgery patients also might help prevent heart attacks.