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Biomedical subjects

M W Otter

Publications and source records attributed to M W Otter.

8 recordsLinked to original sources

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.

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