PubMed Health⌕ Search

Biomedical subjects

B R Duling

Publications and source records attributed to B R Duling.

At least 73 records · Page 4Linked to original sources
PubMed1984

Effect of norepinephrine on penetrating arterioles of rat cerebral cortex.

Penetrating intracerebral arterioles from the rat with mean resting diameters of 26.3 +/- 2.8 micron and maximal diameters of 37.4 +/- 2.5 (SE) micron were isolated, cannulated, and perfused in vitro. Spontaneous tone development and hydrogen ion reactivity indicated that vessels were relatively undamaged and viable. The norepinephrine (NE) reactivity of intracerebral penetrating arterioles is pH dependent. Vessels studied at extraluminal pH 7.30 were unresponsive to NE up to concentrations of 10(-6) M. At NE concentrations above 10(-6) M, vessels dilated to diameters approximately 110% of control. At pH 7.80, vessels contracted to diameters between 75 and 80% of control in response to extraluminal NE concentrations between 10(-11) and 10(-6) M. Vessels in 10(-6) M phentolamine failed to respond to 10(-8) M NE at pH 7.30 and pH 7.80. An aliquot of 10(-8) M NE solution made up at pH 7.80 failed to induce vessel contraction when the pH was readjusted to 7.30, indicating that a NE breakdown product was not responsible for the contraction. These data suggest that adrenergic mechanisms in penetrating cerebral arterioles are significantly different from those seen in peripheral arterioles of similar size.

Animals↗
PubMed1984

Morphology of the constricted arteriolar wall: physiological implications.

Microvessels undergo complex shape changes during constriction that could have profound implications for control of resistance. We exploited in vitro cannulation techniques in combination with electron microscopy to assess the effects of physiological degrees of vasoconstriction on the size and form of the lumen of isolated rat mesenteric arterioles. Photomicrographs of vasoconstricted vessels revealed that the luminal surface is folded and thrown into longitudinal ridges several hundred microns long. These ridges begin to form and encroach on the lumen as the vessel is constricted. Ridge height may increase to 5-10 microns, and as many as 50 ridges were observed around the circumference of a 70-microns vessel. Ridges are comprised of endothelial cells, basal elastic lamina, and portions of the smooth muscle cytoplasm including thick filaments. The ridges are major determinants of the relationships among stress on smooth muscle contractile elements, intraluminal pressure, and luminal diameter. The ridges may also limit the precision of measurement of microvessel diameter in situ since it is not known whether the apex or the base of the ridge is measured under typical conditions of in vivo microscopy. Our findings emphasize the need for additional detailed study of wall morphology to fully understand the regulation of microvessel flow resistance by smooth muscle function.

Animals↗
PubMed1983

Oxygen transport in resting and contracting hamster cremaster muscles: experimental and theoretical microvascular studies.

Intravital microscopy of the superfused cremaster muscle was used to measure the density, diameter, length, hematocrit, red cell velocity, and red cell flux in capillaries of the pentobarbital-anesthetized hamster. Oxygen microelectrodes were used to measure oxygen tension (Po2) at a position 75-100 micrometers deep in the muscle between the venous ends of capillaries and, very importantly, at the superfusate-muscle interface. These parameters were measured in resting and contracting muscles and under three values of superfusate Po2: low (8mm Hg), medium (40 mm Hg), and high (75 mm Hg). These data were complete enough to be useful input parameters in a recently developed mathematical model of oxygen transport in exposed tissue (A. S. Popel, 1981, Math. Biosci. 55, 231-246). The model indicated that with high superfusate Po2, oxygen was supplied to the resting muscle almost exclusively from the superfusate because of the vasoconstriction and reduced blood flow. Oxygen consumption of the resting muscle was estimated to be 0.4 ml O2/100 ml tissue X min, assuming muscle oxygen consumption was uniform and independent of Po2 above 1 mm Hg. The estimated rise in oxygen consumption with exercise was four to eight times resting muscle values, which agrees with previously published data. Also, the model predicted an inlet capillary Po2 of 27 mm Hg with a low superfusate Po2, which is consistent with the few available direct measurements. The model emphasized that with measurement of the Po2 at the superfusate-tissue interface, the complex O2 transport effects of the superfusate can be accurately characterized. Measurement of this and other parameters of the model leads to a potentially useful prediction of the Po2 distribution within tissues under a variety of conditions.

Animals↗
PubMed1983

Capillarity and fiber types in the cremaster muscle of rat and hamster.

We determined muscle fiber type and capillarity in cremaster muscle samples from rats and hamsters of different ages. Histochemical estimation of oxidative capacity was made from the activity of either nicotinamide dinucleotide tetrazolium reductase (NADH-TR) or succinic dehydrogenase (SDH), and fibers were termed fast or slow from myofibrillar ATPase activity. Fibers were classified as type I (low ATPase, high NADH-TR/SDH), type IIa (high ATPase, high SDH/NADH-TR), type IIb (high ATPase, low SDH/NADH-TR), or type IIc (no acid reversal of ATPase, high NADH-TR). Type IIb fibers accounted for 60-80% of the muscle area in both species at all ages. The principal change with maturation was muscle fiber hypertrophy. Mean cross-sectional fiber area increased from 488 +/- 70 (SE) and 453 +/- 19 micron2 in young hamsters and rats, respectively, to 1,255 +/- 99 and 1,540 +/- 101 micron2 in adults. Capillary density (no. of capillaries/mm2 tissue) paralleled fiber hypertrophy; it decreased significantly with maturation from 684 +/- 60 (SE) to 228 +/- 26/mm2 in hamsters and from 341 +/- 15 to 213 +/- 15/mm2 in rats. In vitro estimates of capillary density are compared with previously obtained in vivo data (31), and sources of error are identified. We conclude that reported differences in microvascular function in the cremaster muscle in vivo during maturation or between species cannot be ascribed to changes in muscle composition.

Abdominal Muscles↗
PubMed1983

A computerized system for densitometric analysis of the microcirculation.

An analytical system for measuring size, motion, and light absorption of objects in the field of a microscope is described. The design criteria have been chosen to produce a system that permits acquisition of densitometric information at a number of points within the field and permits computation of important variables from the densitometric data. Relatively simple fiber-optics systems for sampling light intensity at selected locations in the microscope field are described. Computer programs are outlined that permit computation of microvessel diameter, red cell velocity, and hemoglobin oxygen saturation. The sampling systems and programs are quite general in nature and should be applicable to other types of related measurements and computing devices.

Capillaries↗
PubMed1983

Toxic effects of silver-silver chloride electrodes on vascular smooth muscle.

We found that silver, either as silver metal or silver chloride, exerted toxic effects on the smooth muscle of isolated cannulated hamster cheek pouch arterioles. Silver initially stimulated the smooth muscle, producing a marked vasoconstriction. The vessels then dilated back to control diameters. Once the arterioles began to dilate, they became refractory to norepinephrine or potassium stimulation. We caution the use of silver in the presence of smooth muscle, especially when tissue mass is small or free protein concentration is low.

Animals↗
PubMed1983

The oxygen sensitivity of hamster cheek pouch arterioles. In vitro and in situ studies.

We tested the hypothesis that a parenchymally derived mediator is required for arterioles to exhibit oxygen sensitivity. To that end, the parenchyma was dissected and removed from around hamster cheek pouch arterioles, and the oxygen sensitivity of these "aparenchymal arteriolar segments" was studied, either in vitro, after cannulation, or in situ. Arteriolar segments in situ with and without parenchyma had similar oxygen sensitivities (20% constriction as Po2 increased from 15 to 150 mm Hg). Arteriolar occlusion, which eliminated blood flow in the in situ aparenchymal segments, did not eliminate their oxygen sensitivity. The oxygen-induced constriction in the occluded aparenchymal segments was blunted but not eliminated by covering the segments with glass plates to prevent changes in Po2 from occurring around these vessels. We hypothesized that propagation of a portion of the oxygen response might explain the persistent response in the covered and occluded arteriolar segments. Oxygen sensitivity could be shown in only 32% of the in vitro cannulated arterioles (16% mean constriction as Po2 increased from 20 to 150 mm Hg). In contrast, 75% of aparenchymal arterioles were sensitive to changes in Po2 in situ. These data led us to reject the hypothesis that a parenchymally derived mediator is absolutely required for arterioles to exhibit oxygen sensitivity. We infer that the oxygen sensitivity of hamster cheek pouch arterioles results partially or totally from the local action of oxygen on some component of the arteriolar wall or blood, that a portion of the oxygen response may be the result of a propagated phenomenon, and that the oxygen-sensitive component is fragile and is easily lost in preparation for in vitro measurements or in cannulation. It is emphasized that the O2 sensor need not reside in vascular smooth muscle.

Animals↗
PubMed1982

Adenosine and free-flow functional hyperemia in striated muscle.

Striated muscle arteriolar responses to 1.5 min of 1-Hz contraction and/or increased tissue O2 partial pressure (PO2) were observed during exposure of the tissue interstitial space to adenosine deaminase (ADA) to evaluate the role of adenosine (ADO) as a regulator for blood flow. The microvasculature of the hamster cremaster muscle was continuously superfused with a bicarbonate buffer containing 11 micrograms ADA/ml and equilibrated with 5% CO2 and various O2 concentrations. Arterioles (resting diameter less than 30 micrometers) constricted a maximum of 55% when the superfusate gas tension was increased from 0 to 95% O2, but ADA had no effect on this behavior. Arterioles dilated during exercise, but the diameter change was decreased 20-25% during exercise with ADA treatment at both normal and elevated tissue PO2. As ADA had no effect on either the vasodilation to 2-chloroadenosine or resting arteriolar diameter, it was probably specific in its action. Assuming that all extracellular ADO was accessible to ADA and that ADA neutralized most newly formed ADO, we conclude that ADO is one component of a multifactor system mediating short periods of free-flow exercise hyperemia and that the release of ADO is not necessarily dependent on tissue hypoxia.

Adenosine↗
PubMed1982

A study of rat intracerebral arterioles: methods, morphology, and reactivity.

Penetrating, intracerebral arterioles from rat were isolated, cannulated, and studied in vitro. Vessel wall elements were found to consist of an endothelial cell layer, one smooth muscle cell layer, and a thin adventitial layer or leptomeningeal sheath. Smooth muscle cell nuclei were oriented perpendicular to the vessel's longitudinal axis; endothelial cell nuclei were parallel to the axis. Mean vessel diameter with the smooth muscle inactivated (passive diameter) was 36.7 +/- 1.6 (SE) micrometer. Spontaneous smooth muscle tone developed at 37 degrees C and reduced vessel diameter to 70 +/- 4% of passive diameter. Vessels were activated by the extraluminal application of 140 mM KCl solution at pH 8.00, which produced a transient contraction that decayed within 30 s to a steady contraction of somewhat less intensity. Changes in intravascular pressure were used to alter wall tension of the vessels. Tension in the vessel wall was computed, and length-tension curves for the arteriolar smooth muscle were approximated. Length-tension relationships similar to those seen in other smooth-muscle preparations were found with maximal estimated force development of 1.29 x 10(-5) N . m-2. Alterations of bath pH caused changes in vessel diameter that were inversely related to extraluminal pH and varied by approximately 77% in the range from pH 6.85 to 8.00. Adenosine dilated vessels to 140 +/- 6% of control diameter at a concentration of 10(-5) M. The mechanical characteristics and the reactivity to H+, K+, and adenosine of these vessels were quantitatively consistent with in vitro data from larger cerebral vessels and in vivo data from pial arteries.

Adenosine↗
PubMed1982

Direct measurement of microvessel hematocrit, red cell flux, velocity, and transit time.

A method is presented for the in vivo study of red cell flow dynamics. The method permits direct measurement of the red cell volume fraction in microvessel blood without resort to in vitro calibration curves. Furthermore, the method does not require extensive mathematical manipulation and can be applied to any microvascular network in any tissue. The method also enables direct measurement of red cell velocity, flux, and capillary transit time. Fluorescently labeled erythrocytes in tracer quantities, but known concentrations, are used as indicators of the behavior of the total cell population. Erythrocyte transit time across vascular networks and erythrocyte velocity are determined directly by following the behavior of the labeled cells. Hematocrit and red cell flux are measured by standard microcirculatory methods using labeled cells instead of the total cell population. Data are then converted to absolute values from the measured fraction of labeled cells. The method is thus absolutely dependent on the labeled cells being rheologically normal, and the conditions under which this requirement is satisfied are defined. Microvascular data obtained by the use of this method are presented for hamster cheek pouch and cremaster muscle.

Animals↗
PubMed1982

Augmented tissue oxygen supply during striated muscle contraction in the hamster. Relative contributions of capillary recruitment, functional dilation, and reduced tissue PO2.

To investigate the relative contributions of alterations in blood flow, capillary density, and tissue PO2 to elevated oxygen delivery in working muscle, we conducted experiments on the suffused hamster cremaster muscle, using in vivo microscopic techniques. Muscle PO2 was measured during striated muscle twitch contraction at 1 Hz. Tissue oxygenation was changed by using suffusion solutions equilibrated with 0%, 5%, 10%, 21%, or 50% oxygen. Contraction caused an increase in capillary density (capillary recruitment), whose magnitude was related to the equilibration gas and, thus, to the suffusate PO2. Capillary recruitment first increased as the oxygen content was raised, peaked with 10% oxygen, and then diminished with higher oxygen content. Arteriolar functional dilation was also observed; when oxygen was raised above 21%, dilation was decreased. The data suggest that oxygen supply is increased primarily by arteriolar conductance changes with low suffusion solution oxygen (0% to 5%), and by capillary recruitment and increased PO2 gradients above 10% oxygen. When vasomotor tone was increased by addition of norepinephrine to the suffusion medium, the changes observed were similar to those observed when oxygen was increased. Therefore, we propose that the altered microvascular responses during vasoconstriction are a function of vascular tone rather than the levels of tissue PO2. A model is proposed which may partially explain the relations among vascular tone, functional dilation, and capillary recruitment. Our data also suggest that tissue PO2 may not be precisely regulated about a narrowly defined set point in this striated muscle but that, instead, tissue PO2 is a dependent variable controlled by the integrated effects of capillary recruitment, functional vasodilation, and altered metabolism.

Animals↗
PubMed1982

A comparison of microvascular estimates of capillary blood flow with direct measurements of total striated muscle flow.

Relations between bulk flow into skeletal muscles and microscopically observed capillary flow are compared and disagreements between the two types of data are found. Mean capillary blood velocity was computed using data from a variety of literature sources and assuming uniform distribution of flow through a parallel array of capillaries. The average ratio of measured red cell velocity to computed mean blood velocity was 4.4 +/- 1.0. This is statistically different from the measured value reported in the literature of 1.3. In the cremaster muscle, bulk flow of red cells into the tissue was not statistically different from the measured flux of single red cells through capillaries observed microscopically. The factors which contribute to this apparent agreement of mass balance are not understood, however. Capillary hematocrit is very low and the low capillary hematocrit has been explained by others by the presence of nonuniform flow distribution among the capillaries (shunts or flow heterogeneity). However, for the cremaster data sample, red cells were accounted for in observed capillary flow and red cells were distributed rather homogeneously through the capillaries. This suggests that low capillary hematocrit is the result neither of shunting of red cells around the capillaries nor of nonuniform capillary red cell flow alone. There does not appear to be any well-accepted phenomenon which will explain the findings of: 1) low apparent mean blood velocity; 2) low and variable hematocrit; and 3) apparent conservation of red cell mass. The findings can be reconciled, however, if the capillary rheology is more complex than heretofore anticipated, with a stabilized layer of plasma on the inner surface of the capillary in the order of a 1-micrometer thickness. While there is little direct evidence for such a layer at this time, data which are consistent with the possible existence of such a layer are presented.

Animals↗
PubMed1981

Methods for isolation, cannulation, and in vitro study of single microvessels.

A method is described for the isolation and cannulation of microvessels (12-112 micrometers) that permits study, in vitro, of their physiology and pharmacology. Vessels from the hamster cheek pouch, testis, and mesentery and from rat brain have been isolated at 4 degrees C with specially prepared instruments and viewed with an inverted microscope. The vessels were cannulated at one end by equipment developed for renal tubular perfusion. The uncannulated end of the vessel is sealed, and experiments on reactivity and mechanics are carried out at fixed intravascular pressures. The isolated microvessels studied have a modulus of elasticity that is consistent with that observed in large vessels, and they display similar maximal active tension development (approximately 10(6) dyn/cm2). Reactivity to norepinephrine, acetylcholine, and adenosine are in the normal range for microvessels. Spontaneous tone is present, as evidenced by stable tonic contractions as well as phasic contractions in the frequency range of 3-30/min. The vessels display stress activation (myogenic response) consisting of contraction in response to increased intraluminal pressure. Our findings suggest that this preparation will be very useful in elucidating the physiology and pharmacology of the resistance vessels in the terminal vasculature.

Animals↗
PubMed1981

Microvascular adaptations during maturation of striated muscle.

It is well known that capillary density in striated muscle changes during maturation. Capillary density is an important determinant of tissue oxygen supply, the other principal determinants being capillary erythrocyte flow and capillary hematocrit. The microcirculation of the hamster cremaster muscle was studied at different stages of development. We found that the microcirculation of juvenile animals was characterized by small intercapillary distances, short capillary lengths, and tortuous vessels. During maturation, the capillaries elongated and developed the more "typical" parallel pattern. Capillary density decreased from 1,626 +/- 60 capillaries . mm-3 at 35 days of age to 696 +/- 65 capillaries . mm-3 at 132 days; erythrocyte flow per capillary decreased from 1,441 +/- 135 to 583 +/- 47 micrometers 3 . s-1; and capillary hematocrit decreased from 21.5 +/- 0.7 to 14.6 +/- 0.6%. Concomitant with these decreases, the functional reserve increased; in adult muscles, capillary density could increase by 42%, erythrocyte flow per capillary by 457.2%, and capillary hematocrit by 112.4%, compared with 7.7, 20.3, and 24.1%, respectively, in immature animals. These observations show that age significantly modifies microvascular parameters related to tissue oxygen supply and provides an explanation for some conflicting observations in the literature.

Aging↗
PubMed1981

Tissue PO2 and arteriolar responses to metabolic stimuli during maturation of striated muscle.

Tissue O2 tension (PO2) and small arteriolar diameter were measured in hamsters aged 32, 60, and 80 days. The cremaster muscle was isolated and superfused with a solution equilibrated with 0, 5, or 10% O2 stimulated to contract at 1 Hz. Resting muscle tissue PO2 was proportional to superfusate PO2 and was not different between age groups. The decrease in tissue PO2 during contraction was greatest in adult animals when the superfusate PO2 was low but was equal in all groups when the superfusate PO2 was high. Elevated superfusate PO2 was correlated with a vasoconstriction, the magnitude of which varied inversely with age. Resting and contraction-induced vascular diameter were largest in the youngest animals, relative to maximum diameter, but absolute resting and contraction-induced diameters were similar in all groups. We suggest that tissue PO2 at rest was similar because of an age-associated decrease in fiber O2 consumption to maintain a constant proportionality between O2 supply and demand. The relative stability of tissue PO2 during contraction in young animals might have reflected superior regulation. However, a simple numerical analysis predicts smaller tissue PO2 decreases during contraction in young animals because of short intercapillary distances and other altered O2 supply parameters, even if regulation had been identical in all age groups.

Aging↗
PubMed1981

Multiple mechanisms of reactive hyperemia in arterioles of the hamster cheek pouch.

To investigate mechanisms of reactive hyperemia, single arterioles of the hamster cheek pouch were occluded for periods of 1 s-3 min. Arteriolar diameters were measured upstream and downstream from the occlusion. O2 availability to the tissue was controlled by equilibrating the suffusate with low (0% O2) or high (10% O2) O2 gas mixtures. After very brief occlusions downstream sites dilated transiently, but upstream diameters did not change. Upstream and downstream diameters both increased during longer occlusions with O%-O2 and 10%-O2 suffusion. Microvascular pressure decreased at downstream sites and increased at upstream sites within 1-2 s of occlusion. During 0%-O2 suffusion tissue and periarteriolar O2 tensions (PO2's) began to decrease within 2 s of occlusion and had decreased halfway to their minimum value by 7 s. PO2's decreased only slightly during 10%-O2 suffusion. Calculated first-order rate constants for arteriolar diameter recovery decreased and total recovery time increased as occlusion duration was prolonged. This study suggests that multiple mechanisms (metabolic, myogenic, and passive) contribute to reactive hyperemia.

Animals↗