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Biomedical subjects

J B Bassingthwaighte

Publications and source records attributed to J B Bassingthwaighte.

At least 109 records · Page 6Linked to original sources

Bone extraction and blood clearance of diphosphonate in the dog.

The transcapillary extraction of diphosphonate, as [99mTc]EHDP, a substance used in bone scanning and for management of certain metabolic bone diseases, has been examined. The maximum instantaneous extraction for [99mTc]EHDP was 0.27 +/- 0.05 (mean +/- SD, N = 10) and the net extraction at 5 min was 0.18 +/- 0.05 (N = 10). The permeability ratio of [99mTc]EHDP to the freely diffusible compound, sucrose, using the formula PS = -Fs loge (1 - Emax), was 0.71. This is similar to the ratio of diffusion coefficients of EHDP to sucrose, which is estimated to be 0.78. These results suggest that the mechanism by which [99mTc]EHDP passes through the capillaries in bone is passive diffusion. Tissue level estimations of EHDP confirm a rapid blood clearance associated with an increase in the rate of urinary excretion; the level of [99mTc]EHDP in bone, however, remains constant. The fractional excretion of [99mTc]EHDP was 27.3 +/- 2.0% in control dogs and was unchanged by thyroparathyroidectomy and subsequent infusion of parathyroid hormone.

Animals↗

Studies on bone ion exchanges using multiple-tracer indicator-dilution techniques.

Free diffusion appears to be the principal mechanism for movement of ions, known to concentrate in bone, across the capillaries of bone. The interstitial fluid space appears large enough to allow for determination of instantaneous fractional escape by the indicator-dilution method. The mechanism by which large molecules, such as the diphosphonate 99mTc-labeled EHDP or 99mTc-labeled pyrophosphate, pass through capillaries in bone is by passive diffusion. These molecules are larger than 85Sr and their lower extraction rate is presumably due to the effect of their sizes on passage through transcapillary clefts. A corollary of these studies might be that if transcapillary exchange is passive, then partition of anions and cations likely lies beyond the capillary and therefore is controlled by osteal cellular processes.

Blood Flow Velocity↗

Estimation of blood flow with radioactive tracers.

The techniques of tracer dilution in the circulation, and of tracer uptake by and washout from an orgen, may be described using expressions that are general and are not dependent on specific models such as exponentials. The expressions have been applied to the measurement of cardiac output using impulse and constant rate injection techniques. Further expressions have been given for estimating organ blood flow from inflow/outflow concentration-time curves, and from the distribution of deposited tracer. Some problems with respect to the use of deposition techniques as they are ordinarily applied to the estimation of regional blood flow must be considered, particularly when there are capillary beds in series or where there is countercurrent diffusional shunting of diffusible tracers between inflow and outflow. This review deals with these various aspects of tracer theory as they relate to the measurement of blood flow.

Blood Circulation↗

Relationship between internal calcium and outward current in mammalian ventricular muscle; a mechanism for the control of the action potential duration?

In sheep and calf ventricular bundles, increasing the internal calcium by increasing the frequency of voltage-clamping to plateau range potentials increased the time-independent outward current. This effect was more marked with higher [Ca]o, and was reduced if the Ca current blockers Verapamil or D 600 were used. 2. If the internal Ca was increased by the addition of cyanide and reduction of external sodium the outward current was also increased. The frequency-dependent increase in outward current also occurred in this Na-poor (12 mM) solution. 3. Tension measurement on the ventricular bundles showed that a Na-free solution with cyanide did not cause a contracture. On changing from Tyrode to a Na-free solution containing cyanide, and on changing back to Tyrode there was a potentiation of the twitch. 4. In Na-poor solution with cyanide, although no contracture was found, ECa was less positive, suggesting that under these circumstances Ca accumulates at the inner side of the membrane, but not around the myofibrils. 5. The prolongation of the action potential in Cl-free solution is frequency-dependent. A greater prolongation is seen at lower frequencies suggesting that Cl current is relatively more important for repolarization at lower frequencies of stimulation. 6. It is suggested that calcium at the inner side of the membrane sets the level of the background outward current. A feed-back mechanism on this basis is proposed for the control of the action potential duration. Various factors that could influence this basic mechanism are discussed.

Action Potentials↗

Transcapillary exchange of strontium and sucrose in canine tibia.

The walls of haversian capillaries have been proposed as a physiologic membrane controlling flux of solute between blood and bone. In this study, capillary permeability to 85Sr and [14C]sucrose was estimated in the dog tibia by using indicator dilution techniques. Sucrose was chosen as a tracer because it is inert and has no known transport system. The mean (+/-SD) observed ratio of permeabilities of 85Sr and sucrose was 2.36 +/- 0.46 (N = 14) which is not substantially different from the ratio of their free diffusion coefficients, 2.55. This ratio was not influenced when the dogs were made hyperparathyroid by injection of parathyroid hormone (2.16 +/- 0.55; N = 11). This suggests that free diffusion is the principal mechanism for moving 85Sr across the bone capillary wall.

Animals↗

Capillary and cell wall permeability to potassium in isolated dog hearts.

From venous tracer-dilution curves recorded after 36 pulse injections of 42KCl and 131I-labeled albumin into the coronary artery inflow of 15 isolated canine heart preparations, we calculated maximal fractional extractions (Emax) and capillary permeability-surface area products (PScap) for 42K+ over a range of plasma flows (FP) from 0.3 to 1.7 ml min-1 g-u. At low FP (less than 1.0), Emax was 0.60 +/- 0.0l (mean +/- SD) and PScap was 0.72 +/- 0.20 ml min-1 g-1; at high FP (greater than 1.0), Emax decreased to 0.49 +/- 0.05 and PScap increased to 1.06 +/- 0.18. Continuous recording (gamma detector) of residual myocardial 42K+ in seven hearts showed that the mean fractional escape rate of tracer between 30 and 60 min after injection was 0.011-0.023 min-1; higher rates were observed at high FP, when the residue of 42K+ decreased to less than 10% of the injected dose by 60 min. Using PScap measured at high FP and considering the virtual intracellular volume of distribution for K+ to be 20 ml/g, we calculated the permeability-surface area product for sarcolemma (PScw) as 0.54-0.73 ml min-1 g-1, or about 50% of PScap. Considering sarcolemmal surface area (Scw) as 4,200 cm2/g and capillary surface area (Scap) as 500 cm2/g, cell permeability is low, with Pcw:Pcap being less than 0.08.

Animals↗

Strontium-85 extraction during transcapillary passage in tibial bone.

Indicator dilution experiments were done to determine the extraction of 85Sr during a single passage through capillaries of the tibial diaphysis. Extraction was estimated by injection of 85SrCl2 and a nonpermeant, reference tracer, T-1824-labeled albumin, into the nutrient artery and recording of the effluent venous dilution curves (femoral vein). The mean (+/- SD) maximal instantaneous extraction was 0.53 +/- 0.08 (N = 12). Net retention after 10 min, estimated from venous curves, was 0.41 +/- 0.06 (N = 12), which appeared not substantially different from the retention estimated by direct isotope counting of the tibias for 85Sr, 0.35 +/- 0.06 (N = 12). In a second set of experiments in intact animals, tibial 85Sr extraction after intravenous injection was apparently higher, 0.53 +/- 0.28 (N = 15). Values of tibial diaphyseal blood flow, estimated from washout curves for iodoantipyrine after tibial nutrient artery injection, were 1.47 +/- 0.63 ml/min per 100 g (N = 27). The extraction was not much diminished by higher flows. The estimates of permeability-surface area product (PS) for bone capillaries did increase with flow, suggesting recruitment of more capillaries at higher flows. PS values averaged 0.63 +/- 0.29 (N = 12); we conclude that the capillary membrane is a primary barrier to the passage of 85Sr and presumably other small hydrophilic solutes.

Animals↗

Myocardial sodium extraction at varied coronary flows in the dog. Estimation of capillary permeability of residue and outflow detection.

Sudden injections of boluses containing both 131I-albumin and 24NaCl were made into the coronary artery inflow of isolated blood-perfused dog hearts. Indicator dilution curves were recorded using gamma emissions from both the intact heart and the coronary sinus outflow, with plasma flows, Fs, ranging from 0.3 to 1.8 ml/g min-1. Three measures of sodium extraction, E, during transcapillary passage were obtained from each site by comparison of the sodium and albumin curves. The most useful estimates of E were "instantaneous extractions" obtained from the later part of the upslope and the peak of the venous dilution curves (coronary sinus) or from the corresponding early phase of washout of the externally monitored curves (intact organ). Extractions were lower at higher flows. Permeability-surface area products, PS, were computed (1) by the formula PS equals -Fsloge(1 - E), (2) by fitting the observed dilution curves with a Krogh capillary-tissue cylinder model, and (3) by the approximating formula PS equals -Fsloge (1 - 1.14E). The two latter approaches provided a correction for back diffusion of tracer from tissue to blood. For sodium, the values of PS averaged 0.88 +/- 0.36 (SD) ml/g min-1, (n equals 52). At high flows, with Fs greater than 1.0 ml/g min-1, the values of PS averaged 1.01 +/- 0.38 ml/g min-1 (N equals 11). Assuming S equals 500 cm2/g and plasma to be 93% water, our findings suggest capillary permeabilities for sodium of about 3.1 times 10(-5) cm/sec.

Animals↗