University Park, Pa. --- A Penn State bioengineer says his experiments with young and old rats show that the response of their blood vessels to compromised circulation is so different as to suggest that young and old human patients may need different treatment based on age
Dr. Norman R. Harris, assistant professor of bioengineering, says "Most
researchers currently use young, healthy rats for blood vessel research because
they are more readily available, cost less and have fewer health problems.
However, our experiments indicate a fundamental difference between the two age
groups."
Recent research has suggested that I/R-induced inflammation and swelling often
occur as the result of an accumulation of neutrophils, the most abundant white
blood cells, on the walls of the blood vessel.
The Penn State bioengineer has shown that in 2-month-old rats,
neutrophils do, in fact, accumulate and trigger the vessel leakage that leads to
inflammation and swelling, but in 2-year-old rats, no such accumulation occurs.
In his most recent experiments, Harris induced I/R in both young and old
rats and also administered a serum that prevented the accumulation of
neutrophils. In the young rats, the prevention of the accumulation also resulted
in the prevention of the leakage that leads to inflammation and swelling.
However, in the old rats, leakage still occurred after I/R, indicating that some
other cause, other than neutrophil accumulation, was responsible.
Harris says he is currently looking at an imbalance between oxidants and
anti-oxidants as a potential factor in the response in older rats. "With
increasing age, the level of protective anti-oxidants decline. It's possible
that the blood vessel still sustains an injury, even in the absence of an
accumulation of white cells, as the result of oxidative stress, " he notes.
In another recent experiment that highlights the difference between
young and old, Harris showed that higher levels of circulating cholesterol, more
prevalent in older individuals, disrupts the communication between the smallest
blood vessels in the microcirculation. Higher levels of circulating cholesterol
were induced in young rats by a short period of feeding; not long enough to
produce build up of plaques in the larger blood vessels. Preliminary results
suggest that the disruption in microcirculatory communication mimics that found
in older rats.
The Penn State researcher notes, "Even though further studies need to be
performed to more completely describe how responses to I/R injury are altered
with age, our studies suggest that the mechanisms may be sufficiently different
in young and old patients as to demand differential therapy of clinical I/R
based on age."
Harris recently reported his findings at the Summer Bioengineering
Conference in Big Sky, Montana, June 16-20, in a paper, "Role of Nitric Oxide in
Arteriovenular Control of Capillary Perfusion and Filtration." Earlier this
year, he made two presentations at the Experimental Biology Conference in
Washington, D. C. The presentations were: "Neutrophil Depletion Attenuates
Ischemia-Reperfusion-induced Increases in Protein Leakage in Young But Not Aged
Rats" and "Arteriovenular Pairing and Capillary Perfusion: Effect of
Hypercholesterolemia." He has also published his earlier results in a paper,
"Age-Dependent Responses of the Mesenteric Vasculature to Ischemia-Reperfusion"
in the American Journal of Physiology.
Harris's research has been supported, in part, by grants from the
National Heart, Lung and Blood Institute and the Biomedical Research Foundation
of Northwest Louisiana. He joined the Penn State faculty last year and was
previously a faculty member at Louisiana State University Medical Center where
he conducted some of these studies.