Microspheres Accurately Predict Regional Bone Blood Flow

Anetzberger, H.; Thein, E.; Becker, Markus; Zwißler, Bernhard; Meßmer, K.

doi:10.1097/01.blo.0000128281.67589.b4

Cited by 19 publications

(15 citation statements)

References 65 publications

(89 reference statements)

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“…Different methods measure different levels of the circulatory system, such as limb blood flow and local microcirculation. Blood flow in bone tissue has been evaluated using bone scintigraphy [8], single-photon emission computed tomography [11], Doppler ultrasonography [21], radionuclide-labeled and fluorescent microspheres [1], positron emission tomography [15], laser-Doppler flowmetry [14,25], and intravital microscopy television system in combination with confocal laser-scanning optics [20]. The last two techniques require surgical manipulation of the bone and therefore may introduce artifacts attributable to local manipulation of the vessels.…”

Section: Clinical and Anatomical Backgroundmentioning

confidence: 99%

Non-invasive continuous estimation of blood flow changes in human patellar bone

et al. 2006

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A photoplethysmographic (PPG) technique to assess blood flow in bone tissue has been developed and tested. The signal detected by the PPG consists of a constant-level (DC) component-which is related to the relative vascularization of the tissue-and a pulsatile (AC) component-which is synchronous with the pumping action of the heart. The PPG probe was applied on the skin over the patella. The probe uses near-infrared (804 nm) and green (560 nm) light sources and the AC component of the PPG signals of the two wavelengths was used to monitor pulsatile blood flow in the patellar bone and the overlying skin, respectively. Twenty healthy subjects were studied and arterial occlusion resulted in elimination of PPG signals at both wavelengths, whereas occlusion of skin blood flow by local surface pressure eliminated only the PPG signal at 560 nm. In a parallel study on a physical model with a rigid tube we showed that the AC component of the PPG signal originates from pulsations of blood flow in a rigid structure and not necessarily from volume pulsations. We conclude that pulsatile blood flow in the patellar bone can be assessed with the present PPG technique.

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Section: Clinical and Anatomical Backgroundmentioning

confidence: 99%

Non-invasive continuous estimation of blood flow changes in human patellar bone

et al. 2006

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“…Femur, tibia, paw, and tail vertebrae (caudal 1-4) were immediately harvested and cleaned of soft tissue. Microspheres were recovered after published digestion/filtration methods (18,(41)(42)(43). In brief, individual bones were weighed, demineralized in Cal-Ex (Fisher Scientific), and digested in ethanolic KOH.…”

Section: Methodsmentioning

confidence: 99%

“…To determine whether a cold-induced reduction in skeletal blood supply contributed to extremity foreshortening, we measured relative bone blood flow (BBF) to the hindlimb bones and tail base of juvenile mice by using fluorescent microspheres, a reliable standard for quantifying regional organ and bone perfusion (18). We predicted that BBF would positively covary with rearing temperature and bone elongation as previously hypothesized.…”

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confidence: 99%

Temperature regulates limb length in homeotherms by directly modulating cartilage growth

Serrat

King

Lovejoy

2008

Proc. Natl. Acad. Sci. U.S.A.

130

121

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Allen's Rule documents a century-old biological observation that strong positive correlations exist among latitude, ambient temperature, and limb length in mammals. Although genetic selection for thermoregulatory adaptation is frequently presumed to be the primary basis of this phenomenon, important but frequently overlooked research has shown that appendage outgrowth is also markedly influenced by environmental temperature. Alteration of limb blood flow via vasoconstriction/vasodilation is the current default hypothesis for this growth plasticity, but here we show that tissue perfusion does not fully account for differences in extremity elongation in mice. We show that peripheral tissue temperature closely reflects housing temperature in vivo, and we demonstrate that chondrocyte proliferation and extracellular matrix volume strongly correlate with tissue temperature in metatarsals cultured without vasculature in vitro. Taken together, these data suggest that vasomotor changes likely modulate extremity growth indirectly, via their effects on appendage temperature, rather than vascular nutrient delivery. When combined with classic evolutionary theory, especially genetic assimilation, these results provide a potentially comprehensive explanation of Allen's Rule, and may substantially impact our understanding of phenotypic variation in living and extinct mammals, including humans.Allen's Rule ͉ bone growth ͉ bone tissue culture ͉ cartilage biology ͉ thermoregulation E cogeographical rules relating climate to extremity length and body mass have long been central tenets of biology, and are among the best supported observations in natural-dwelling species (1). Allen's Rule codifies the observation that appendages (ears, limbs, and tails) of animals living in cold geographical regions are consistently shorter than those of closely related counterparts occupying warmer climes (2). Shortened extremities minimize heat loss by reducing surface area relative to volume and have long been viewed as genetically determined thermoregulatory adaptations (1). However, the heritability of extremity length is largely unknown, because similar phenotypes can be reproduced in laboratory mammals by modifying their ambient rearing temperature (3-6) (Fig. 1). The mechanism by which environmental temperature modulates extremity growth has remained elusive (7,8). Understanding growth plasticity is critical to basic evolutionary analyses, because many characters that have long been hypothesized to be adaptations may instead be partial or even entirely effects of ambient temperature (9, 10). Moreover, knowledge of this phenotypic plasticity will be a key factor in ecological conservation strategies for anticipated changes in global climate that may have direct impacts on human economics and sustainability (11).The traditional explanation for temperature-growth effects in skeletal extremities is an altered supply of essential nutrients and growth factors via increased or decreased blood flow that results from changes in vasomotor tone (i.e., t...

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“…Of particular consideration are the many parameters that need to be accurately accounted for: sufficient mixing in the central circulation, good first pass extraction, no separation from the blood, no measurement possible in the second of two capillary beds in series, no obstruction of arterioles, tracer leakage from particle, homogenous particle size, and label intensity. 48 Despite these limitations, it has been used under many different experimental circumstances to measure regional bone blood flow 2,33,37,39,40,43,45, and has been used to validate new blood flow methods in bone such as noble gas washout 34 and laser Doppler flowmetry. 70 The hydrogen washout method of regional blood flow measurement was developed by the Norwegian physiologist Aukland and colleagues 38 and first applied to bone tissue by Whiteside et al 6 in the rabbit; he assumed that his measurements were accurate because they were similar to those reported by other methods.…”

Section: Discussionmentioning

confidence: 99%

“…8,32 Radioactive labeled microsphere entrapment is widely regarded as the gold standard of indirect methods of blood flow measurement and has been used to validate other techniques. [33][34][35] The use of high-energy gamma-emitting radioactive labels and the necessity to remove tissues for measurement means that it is unsuited for the clinical setting. Furthermore, tissues of sufficient size and/or blood flow to allow sufficient entrapment in the capillary bed are needed.…”

mentioning

confidence: 99%

Measurement of bone blood flow using the hydrogen washout technique—part II: Validation by comparison to microsphere entrapment

Larsen

Pelzer

Friedrich

et al. 2008

Journal Orthopaedic Research

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Accurate and reproducible measurement of bone blood flow has important clinical and experimental applications. Hydrogen washout is simple, safe, and widely used, but its use in bone tissue has not been validated. To this end, we have compared cortical bone blood flow measurements obtained by radioactive-labeled microsphere entrapment with those from hydrogen washout. Blood flow was measured in tibial cortical bone of 12 New Zealand White rabbits by radioactive microsphere entrapment and by hydrogen washout. Besides a control group (n ¼ 6), four animals were treated with systemic epinephrine (0.8 mg/kg/min) (group 2) and two with nitroprusside (100 mg/kg/min) (group 3). Furthermore, nine femora from seven rats were isolated on their vascular pedicles and repeated bone blood flow measurements were made at each location with the hydrogen washout method to confirm reproducibility of blood flow determinations by hydrogen washout. An average flow of 2.3 AE 2.0 mL/min/100 g was obtained with the microsphere method and 2.0 AE 0.5 mL/min/100 g with the hydrogen washout method. There was a significant correlation and agreement: R 2 ¼ 0.97 (p < 0.01). No consistent flow variations were found with systemic vasoactive drug administration. Hydrogen washout provided reproducible results and showed high sensitivity to flow changes. Hydrogen washout is both sensitive and reproducible in measuring bone blood flow. Results agree well with flow values obtained by labeled microsphere entrapment. ß

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Microspheres Accurately Predict Regional Bone Blood Flow

Cited by 19 publications

References 65 publications

Non-invasive continuous estimation of blood flow changes in human patellar bone

Non-invasive continuous estimation of blood flow changes in human patellar bone

Temperature regulates limb length in homeotherms by directly modulating cartilage growth

Measurement of bone blood flow using the hydrogen washout technique—part II: Validation by comparison to microsphere entrapment

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