UpDate - Vol. 12, No. 4, Page 1
September 24, 1992
Research aims to reduce heart disease, infant death
Two Delaware researchers-with support from the American Heart
Association (AHA) of Delaware Inc.-are conducting research that may
lead to a better medical understanding of the Sudden Infant Death
Syndrome (SIDS) and to enhanced treatment of those at risk of heart
disease and stroke.
David Usher, associate professor of life and health sciences, and
Harold White, professor of chemistry and biochemistry, each have
received a $20,000 grant from the AHA for 1992-93.
Ushering in another risk factor
Usher's research is focused on lipoprotein (a), or Lp(a), a type
of cholesterol-carrying particle that interferes with the ability to
dissolve clots formed in damaged arteries as part of the body's repair
mechanisms.
According to Usher, cholesterol is a necessary element in the
diet, to form membranes as new cells develop, and for synthesizing
hormones such as adrenalin and sex hormones. However, when too much
cholesterol is present, it begins to build up, causing damage to blood
vessels.
Clots that are formed when blood vessels are damaged can be
dissolved by the blood protein, plasminogen. Lp(a), however, seems to
prevent plasimogen from dissolving clots, which accelerates the
blockage of arteries, causing cardiovascular disease. This process may
go on for years before problems emerge, Usher said.
Lp(a) was discovered 25 years ago, but only recently is it
thought to be linked to arteriosclerosis or clogging of arteries. In
previous research, Usher has developed a clinical test for Lp(a),
which is used in Europe and Japan, and is awaiting approval by the
Federal Drug Adminstration. Those who have a significant amount in
their bloodstreams have six-times the risk of heart attack, some
researchers believe. It is thought that the amount of Lp(a) in the
bloodstream is genetically controlled, Usher said
Lp(a) molecules vary in size in different individuals, with some
carrying heavy particles and some light. Oddly enough, it is persons
with the light particles that seem most at risk, while those with
heavy particles are less so, Usher said.
Usher's research examines these heavy and light Lp(a) molecules,
using enzymes that cut proteins to study their structure and to
determine differences in their structure and function and how their
size relates to the ability of the particles to bind to clots, leading
to blockage.
"Understanding Lp(a) in relation to heart disease and stroke may
lead to better treatments of those at risk," Usher said.
Usher also is a co-investigator in another AHA-funded project
with Michael Spear, a physician who heads neonatology at the Delaware
Medical Center.
Premature babies are fed fats intravaneously in order to survive.
Some infants form an abnormal type of lipoprotein and cannot seem to
remove these lipoproteins from their bodies.
By taking periodic blood samples and analyzing these samples over
a period of time, it is hoped to discover what changes are taking
place in the blood lipoproteins of these infants.
The white of the egg
White is conducting research on embryonic distress in chickens,
which may provide insights into human Sudden Infant Death Syndrome
(SIDS). "The heartbeat of a chick embryo is so difficult to detect
that a heart monitor that amplifies the sound a half million times
must be attached to the egg to record it," he said.
White studies fertilized eggs that lack riboflavin, or Vitamin
B2, because of a genetic defect in the research hens that lay them.
Without this essential vitamin, the chicken embryos die approximately
13 days after fertilization, instead of hatching in the usual 21 days.
For his research, it is important to monitor the embryos and to
study the onset and progress of heart dysfunction and determine
precisely the time of death. For this purpose, he uses a miniature
microphone (heart monitor), which feeds information into a computer.
White currently has one monitor, and the AHA grant will enable
him to design and build 16 monitors to study the hearts of several
embryos simultaneously. One of White's related research goals is to
further the development of such sophisticated heart monitors.
The computer analysis of an embryo heart resembles a miniature
EKG, showing a sharp dip when the heart ceases to function and the
embryo dies. By comparing these print-outs, White looks for consistent
signs of the onset of embryonic distress. He also compares these
riboflavin deficient eggs with viable eggs from the same flock that
have received ribloflavin injections
"The heart is a muscle," White said, "and it requires oxygen to
function. If there is no riboflavin, an inability to use oxygen occurs
and the heart stops.
While no SIDS deaths have been linked to riboflavin deficiency,
there are some metabolic similarities between the rapidly developing
chicken embryo and infants at the age when most SIDS deaths occur,
White said.
In a summary of his research, White wrote, "While we find our
specific scientific research on the biochemistry of riboflavin most
interesting, the greatest impact of this work may well be its
unforeseen influence on other research areas that could use a heart
monitor.
"Sydney Brenner once said, 'Progress in science depends on new
techniques, new discoveries and new ideas, probably in that order.'
Certainly we hope that the major effect of our work will be on the new
work that it makes possible in this and other laboratories," White
wrote.
-Sue Swyers Moncure