An Analysis of the Acceleration of Wound Healing in Diabetics using NMES
Using NEUROMUSCULAR ELECTRONIC STIMULATION for ALTERING ABNORMAL HEMORHEOLOGICAL CONDITIONS:
ITS POSSIBLE EFFECT UPON DIABETIC MICROANGIOPATHY AND NEUROPATHY
James B. Bingham
co-author & advisor
Thomas G. Oliver, Sr.
Although it has long been recognized that physical exercise is good for some diabetics, it has not been known what physiological changes take place in the diabetic which promote improved health. After many months of research review by the writers, it is now believed that observed enhancements in wound healing can be explained by the effect of increased flow rates of blood upon blood rheology, and specifically, the platelet aggregation enhancing factor and intermittent capillary inversion phenomenon. Another possible explanation for the observed enhancement of wound healing in diabetics is through increasing the rate of flow of lymphatic fluids. The contracting muscle enables the lymphatic system to more speedily remove bacteria from the tissue due to this increase in flow. Until now other neuromuscular stimulators have not been effective for its clinical application due to two primary reasons. First, the degree of muscle contraction was not adequate to significantly increase flow rates of blood. Secondly, due to discomfort, the tolerance level of the great majority of these devices was low and could not be used for long enough periods of time by the patient to cause an observable change in the patient’s status.
The Neurocare 2000™, does achieve a high level of muscle recruitment by contracting those deep-layered muscles in the peroneal and tibial areas – the flexor digitorum longus, the flexor hallicus longus, the peroneus longus, and the tiila posterior. These deep muscle contractions cause greatly increased flow rates (both lymphatic fluids and blood) in the tibioperoneal trunk, the peroneal artery, the posterior tibial artery resulting in dramatic increases in flow to the smaller subdivisions of the vascular tree – the arterioles, and the venules. Likewise, the small muscles of the foot, which are deeply sheathed by synovial tendons, contract strongly, forcing blood into the arteries and into the microcirculation of the feet. Despite rapidly advancing research, prevention of peripheral vascular disease and peripheral neuropathy have not been accomplished. It is the assertion of these writers that a protocol using the Neurocare 2000™ on a daily basis achieving sufficient intensity of muscle contraction and for adequate time periods, will retard the deterioration of the microvascular system.
It is also the assertion of these writers that such a treatment protocol will have a similar effect on retardation of diabetic neuropathy. Because the diabetic foot frequently has loss of sensation, it is a vulnerable foot and is especially prone to vascular disease and neuropathy. What may seem to be trivial trauma can very quickly lead to ulceration, infection, gangrene, and the ultimate event amputation. Utilization of NeuroMuscular Electronic Stimulation (NMES) for the enhancement of wound healing in diabetics by altering abnormal blood flow properties. Although it has long been recognized that physical exercise is good for some diabetics, it has not been known what physiological changes take place in the diabetic which promote improved health. After many months of research review by the writers, it is now believed that observed enhancements in wound healing can be explained by the effect of increased flow rates of blood upon blood rheology, and specifically, the platelet aggregation enhancing factor and intermittent capillary inversion phenomenon. Another possible explanation for the observed enhancement of wound healing in diabetics is through increasing the rate of flow of lymphatic fluids. The contracting muscle enables the lymphatic system to more speedily remove bacteria from the tissue due to this increase in flow. Until now other neuromuscular stimulators have not been effective for its clinical application due to two primary reasons. First, the degree of muscle contraction was not adequate to significantly increase flow rates of blood. Secondly, due to discomfort, the tolerance level of the great majority of these devices was low and could not be used for long enough periods of time by the patient to cause an observable change in the patient’s status. The Neurocare 2000™, does achieve a high level of muscle recruitment by contracting those deep-layered muscles in the peroneal and tibial areas – the flexor digitorum longus, the flexor hallicus longus, the peroneus longus, and the tiila posterior. These deep muscle contractions cause greatly increased flow rates (both lymphatic fluids and blood) in the tibioperoneal trunk, the peroneal artery, the posterior tibial artery resulting in dramatic increases in flow to the smaller subdivisions of the vascular tree – the arterioles, and the venules. Likewise, the small muscles of the foot, which are deeply sheathed by synovial tendons, contract strongly, forcing blood into the arteries and into the microcirculation of the feet. Despite rapidly advancing research, prevention of peripheral vascular disease and peripheral neuropathy have not been accomplished. It is the assertion of these writers that a protocol using the Neurocare 2000™ on a daily basis achieving sufficient intensity of muscle contraction and for adequate time periods, will retard the deterioration of the microvascular system. It is also the assertion of these writers that such a treatment protocol will have a similar effect on retardation of diabetic neuropathy. Because the diabetic foot frequently has loss of sensation, it is a vulnerable foot and is especially prone to vascular disease and neuropathy. What may seem to be trivial trauma can very quickly lead to ulceration, infection, gangrene, and the ultimate event amputation.
The interaction of these complications can produce a wide range of clinical findings, including nail disorders, callous formation, skin lesions, and diabetic foot ulcers. Changes in muscles and bones lead to foot deformities. The artherosclerotic process, which is more common in the diabetic than non-diabetic, appears at a younger age, advances more rapidly, and is almost as common in women as in men. The vessels most commonly involved in the diabetic are those below the knee – the tibial and peroneal arteries occurred 53 times more frequently in diabetic men and 71 times more frequently in diabetic women when compared with non-diabetic men and women. Bell also found gangrene to be 156 times more common in the diabetic than in the non-diabetic in the fifth decade, 85 times more common in the sixth decade, and 53 times more common in the seventh decade. Fifteen percent of all diabetics develop foot ulcers, primarily because of trauma and repetitive stress to insensitive feet. Twenty percent of those diabetics entering the hospital are admitted for foot problems, and 30% have peripheral vascular disease. Six of every thousand diabetics undergo amputation and, in fact, 50% of all non-traumatic amputations occur in diabetics. In the United States alone, over 40,000 diabetic amputations take place each year. Rosenquist studied the prevalence of diabetic foot problems in an urbanized area of Stockholm County, Sweden. The study showed that in a randomized sample of 742 diabetics, only one third were free of diabetic foot symptoms. Furthermore, many patients with severe foot difficulties were living alone and were not seeking professional help for their diabetes care. Today the total cost for diabetic care in this country exceeds $14 billion, not including the expenses of welfare payments, prostheses, rehabilitation, lost income, and frequently lost jobs. Loss of family income as a result of death adds to these expenses. A single example is a patient who had stepped on a nail. The foot became infected, there was a prolonged hospitalization for treatment of the infection, and ultimately three toes were amputated resulting in a total cost of $50,000.
The signs and symptoms of vascular insufficiency are as follows:
- Intermittent claudication
- Cold feet
- Nocturnal pain
- Rest pain
- Nocturnal and rest pain relieved with dependency
- Absent pulses
- Blanching on elevation
- Delayed venous filling after elevation
- Dependent rubor
- Atrophy of subcutaneous fatty tissues
- Shiny appearance of skin
- Loss of hair on foot and toes
- Thickened nails, often with fungal infection
- Misc. (a) Bluetoe syndrome, and (b) acute vascular occlusion.
According to the book, The Diabetic Foot, strategies for saving the diabetic foot are as follows:
- Correcting vascular risk factors
- Improve the circulation
- Regular foot inspections
- Treatment of foot ulcers
- Prescribing special shoes
- Teamwork among medical disciplines
- Patient education
It has been known for many years that peripheral vascular insufficiency is one of the major factors contributing to the increased incidence of infection of the lower extremity with treatment of the infection being difficult because of poor blood supply. These ulcerations heal very slowly and frequently become infected. Despite the dramatic events associated with angiopathy, it is the development of neuropathy that cause most diabetic foot problems and hospitalizations. Approximately three times as many patients are admitted for foot problems due to painless trauma as are admitted for ischemic pain. The most important neuropathic factor is the loss of pain and temperature sensation. The patient having such impairment develops the insensitive foot and endures painless trauma that may be mechanical, chemical or thermal, until ulceration occurs. Infection of these ulcers, if not controlled, can destroy tissue and lead to microthrombi, thus further compromise the vascular system, which results in gangrene and amputation. Despite much research and numerous publications, the precise etiology of diabetic neuropathy remains a mystery. Diabetic neuropathy in the lower extremity is frequently bilateral and tends to be symmetrical. The sensory involvement is characterized by two major system complexes. The first consists of pain and paresthesias and the second, paradoxically, consists of a decreased or absent sensation of pain and temperature. The paresthesias may be manifested as tingling or burning. The pain may be severe and knife-like or shooting with the patient not being able to stand even the slightest touch, such as bed sheets or pajamas. This pain may require the use of narcotics for relief. The pain of vascular insufficiency is made worse by walking; the pain of diabetic neuropathy actually may be relieved by walking. One of the most frustrating aspects of painful neuropathy is its resistance to therapy.
In 1892 Starling wrote, “The capillaries may be retarded as the chief part of the circulation since the sole object of the varied arrangements of the heart and arterioles is to secure an adequate flow of blood through these smaller vessels – that is a sup ply of blood adequate to meet the needs of the tissues in which the capillaries are imbedded.” When a muscle contracts, there is a dramatic and sudden increase in the rate of flow of blood anywhere from 15 to 30 times the normal 5 ml/sec. per 100 grams of muscle tissue. In the contraction using Neurocare 2000™, the milking action of the rhythmic ally contracting muscles causes the venous blood to be forcibly and speedily removed from the muscle. Thus the capillary blood pressure is kept low so that the arterial blood in arterioles finds very little resistance to its entrance into the capillaries, and the venous blood is sent rapidly to the heart to be returned to the lungs for oxygenation. During muscle contraction, the arterioles to the active muscles dilate, thereby ensuring a good supply of blood to the capillaries. A major source of increased blood flow results from the opening up of previously dormant capillaries. The enormous increase in the available capillary beds serves to furnish the larger amount of nutrients and oxygen demanded by the active muscle. As the muscle contraction continues, vasodilator substances are secreted which cause increase perfusion. The pathogenesis of peripheral ischemia is associated with narrowing of the arterial lumens. Some factors which contribute to this process include endothelial cell damage, platelet adhesions, migration of atypical cell types to the site of the injury, and accumulation of cholesterol and fats. The decrease in vessel lumen results in decreased blood flow and eventual tissue hypoxia. Recently other factors, particularly increased blood viscosity, have been found to contribute to reduction of blood flow.
The study of viscosity and flow properties of blood is called hemorheology. Microvessel hemorheology involves red and white blood cell deformability. In order for red blood cells, which are approximately 7.5 microns in diameter, to enter the capillary lumen, which is about 5 microns, the cell must deform in shape as normal erythrocytes do. Diabetes is a state of hyper coagulation with red blood cells, white cells, and platelets having very high rates of aggregation and adhesion. Rouleaux formations are developed from red blood cell aggregation and high platelet aggregation causes the formation of white thrombi.
Factors contributing to hyper viscosity of blood in diabetics are as follows:
- Hematocrit values
- Red cell rigidity
- Red blood cell deformability
- Whole blood viscosity
- Plasma viscosity
- Platelet aggregation
- Tendency to the formation of thrombi or emboli
Factors which contribute to red blood cell rigidity are: oxygen pressure, crenation, Ph level, abnormalities of the cell membrane, or the presence of parasites within the cell membrane. Of these various factors involving hyperviscosity and cell rigidity, increased vascular activity through muscle stimulation would have the following effects: (1) Tissue oxygen pressure would be raised due to the oxygen loading of red blood cells, and (2) Because of effective oxygenation, hypoxic reduction in red blood cells would not occur.
In diabetics, clotting factors, as mentioned previously, are greatly increased with platelets having an increased tendency toward adherence and aggregation which, some researchers say, may contribute to the incidence of arteriosclerosis. Information suggests that abnormal platelet adhesiveness and aggregation may be critical factors in the genesis of vascular lesions and microthrombi. This tendency toward increased platelet aggregation may be critical factors in the genesis of vascular lesions and microthrombi. This tendency toward increased platelet aggregation in the diabetic has been attributed to the presence of a plasma factor that potentates ADP-induced platelet aggregation. This factor has been termed PLATELET AGGREGATION ENHANCING FACTOR and has been demonstrated by Kwaan et al, in approximately 50% of the diabetic patients tested. The presence of abnormal levels of platelet aggregates can cause intermittent inversion phenomenon in capillaries and small veins. In this inversion of the Fahreaus-Lindquest phenomenon, there is a sudden and dramatic increase in the resistance to flow and an increase in the viscosity of blood which is caused by the effect platelet aggregates have on the critical radius of capillaries. Even small changes in the rigidity of red blood cells would be greatly magnified by the amplification mechanism of the inversion phenomenon is small vessels which lead to increased resistance to flow and apparent vasoconstriction. Aggregation of red cells might also have a role to play in the inversion phenomenon, especially if compact and sludge-like aggregates of the type observed in cancer or infarction are present.
Jonason et al. Demonstrated the beneficial effects of a supervised training and exercise program in patients with intermittent claudication. Some of this improvement may be attributed to the effect of exercise on platelets. Peterson demonstrated that the percentage of platelet adhesiveness in diabetic subjects fell from 74% before exercise to 53% after exercise. In this study of diabetic patients, the decreased platelet adhesion was maintained at nine hours after exercise in one subject and at 24 hours after exercise in another.
ALTERATION OF ABNORMAL HEMORHEOLOGICAL STATUS
BY INCREASING FLOW RATES OF BLOOD
Changes in hemorheological properties of blood can produce changes in flow that are independent of changes in pressure. For example, a decrease in plasma viscosity can produce and increase in blood flow and tissue oxygenation even though pressure may remain constant. In other words variables other than pressure or pressure differentials must be employed to evaluate changes in flow because of hemorheological alterations. A major factor determining blood viscosity is the ability of the red blood cells to aggregate. These large aggregates of red blood cells, which form rouleaux formations, significantly decrease blood flow. Several factors have been demonstrated to enhance red blood cell aggregation.
An increase in the hematocrit, or red blood cells as a percentage of whole blood, increases aggregation. The velocity of blood flow also has an inverse correlation with viscosity which is demonstrated by Poiseuille’s Law. As velocity decreases, the natural tendency for aggregation stimulates rouleaux formations, leading to increased viscosity. Another factor determining viscosity is, as previously mentioned, red blood cell deformability. As the velocity of flow increases, red blood cells orient themselves with the direction of the flow and take an ellipsoidal shape with the red blood cell membrane rotating around the cell contents like the caterpillar tread of a tank. Both of these actions enhance blood flow by reducing viscosity. At the capillary level, a major determinant of flow is red blood cell deformability. Some factors tat determine RBC deformability are viscosity of the cell contents, surface area to volume ratio, and flexibility of the cell membrane. It has also been found that alterations in pH level, red blood cell adenosine triphosphate content, and concentrations of metabolic end products alter the membrane skeleton and thus red blood cell deformability.
The flexibility of red blood cells influences blood viscosity through the effect on streamlines in flow. Because normal RBC’s change into ellipsoids which conform to the flow patterns, a minimal perturbation of streamlines occurs. Studies using chemically stiffened RBC’s have shown that the less deformable the cell, the greater the disturbance of streamlines in flow and the higher the shear rate of viscosity. Flow problems in capillaries occurs by poorly deformable RBC’s having diameters larger than that of the capillaries. If intracapillary pressure does not rise sufficiently to cause the stiffened red blood cells to deform, flow will resume, but transudation will be enhanced. If the transudation rate exceeds the lymphatic drainage rate, tissue fluid will accumulate and frank edema will develop. By increasing the rate of flow of blood the red blood cell rigidity will be decreased due to the prevention or retardation of hypoxia which is a major cause of red blood cell rigidity.
It was concluded by Brown and Asbury, that the likely cause of diabetic neuropathy was multi-factoral, with biochemical factors being responsible for early diabetic neuropathy, while actual nerve damage was a consequence of the microangiology of diabetic neuropathy. It was noted that altered rheologic and other variables combined with the effects of microangiopathy would impair nerve blood flow. In recent articles on the pathogenesis of diabetic neuropathy, it was stated that by impairing capillary blood flow, altered blood rheology might be a causal factor in the disorder. The authors of these articles did not , however, advocate the correction of the hemorheological problem to attempt to improve nerve function. Due to the ability of the improved neuromuscular stimulator to achieve maximal muscle recruitment of deep-layered muscles in the peroneal and tibial proximity’s, alteration of abnormal hemorheological conditions occurs resulting in measurable and observable effects. Simpson et al drew attention to the possibility that both the early changes in nerve function and the late changes involving endoneurovascular lesions are not explainable in terms of the abnormal flow properties of diabetic blood. Because of the interaction between the abnormal flow properties and the capillary dimension, blood viscosity will increase and may lead to stasis in small endoneural vessels. If irreversible stasis does develop, the result will be a localized region of focal ischemic necrosis with its functional significance being determined by the anatomical location of the lesion. When blood rheology is abnormal, the effects in the microcirculation become so complex that it is difficult to separate cause and effect. Low and Tuck found that increases in or decreases in arterial blood pressure produced comparable changes in the nerve blood flow. They concluded that the blood supply to the peripheral nerve does not tend to autoregulate. They also found that nerve blood flow was reduced by 56% and that vascular resistance increased 85% in rats made hypoxic by breathing oxygen for 10 minutes. When blood rheology was abnormal, oxygen delivery was reduced and capillary blood flow was impaired systemically. Irreversible stasis in the smallest capillaries leading to focal ischemic necrosis would occur during an episode of worsened blood rheology. When blood rheology is improved, damage resulting from the ischemic lesions would be repaired and capillary regeneration would take place. The Poiseuille equation show that the flow rate of Newtonian fluids through narrow tubes is determined by fluid viscosity and the fourth power of the tube radius. Therefore even small differences in tube dimension would give rise to significant changes in flow rate. Since blood is a non-Newtonian fluid, the direct application of the Poiseuille equation is inappropriate, but because of the implications of that formula, it seems that when blood rheology is abnormal, the consequences will be manifested first in the smallest vessels of the microcirculation. Because of this, any study of blood flow in nerve capillaries, the dimensions of endoneural capillaries could be significant. A functional difference in blood supply to muscle and nerve is that muscle is more sensitive to ischemia than nerve. Even though peripheral nerve blood flow may have a significant protective reserve against ischemia, the absence of autoregulation and the apparent lack of lymphatic drainage may render the endoncurim particularly prone to edema. In keeping with the concepts of capillary permeability, increased transudation leading to edema implies increased capillary pressure and/or an increased exposure of basement membrane as a result of the altered disposition of endothelial cell cyoplasm. Due to the physical nature of blood, even the smallest focal reductions in vessel lumen diameter could have hemorheological repercussions. These changes appear to be important in the development of diabetic polyneuropathy.
There are several reasons for believing that oxygen levels determine both the efficiency of nerve function and endoneural blood flow. The following situations are envisaged which parallel some reported studies.
- When systemic blood pressure is lowered, the rate of endoneural blood flow will be reduced. As a result, thixotrophic amplification of blood viscosity will occur, increasing vascular resistance and thus further reducing the rate of flow of blood. Although in such circumstances oxygen delivery will be enhanced proximally, oxygen tension will be low distally.
- When systemic blood pressure remains normal but red blood cell deformability is poor, blood flow in the smallest capillaries will be impaired and, in the absence of autoregulation, could lead to stasis and possibly focal neurosis subsequent to anoxia.
- When systemic blood pressure is raised to overcome the peripheral resistance to abnormally viscous blood, and poorly deformable red blood cells, endoneural blood vessel perfusion pressure will be enhanced. By contracting the muscle with the neuromuscular stimulator and thereby increasing systemic blood pressure, oxygen loading of red blood cells, increasing the rate of nutrient/metabolic waste exchange, hypoxia will be reduced significantly and neural conductivity increased.
EFFECT OF INCREASED RATES OF LYMPHATIC FLUIDS
ON WOUND HEALING ENHANCEMENT
Whatever increases the flow of blood in the veins also aids the lymph flow. Lymph does not flow from a resting limb, but in a muscular activity the rhythmically contracting muscles squeeze out the lymph by exerting external pressure upon the lymph vessels resulting in a considerable flow. The contracting muscle and resultant increase in flow rates enables the lymphatic system to more speedily remove the waste products from the tissues. The effect of increased flow rates of lymphatic fluids upon enhancement of wound healing are to be found within the four functions of the lymph nodes which are:
- Formation of lymphocytes
- Disposal of bacteria
- Production of antibodies.
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