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Biomedical subjects

M W Otter

Publications and source records attributed to M W Otter.

13 recordsLinked to original sources

On the relationship between streaming potential and strain in an in vivo bone preparation.

Transcortical streaming potentials were measured at each of two cortical-surface sites with respect to a reference electrode in the medullary canal, in the left ulnae of six live, adult (2 yr-old), male 18.2 +/- 1.4 kg domestic turkeys, under general anesthesia, for each of two loading conditions. We observed that the relationship among streaming potential magnitude, surface strain, and strain gradient is not as simple as anticipated. Under predominantly axial and bending load conditions, significantly different strain and strain gradients were generated at the two recording sites. However, no significant differences were detectable in transcortical streaming potentials for one of the loading conditions, and only a slight difference was detected in the other. Conversely, correlations of streaming potential magnitude to strain at both sites show robust relationships (r2 = 0.45, P - 0.02), albeit with different slopes for the two sites. These findings may have implications for the contribution of streaming potentials, or at least, fluid flow to the stimulation of bone cells.

Animals↗

Does bone perfusion/reperfusion initiate bone remodeling and the stress fracture syndrome?

Stress fractures have been proposed to arise from repetitive activity of training inducing an accumulation of microfractures in locations of peak strain. However, stress fractures most often occur long before accumulation of material damage could occur; they occur in cortical locations of low, not high, strain; and intracortical osteopenia precedes any evidence of micro-cracks. We propose that this lesion arises from a focal remodeling response to site-specific changes in bone perfusion during redundant axial loading of appendicular bones. Intramedullary pressures significantly exceeding peak arterial pressure are generated by strenuous exercise and, if the exercise is maintained, the bone tissue can suffer from ischemia caused by reduced blood flow into the medullary canal and hence to the inner two-thirds of the cortex. Site specificity is caused by the lack, in certain regions of the cortex, of compensating matrix-consolidation-driven fluid flow which brings nutrients from the periosteal surface to portions of the cortex. Upon cessation of the exercise, re-flow of fresh blood into the vasculature leads to reperfusion injury, causing an extended no-flow or reduced flow to that portion of the bone most strongly denied perfusion during the exercise. This leads to a cell-stress-initiated remodeling which ultimately weakens the bone, predisposing it to fracture.

Bone Remodeling↗

Skeletal cell stresses and bone adaptation.

There is no tissue in which mechanical stresses have been studied in more detail than the skeletal system, this focus arising primarily because bone plays a clear structural role in the body. However, the hypothesis that the skeleton represents an optimally designed structure has contributed remarkably little to our understanding of the development and adaptive capabilities of bone tissue. Recent investigations on the consequences of mechanical, hydrostatic, and electrical stresses on the cells of bone tissue have served to redirect the discussion of bone modeling and remodeling processes. These studies have refocused attention on the importance of chronic low-level dynamic stresses in mediating the physiologic response of bone tissue. Important recent observations suggest that an approach premised on the self-organizational properties of bone tissue may lead to significant improvements in our understanding and control of bone morphologic development, adaptation, and healing.

Adaptation, Physiological↗

Effects of electromagnetic fields in experimental fracture repair.

The clinical benefits of electromagnetic fields have been claimed for 20 centuries, yet it still is not clear how they work or in what circumstances they should be used. There is a large body of evidence that steady direct current and time varying electric fields are generated in living bone by metabolic activity and mechanical deformation, respectively. Externally supplied direct currents have been used to treat nonunions, appearing to trigger mitosis and recruitment of osteogenic cells, possibly via electrochemical reactions at the electrode-tissue interface. Time varying electromagnetic fields also have been used to heal nonunions and to stabilize hip implants, fuse spines, and treat osteonecrosis and osteoarthritis. Recent research into the mechanism(s) of action of these time varying fields has concentrated on small, extremely low frequency sinusoidal electric fields. The osteogenic capacity of these fields does not appear to involve changes in the transmembrane electric potential, but instead requires coupling to the cell interior via transmembrane receptors or by mechanical coupling to the membrane itself.

Bone and Bones↗

Streaming potentials in gap osteotomy callus and adjacent cortex. A pilot study.

This study documented streaming potentials generated in vivo by maturing osteotomy calluses in 10 canine tibiae. Gap osteotomies were allowed to heal for 6 or 12 weeks and were stabilized by an external fixator. Then, with the dogs under anesthesia, electrical measurements were made from 3 silver-silver chloride electrodes placed surgically in direct contact with the callus, with adjacent cortical bone, and with the medullary canal (reference electrode). Streaming potentials were recorded during step loading and sinusoidal bending (0.1-30 Hertz) as the tibia was deformed by 2 threaded pins coupled to a servohydraulic device. Streaming potentials were generated at callus and adjacent cortical sites, but the magnitude was greater on the immature, flexible callus, where bending strain was concentrated; as the callus became increasingly rigid, strain and streaming potential magnitude were distributed more evenly over the callus and adjacent cortical fragments. When normalized to surface strain, mean streaming potential per strain was less dependent on the microscopic structure, although on individual specimens streaming potential per strain at callus and adjacent cortical bone sites tended to increase with decreasing porosity. Despite a wide variation in data in this pilot series, these observations are consistent with the natural history of callus maturation: the maximum magnitude of streaming potentials in callus appears to decrease as the strain gradient across the site decreases, whereas streaming potentials normalized to strain increase as bone matures and becomes more dense.

Animals↗

Inflatable brace-related streaming potentials in living canine tibias.

In a canine osteotomy model, application of a pressurized brace increased the density of periosteal bone and, at 12 weeks postfracture, yielded a stronger union compared with fractures treated by conventional cast, as determined by biomechanical testing. Pulsatile transcortical electric potentials were caused by the fluctuations in intramedullary pressure that result from active circulation. This report describes a collaborative effort designed to determine whether pressure fluctuations within an inflatable brace, placed over a canine calf, can affect endogenous transcortical electric potentials. Pressure within a brace placed over a canine hindlimb was observed to oscillate between 20 and 52 mm Hg during normal ambulation in 3 dogs. Manual pulsatile inflation of a similar brace, causing brace pressure fluctuations between 12 mm Hg and 130 mm Hg, produced fluctuating transcortical electric potentials ranging from 1.2 microvolts to 87 microvolts in anesthetized canines. These electric potentials were proportional to intramedullary pressures between 3.4 mm Hg and 59 mm Hg. Transcortical electric potentials resulting from the application of a pressurized brace, rather than conventional casting, may be part of the mechanism by which the changes in fracture healing are achieved.

Animals↗

Streaming potential measurements at low ionic concentrations reflect bone microstructure.

Streaming potentials (SPs) have been proposed as one transduction pathway for mechanically driven bone remodeling. The fluid spaces in which SPs are generated will determine, in part, the structural information that they can provide to bone cells. Streaming potential measurements across cortical bone strips soaked in a range of saline concentrations were used to estimate the mean radii of fluid spaces that contribute to generation of electrokinetic fields. Using a cylindrical pore model, a pore radius of less than 200 A fit SP magnitude as a function of concentration. This pore size was shown to be consistent with estimates obtained from data reported earlier for SP as a function of concentration using a non-specific model, but was smaller than previously reported estimates for pore radius. A pore size in this range indicates that flow either in bone microporosity, or canaliculi that are substantially occluded by cellular material, must generate streaming potentials. Further, the fact that such small pores generate SPs in bone indicates that SPs could provide information regarding local matrix structure to bone cells.

Animals↗

Mechanotransduction in bone: do bone cells act as sensors of fluid flow?

When compact bone is subjected to bending loads, interstitial fluid in the bone matrix flows away from regions of high compressive stress. The amount of interstitial fluid flow is strongly influenced by the loading rate in a dose-dependent fashion. We hypothesize that interstitial fluid flow affects bone formation, and we tested this hypothesis indirectly by measuring the effect of different loading frequencies on bone formation rate in vivo. The right tibiae of adult female rats were subjected to applied bending at frequencies of 0.05, 0.1, 0.2, 0.5, 1.0, and 2.0 Hz for a 2-wk period. The rats were then killed and histomorphometric measurements of bone formation were made of the midshaft of the tibia. Bending of the tibia increased bone formation rate in the higher-frequency (0.5 to 2.0 Hz) loading groups as much as fourfold, yet no increase in bone formation rate was observed for loading frequencies below 0.5 Hz. In a separate experiment, we found stress-generated potentials (SGP) in the rat tibia to increase monotonically with increasing loading frequency. The dose-response relationship between loading frequency and the bone formation response closely resembles the relationship between loading frequency and SGP within bone. The qualitative similarity between these two relationships suggests that increased bone formation is associated with increased SGP, which are caused by interstitial fluid flow. Bone cells are known to be sensitive to electric fields and may respond directly to SGP. Also, fluid shear forces have been shown to stimulate bone cells in culture, so it is possible that increased interstitial fluid flow directly affects bone formation.

Animals↗

Intraarterial protamine sulfate reduces the magnitude of streaming potentials in living canine tibia.

Using previously described techniques, transcortical streaming potentials were measured at two middiaphyseal sites on one tibia of each of nine anesthetized canines during sinusoidal bending (approximately 0 to -200 mu epsilon periosteal surface strain) at 2 Hz. Measurements were made for 60 minutes prior to and up to 180 minutes following bolus injection of protamine sulfate (42-126 mg/kg) dissolved in Hanks Balanced Salt Solution, directly into the femoral artery without interrupting circulation. Shortly after injection, the protamine sulfate caused a clear reduction in the magnitude of streaming potentials. Subsequent injections of additional protamine sulfate resulted in further reductions, and in several instances, voltage sign reversals. This study represents the first observation that circulating proteins may alter electromechanical transduction in living bone, and suggests the possibility that specific agents, which are known to affect bone remodeling, may do so, in part, by altering these endogenous electrical potentials.

Animals↗

A comparative analysis of streaming potentials in vivo and in vitro.

Streaming potentials (SPs) measured in vivo at a specific site on intact cortical bone (canine tibia) have been compared with measurements from the same site in vitro, tested as an excised bone strip soaked in Hank's balanced salt solution. The amplitude of SPs per periosteal strain in vitro was larger in 13 tibias than in vivo (by an average x6.5 at 1 Hz), but values per transcortical strain difference were similar. In vitro, SP magnitudes rose more sharply to an asymptotic value as a function of bending frequency than did in vivo signals, possibly because of a difference in the internal state of canaliculi and/or Haversian systems. Similarly, SP response to step-loading decreased to zero more slowly with time in vitro than in vivo. Difficulties encountered in preliminary measurements due to electrical shunting through electrolyte and soft tissues suggest the need for caution in using both in vivo and in vitro SP measurements to extrapolate to electric field strengths on the cellular level.

Animals↗

Transcortical streaming potentials are generated by circulatory pressure gradients in living canine tibia.

Electrical potentials associated with the pulse pressure have been observed in a canine tibia model in vivo. As the medullary pressure rises during pulsing, the periosteal bone surface becomes positive with respect to the endosteal surface. This pattern is consistent with streaming potentials generated by outward flow of fluid through bone with a negatively charged matrix (negative zeta potential). Both the medullary pressure and electric potential oscillations are halted by occlusion of the femoral artery. Furthermore, systemic administration of epinephrine decreases the amplitude of the medullary pressure and the electric potential by the same fraction. Streaming potentials generated by blood flow are distinct from those generated by mechanical deformation and may have additional significance in relation to fracture healing and/or etiology of osteoporosis.

Animals↗

An improved design of electrodes for measurement of streaming potentials on wet bone in vitro and in vivo.

Streaming potentials are generated by mechanical stress in wet bone and may constitute a control mechanism for bone remodeling. Measurement of streaming potentials in bone has attracted considerable effort in past years but quantitative studies have been hampered by relatively poor repeatability when using Ag.AgCl electrodes which contact bone via a wick moistened with electrolyte. Improvement now has been achieved with an electrode design that limits the specific area of contact of an agar/salt bridge by means of a silastic seal, thus permitting the same equipotential surface to be contacted for each set of measurements. This reduces variations caused by bone structure and impedance, and facilitates quantitative comparisons of the response of bone samples to selected variables. The new design also permits considerable qualitative improvement in recordings made from bone during locomotor function in experimental animals in vivo.

Acrylic Resins↗