Extraction of minerals after experimental fractures of the tibia in dogs

Abstract

In a study of a standardized fracture of the tibia in dogs, we examined the relationship between extraction of strontium-85, as measured by a multiple indicator-dilution technique, and blood flow, as determined by an iodoantipyrine-washout technique. Although the blood flow at the fracture site increased from a control value of 1.5 milliliters per 100 grams of bone per minute to a value of 6.65 milliliters per 100 grams of bone per minute at two weeks, the maximum instantaneous extraction of ⁸⁵Sr by the fractured tibiae did not change from a value of about 0.77 of the amount injected. These results suggest that the increase in blood flow is accomplished by recruitment of capillaries, that the permeabilities of the capillary beds in the fractured tibia and in the normal tibia are similar, and that the pattern of flow in the fractured tibia remains non-uniform. The increased capillary surface area available for exchange is suggested as the reason that strontium extraction was unchanged despite the increased flow.

Clinical Relevance: This study has shown that calcium is only moderately rapidly exchangeable across the capillary membrane and made available for uptake by osteoblasts and deposition in callus at the fracture site. Because calcium delivery via capillary is essential, and because capillary surface area is ordinarily increased in the region of a healing fracture, we can now see clearly that clinical treatment, in particular manipulative intervention, should be carried out in a fashion that minimizes damage to the capillary bed. The exchange processes described in this study are the same as those involved in the deposition of agents used for bone-scanning, and thus this information provides a basis for the timing of scanning studies and for their interpretation.

Fig. 1

Tracers are injected into the nutrient artery and blood is collected from the femoral vein.

Fig. 2

Top: Indicator-dilution curves showing changes in the fraction of the reference tracer, h_R(t), and in the fraction of the test tracer, h(t), in the outflow in the femoral vein with time. Bottom: Instantaneous extraction, E(t), and the maximum instantaneous extraction, E_max, calculated from the indicator-dilution curves by the equation shown (see text).

Fig.3

Net extraction, E_net, is equivalent to the shaded areas between the indicator-dilution curves of the reference and of the test tracers divided by the total area beneath the curve of the reference tracer up to time t (see Fig. 2). The cross-hatched area to the right of where the curves cross indicates the extent to which back-diffusion has become greater than efflux from the capillaries. The net extraction, E_net, shown in the bottom graph, is calculated by using Equation 14, as shown (see text).

Fig. 4

Proximal tibial diaphyseal blood flow measured from the washout curve determined by a modification of the height/area method of Zierler (Equation 2). C*(0) is peak activity recorded over the tibia, C*(T) is activity recorded at fifteen minutes, when recording was stopped, and C*(t) is the counts per minute at time t (see text).

Fig. 5

A Indicator-dilution curves for albumin-⁵¹Cr, sucrose-¹⁴C, and ⁸⁵Sr, after a forty-seven-second infusion into the nutrient artery of a dog’s tibia. B Corresponding instantaneous extractions, E(t), calculated by Equations 10 and 14. Maximum instantaneous extraction, E_max, is the highest initial instantaneous extraction, which in this case is at thirty seconds and not eighty-six seconds, when back-diffusion has occurred (see Fig. 3). Net extraction. E_net(t), is 1.0 minus the ratio of the fraction of the injected tracer. ⁸⁵Sr, that has emerged at time t divided by the fraction of the non-permeant albumin which has emerged by that time; therefore, in the late phase, such as at 180 seconds. E_net (t) = 180 is a measure of the retention of strontium by the bone at this time. Mean transit time of injection. T_in, for albumin is 23.5 seconds.

Fig. 5

A Indicator-dilution curves for albumin-⁵¹Cr, sucrose-¹⁴C, and ⁸⁵Sr, after a forty-seven-second infusion into the nutrient artery of a dog’s tibia. B Corresponding instantaneous extractions, E(t), calculated by Equations 10 and 14. Maximum instantaneous extraction, E_max, is the highest initial instantaneous extraction, which in this case is at thirty seconds and not eighty-six seconds, when back-diffusion has occurred (see Fig. 3). Net extraction. E_net(t), is 1.0 minus the ratio of the fraction of the injected tracer. ⁸⁵Sr, that has emerged at time t divided by the fraction of the non-permeant albumin which has emerged by that time; therefore, in the late phase, such as at 180 seconds. E_net (t) = 180 is a measure of the retention of strontium by the bone at this time. Mean transit time of injection. T_in, for albumin is 23.5 seconds.

Fig. 6

Plots of the peak instantaneous extractions, E_max, and of net extractions, E_net, of strontium and sucrose against the plasma flow including least-squares regression lines. Note that peak extraction (E_max), especially of strontium, is not affected by the amount of plasma flow.

Fig.7

Plot of permeability-surface area product, PS, against flow of plasma, F_s, to demonstrate linear relationship.