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Biomedical subjects

A P Shepherd

Publications and source records attributed to A P Shepherd.

At least 37 records · Page 2Linked to original sources
PubMed1988

Intramural distribution of intestinal blood flow during sympathetic stimulation.

Recent studies indicate that the mucosal circulation of the small intestine possesses more potent local circulatory control mechanisms than the muscularis. Several lines of evidence support this assertion: the absence of reactive hyperemia in the muscularis, the confinement of glucose-induced hyperemia to the mucosal circulation, and the more effective autoregulation of villus blood flow in comparison with total blood flow. Therefore, we postulated that the mucosal circulation would exhibit a more pronounced ability to escape the vasoconstrictor influence of sympathetic nerve stimulation. To test this hypothesis, we used laser-Doppler velocimetry (LDV) to study the effects of perivascular nerve stimulation on blood flow in the muscularis and mucosa of isolated dog intestine. In two series of experiments, we measured total blood flow to a gut loop with an electromagnetic flow probe on the supply artery, while LDV measurements were made either on the mucosa or on the muscularis. Sympathetic stimulation (10 Hz) transiently reduced total blood flow to approximately 10% of control in both studies. Muscularis and mucosal blood flow both reached minimal values. Subsequently, total blood flow and the two regional perfusions exhibited "autoregulatory escape," but the propensity for blood flow to escape from sympathetic vasoconstriction was significantly greater in the mucosa than in the muscularis. These data provide more evidence that, compared with the muscularis, the intestinal mucosa possesses more potent local control mechanisms that oppose neurogenic vasoconstriction.

Animals↗
PubMed1988

Diffusion model of the optical absorbance of whole blood.

Photon-diffusion theory has had limited success in modeling the optical transmittance of whole blood. Therefore we have developed a new photon-diffusion model of the optical absorbance of blood. The model has benefited from experiments designed to test its fundamental assumptions, and it has been compared extensively with transmittance data from whole blood. The model is consistent with both experimental and theoretical notions. Furthermore, when all parameters associated with a given optical geometry are known, the model needs no variational parameters to predict the absolute transmittance of whole blood. However, even if the exact value of the incident light intensity is unknown (which is the case in many situations), only a single additive constant is required to scale experiment to theory. Finally, the model is shown to be useful for simulating scattering effects and for delineating the relative contributions of the diffuse transmittance and the collimated transmittance to the total optical density of whole blood. Applications of the model include oximetry and measurements of the arteriovenous oxygen difference in whole, undiluted blood.

Absorption↗
PubMed1987

Autoregulation of canine gastric mucosal blood flow.

Although autoregulation of total blood flow has been demonstrated in the stomach, autoregulation of gastric mucosal blood flow has not been investigated due to the limitations of previously available mucosal blood flow measuring techniques. We recently evaluated laser-Doppler velocimetry for use in the stomach and found it to yield continuous, superficial measurements of either mucosal or muscularis blood flow. In the present study, simultaneous measurements of total, mucosal, and muscularis blood flows and arteriovenous oxygen difference were made during step decreases in perfusion pressure in chambered segments of resting canine stomach. As perfusion pressure was decreased from 180 to 35 mmHg, oxygen consumption remained relatively constant at 1.5 ml/min X 100 g and only became blood flow-dependent when perfusion pressure was set below 90 mmHg and total blood flow fell below 35 ml/min X 100 g. Oxygen consumption was maintained partly by increased oxygen extraction; however, there was also a progressive increase in the tendency for total blood flow autoregulation after each drop in perfusion pressure. Mucosal blood flow was also well autoregulated over the physiologic range of perfusion pressure and remained relatively constant during the plateau portion of the oxygen consumption curve. Our results indicate that in the resting stomach, oxygen consumption is maintained by changes in oxygen extraction in conjunction with autoregulation of mucosal and total blood flow.

Action Potentials↗
PubMed1987

Local control of canine gastric mucosal blood flow.

The hemodynamic responses to venous pressure elevation and the effect of metabolic stimulation on reactive hyperemia and autoregulation were assessed in chambered segments of the canine gastric corpus perfused by a pressurized reservoir. Arteriovenous oxygen difference, mucosal pH, and total, mucosal, and muscularis blood flow were monitored continuously. Pentagastrin increased acid secretion, oxygen consumption, and both total and mucosal blood flow. Before and after pentagastrin, the magnitude of reactive hyperemia was correlated with the occlusion duration. During stepwise reductions in perfusion pressure, oxygen consumption was relatively constant and blood flow-independent over most of the pressure range. Mucosal blood flow was well maintained except at the lowest perfusion pressure. Pentagastrin did not enhance autoregulation in the mucosa or muscularis, but did enhance the autoregulation of total blood flow. A myogenic vasoconstriction occurred during 20-mmHg venous pressure elevations. Our results indicate that both metabolic and myogenic mechanisms regulate the gastric mucosal circulation.

Animals↗
PubMed1987

Evaluation of an infrared laser-Doppler blood flowmeter.

Several laser-Doppler blood flowmeters are now commercially available; however, only one utilizes an infrared laser diode (Laserflo, TSI, St. Paul, MN). Because of this and other unique features such as its microprocessor-based signal analyzer, we evaluated this device's ability to measure tissue perfusion. Initially, we determined whether laser illumination directly affected the microvasculature. Intravital microscopic observations in the hamster cremaster muscle indicated that neither He-Ne nor infrared laser light affected the diameters of arterioles that were responsive to vasoactive agents. To test the flowmeter for linearity and repeatability, we used a rotating disk to simulate a light-scattering, flowing medium. The "flow" signal was highly correlated (r = 0.99) with the rotational velocity of the disk, was consistent among flow probes, and showed a high degree of reproducibility. The second model consisted of microsphere suspensions pumped through cuvettes. The laser-Doppler velocimeter (LDV) flow signal was linear with respect to pump output. With red blood cells in the perfusate, we examined the effects of blood oxygenation on the flowmeter's performance. The LDV flow signal was unaffected by changes in blood oxygenation. We evaluated linearity in vivo in isolated, perfused rat livers and in isolated canine gastric flaps. We observed linear relationships between total flow and laser-Doppler flow measured on the surface of the liver (r = 0.98) and in the gastric mucosa (r = 0.98), but the slopes of the relationships between total and local LDV flow showed considerable variability not noted in the in vitro studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Hybrid blood flow probe for simultaneous H2 clearance and laser-Doppler velocimetry.

To perform two independent regional blood flow measurements in tissue volumes of similar dimensions, we designed a hybrid blood flow probe capable of measuring regional perfusion by both laser-Doppler velocimetry (LDV) and H2 clearance. The probe consisted of two fiber-optic light guides to conduct light between the surface of tissue of interest and a laser-Doppler blood flowmeter. Also contained within the probe were a platinum 25-microns H2-sensing electrode and a 125-microns H2-generating electrode. The probe can thus be used to measure local perfusion with H2 clearance. The H2 can either be inhaled or can be generated electrochemically at the locus of interest. Evaluation of the probe in the canine gastric mucosa indicated 1) that the relationship between mucosal flow measurements made simultaneously with H2 clearance and LDV was highly significant and linear and 2) that H2 clearance could potentially be used to calibrate the laser-Doppler blood flowmeter in absolute units. The methods of constructing the flow probes are discussed in detail.

Animals↗
PubMed1987

Reflectance measurements of hematocrit and oxyhemoglobin saturation.

Fiberoptic oximeters measure oxyhemoglobin saturation from the optical reflectance of whole blood, but the calibration of such oximeters is hematocrit dependent. Therefore, using photon-diffusion theory and an empirical approach, we have developed a new reflectance method that determines hematocrit and correspondingly corrects the oxyhemoglobin-saturation measurement. Our method employs four fiber-optic light guides, a photodetector, and three inexpensive light-emitting diodes (one with emissions at 660 nm and two at 813 nm). Hematocrit is determined from the ratio of reflectances from the differently spaced emitting fibers at 813 nm and is used to correct the 813-660 nm measurement of oxyhemoglobin saturation. In red cell suspensions, the mean difference between reflectance measurements of hematocrit and conventional determinations was only 2.09% (r = 0.99), and when compared with conventional gasometric measurements of oxyhemoglobin saturation, the reflectance method yielded the same calibration curve for different hematocrits and gave a mean difference of only 2.67%. Although the technique is demonstrated with a cuvette appropriate for an extracorporeal circulation in animal experiments, it could possibly be further developed for fiber-optic catheter oximeters.

Animals↗
PubMed1986

Estimation of the distribution of blood vessel diameters from the arteriovenous passage of microspheres.

We present an estimator of the probability density of capillary diameters based on a simple probabilistic model of microsphere passage through a microvascular bed. With this model, an estimate of the density is obtained as the solution of an integral equation. The density is approximated by a linear combination of B-splines with the coefficients restricted to be nonnegative. Equations for maximum likelihood estimates of the coefficients are obtained. The proposed method is applied to data from the dog intestinal circulation.

Animals↗
PubMed1985

Reduced vascular sensitivity to norepinephrine in portal-hypertensive rats.

The development of portal hypertension following chronic portal vein stenosis is accompanied by a significant increase in intestinal blood flow. The present study was designed to determine whether intestinal vascular sensitivity to norepinephrine (NE) is also affected by chronic portal vein stenosis. Using a blood-perfused, in situ rat small intestine preparation, we found that, when compared with control animals, a significantly greater molar concentration of NE was required to achieve the same proportional increase in intestinal vascular resistance in portal-hypertensive animals. The mean ED50 value (+/-SE) for the portal-hypertensive group (704.3 +/- 186.1 nM) was significantly greater (P less than 0.05) than the mean ED50 value for the control group (271.4 + 48.1 nM). This finding implies that sympathetic maintenance of intestinal vascular tone may be impaired following chronic portal vein stenosis, possibly accounting for part of the intestinal hyperemia associated with portal hypertension.

Animals↗
PubMed1985

Effect of hypoxia on feline intestinal capillary permeability.

The multiple-indicator dilution technique was used to investigate the permeability characteristics of capillaries in the cat small intestine during hypoxia. Reducing the arterial oxygen tension from 108 to 35 mmHg for 10 min increased the calculated equivalent pore radius of intestinal capillaries from 59 to 67 A. This effect was sustained for at least 15 min after the hypoxic episode. Hypoxia did not alter intestinal lymphatic protein clearance. Thus, the dimensions of the large pores did not change. This study demonstrates that 10 min of severe hypoxia increases vascular permeability in the small intestine and that this change occurs only in the small pores and is sustained, at least briefly, after restoration of normoxia. Hypoxia does not significantly change the permeability to macromolecules.

Animals↗
PubMed1985

Laser-Doppler blood flowmetry of intestinal mucosal hyperemia induced by glucose and bile.

To determine whether the functional hyperemia evoked by solute transport is confined to the intestinal mucosa or whether blood flow increases throughout the bowel wall, we measured blood flow in the mucosa and muscularis-serosa with laser-Doppler velocimetry. Ileal loops were vascularly isolated in pentobarbital sodium-anesthetized dogs. Total blood flow to the loop was measured electromagnetically, while blood flow in the superficial mucosa and muscularis-serosa was monitored by laser-Doppler velocimetry. Perfusion pressures and arteriovenous oxygen difference were also recorded continuously. When a mixture of 5% bile and glucose was placed in the lumen of the isolated loop, total blood flow and oxygen uptake increased 21 and 62%, respectively. During this hypermetabolic state, laser-Doppler measurements indicated blood flow in the muscularis-serosa fell by 10%, but blood flow in the mucosa increased 42%. These findings with laser-Doppler velocimetry confirm earlier studies in which the radioactive microsphere technique indicated that low-fat, low-protein test meals induce a postprandial hyperemia confined to the mucosal circulation. These findings also demonstrate a metabolic flow-controlling mechanism closely linked to the absorptive process.

Animals↗
PubMed1985

Laser-Doppler, H2 clearance, and microsphere estimates of mucosal blood flow.

In autoperfused preparations of feline jejunum, blood flow was measured from the mucosal surface with laser-Doppler velocimetry (LDV) and hydrogen gas (H2) clearance techniques while blood flow was altered by intra-arterial infusions of isoproterenol. LDV and H2 clearance estimates of blood flow were compared with total-wall and mucosal-submucosal blood flows measured with the radiolabeled microsphere technique. Over the range (26.3-73.6 ml X min-1 X 100 g-1) of blood flows attained, a series of direct linear relationships were obtained among LDV, H2 clearance, and microsphere estimates of jejunal blood flow. The slopes of these relationships indicated that the H2 clearance technique over-estimates total intestinal blood flow but reflects mucosal-submucosal flow as measured with microspheres. LDV measurements of blood flow from the mucosal surface were equally well correlated with total and mucosal-submucosal blood flow measured by microspheres, thereby not allowing for a definitive conclusion on the measurement depth of the LDV method. However, the ability of the LDV method to detect changes in blood flow in the perfused gut, even through 3 mm of unperfused tissue, casts a doubt on the assumption that the LDV method has a spatial resolution of less than 0.5-1.0 mm. The results of this study indicate that the H2 clearance technique can be used to measure mucosal blood flow in the small intestine. By contrast, the precise measurement depth of the LDV method is still uncertain and requires further evaluation.

Animals↗
PubMed1985

Gastric mucosal blood flow measured by laser-Doppler velocimetry.

To determine the feasibility of measuring gastric mucosal blood flow by laser-Doppler velocimetry (LDV), we utilized two LDV flowmeters to monitor blood flow in mucosa and serosa of chambered canine stomach. In isolated, nonautoregulating gastric segments vasodilated with isoproterenol, LDV mucosal and muscularis blood flows were both linearly related to total electromagnetic blood flow during step increases in perfusion pressure. To assess the depth of the LDV measurement, we recorded reactive hyperemia following arterial occlusion. Reactive hyperemia was frequently registered in the mucosa but rarely in muscularis. Placing a layer of nonperfused mucosa-submucosa between the probe and the perfused mucosa abolished the resting LDV mucosal flow signal and attenuated the recording of peak hyperemia by 85%. Furthermore, intra-arterial infusions of both adenosine and isoproterenol frequently increased LDV mucosal flow and decreased LDV muscularis flow, although total flow was consistently increased. These findings indicate that our LDV instruments yield linear, superficial measurements of gastric blood flow in either mucosa or muscularis. Although calibration in absolute units remains to be achieved, our results demonstrate that LDV is a practical means of studying the gastric mucosal microcirculation.

Animals↗
PubMed1985

Microsphere passage through intestinal circulation: via shunts or capillaries?

Significant quantities of 9-micron microspheres (20-30%) are not trapped in the intestine following intracardiac or intra-arterial injection, but reach venous blood. Some investigators propose that the passage of 9-micron spheres measures blood flow through noncapillary connections. Because frequency distributions of intestinal capillary diameters and 9-micron spheres overlap, microspheres could simply pass through capillaries. Therefore, we developed simple probabilistic models to predict both the size distribution and the percentage of injected spheres [9 +/- 1 (SD) micron] that should appear in venous blood. Chief assumptions in models are that microsphere delivery and sphere diameter are independent and that microspheres pass through capillaries of equal or larger size. The passage predicted by the models was consistent with values in canine intestinal circulation, demonstrating that passage through capillaries [7.38 +/- 1.4 (SD) micron] adequately accounts for spheres in venous blood. Because the diameters of nominal 9-micron spheres were distributed too narrowly to show a marked sieving effect on passage through the intestinal circulation, we also injected microspheres varying from 5 to 20 micron in diameter. This mixture demonstrated a marked sieving effect. The predicted frequency distribution for microsphere diameters in venous blood agreed with the observed distribution. Our models demonstrate that the passage of 9-micron spheres through capillaries, rather than through "shunts," adequately accounts for the appearance of spheres in venous blood and suggests that the frequency distribution of venous microspheres can provide an in vivo method for estimating the frequency distribution of intestinal capillary diameters.

Animals↗
PubMed1985

Drop-counting flow computer.

An inexpensive microcomputer (VIC-20) was adapted to count drops of fluid and calculate flow. To minimize both the expense and the bench space occupied by the flow computer, we eliminated the need for a video monitor by employing a liquid crystal alphanumeric display. Neither tape recorders nor disk drives are needed because the flow-computing program resides in a "game cartridge." Furthermore, the power supply of the computer powers the interface and display. The computer's real-time clock is utilized to time intervals between drops falling through an infrared beam. The computed flow values are then shown on the liquid crystal display, and they are sent to an external recorder via a digital-to-analog converter. A second digital-to-analog converter can be used to trigger a fraction collector. When compared with timed manual collections, the flow computer was shown to yield highly accurate, linear measurements of water and blood flow. Although the drops-per-milliliter constant varied with orifice size and hematocrit, the hematocrit fluctuations observed in typical isolated organ experiments would not appreciably affect the blood flow determinations.

Calibration↗