Animal models are necessary to further understand the etiology and
pathophysiology of PrUs, as well as to facilitate the development of new
therapeutic alternatives. The majority of available models of experimentally
induced PrUs has focused on examination of the role of ischemia alone, or the
focus was switched to ischemia reperfusion injury. The use of small animals,
such as fuzzy rats and mice, allows researchers to overcome the impediments
presented by large animals, which interfere with the ability to conduct
large-scale studies inexpensively.
Ischemia reperfusion injury, defined as cellular injury resulting from the
reperfusion of blood to previously ischemic tissue, has been recently
considered as a significant factor in etiology of PrUs. Tissues that are
deprived of their blood supply for a measurable period during the ischemic
episode reduce metabolism in the target tissue in an effort to preserve tissue
When reperfusion occurs, free radicals are delivered in the previously ischemic
tissue, thus advancing the damage produced by hypoxia and ischemia.
Research in experimentally induced PrUs has focused on determination of the
degree of external pressure that will consistently lead to tissue damage. In
animal studies, soft tissues prone to PrUs are loaded with standardized
pressure or shear stresses, whereas the tissue breakdown is generally observed
from histological examinations after predetermined periods of reperfusion. Most
of studies revealed an inverse relationship between magnitude of external force
and duration of loading crucial to initiate tissue breakdown (19).
Mechanical properties of muscle tissue exposed to prolonged and intensive
pressure change in time. Such changes may affect the distribution of stresses
in soft tissues under bony prominences and potentially expose additional
uninjured regions of muscle tissue to intensified stresses. Using finite
elements model, Linder-Ganz (20)
demonstrated that muscle stiffening, documented by the increased tangent
elastic moduli of muscles, results in elevated tissue stresses that exacerbate
the potential for tissue necrosis.
In the clinical sense, there were several etiological factors already
implicated in the development of pressure sores (eg, debilitation, poor
nutrition), as well as other extrinsic factors (eg, localized moisture). Also
in the 1990s, new laboratory techniques and precision instruments allowed for
further refinement by permitting investigators to combine measurement tools and
techniques, including the measurement and real-time monitoring of external
pressures to the skin. These techniques were focused on histological and
biochemical changes of the epidermis and dermis while administering applied
examine two main factor in applying focre by mechanichal device : magnitude and
duration of the force. As a result of his research, standard indices were
acquired. Thus, future studies could compare and define the important
parameters in PrU research.
Lindan studied the blood vessel
changes of rabbit ears for ease of
detection and comparison with the endothelial cells of human skin, ,he used
mechanichal device to deliver varying degrees of pressure. The primary concern
for PrU research appeared to be with blood vessels’ sensitivity to ischemia,
endothelial changes, and thrombosis as relevant factors to the etiologies of
In 1973, Dinsdale (21)
use paraplegic and normal swin and utilized light and electron microscopy to
characterize experimentally derived PrUs from biopsies of normal and paraplegic
swine animal models. Paraplegic swine underwent pressure application in the
trochanteric region along with friction
by electromechanical device that converted rotary to linear motion generated
friction. And on some reiogn only pressure was applied. Dinsdale study showed
that there is no significance difference
in blood perfusion between each sides.
Dinsdale’s electron microscopy results noted similarities in damage caused
by (a) the exertion of pressure alone and (b) the action of both pressure and
In Dinsdale’s swine model, PrUs resulted from 2 main factors: friction and
ischemic pressure, with friction as noncontributing to the ischemic mechanism
entailed by the production of PrU. The study used light and electron microscopy
to verify the sequence of what Dinsdale believed was the pathogenesis of a typical
PrU on a swine.
focused on the wound healing sequence by studying wound contraction in swine
and rat animal models. His study yielded 2 major conclusions. The first was
that the force of wound contraction is partly attributed to contractile cells
known as myofibroblasts, which are scattered throughout the entire contracting
wound. The second major finding consisted of similarities contrasting the
results of both pig and rat wounds. In both animal models, myofibroblasts were
seen within the first week and then eventually decreased as the wounds healed.
Healing times were different for the 2 animals, those belonging to the pigs
being substantially longer than those inflicted on the rats. Rudolph believed
the main factor for wound contraction in the pig and rat models consisted of
myofibroblastic activity and the “pull theory” (excision of central granulation
tissue leads to retraction of wound edges).
Nola and Vistnes (31)
studied the role of skeletal muscle in PrU development in the dorsal skin
overlying the greater trochanter on male rats. Two protocols were followed. One
consisted of pressure applied to skin in trochanteric area and muscle overlying
the midshaft of the tibia. The other consisted of a group of rats undergoing a
procedure in which the gluteus maximus muscle flap was transposed to cover their
greater trochanters on one side only. No major blood and nerve supplies were
injured. Three weeks later, the animals that had undergone this procedure were
subjected to pressure on both sides of their trochanteric regions, while the
incidence of pressure lesions were recorded and compared. After sustaining
100-mmHg pressures to unoperated trochanters of skin alone for the time frame
mentioned above, there was epidermal breakdown, cellular infiltrate,
thrombosis, and vacuolization of the muscle fibers. Furthermore, there was
noticeable edema of the skin and muscle, a mild to moderate degree of increased
cellularity (due to inflammatory infiltrate), and muscle fiber necrosis.
Results of the second protocol demonstrated that when pressure was exerted on the
skin-only side, there was ulceration in all the animals. However, skin
ulceration occurred in 69% of the skin/muscle flap side, while muscle necrosis
occurred in 100% of this treatment side.
In 1981, Daniel et al (23)
utilized electromechanical pressure system device were pressure adjusted throughout each
experiment. The pigs underwent applications of 30 to 1,000 mmHg of pressure on
their trochanters for periods of 2 to 18 hours. They were constantly monitored
with carotid artery catheters, electrocardiograms, and rectal thermometers.
Results of Daniel’s studies were very interesting because they included the
4 layers of soft tissues believed to be most vulnerable to PrUs, all localized
in the greater trochanter areas,his study was first to showed that the pathologic changes is occurred initially in muscle and then progress to the
skin with increasing pressure and duration.
Therefore, muscle must be extremely sensitive
to ischemia. Also, because their findings indicated that soft tissue could
uphold large pressure loads for long durations without skin necrosis, there may
be contributory factors other than pressure and time resulting in the
damage-resistant soft tissues. These factors may be scar replacement, which
occurs during destruction of muscle and subcutaneous tissues with the repeated
pressure loads, or other secondary factors, such as infection and external
Base on previouse study in 1988, Hagisawa and colleagues (24)
searched for biochemical predictors of the muscle injury as a harbinger of
pressure-sore formations. The activities of serum creatine phosphokinase,
inorganic phosphate, and lactate dehydroge-nase in the systemic blood of pigs
were examined before, during, and after indentations were inflicted on their
thoracic paraspinal areas. Creatine phosphokinase is extremely sensitive to
muscle damage (25).
Therefore, elevated creatine phosphokinase levels in serum samples obtained
after 2 and 6 hours and 1 to 7 days in Hagisawa’s study demonstrated that
muscle damage is indeed a result of pressure insult.