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A P Shepherd

Publications and source records attributed to A P Shepherd.

At least 19 recordsLinked to original sources
PubMed1992

A model of countercurrent shunting of oxygen in the intestinal villus.

This report describes a mathematical model of the countercurrent shunting (CCS) of O2 in the intestinal villus. The anatomic basis for the model is the close proximity of the arteriole and venule between which O2 is free to diffuse. The model divides the villus into four segments from base to tip. Steady-state equations describe the convective and diffusive fluxes of O2 in the arteriolar, capillary, and tissue compartments within each segment. Longitudinal diffusion along the length of the villus is assumed to be negligible. Simulations with the model led to the following observations: 1) CCS shifted the VO2 vs. blood flow curve down and to the right, slightly impairing VO2 at a given blood flow; 2) the base-to-tip PO2 gradient caused by the tissue O2 consumption was reduced by CCS; 3) when blood flow was reduced, the base-to-tip PO2 gradient increased until the tip PO2 fell to zero and then fell with further flow reductions; 4) lowering blood flow initially caused slight increases in shunting but further decreases in flow reduced shunting; 5) in the blood flow range in which VO2 was flow independent, increasing the O2 demand or decreasing the intervascular distance increased shunting because of the greater arteriole-to-capillary O2 concentration gradient and the decreased diffusion distance, respectively; and 6) lowering the hemoglobin's P50 to simulate fetal blood caused slight reductions in shunting and reduced VO2 at a given flow. In summary, the model confirms the potentially deleterious effects of CCS on intestinal oxygenation, and, in contrast to assertions in the literature, it shows that a base-to-tip PO2 gradient is not prima facie evidence of counter-current shunting.

Animals↗
PubMed1992

Effects of temperature on optical absorbance spectra of oxy-, carboxy-, and deoxyhemoglobin.

The optical absorbance spectra of oxy-, carboxy-, and deoxyhemoglobin were recorded at wavelengths from 479 to 651 nm and at temperatures of 20, 30, and 40 degrees C. As noted in earlier reports, a major effect of lowering the temperature was an increase in the absorptivities at or near the absorbance maxima. However, at other wavelengths, reducing the temperature increased, decreased, or caused no change in absorbance. At wavelengths where temperature-induced shifts did occur, the absorbance change appeared to be a linear function of temperature. Unlike previous reports, the data presented here are quantitative and thus can be used to predict temperature-induced errors in spectrophotometric measurements of the relative concentrations of these hemoglobin species. Examples are given of the error that would occur in a widely used CO-Oximeter, the IL482, if it were not temperature controlled. Thus, the data presented here should be particularly useful to the operators and designers of spectrophotometric instruments such as oximeters, CO-Oximeters, and hemoglobinometers.

Carboxyhemoglobin↗
PubMed1992

Autoregulation of choroidal blood flow in the rabbit.

Previous studies show that choroidal blood flow is not autoregulated when intraocular pressure (IOP) is increased to raise venous pressure and lower the perfusion pressure gradient. However, the autoregulatory response to changes in mean arterial pressure (MAP) is unclear. In the current study, the perfusion pressure gradient (MAP-IOP) was altered by (1) decreasing MAP while IOP was held at 5, 15, and 25 mmHg, and (2) increasing the IOP at the prevailing MAP in anesthetized rabbits (n = 8). An occluder on the thoracic vena cava was used to vary MAP; this was monitored through an ear artery catheter. Two catheters were inserted in the vitreous to monitor and control IOP. Choroidal blood flow was measured by laser Doppler flowmetry using a slender stainless-steel probe positioned next to the retinal surface. The efficacy of autoregulation depended on the IOP. When IOP was held constant at 5 mmHg, choroidal blood flow did not fall until the perfusion pressure gradient was less than 40 mmHg. The pressure-flow relationship became progressively more linear (ie, the efficacy of autoregulation decreased) when the IOP was held constant at 15 and 25 mmHg. When IOP was varied and MAP was held constant, the pressure-flow relationship was linear at IOPs greater than 20-25 mmHg. However, choroidal blood flow was pressure independent when the IOP was less than 20-25 mmHg. Simultations using a myogenic mathematic model of the choroid gave results similar to the experimental observations. It was concluded that a myogenic mechanism may be responsible for the autoregulation of choroidal blood flow in the rabbit.

Animals↗
PubMed1991

Norepinephrine release during autoregulatory escape: effects of alpha 2-receptor blockade.

The partial recovery that intestinal blood flow undergoes during continued sympathetic nerve stimulation is termed autoregulatory escape. This study tested two hypotheses that might explain escape: 1) diminishing norepinephrine (NE) release during sustained stimulation and 2) an alpha 2-receptor-mediated competition between local and neural control mechanisms. The rates of NE release before and during stimulation of the perivascular sympathetic nerves were determined by measuring blood flow in isolated loops of canine small intestine and assaying the concentrations of NE in arterial and venous blood. The presence of functional alpha 2-receptors was demonstrated by clonidine injections, and the effects of alpha 2-receptor blockade were studied during yohimbine infusions. The time course of NE release was inconsistent with a cause-effect relationship; NE release was greatest during the phase when resistance had already escaped. Deliberately altering NE release by changing the stimulus duration did not affect escape. The study demonstrated 1) that diminished NE release during continued sympathetic stimulation does not occur and cannot account for escape, 2) that resistance vessels in the canine intestinal circulation possess functional alpha 2-receptors which are responsible for part of the vasoconstriction caused by sympathetic stimulation, 3) that blockade of presynaptic alpha 2-receptors significantly enhanced NE release during the initial 30-s period but not during the escape phase, and 4) that alpha 2-receptor blockade enhances autoregulatory escape. Altogether these findings indicate that the postsynaptic alpha 2-receptors on intestinal resistance vessels deserve further investigation as the possible site at which local and neural mechanisms compete to influence vascular resistance.

Adrenergic alpha-Agonists↗
PubMed1991

Role of H+ and alpha 2-receptors in escape from sympathetic vasoconstriction.

In a previous study, we noted that mesenteric venous pH falls during the reductions in intestinal blood flow caused by sympathetic stimulation and that alpha 2-receptor antagonists enhanced autoregulatory escape (the partial recovery that blood flow undergoes despite sustained sympathetic stimulation). In addition, other studies indicated that increased [H+] selectively inhibits the responsiveness of postjunctional alpha 2-receptors to norepinephrine (NE). Therefore, we investigated the role of H+ in escape by 1) measuring the rate of unbuffered H+ release during sympathetic stimulation in isolated loops of canine small bowel, 2) infusing acidic buffer intra-arterially and determining the effects of acidosis on sympathetic vasoconstriction and escape, 3) ascertaining the effects of acidosis on the release rate of endogenous NE during sympathetic stimulation, and 4) determining whether acidosis exerts effects in vivo on post-junctional responses to the selective alpha 1- and alpha 2-agonists, phenylephrine and clonidine, respectively. Our findings were that 1) the rate at which the gut released H+ into blood increased during sympathetic stimulation, 2) infusing acidic buffer to lower venous pH from 7.3 to 7.1 attenuated the initial vasoconstrictor response after 30 s of stimulation, 3) acidosis caused blood flow to return further toward control despite continued stimulation and thus enhanced escape, 4) acidosis did not impair NE release at either 30 s or 6 min of stimulation, and 5) acidosis inhibited the intestinal vasoconstrictor effects of selective alpha 2- but not alpha 1-agonists. The results support the hypothesis that escape from sympathetic vasoconstriction occurs, in part, because increased [H+] inhibits alpha 2-mediated postjunctional responses to neuronally released NE.

Acidosis↗
PubMed1989

Gastric oxygen uptake during autoregulatory escape from sympathetic stimulation.

To assess the effects of sympathetic stimulation on gastric blood flow and oxygen utilization, the perivascular nerves were stimulated at 2, 4, 6, and 8 Hz in chambered segments of canine gastric corpus perfused at constant pressure. Spectrophotometric arteriovenous oxygen difference and electromagnetic blood flow were recorded continuously. Except at the lowest frequency of stimulation (2 Hz), total blood flow exhibited autoregulatory escape, i.e., blood flow decreased initially but then returned toward control. The fall in total blood flow at the onset of sympathetic stimulation was smaller at 2 Hz than at 4 Hz, but stimulation at 6 and 8 Hz caused no further reductions in total blood flow. However, at all frequencies, total blood flow escaped to the same steady-state value (approximately 17 ml.min-1.100 g-1). Although total blood flow was still less than control (approximately 25 ml.min-1.100 g-1), oxygen extraction increased proportionately so that oxygen consumption was not significantly less than control at any frequency of stimulation. We conclude that autoregulatory escape from sympathetic stimulation is mediated by local mechanisms acting to maintain tissue oxygenation in the stomach.

Animals↗
PubMed1989

Effects of hemodilution on gastric and intestinal oxygenation.

To determine the effects of hemodilution on gastric and intestinal oxygenation, isolated segments of canine stomach and small bowel were perfused by a pressurized reservoir with blood at hematocrits of 40 and 20%. Arteriovenous O2 difference, blood flow, and arterial and venous pressures were monitored continuously as perfusion pressure was reduced in 30-mmHg steps from 180 to 30 mmHg. O2 consumption was calculated as the product of the steady-state arteriovenous O2 difference and blood flow at each perfusion pressure. Gastric and intestinal O2 uptake were relatively well maintained over most of the pressure range when the hematocrit was set at 40%. After hemodilution, gastric O2 uptake decreased significantly only at 90 and 60 mmHg, but intestinal O2 uptake was significantly reduced except at 30 mmHg. When gastric and intestinal O2 uptake were plotted as a function of blood flow, the O2 uptake vs. blood flow relationship were shifted down and to the right by hemodilution. Hemodilution also linearized the O2 uptake vs. blood flow relationship in the intestine. However, when O2 uptake was plotted as function of O2 delivery, the gastric O2 uptake vs. delivery curves at the two hematocrits were superimposed on each other, but the O2 uptake vs. delivery curves for the intestine diverged except at low rates of O2 delivery. We conclude that by reducing the O2-carrying capacity of the blood, hemodilution adversely affects gastric and intestinal oxygenation. Our results also indicate that hemodilution lowers gastric O2 uptake by reducing O2 delivery; however, hemodilution lowers intestinal O2 uptake not only by reducing O2 delivery but also by impairing O2 extraction.

Analysis of Variance↗
PubMed1989

Optimal hematocrit for canine gastric oxygenation.

To determine whether an optimal hematocrit exists at which gastric tissue is maximally oxygenated, chambered segments of resting canine stomach were perfused at a constant pressure while hematocrit was decreased in steps from 60 to 10%. The two groups of animals used were a control group and a second group given pentagastrin to elevate metabolic activity. Total blood flow was inversely related to hematocrit in both the control and pentagastrin-treated animals, and arteriovenous oxygen difference was directly related to hematocrit. Consequently, the relationship between gastric oxygen consumption and hematocrit was parabolic in both groups. Therefore, the oxygen uptake vs. hematocrit data from each experiment were fit to a quadratic equation that was used to calculate the maximal oxygen uptake and the optimal hematocrit for each preparation. Both the maximum oxygen uptake and the optimal hematocrit in the pentagastrin-treated group (2.1 +/- 0.4 ml.min-1.100 g-1 and 45.7 +/- 1.4%, respectively) were significantly greater than in the control group (1.5 +/- 0.4 ml.min-1.100 g-1 and 38.2 +/- 0.7%, respectively). We conclude that an optimal hematocrit exists for the oxygenation of gastric tissue and that it is within the normal hematocrit range under resting conditions. However, the optimal hematocrit is slightly higher than normal during periods of increased metabolic activity.

Animals↗
PubMed1989

An optical hemoglobinometer for whole blood.

To overcome the disadvantages of the presently available hemoglobinometers, we have developed an optical instrument that measures the total hemoglobin (Hb) concentration in whole, undiluted blood. The device uses an infrared light-emitting diode to illuminate a capillary tube filled with a sample of whole blood. Light scattered in the blood travels a short distance down the length of the capillary tube, passes through a second light path, and reaches a photodetector, the output of which is amplified, digitized, and fed into a microprocessor. The microprocessor computes the Hb concentration as a nonlinear function of the light intensity. The optical device yielded Hb content measurements that correlated well with standard methods (r = 0.99, slope = 0.94, mean absolute difference = 0.75 g Hb/dl). Thus the accuracy appears to be less than 1 g Hb/dl. The advantages of the present device are as follows: 1) no chemical reaction is required (hence neither accurate dilutions nor toxic reagents are necessary); 2) it reads Hb concentration within a few seconds; 3) it can be operated by unskilled personnel; 4) it could be made portable and thus could be operated in the field, in rural settings, or at accident sites; 5) sample size is small (25-70 microliters); and 6) the same capillary tube can be centrifuged if a measure of hematocrit is also desired. A detailed parts list and circuit diagram are presented, and sources of error are discussed.

Autoanalysis↗
PubMed1989

An oximeter for measuring hemoglobin concentration and oxygen content.

We have developed an oximeter that measures both the total hemoglobin concentration in whole blood and the percentage of the hemoglobin saturated with oxygen. The oximeter uses red and infrared light-emitting diodes to illuminate a capillary tube filled with a sample of whole blood. Light scattered by the blood travels a short distance down the length of the capillary tube and reaches a photodetector, the output of which is amplified, digitized, and fed into a microprocessor. The microprocessor computes the total hemoglobin concentration as a nonlinear function of the infrared light intensity. Oxyhemoglobin saturation is computed from the ratio of the logarithms of the intensities of red and infrared light. Our instrument has the following advantages over existing oximeters: 1) it provides a measurement of total hemoglobin concentration, 2) it is immune to the calibration shifts that fluctuations in total hemoglobin concentration cause in other oximeters, 3) it is accurate over a wide range of oxygen saturation, and 4) the blood samples are not diluted and can thus be preserved for further analysis. A detailed parts list and circuit diagram are presented, and sources of error are discussed.

Animals↗
PubMed1988

Perfused rat intestine for study of norepinephrine release.

Previous preparations for studying the neuronal release of norepinephrine (NE) employed relatively large vessels, nonsanguinous perfusates, and the preloading of [3H]NE. To study the stimulated release of endogenous NE and the responses of true resistance vessels, we developed a rat intestine preparation that is pump perfused with canine red blood cells suspended in bicarbonate buffer with 6% albumin. In a pentobarbital-anesthetized rat, the duodenum, colon, and cecum are extirpated to isolate the ileum vascularly. After the superior mesenteric artery and vein are cannulated, the perivascular nerves are isolated to stimulate the postganglionic sympathetic fibers. To evaluate the preparation, we stimulated the sympathetic fibers at 1-10 Hz with supramaximal pulses. Resistance changes were assessed by monitoring perfusion pressure, and the concentration of NE was assayed in the venous effluent by the single-isotope radioenzymatic method. During nerve stimulation, the increases in both resistance and NE release rate were frequency dependent. Repetitions of electrical stimulation yielded reproducible frequency-response curves. Pretreatment with phentolamine (10 microM) abolished the resistance response and enhanced stimulated NE release, which roughly tripled at 10 Hz. Phentolamine at smaller doses (1 microM) eliminated the resistance responses to stimulation but did not enhance NE release. Cocaine alone (30 microM) increased base-line resistance and unstimulated NE release. After cocaine pretreatment, phentolamine at 1 microM enhanced the stimulated NE release rate. We conclude that the isolated rat intestine contains postsynaptic alpha-adrenoceptors that mediate vasconstriction and prejunctional alpha 2-adrenoceptors that mediate the inhibition of NE release. Thus the rat intestine is a responsive preparation for studying the release of endogenous NE and noradrenergic neurotransmission.

Animals↗
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↗