Animal models are necessary to further understand the etiology andpathophysiology of PrUs, as well as to facilitate the development of newtherapeutic alternatives.
The majority of available models of experimentallyinduced PrUs has focused on examination of the role of ischemia alone, or thefocus was switched to ischemia reperfusion injury. The use of small animals,such as fuzzy rats and mice, allows researchers to overcome the impedimentspresented by large animals, which interfere with the ability to conductlarge-scale studies inexpensively.Ischemia reperfusion injury, defined as cellular injury resulting from thereperfusion of blood to previously ischemic tissue, has been recentlyconsidered as a significant factor in etiology of PrUs.
Tissues that aredeprived of their blood supply for a measurable period during the ischemicepisode reduce metabolism in the target tissue in an effort to preserve tissuefunction (18).When reperfusion occurs, free radicals are delivered in the previously ischemictissue, thus advancing the damage produced by hypoxia and ischemia.Research in experimentally induced PrUs has focused on determination of thedegree of external pressure that will consistently lead to tissue damage. Inanimal studies, soft tissues prone to PrUs are loaded with standardizedpressure or shear stresses, whereas the tissue breakdown is generally observedfrom histological examinations after predetermined periods of reperfusion.
Mostof studies revealed an inverse relationship between magnitude of external forceand duration of loading crucial to initiate tissue breakdown (19).Mechanical properties of muscle tissue exposed to prolonged and intensivepressure change in time. Such changes may affect the distribution of stressesin soft tissues under bony prominences and potentially expose additionaluninjured regions of muscle tissue to intensified stresses.
Using finiteelements model, Linder-Ganz (20)demonstrated that muscle stiffening, documented by the increased tangentelastic moduli of muscles, results in elevated tissue stresses that exacerbatethe potential for tissue necrosis.In the clinical sense, there were several etiological factors alreadyimplicated in the development of pressure sores (eg, debilitation, poornutrition), as well as other extrinsic factors (eg, localized moisture). Alsoin the 1990s, new laboratory techniques and precision instruments allowed forfurther refinement by permitting investigators to combine measurement tools andtechniques, including the measurement and real-time monitoring of externalpressures to the skin. These techniques were focused on histological andbiochemical changes of the epidermis and dermis while administering appliedexternal pressures.
Lindan (7)examine two main factor in applying focre by mechanichal device : magnitude andduration of the force. As a result of his research, standard indices wereacquired. Thus, future studies could compare and define the importantparameters in PrU research.
Lindan studied the blood vesselchanges of rabbit ears for ease ofdetection and comparison with the endothelial cells of human skin, ,he usedmechanichal device to deliver varying degrees of pressure. The primary concernfor PrU research appeared to be with blood vessels’ sensitivity to ischemia,endothelial changes, and thrombosis as relevant factors to the etiologies ofPrUs.In 1973, Dinsdale (21)use paraplegic and normal swin and utilized light and electron microscopy tocharacterize experimentally derived PrUs from biopsies of normal and paraplegicswine animal models. Paraplegic swine underwent pressure application in thetrochanteric region along with friction by electromechanical device that converted rotary to linear motion generatedfriction. And on some reiogn only pressure was applied. Dinsdale study showedthat there is no significance differencein blood perfusion between each sides.
Dinsdale’s electron microscopy results noted similarities in damage causedby (a) the exertion of pressure alone and (b) the action of both pressure andfriction. In Dinsdale’s swine model, PrUs resulted from 2 main factors: friction andischemic pressure, with friction as noncontributing to the ischemic mechanismentailed by the production of PrU. The study used light and electron microscopyto verify the sequence of what Dinsdale believed was the pathogenesis of a typicalPrU on a swine. Rudolph (22)focused on the wound healing sequence by studying wound contraction in swineand rat animal models. His study yielded 2 major conclusions. The first wasthat the force of wound contraction is partly attributed to contractile cellsknown as myofibroblasts, which are scattered throughout the entire contractingwound.
The second major finding consisted of similarities contrasting theresults of both pig and rat wounds. In both animal models, myofibroblasts wereseen within the first week and then eventually decreased as the wounds healed.Healing times were different for the 2 animals, those belonging to the pigsbeing substantially longer than those inflicted on the rats. Rudolph believedthe main factor for wound contraction in the pig and rat models consisted ofmyofibroblastic activity and the “pull theory” (excision of central granulationtissue leads to retraction of wound edges).Nola and Vistnes (31)studied the role of skeletal muscle in PrU development in the dorsal skinoverlying the greater trochanter on male rats. Two protocols were followed. Oneconsisted of pressure applied to skin in trochanteric area and muscle overlyingthe midshaft of the tibia. The other consisted of a group of rats undergoing aprocedure in which the gluteus maximus muscle flap was transposed to cover theirgreater trochanters on one side only.
No major blood and nerve supplies wereinjured. Three weeks later, the animals that had undergone this procedure weresubjected to pressure on both sides of their trochanteric regions, while theincidence of pressure lesions were recorded and compared. After sustaining100-mmHg pressures to unoperated trochanters of skin alone for the time framementioned above, there was epidermal breakdown, cellular infiltrate,thrombosis, and vacuolization of the muscle fibers. Furthermore, there wasnoticeable edema of the skin and muscle, a mild to moderate degree of increasedcellularity (due to inflammatory infiltrate), and muscle fiber necrosis.Results of the second protocol demonstrated that when pressure was exerted on theskin-only side, there was ulceration in all the animals. However, skinulceration occurred in 69% of the skin/muscle flap side, while muscle necrosisoccurred in 100% of this treatment side.In 1981, Daniel et al (23)utilized electromechanical pressure system device were pressure adjusted throughout eachexperiment. The pigs underwent applications of 30 to 1,000 mmHg of pressure ontheir trochanters for periods of 2 to 18 hours.
They were constantly monitoredwith carotid artery catheters, electrocardiograms, and rectal thermometers.Results of Daniel’s studies were very interesting because they included the4 layers of soft tissues believed to be most vulnerable to PrUs, all localizedin the greater trochanter areas,his study was first to showed that the pathologic changes is occurred initially in muscle and then progress to theskin with increasing pressure and duration. Therefore, muscle must be extremely sensitiveto ischemia. Also, because their findings indicated that soft tissue coulduphold large pressure loads for long durations without skin necrosis, there maybe contributory factors other than pressure and time resulting in thedamage-resistant soft tissues.
These factors may be scar replacement, whichoccurs during destruction of muscle and subcutaneous tissues with the repeatedpressure loads, or other secondary factors, such as infection and externalmoisture (23).Base on previouse study in 1988, Hagisawa and colleagues (24)searched for biochemical predictors of the muscle injury as a harbinger ofpressure-sore formations. The activities of serum creatine phosphokinase,inorganic phosphate, and lactate dehydroge-nase in the systemic blood of pigswere examined before, during, and after indentations were inflicted on theirthoracic paraspinal areas. Creatine phosphokinase is extremely sensitive tomuscle damage (25).Therefore, elevated creatine phosphokinase levels in serum samples obtainedafter 2 and 6 hours and 1 to 7 days in Hagisawa’s study demonstrated thatmuscle damage is indeed a result of pressure insult.