Fluids flushed with promise.

Fluid flushed with promise

People who have offered to donate their body parts upon death can bring life to those in desperate need of a kidney, liver or other organ. But if the organs harvested from a cadaver cannot be preserved long enough or well enough to be successfully transported and transplanted to a recipient, all will be for naught.

Now it appears that such stories may have happier endings, because physiological chemist James F. Southard and his colleagues at the University of Wisconsin in Madison are making significant headway in improving organ preservation. Last week in Edmonton, Alberta, at the 24th annual meeting of the Society for Cryobiology, Southard reported that in dog studies, his group has extended the preservation times for a number of organs by using a preserving solution originally developed by Southard's co-worker Folkert O. Belzer.

Researchers have shown that, unlike most conventional preserving fluids, an improved version of Belzer's solution can be used in more than one kind of organ and in more than one preserving process. If the roup is as successful in human studies, Belzer's solution may well replace the exiting fluids and make the preservation and distribution of dono organs much simpler and more efficient.

Scientists and surgeons have generally taken two routes in organ preservatio: continuous hypothermic perfusion and simple cold storage. With continuous hypothermic perfusion, organs are kept at 5[deg.] to 10[deg.]C and are pumped with a cold preserving fluid that supplies nutrients and oxygen, removes waste products and keeps cells and membranes intact. With conventional perfusing fluids, says Southard, kidneys can be kept alive for three days. Now, using Belzer's solution, the Wisconsin researchers have extended that time to five days. All five of the dogs receiving the preserved kidneys have survived.

Belzer's solution was originally developed for continuous hypothermic perfusion, but Southard's group is the first to demonstrate that their perfusion fluid works as well in simplecold storage. In this method, organs are kept at 0[deg.] to 4[deg.]C after being flushed with certain fluids. With Belzer's solution -- a fluid far more complex than those traditionally used -- the researchers successflly preserved dog pancreases for 72 hours (clinically they are now preserved for only six to 10 hours). In addition, they showed that kidneys can be cold-stored for three days, more than 12 hours longer than current cold storage of human kidneys.

Perhaps most significantly, the group has succeeded in preserving dog livers for 24 to 36 hours. "Currently the liver is [cold] stored for about six to 10 hours in clinics," says Southard. "This makes the whole procesure extremely difficult ... [often requiring the use of Lear jets to pick up organs].... What you really need is about 30 hours of preservation." This would minimize the number of operations performed under emergency settings and increase the number of livers available to the people who need transplants, he says.

The researchers believe their solution works better than other fluids for a number of reasons. For one, it contains hydroxyethyl starch, which acts as a colloid in th blood vessels of organs. During perfusion, water may be pumped into cells; the purpose of a colloid is to draw the water out, so tha the cells don't swell and burst. Other perfusing fluids have used albumin as a vascular colloid, but Southard says albumin can damage and leak out of the vessels. He suspects that, in cold storage, the starch also helps to flush out the organ better by keeping the vascular areas dilated.

Another improvement, according to Southard, is the use of anions with large molecular weight as a replacement for the chloride anions used in other fluids. Anions, or negatively charged ions, are usually added to make fluids neutral. The problem with chloride anions, says Southard, is that they are small enough to get inside the cells, and this can draw water into the cells. The anions in Belzer's solution are too large to permeate the cell membrane.

Southard's group plans to try Belzer's solution on other organs, including the heart lung and small bowel. As for the kidneys, he says the researchers have applied to the Food and Drug Administratin to use their starch-based fluid in human trials. If they can show that it works well in many organ types being either perfused or cold-stored, then they may have solved a problem plaguing the donor-organ network.

When the organs of a body are to be preserved, says Outhard, the whole body ends up being flushed with preservation fluids. The problem is that a conventional fluid that preserves the liver, for example, may damage other organs such as the kidneys. Moreover, the preservation method and hence type of fluid used by different centers varies; small centers rarely have the resources to maintain a perfusion machine, and large centers sometimes hae too many transplants to erform in too short a time to rely on the shorter-lasting cold-storage approach.

"One way to resolve this is to use one fluid [that works for both storage methods], letting surgeons decide what method they want," says Southard. "And we think [Belzer's] solution is close to a universal preservation fluid for all solid organs."