Structure and Biomechanics of Peripheral Nerves: Nerve Responses to Physical Stresses and Implications for Physical Therapist Practice

Nevner det aller meste om perifere nerver og hvordan de får plager av «normale» sitasjoner, som f.eks. musearm.

http://www.ncbi.nlm.nih.gov/pubmed/16386065

http://ptjournal.apta.org/content/86/1/92.long

Abstract

The structural organization of peripheral nerves enables them to function while tolerating and adapting to stresses placed upon them by postures and movements of the trunk, head, and limbs. They are exposed to combinations of tensile, shear, and compressive stresses that result in nerve excursion, strain, and transverse contraction. The purpose of this appraisal is to review the structural and biomechanical modifications seen in peripheral nerves exposed to various levels of physical stress. We have followed the primary tenet of the Physical Stress Theory presented by Mueller and Maluf (2002), specifically, that the level of physical stress placed upon biological tissue determines the adaptive response of the tissue. A thorough understanding of the biomechanical properties of normal and injured nerves and the stresses placed upon them in daily activities will help guide physical therapists in making diagnoses and decisions regarding interventions.

Figure 1.

Structural components of peripheral nerves. In the endoneurial compartment (En), a single Schwann cell envelops several unmyelinated axons, and another Schwann cell provides multiple wrappings of plasma membrane forming the myelin sheath of a myelinated axon. The portion of a myelinated axon myelinated by a single Schwann cell is called the internode, and internodes are separated by nodes of Ranvier. Schwann cells associated with both unmyelinated and myelinated axons are covered with a continuous basal lamina (BL). Capillaries (Cap) are present within the endoneurial compartment, and collagen fibers (Col) run primarily longitudinally between the axons. The axons, Schwann cells, collagen, and endoneurial fluid are bundled into a fascicle by the perineurium (Pe). The perineurium consists of several layers of flattened perineurial cells connected by tight junctions and covered internally and externally by a basal lamina. The layers of perineurial cells are separated by collagen fibers (Col) oriented obliquely. Several fascicles are bundled together by the epineurium (Ep) to form a nerve. The epineurium consists primarily of fibroblasts, collagen fibers (Col), and elastic fibers. The epineurium between fascicles is termed the interfascicular epineurium, and that encompassing all of the fascicles is termed the epifascicular epineurium. Arterioles (A) and veins are oriented primarily longitudinally within the epineurium.

Blood supply

The blood supply to nerves is provided by coiled segmental arteries that enter the epineurium periodically along the length of the nerve and form the vasa nervorum. Arteries divide into epineurial arterioles that form an anastomotic network running primarily longitudinally within the epifascicular epineurium and the interfascicular epineurium (Fig. 3). Epineurial arterioles are supplied with a perivascular plexus of serotoninergic, adrenergic, and peptidergic nerves.17,18 Perforating arterioles cross the perineurium at oblique angles and carry a short sleeve of perineurial cells into the fascicle.3,19 Perineurial arterioles have poorly developed smooth muscle and thus have limited ability to regulate intrafascicular blood flow.20 Within the endoneurium, arterioles immediately turn into large-diameter, longitudinally oriented capillaries that allow blood flow in either direction (Fig. 3).21 The endothelial cells of endoneurial capillaries are connected by tight junctions, thus forming the tight blood-nerve barrier.7 Venules return blood to the venous system. Of note, lymphatic capillaries are present only within the epineurium; there is no lymphatic drainage from the intrafascicular or endoneurial space.22

Biomechanical properties

Under normal physiological conditions imposed by posture and movement, nerves are exposed to various mechanical stresses. Stress is defined as force divided by the area over which it acts9,2325 and can be applied to a nerve as tensile, compressive, or shear stress or as a combination of stresses (Fig. 4). Tensile stress may be applied to tissues either parallel or perpendicular to the length of the nerve, causing respective longitudinal or transverse stress in the nerve. When joint motion causes elongation of the nerve bed, the nerve is inherently placed under tensile stress and accommodates the stress by both elongating and gliding.15 The deformation or change in nerve length induced by longitudinal tensile stress is called strain and is expressed typically as percent elongation.23,2628 Displacement or gliding of a nerve relative to the surrounding nerve bed is called excursion.2931 The direction of excursion may be longitudinal or transverse, or both, relative to the nerve tract31,32 and is measured in millimeters.

Figure 4.

Physical stresses placed on peripheral nerve. Tensile stress applied longitudinally to peripheral nerve creates an elongation of the nerve (an increase in strain). The transverse contraction that occurs during this elongation is greatest at the middle of the section undergoing tensile stress.

When the nerve bed is elongated, the nerve is placed under increased tensile stress. With the elongation of the nerve bed, the nerve glides toward the moving joint,1,33,34 a movement termed convergence.1 Conversely, if the nerve bed tension is relieved during joint motion, the nerve will realign along the shortened nerve bed by gliding away from the moving joint, a movement termed divergence.33 Convergence in the median nerve may be demonstrated during elbow extension (Fig. 5). The motion elongates the bed of the median nerve, causing the nerve segment in the arm to glide distally toward the elbow and the nerve segment in the forearm to glide proxi mally toward the elbow. In contrast, elbow extension relieves the tensile stresses in the ulnar nerve bed, causing the ulnar nerve to diverge away from the elbow (Fig. 5).

Figure 5.

Excursion of the median nerve (solid line) and the ulnar nerve (dotted line) during elbow extension followed by wrist extension. The concepts of nerve convergence toward and divergence away from a moving joint are illustrated in measurements of excursion taken at each site indicated. All measurements are reported in millimeters of proximal (P) or distal (D) excursion. The direction of excursion is also represented by solid arrows for median nerve excursion and open arrows for ulnar nerve excursion. (A) With elbow extension from 90° of flexion to 0° of flexion, the median nerve bed lengthens and the median nerve glides toward the elbow (converges). With the same joint motion, the ulnar nerve bed shortens and the ulnar nerve glides away from the elbow (diverges). (B) With wrist extension from 0° of extension to 60° of extension, both nerve beds lengthen; thus, both nerves converge toward the wrist. The magnitude of excursion is greatest closest to the moving joint. Data were obtained from: aDilley et al,29 bWright et al,27 and cWright et al.33 Measurements of nerve excursion at the wrist and elbow in panel A were extrapolated from studies of nerve excursion during elbow flexion from 0° to 90°.27

Nerve Stiffness

First, a recent study43 measured greater nerve compliance in nerve segments that cross joints than in segments that do not cross joints.

Second, nerve stiffness is greater in long nerve sections and in nerve sections with numerous branches.15 Severing nerve branches or vessels but leaving the nerve in situ results in increased compliance and decreased stiffness.15

Third, nerve stiffness is greater when a nerve is elongated rapidly rather than slowly. In addition, the ultimate strain at the point of failure appears to be dependent on the rate of elongation.

When a nerve is placed under tension and maintained at that new fixed length over time, there is a reduction in the tension in the nerve or the force required to maintain the fixed length. The observed reduction in tension may be plotted in a stress-relaxation curve (Fig.8).25,44 The majority of relaxation occurs in the first 20 minutes of fixed elongation.25,44Stress relaxation in nerves that are stretched slowly is greater than in nerves that are stretched rapidly.25,37,4446 This phenomenon was observed when comparisons were made for rabbit tibial nerves stretched at different rates to lengths 6% longer than their resting lengths. Over the 60-minute relaxation time, there was a 57% reduction in stress in nerves elongated at 0.08% per second,45 but only a 34% reduction in stress in nerves elongated at 3.0% per second.44

Figure 8.

Stress-relaxation curve demonstrating viscoelastic properties of peripheral nerve. When a nerve is elongated and the new length is kept constant, there is a rapid reduction in the stress within the nerve, expressed as percent reduced relaxation. Most of the relaxation occurs in the first 20 minutes. The degree of elongation affects the amount of stress relaxation that will occur. The dotted line represents a nerve that has been elongated to 6% above its resting length. The solid line represents nerves that have been elongated to 9% and 12% above their resting lengths. Greater stress relaxation was documented in nerves that underwent less elongation.25,44 Modified from Kwan MK, Wall EJ, Massie J, Garfin SR. Strain, stress, and stretch of peripheral nerve: rabbit experiments in vitro and in vivo. Acta Orthop Scand. 1992;63:267–272, with permission of Taylor and Francis AS.

However, a nerve stretched repetitively to 8% or 10% strain exhibits a reduced slope of the stress-strain curve, indicating that that nerve undergoes less stress with successive elongations because of increased compliance and decreased stiffness.

Compression of nerve

In addition to tensile stress, nerves are exposed statically and dynamically to compressive stresses. As mentioned previously, the laws of physics dictate that the cross-sectional area of a cylindrical object is reduced as the cylinder is elongated. As a nerve is elongated under tensile force, the nerve undergoes transverse contraction, which is resisted by the fluid and nerve tissue contained within the connective tissue sheath.15,39The magnitude of the transverse contraction stress is greatest at the center of the elongating segment15 (Fig. 4). Nerves also may be compressed externally by approximation to adjacent tissues, such as muscle, tendon, or bone, or by pressure increases in the extraneural environment. Compression of a nerve segment causes displacement of its internal contents in transverse and longitudinal directions. As shown in rat nerve, extraneural compression causes an immediate displacement of endoneurial fluid to the edges of a compressive cuff over 5 to 10 minutes and a much slower displacement of axonal cytoplasm over the course of hours.48 The damage to axons and myelin is greatest at the edges of the compressed zone,48,49 where the shear forces are highest.50

At the edges of the cuff, however, myelin retraction with resultant widening of nodes and paranodal demyelination occurred. These structural alterations in myelin may be expected to result minimally in impaired impulse conduction or maximally in demyelination and a conduction block.

In response to biomechanical stresses placed on a nerve as an individual assumes a posture or movement, the nerve follows the path of least resistance.29 Combinations of tensile, shear, and compressive stresses result in combinations of nerve excursion, strain, and transverse contraction. Because the biomechanical forces on the nerve are so intricately linked, the sequencing and range of joint movement affect the magnitude and direction of excursion,27,29 the magnitude of nerve strain,27,29,35 and the degree of transverse contraction at different sites along the nerve.27

Simultaneous nerve excursion, strain, and transverse contraction may be seen in the ulnar nerve as an example of responses to physical stresses imposed during movements of the upper limb. When the upper limb is maintained in a position of 90 degrees of shoulder abduction and 90 degrees of shoulder external rotation with the wrist neutral, and when the elbow is moved from 90 degrees of flexion to full extension, the ulnar nerve bed is shortened and the tensile stress on the nerve is decreased. With this motion, there is divergence of the ulnar nerve away from the elbow (Fig. 5), decreased nerve strain, especially at the elbow (Fig. 6), and decreased compression within the cubital tunnel.27,29,33 When the wrist then is extended from neutral to full extension, the ulnar nerve bed is lengthened, resulting in convergence of the nerve toward the wrist (Fig. 5), an increase in nerve strain (Fig. 6), and transverse contraction greatest in the nerve segment across the carpal bones and at the tunnel of Guyon.27,29,33 The magnitude of nerve strain and excursion will be greatest near the wrist, and the fascicles will rearrange as the nerve assumes a flattened oval shape. Because the nerve does not lie directly on the rotational axis of joint motion, the fascicles farthest from the axis will undergo greater strain than those closer to the center of rotation51

Figure 6.

Strain of the median nerve (solid line) and the ulnar nerve (dotted line) during elbow extension followed by wrist extension. Measurements at the sites indicated are reported as percent increase (↑) or percent decrease (↓) in strain. (A) With elbow extension from 90° of flexion to 0° of flexion, median nerve strain increases because of elongation of the nerve bed. Conversely, ulnar nerve strain decreases as the ulnar nerve bed shortens. (B) With wrist extension from 0° of extension to 60° of extension, the strain at the sites measured increases in both nerves as both nerve beds elongate. The magnitude of the strain is greatest closest to the moving joint. Data were obtained from: aWright et al27and bWright et al.33 Measurements of nerve excursion at the wrist and elbow in panel A were extrapolated from studies of nerve excursion during elbow flexion from 0° to 90°.27

Continuum of physical stress states

First, levels of physical stress lower than the levels required for tissue maintenance (low stress) result in a reduced ability of the tissue to tolerate subsequent stress and are consistent with tissue plasticity and response to functional demand.

Second, levels of physical stress in the range required for tissue maintenance (normal stress) result in no tissue adaptations and are considered to maintain a state of equilibrium.

Third, physical stress levels that exceed the range required for tissue maintenance (high stress) result in an increase in the tolerance of the tissue for stress in an effort to meet the mechanical demand.

Fourth, physical stress levels that exceed the capacity of some components of the tissue (excessive stress) result in tissue injury.

Fifth, levels of physical stress that are extreme (extreme stress) result in tissue death.

Finally, it is important to note that the physical stress level is a composite value with variable components of magnitude, time, and direction or type of stress.

 In the functional zone, the physical stresses on the nerve are sufficient to maintain a state of equilibrium and normal physiological function. In the dysfunctional zone, various levels of physical stress have altered the ability of the nerve to tolerate subsequent stress.

Figure 9.

Continuum of physical stress states. The white area represents the functional zone in which the physical stresses on the nerve are sufficient to maintain a state of equilibrium and normal physiological function. The shaded areas represent dysfunctional zones resulting from various levels of physical stress placed on the nerve tissue. Under conditions of prolonged low stress, the functional zone will shrink in width and shift to the left, reducing the ability of the tissue to tolerate subsequent stresses even of previously normal levels. Under conditions of high stress, the functional zone may expand and shift to the right, improving the ability of the tissue to tolerate subsequent physical stress. If the nerve is exposed to prolonged or repeated excessive stress, the functional zone will shrink in width. Although scarring of damaged tissue may enable the nerve to tolerate subsequent physical stresses, the physiological function of the nerve will be reduced. Exposure to extreme stress will result in disruption of axon continuity or neural cell death and significantly reduced physiological function.

Immobilization Stresses

Under conditions of immobilization, such as casting, splinting, and bracing, peripheral nerves are exposed to levels of physical stress that are lower than those necessary to maintain the nerves in a state of equilibrium or in a functional zone (Fig. 9). According to the Physical Stress Theory, nerve will undergo predictable physiological and structural modifications proportional to the levels of reduced stress and the duration of immobilization.2 Immobilization induces cell biological changes in axons and axon terminals5254 and structural changes in myelin and nerve connective tissue layers that likely alter the ability of nerves to tolerate subsequent physical stress.

We hypothesize that after a period of immobilization, the width of the functional zone on the continuum of physical stress states will shrink and shift toward the left (Fig. 9).

Lengthening Stresses

Nerves are exposed to various levels of longitudinal tensile stress during limb-lengthening procedures, such as distraction osteogenesis (Ilizarov procedures), traction injuries, and stretching maneuvers. The tissue response is dependent upon the magnitude and duration of the tensile stress. The extant data indicate that lengthening of 6% to 8% for a short duration causes transient physiological changes that appear to be within the normal stress tolerance of the tissue, whereas acute strains of 11% and greater cause long-term damage and may be considered to be excessive or extreme stress states.

In cadavers, positioning in shoulder depression, 90 degrees of shoulder abduction, 90 degrees of shoulder external rotation, 70 degrees of forearm supination, 60 degrees of wrist extension, full finger extension, and full elbow extension resulted in 7.6%±8.2% (X̄±SD) strain in the median nerve measured just proximal to the wrist.28 Adults who were healthy and who were placed in this same position lacked 12±13 degrees (X̄±SD) of elbow extension because of substantial discomfort in the limb.61 The subjects reported pain of 5.1±1.9 (X̄±SD) on a 10-point visual analog scale, and 36% of the subjects reported paresthesia in the upper limb. Taken together, these findings suggest that many people are unable to tolerate levels of strain below the theoretical 11% threshold.

Compression Stresses

Compression on a nerve may be the result of extraneural force or may occur as transverse contraction secondary to increased longitudinal strain (Fig. 4). Compression stress of a low magnitude and a short duration may result in reversible physiological and minor structural changes. Compressive stress of a high magnitude, however, may result in structural alterations in myelin sheaths and even disruption of axons. Low-magnitude compressive stress applied over a long period of time may cause significant structural changes in the nerve secondary to impairment of blood flow and sequelae of ischemia.

As with strain-induced injury, a threshold for compression-induced nerve injury is difficult to determine. Common functional positions may result in compression pressures that approach or exceed the 20 to 30 mm Hg demonstrated to impair nerve blood flow.75 The carpal tunnel is a site well known for compressive damage to the median nerve and thus has been well studied. Carpal tunnel pressure in subjects who were healthy was measured at 3 to 5 mm Hg with the wrist in a neutral position.7678 Simply placing the hand on a computer mouse was shown to increase the tunnel pressure from the resting 5 mm Hg to 16 to 21 mm Hg,79 and actively using the mouse to point and click increased the tunnel pressure to 28 to 33 mm Hg, a pressure high enough to reduce nerve blood flow.

In subjects with carpal tunnel syndrome, pressure in the carpal tunnel was 32 mm Hg with the wrist in a neutral position and rose to a mean of 110 mm Hg with full wrist extension in subjects with carpal tunnel syndrome.76 These tunnel pressures exceed the threshold of 20 to 30 mm Hg for vascular perfusion even at rest. Taken together, these findings suggest that even functional positions, such as the use of a computer keyboard and mouse, place the wrist in a position of increased carpal tunnel pressure, compromising nerve blood flow and placing people at risk for median nerve injury.

Direct damage to myelin and axons has been shown to occur with extraneural compression of as low as 50 mm Hg maintained for 2 minutes,48 and the percentage of damaged fibers increases with increasing force. Ten days after the application of compressive stress at 50 mm Hg, 30% of the axons in the region under the compressive cuff showed evidence of demyelination, focal myelin thickening, remyelination, and axonal degeneration or regeneration.48

The pathological consequences of prolonged compression include subperineurial edema; inflammation; deposition of fibrin; activation of endoneurial fibroblasts, mast cells, and macrophages; demyelination; axon degeneration; and fibrosis.83 Compression of a very long duration has been modeled in animals with loose ligatures,88 Silastic* tubes,89,90and pressure balloons placed within an anatomical tunnel.91 The pathological findings are thought to result from both inflammatory and cellular phenomena and include changes in the blood-nerve barrier, thickening of the perineurium and epineurium, thinning of myelin, demyelination and degeneration of axons in the fascicle periphery, and slowed nerve conduction velocity.

In the case of chronic compression, decompression is paramount. Physical therapy intervention should focus on reduction of inflammation, improvement in blood flow, and enhancement of the capacity of the nerve for strain and excursion along its full length in an effort to reduce the physical stress on the compressed region.

Repetitive Stresses

Vibration constitutes one form of repetitive stress. We know from studies of humans who use hand-held vibrating tools that vibration stresses can cause reductions in tactile sensation, as well as other sensory disturbances96 and reduced grip force.97,98Furthermore, myelin breakdown and fibrosis have been seen in the dorsal interosseous nerve at the wrist in people with vibration-induced neuropathy.99 Long-term exposure to vibration stresses has been shown to result in the grouping of muscle fiber types in muscle biopsies, indicative of denervation and reinnervation.98

Repetitive movements, such as those that occur in work-related musculoskeletal disorders, were discussed in detail recently by Barr and Barbe.102 The stresses placed upon the tissues may be variable in terms of type, magnitude, frequency, and duration, and the combination of these factors may place nerves in normal to extreme levels of physical stress. The chronic inflammation associated with repetitive movements places nerves under constantly higher hydrostatic compressive stress, which may increase further with contraction of the surrounding muscles. Chronic inflammation elicits within the nerves a remodeling response that seeks to add mechanical stability.103 The most common outcome is the deposition of collagen in the connective tissue layers, which leads to decreased compliance of the nerves to elongation. As with chronic compression, the approach for assessment and treatment of injuries attributable to repetitive movements must address the chronic inflammatory state and connective tissue changes. Of primary importance in interventions for all stress-induced injuries are the identification and characterization of physical stresses and the modification of their components, magnitude, time, and direction, as outlined in the physical stress theory.2

Summary

This assessment should guide treatment interventions to normalize the stresses on the nerves, be they rest, soft tissue or neurodynamic mobilization, stretching, modalities, exercise, or patient education. Treatment rationale should be based on an educated understanding of the biomechanical properties of normal and pathological nerves. The concept of a continuum of low-normal-high-excessive-extreme stresses may be used as a training tool for patient education, pointing out examples of daily activities that fall under the different categories.

Treating Diabetes with Exercise – Focus on the Microvasculature

Veldig viktig studie som nevner at det ikke finnes glatt muskulatur i kapillærene, så det er arteriolene som avgjør blodsirkulasjonen i kapillærene. His blodsirkulasjonen i en arteriole blir dårlig stopper sirkulasjonen opp i et område av muskelen som serveres av kapillærene.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4000229

Abstract

The rising incidence of diabetes and the associated metabolic diseases including obesity, cardiovascular disease and hypertension have led to investigation of a number of drugs to treat these diseases. However, lifestyle interventions including diet and exercise remain the first line of defense. The benefits of exercise are typically presented in terms of weight loss, improved body composition and reduced fat mass, but exercise can have many other beneficial effects. Acute effects of exercise include major changes in blood flow through active muscle, an active hyperemia that increases the delivery of oxygen to the working muscle fibers. Longer term exercise training can affect the vasculature, improving endothelial health and possibly basal metabolic rates. Further, insulin sensitivity is improved both acutely after a single bout of exercise and shows chronic effects with exercise training, effectively reducing diabetes risk. Exercise-mediated improvements in endothelial function may also reduce complications associated with both diabetes and other metabolic disease. Thus, while drugs to improve microvascular function in diabetes continue to be investigated, exercise can also provide many similar benefits on endothelial function and should remain the first prescription when treating insulin resistance and diabetes. This review will investigate the effects of exercise on the blood vessel and the potential benefits of exercise on cardiovascular disease and diabetes.

At rest, a low proportion of capillaries are exposed to blood flow at one time, with a rapid increase in the number of perfused capillaries after exercise [31], thus increasing functional capillary density.

Vascular smooth muscle cells are located around the arterioles and some venules, and can constrict to change blood flow patterns, while capillaries do not typically contribute to blood flow changes [30] (Figure 1). Blood flow through capillaries is controlled upstream by small arterioles at rest, and the rapid recruitment of unperfused capillaries by exercise could suggest that nerves are responsible for this action [34]. The sympathetic nervous system is mainly responsible for the vasoconstrictor responses, and as the arterioles and larger vessels are innervated [38] the majority of sympathetic nervous system activity is localized to that area of the vascular tree. Physical exercise can enhance sympathetic nerve activity [39] to maintain arterial pressure, and may be involved in maintaining exercise tolerance, as reviewed by Thomas and Segal [38].

Structural differences between artery, arteriole and capillary. No vascular smooth muscle is located on the capillary; therefore flow through capillaires is modified by pre-capillary arterioles. Cessation of flow through arterioles will prevent flow through a portion of the muscle.

Insulin relies on endothelium-dependent vasodilation to enhance perfusion, thus endothelial dysfunction reduces insulin-mediated increases in muscle perfusion, which can contribute to the metabolic deficit in diabetes. As exercise-mediated changes in perfusion are typically endothelium-independent, exercise is still able to recruit capillaries and thus increase muscle perfusion in obesity and type 2 diabetes, even in the face of endothelial dysfunction. Numerous studies have now shown that while insulin’s vascular effects may be blocked in diabetes, exercise still maintains its ability to increase the distribution of blood flow through muscle [42].

Nitric oxide (NO) is the main vasodilator from the endothelium specifically involved in blood flow and blood distribution, and while reduction in nitric oxide synthesis lowered total blood flow, exercise-mediated capillary recruitment was not affected [46]. In fact, inhibition of NO formation enhances both resting and exercise-mediated muscle oxygen uptake [47]; despite a reduction in total flow, microvascular flow was not affected, suggesting that NO is not involved in the vascular response to exercise.

The distribution of blood through muscle increases the capacity for nutrient exchange. In exercise the primary purpose of functional hyperemiais for oxygen delivery, as the oxygen required by exercising muscle is much higher than resting muscle (reviewed in [37]). Recruitment of capillaries can decrease the velocity of blood flow by increasing the cross-sectional area of the capillary bed and the time available for exchange. Recruitment also increases surface area for exchange and decreases perfusion distances to promote oxygen delivery to tissues with exercise [34] (Figure 2). While in exercise the main metabolite required at the working muscle is oxygen, distribution of other nutrients can also be affected, including glucose, fats, other hormones and cytokines. Muscle metabolism can therefore be altered by perfusion of the tissue [48,49]. While there can be regulated transport of certain larger hormones across the vasculature [50,51], smaller molecules can diffuse across the endothelium easily, possibly making muscle perfusion a more important player in the delivery of glucose and oxygen to the tissue.

Vasodilation affects delivery, and thus metabolism. The rate of transfer across the endothelium is dependent on surface area, permeability of the endothelium, diffusion distance, and concentration difference (Fick’s first law of diffusion). Vasodilation increases surface area in arterioles for exchange, but will also recruit downstream capillaries, which will reduce diffusion distance and increase surface area for exchange. Working muscle increases oxygen utilization, increasing the concentration difference from the blood vessel to the tissue.

Mitochondrial dysfunction has been proposed to be both a cause [72] and a consequence [73] of insulin resistance, and may contribute to endothelial dysfunction [74]. If oxygen delivery is a component of mitochondrial health and biogenesis, it is possible that impaired perfusion may contribute to fiber type switching, where an oxidative fiber, which is typically highly vascularized and contains mitochondria, switches to a glycolytic fiber with less vascularity and mitochondria. As exercise can improve oxidative capacity, increase mitochondria content [75], and also increase muscle perfusion [31,32,34,45,76], the relationship between muscle perfusion, fiber type and mitochondrial function needs to be clarified.

The vascular component of exercise may well be linked to the reduction of diabetic complication such as retinopathy, peripheral neuropathy and nephropathy, as there is a vascular basis to many of these complications. The endothelium has been implicated in diabetic nephropathy [88], and the blood vessels formed in response to reduced perfusion in retinopathy show abnormal structure and function [89].

Microvascular Perfusion Changes in the Contralateral Gastrocnemius Following Unilateral Eccentric Exercise

Spennende studie som nevner at blodsirkulasjonen øker i området som har stølhet. Og den økte blodsirkulasjonen vedvarer i mer enn 48 timer etter treningen. I dette tilfellet i leggen som ble trent. De mener det er pga økt betennelse i muskelen.

http://omicsgroup.org/journals/microvascular-perfusion-changes-in-the-contralateral-gastrocnemius-following-unilateral-eccentric-exercise-2165-7025-3-163.php?aid=16679

 

There was a significant main effect for time for blood volume (p=0.023) and blood flow (p=0.010), with no significant difference in blood flow velocity (p=0.316). There were significant increases in blood volume (p=0.001) and blood flow (p<0.001) immediately postexercise (9.77 ± 3.19 dB and 3.53 ± 0.86 dB/sec), respectfully in the contralateral limb compared to baseline (6.18 ± 2.05 dB and 2.40 ± 0.69), with no change in blood flow velocity (p=0.487). The effect size for blood volume was 1.34 (0.09, 2.60) and blood flow was 1.41 (0.15, 2.68). The increases in contra lateral blood volume (p=0.002) and blood flow (p=0.003) were maintained at 48 hours (9.41 ± 1.90 dB and 3.51 ± 0.47 dB/sec) compared to baseline, with again no change in blood flow velocity (p=0.411). The effect size for blood volume was 1.62 (0.32, 2.92) and blood flow was 1.86 (0.51, 3.22). There were no changes in blood volume (p=0.814), blood flow (p=0.962), or blood flow velocity (p=0.493) between post-exercise and 48 hours for the contra lateral limb.

Following eccentric exercise to a single limb, the contralateral limb resulted in increased blood volume and blood flow immediately after exercise and at 48 hours post exercise. From previous research in our lab [12] immediately after eccentric exercise, blood volume and blood flow increased in the exercise leg by 42% and 80%, respectfully. From this study, the contra lateral leg increased 17% and 35% for blood volume and blood flow, respectfully. This finding supports earlier work by Seals [7] and Taylor et al. [8] that identified vasodilatation of the contra lateral limb after exercise initiation. Blood flow velocity did not change in the contra lateral limb after exercise and at 48 hours. Since this limb was not exercised, recruitment of capillaries is not necessary, as would be in exercised muscle [14].

Eccentric exercise increased microvascular perfusion immediately after exercise in the contralateral limb, which had not been examined before. The increased perfusion was maintained over 48 hours, so the prolonged increased in perfusion of the contralateral limb may have been due to an inflammatory response or the extra demands placed on the contralateral limb for support during walking.

Structure and Biomechanics of Peripheral Nerves: Nerve Responses to Physical Stresses and Implications for Physical Therapist Practice

Denne sier mye om nervenes blodgjennomstrømmning. Spesielt interessant er avnittet om hvor lite trykk som skal til før blodgjennomstrømningen stopper. Om trykket opprettholdes i 8 timer vil det skje en skade i nerven. Så lite som 20 mm Hg er nok til at blodsirkluasjonen blir dårligere.

http://ptjournal.apta.org/content/86/1/92.full

Simply placing the hand on a computer mouse was shown to increase the tunnel pressure from the resting 5 mm Hg to 16 to 21 mm Hg,79 and actively using the mouse to point and click increased the tunnel pressure to 28 to 33 mm Hg, a pressure high enough to reduce nerve blood flow.

In subjects with carpal tunnel syndrome, pressure in the carpal tunnel was 32 mm Hg with the wrist in a neutral position and rose to a mean of 110 mm Hg with full wrist extension in subjects with carpal tunnel syndrome.76 These tunnel pressures exceed the threshold of 20 to 30 mm Hg for vascular perfusion even at rest. Taken together, these findings suggest that even functional positions, such as the use of a computer keyboard and mouse, place the wrist in a position of increased carpal tunnel pressure, compromising nerve blood flow and placing people at risk for median nerve injury.

Arterial and endoneurial capillary blood flows were stopped at pressures of 50 to 70 mm Hg67 and 80 mm Hg,75 respectively. Interestingly, in humans, intraneural blood flow and sensory responses are blocked at extraneural tissue pressures 45 mm Hg below the mean arterial pressure.82 A compressive stress of only 30 mm Hg, if maintained for 2 hours, results in endoneurial edema,83 and, if maintained for 8 hours, results in endoneurial pressure high enough to subsequently impair blood flow.84 The endoneurial edema is thought to result from ischemic damage to endoneurial capillary endothelial cells and an alteration in the blood-nerve barrier. The same compressive stress of 30 mm Hg applied for 8 hours is sufficient to impair both anterograde axonal transport and retrograde axonal transport.85,86Increasing pressure results in greater tissue damage, as a compressive force of 150 mm Hg maintained for 30 minutes was shown to induce a degeneration of 30% of the distal fibers,48 and compressive forces of 200 and 400 mm Hg maintained for 2 hours were shown to block axonal transport for 1 and 3 days, respectively.87

The pathological consequences of prolonged compression include subperineurial edema; inflammation; deposition of fibrin; activation of endoneurial fibroblasts, mast cells, and macrophages; demyelination; axon degeneration; and fibrosis.83 Compression of a very long duration has been modeled in animals with loose ligatures,88 Silastic* tubes,89,90and pressure balloons placed within an anatomical tunnel.91 The pathological findings are thought to result from both inflammatory and cellular phenomena and include changes in the blood-nerve barrier, thickening of the perineurium and epineurium, thinning of myelin, demyelination and degeneration of axons in the fascicle periphery, and slowed nerve conduction velocity.

Differential blood flow responses to CO2 in human internal and external carotid and vertebral arteries

Denne viser hvordan CO2-responsen er litt forskjellige i forskjellige blodkar. Den er sterkere i blodkar inni hjernen enn i blodkar i kraniet, ansiktet og ryggraden. Blodkar i ryggraden har større respons enn blodkar i ansiktet, men mindre respons enn blodkar i hjernen.

http://jp.physoc.org/content/590/14/3277.long

Because of methodological limitations, almost all previous studies have evaluated the response of mean blood flow velocity (Vmean) in the middle cerebral artery (MCA) to changes in CO2 as a measure of CO2 reactivity across the whole brain (Aaslid et al. 1989Ainslie & Duffin, 2009Ainslie & Ogoh, 2009).

 

ICA, VA and BA CO2 reactivity was significantly higher during hypercapnia than during hypocapnia (ICA, P < 0.01; VA, P < 0.05; BA, P < 0.05), but ECA and MCA were not significantly different.

The major finding from the present study was that cerebral CO2 reactivity was significantly lower in the VA and its distal artery (BA) than in the ICA and its distal artery (MCA). These findings indicate that vertebro-basilar circulation has lower CO2 reactivity than internal carotid circulation. Our second major finding was that ECA blood flow was unresponsive to hypocapnia and hypercapnia, suggesting that CO2 reactivity of the external carotid circulation is markedly diminished compared to that of the cerebral circulation. These findings suggest that different CO2 reactivity may explain differences in CBF responses to physiological conditions (i.e. dynamic exercise and orthostatic stress) across areas in the brain and/or head.

Hypercapnic cerebral CO2 reactivity in global CBF was greater than the hypocapnic reactivity (Ide et al. 2003) (Table 3). The mechanisms underlying this greater reactivity to hypercapnia compared with hypocapnia may be related to a greater influence of vasodilator mediators on intracranial vascular tone compared with vasoconstrictive mediators (Toda & Okamura, 1998Ainslie & Duffin, 2009). In humans, Peebles et al.(2008) recently reported that, during hypercapnia, there is a large release of nitric oxide (NO) from the brain, whereas this response was absent during hypocapnia.

The difference in CO2 reactivity between vertebro-basilar territories (VA and BA) and the cerebral cortex (ICA and MCA) may be due to diverse characteristics of vasculature, e.g. regional microvascular density (Sato et al. 1984), basal vascular tone (Ackerman, 1973Haubrich et al. 2004Reinhard et al. 2008), autonomic innervation (Edvinsson et al. 1976Hamel et al. 1988) and regional heterogeneity in ion channels or production of NO (Iadecola & Zhang, 1994Gotoh et al. 2001).

Interestingly, the response of the ECA to changes in CO2 may be similar to other peripheral arteries. It has long been appreciated that the vasodilatory effect of hypercapnia is much more profound in cerebral than in peripheral vasculature, particularly leg (Lennox & Gibbs, 1932Ainslie et al. 2005) and brachial arteries (Miyazaki, 1973). These findings suggest that control of CO2 is particularly important in the cerebral circulation. The high resting metabolic requirements of the brain, compared with that of other vasculature, might be one reason why this circulatory arrangement is desirable (Ainslie et al. 2005). Specifically, high CO2 reactivity may be a way for the brain to match metabolism with flow (Ainslie et al. 2005).

Lower CO2reactivity in the vertebro-basilar system may be important for maintaining central respiratory function because Graphic in central chemoreceptors is regulated by Graphic and blood flow to maintain breathing stability.

In summary, our study shows that cerebral CO2 reactivity in the vertebro-basilar circulation is lower than that in the internal carotid circulation, while CO2 reactivity in the external carotid circulation is much lower compared with two other cerebral arteries. These findings indicate a difference in cerebral CO2 reactivity between different circulatory areas in the brain and head, which may explain different CBF responses to physiological stress. Lower CO2 reactivity in the vertebro-basilar system may be beneficial for preserving blood flow to the medulla oblongata to maintain vital systemic functions, while higher CO2 reactivity in the internal carotid system may imply a larger tolerance for varied blood flow in the cerebral cortex.

Morning attenuation in cerebrovascular CO2 reactivity in healthy humans is associated with a lowered cerebral oxygenation and an augmented ventilatory response to CO2

Denne beskriver hvordan blodkarenes respons på CO2 er dårligere om morgenen, og det er derfor det skjer flere slag og slikt om morgenen. Den nevner mange interessante prinsipper. Bl.a. at lavere vasomotor respons (på CO2) gir mindre oksygen til hjernen. Og at i opptil 20 sekunder etter en 20 sekunder holdning av pust (etter utpust) øker fortsatt oksygenmengden og blodgjennomstrømningen i hjernen. Nevner også at siden blodkarene i hjernen reagerer dårligere på CO2 om morgenen blir det lett at pusten over- eller underkompenserer, så pustemønsteret blir uregelmessig om morgenen. Spesielt om man har underliggende faremomenter som hjerte/karsykdommer.

http://jap.physiology.org/content/102/5/1891

 

Furthermore, our results suggest that morning cerebral tissue oxygenation might be reduced as a result of a decreased cerebrovascular responsiveness to CO2 or other factors, leading to a higher level of desaturation.

Our data indicate that the cerebrovascular reactivity to CO2 in healthy subjects is significantly reduced in the morning and is strongly associated with an augmented ventilatory response to CO2. It is likely that this reduction in MCAV CO2 reactivity, by reducing blood flow through medullary respiratory control centers, increases both the arterial-brain tissue PCO2 difference and the H+ concentration presented to the central chemoreceptor(s) (1144). In effect, it appears the brain tissue is more susceptible in the morning to changes in arterial PCO2, which could increase the likelihood of ventilatory overshoots and undershoots.

However, as was the case with the hypercapnic challenge, subjects holding their breath in the morning experienced a significantly blunted increase in MCAV compared with evening, likely a result of a reduced cerebrovascular responsiveness to CO2.

In conclusion, our results suggest that early morning reductions in cerebrovascular CO2 reactivity strongly influence the magnitude of the ventilatory response to CO2. This may have significant implications for breathing stability, increasing the chances of periodic breathing in the morning in patients with additional risk factors. The early morning reduction in cerebral oxygenation with hypercapnic challenge, mild hypoxemia, or during apnea may be a contributing factor in the high prevalence of early morning stroke. Whether differences in the responses of CBF, oxygenation, or V̇E to CO2challenge are associated with other risk factors for stroke, such as gender or age, remains to be elucidated.

CO2-beriket vann til fotbad

Å bade i CO2 beriket vann har vært brukt som medisin i alle år. Hellige og mirkauløse kilder har ofter vært vann med et høyt innhold av karbondioksid. Og det har blitt brukt i spa behandling i århundrer, spesielt i Bulgaria. Man finner Co2-rikt vann spesielt ved sovende og inaktive vulkaner.

CO2 er et veldig lite molekyl som diffunderer lett igjennom huden. I CO2-beriket vann kommer derfor CO2 inn i huden og inn til blodkarene i underhuden, hvor alle sansenerver ligger. Den økte CO2 en gjør at blodkarene rundt nervetrådene og i muskelvevet utvides (vasodilasjon) og at oksygene letter hopper av blodcellene slik at det kan bli brukt til energi i celler som vanligvis har lite tilgang på oksygen.

CO2 beriket vann kan vi lage selv på en svært enkel måte: blande Natron, Sitronsyre og vann. Begge disse stoffene fåes kjøpt på vanlig daglivarebutikk. Vannet begynner å bruse, og dette er CO2.

Studier nevner at man bør ha 900-1200 mg CO2 pr liter vann. Ved å måle pH kan vi regne med at vi har det når pH er nede på 5.

Vi kan se CO2 effekten på huden ved at det kommer tett-i-tett med ørsmå bobler. I f.eks. fotbad vil vi se at når vi tar foten opp fra vannet så er den rød, noe som er et tegn på økt blodsirkulasjon i huden.

For alle med nevropatier, diabetes, sår, nevromer, leggspenninger, restless leg syndrom, som lett blir sliten i bena av å gå, så vil dette være verdt et forsøk.

2-3 ganger i uka pleier å være den vanlige oppskriften. Noen studier har brukt det hver dag i mange uker. Spesielt når det gjelder diabetes sår.

Oppskrift: Bland 1 poseNatron med 2 poser Sitronsyre (blandingsforhold ca. 1:1) og hell innholdet i 5L vann. Det bruser veldig pga reaksjonen som lager CO2. Når du setter føttene nedi skal det komme mange små bobler som dekker huden. Etter 5-10 minutter vil huden som er under vann bli rød. Dette er et tegn på økt blodsirkulasjon.

5-15 minutter etter du er ferdig med fotbadet vil du sannsynligvis kjenne det prikker og strømmer ellers i kroppen også. Vanligvis kjennes det først og fremst i armer og bein, som er de stedene vi lettest kjenner økt blodsirkulasjon.

Her er noen studier som bekrefter effektene av CO2 beriket vann.

Beskriver det meste om balneotherapy, som det også heter. Inkludert kontraindikasjoner(hjerteproblemer og hypercapni som følge av lungeskade): http://www.centro-lavalle.com/edu/wp-content/uploads/2010/05/Carbon_Dioxide_Bath.pdf

Table 4. Major Indicators for CO2 Balneotherapy

1. Hypertension, especially borderline hypertension

2. Arteriolar occlusion, Stages I and II

3. Functional arteriolar blood flow disorders

4. Microcirculatory disorders

5. Functional disorders of the heart

Beskriver alt om hvordan det øker blodsirkulasjon og oksygenmetning: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3169585/?report=classic

Viser at det øker blodsirkulasjonen i huden og oksygenmetningen i muskelvev hos de som lett blir trøtte i beina: http://www.ncbi.nlm.nih.gov/pubmed/9112881/

Viser at det øker blodsirkulasjon og produksjonen av blodkar (angiogenese): http://circ.ahajournals.org/content/111/12/1523.long

Viser at det reparerer sår som ikke vil gro: http://iv.iiarjournals.org/content/24/2/223.long

Viser at det reparerer muskelskade: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3805014/

Viser at det reparerer muskelskade og atrofi (muskelsvikt) etter langtids post-operative sengeliggende: http://www.ncbi.nlm.nih.gov/pubmed/21371433

Viser at det reduserer hjertefrekvens gjennom å dempe sympaticus aktivering (ikke ved å øke parasymptaticus aktivering): http://jap.physiology.org/content/96/1/226

Viser at det øker mitokondrier og fjerner syster: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3499556/

Viser at det øker antioksidant status, reduserer frie radikaler og øker blodsirkulasjon i kapuillærene (mikrosirkulasjon): http://www.ncbi.nlm.nih.gov/pubmed/21248668

Viser at det hjelper til å reparere sår etter operasjon: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3595724/

Dr. Sircus sin forklaring av CO2 medisin som nevner mange måter å gjøre det på: http://drsircus.com/medicine/co2-medicine-bath-bombing-your-way-to-health

Denne artikkelen beskriver mye om historien til CO2-bad. http://ndnr.com/dermatology/cellulite-and-carbon-dioxide-bath/

Mange bilder av diabetes sår (OBS: ikke for sarte sjeler) som blir regenerert i løpet av få uker med 20-30 min fotbad. Disse bruker 900-1000ppm CO2 konsentrasjon. Jeg er usikker på om det er mulig med å blande Sitronsyre og Natron: http://www.iasj.net/iasj?func=fulltext&aId=48581

Denne artikkelen beskriver de fleste sider ved forskjellig bruk av CO2 behandling. God gjennomgang av hvordan blodsirkluasjonen påvirkes. http://www.scuolaeuropeamedicinaestetica.it/public/CARBOXYTHERAPY.pdf