Cat Mesentery Research Articles

Morphological changes in the small intestine mesentery of cats with infectious peritonitis

The research relevance is determined by an insufficient study of morphological changes in the mesentery of cats with infectious peritonitis, even though their understanding is necessary to explain the mechanism of development of the main symptom of the disease – the effusion of fluid into the abdominal cavity. The research aims to establish gross and microscopic changes in the mesentery of the small intestine of cats with infectious peritonitis. The research employs gross and histological examination of the mesentery of the small intestine of cats at the infectious peritonitis. Slides of the mesentery were stained with haematoxylin and eosin. At dry and mixed forms of infectious peritonitis, gross and microscopic changes in the mesentery of the small intestine of cats are similar. In the mesentery grossly, small white spots were found, which protruded above the general surface and had a homogeneous appearance on the section. Microscopic changes in the mesentery of the small intestine of cats with dry and mixed forms of infectious peritonitis were also similar. When conducting histological studies, it was established that the mesothelium on the surface of the mesentery was necrotized or absent. The submesothelial layer of collagen fibres was necrotized or contained partially lysed and fragmented fibres. The loose fibrous connective tissue of the mesentery was swollen, necrotized in places, and infiltrated by lymphocytes, monocytes, and macrophages. Eosinophilic inclusion bodies were detected in the cytoplasm of some monocytes and macrophages. Foci of adipose tissue in the mesentery of the small intestine were infiltrated by lymphocytes and monocytes. Necrosis and destruction of their walls were found in blood vessels and destruction of endothelial cells in lymphatic vessels. Perivascular lymphoid nodules were markedly enlarged due to their swelling and an increase in the number of cells in them. In perivascular lymphoid nodules, expansion of lymphatic vessels and destruction of part of their endothelium cells were also established. Some of the lymphatic vessels of the mesentery were expanded and filled with lymph, which contained a significant number of lymphocytes, monocytes, and single neutrophils. The materials presented in the article are of practical value for anatomists, histologists and pathomorphologists, as well as for scientists who study the pathogenesis of infectious peritonitis in cats

Mesenteric and tactile Pacinian corpuscles are anatomically and physiologically comparable

Pacinian corpuscles (PCs) in cat mesentery have been studied extensively to help determine the structural and functional bases of tactile mechanotransduction. Although we, like many other investigators, have found that the mesenteric receptors are anatomically very similar to those found in mammalian skin, few physiological characteristics of the mesenteric PCs and those of the skin have been compared. Action-potential rate-amplitude and frequency characteristics (10 Hz–1 KHz), as well as interval (IH) and peri-stimulus-time (PSTH) histograms in response to sinusoidal displacements were obtained from nerve fibers innervating mesenteric PCs and from PC fibers innervating cat glabrous skin. The intensity characteristics obtained on both preparations showed similar response profiles, including equal slopes for low stimulus intensities (approximately 10, with impulse ratios/20 dB displacement) and one and two impulse/cycle entrainment. The frequency characteristics of both groups were U-shaped with similar low-frequency slopes (−12.5 dB/octave) and bandwidths (Q3dB = 1.4). The best frequency for both the tactile PCs' and mesenteric PCs was 250 Hz, which is in the expected range. The IHs showed entrainment and the PSTHs showed neither transient responses nor adaptation to steady-state sinusoidal stimuli. The functional similarity between mesenteric PCs' nerve responses and those of tactile PC afferents, as well as the receptors’ anatomical similarity, lead us to suggest that the mesenteric PC can act as a model for those in the skin. Furthermore, since the frequency characteristics of the two PC types are similar, it is concluded that the skin, while attenuating stimulus intensity, does not impart temporal filtering of vibratory stimuli.

Immunocytochemical identification of proteins within the Pacinian corpuscle

Light- and electron-microscopic immunocytochemistry (ICC) was performed on Pacinian corpuscles (PCs) obtained from cat mesentery to determine the presence and location of various proteins within the accessory capsule and the neurite. Antibodies to tubulin, neurofilament 200, actin, collagen II and V, glial fibrillary acidic protein (GFAP) and S-100 were used. Type II collagen was localized only in the outer core of the accessory capsule, which is composed of an inner core, an intermediate layer or growth zone, an outer core and an external capsule. Type V collagen was found only in the intermediate growth zone. Intermediate filaments labeled with anti-GFAP were only found in the inner core. The calcium-binding protein that was labeled by anti-S-100 was found only in the inner core. Diffuse and variable staining for actin is present throughout the accessory capsule. The differences in distribution of these various proteins within the capsule suggest different structural/functional properties of the various capsule regions. The neurite was found to contain microtubules (i.e., tubulin) and neurofilaments throughout, but these cellular inclusions were not found within the cytoplasmic extensions (filopodia) that project from the neurite into the hemilamellar clefts formed by the inner-core hemilamellae. The extensions, however, were found to contain actin in a much greater density than that seen in the neurite proper. The presence of actin, but apparent lack of other cytostructural elements within the extensions, is highly reminiscent of the composition of stereocilia found on vestibular and auditory hair cells. Since stereocilia have been shown to play a role in hair-cell mechanotransduction, it is possible that the cytoplasmic extensions are significantly involved with mechanotransduction within the PC.

Inhaled NO reaches distal vasculatures to inhibit endothelium- but not leukocyte-dependent cell adhesion.

Nitric oxide (NO), in addition to being a potent vasodilator, also prevents leukocyte adhesion in the microvasculature. Based on the antiadhesive properties of NO and work suggesting that NO is transported by proteins in the circulation, we tested the possibility that inhaled NO could impart antiadhesive effects in peripheral microvessels. We also determined the underlying mechanisms of actions. Three well-established models that induce local microvascular changes (either endothelium or leukocyte) were used. Hydrogen peroxide (H(2)O(2); 100 microM) was superfused onto the cat mesentery to induce an endothelium-derived, P-selectin- and platelet-activating factor-dependent, oxidant-dependent leukocyte recruitment. In a second series of experiments, the cat mesentery was superfused with histamine (100 microM) to induce rapid endothelium-derived, P-selectin- and platelet-activating factor-dependent, oxidant-independent leukocyte recruitment. Finally, in a third series of experiments to target the leukocyte (but not the endothelium) directly in the periphery, the chemotactic molecule leukotriene B(4) (20 nM) was superfused onto the cat mesentery. The above experiments were performed with and without cats breathing NO (80 parts/million). Intravital microscopy was used to visualize the mesenteric microcirculation. Inhaled NO reduced the increased leukocyte rolling and adhesion associated with H(2)O(2) superfusion of the feline mesentery via a cGMP-dependent mechanism. In contrast, inhaled NO had no effect on the histamine-induced increase in leukocyte rolling flux but partially inhibited the subsequent adhesion. The leukocyte chemotactic mediator leukotriene B(4) induced a significant increase in leukocyte adhesion, but NO inhalation did not impair this chemotactically induced leukocyte recruitment. These data suggest that inhaled NO can reach the endothelium in the distal microvasculature and alter the response to an oxidative and a nonoxidative activator of endothelium but imparts no antiadhesive effect directly on circulating leukocytes.

A new approach for predicting the enhancement in the effective conductivity of perfused muscle tissue due to hyperthermia.

This study attempts to measure the hyperthermic response of individual microvessels in skeletal muscle tissue subject to local heating and then to predict the enhancement in thermal conductivity that results from the observed changes in vascular diameter and flow. In contrast to existing studies, which have tried to relate changes in tissue thermal conductivity to local blood perfusion using thermal clearance and self-heated thermistor techniques, we have developed a two-dimensional muscle tissue preparation in which the hyperemic response has been quantified by measuring the in vivo changes in diameter and blood flow of 1A to 4A generation vessels of rat cremaster muscle when the temperature was raised in 2 degrees increments from 34 to 42 degrees C. Only 3A and 4A vessels showed vasodilation when subject to hyperthermia, indicating that the measured increase in flow in the 1A and 2A vessels was the result of a decrease in downstream resistance. Our cremaster muscle preparations have also been used to obtain the first detailed anatomic measurements of the number density and length of countercurrent vessel pairs between 50-200 microns diameter. These combined measurements have been used to establish the limits of validity of the Weinbaum-Jiji theory. Our experimental data indicate that the Weinbaum-Jiji expression for keff is valid in cremaster muscle and cat mesentery tissue for both normal and hyperthermic conditions provided the largest vessels are < 200 microns in diameter. The theory predicts that significant enhancements in keff start to occur for vessels that are 70 microns in diameter or larger, that a 2.5-fold increase in keff can be achieved for a maximally dilated 200 microns diameter 1A vessel pair in cremaster muscle of larger rats, and a 6-fold increase is predicted for maximally dilated 200 microns diameter vessels in the cat mesentery. The experiments also show that maximally dilated 1A to 4A vessels in the microcirculation closely satisfy the condition Q(flow)/(2a)3 = constant, which is consistent with the hypothesis that there is an adaptive regulation of vessel diameter which keeps the wall shear stress nearly constant during temporal changes in flow.

The effect of stimulus duration on frequency-response functions in the Pacinian (P) channel.

Psychophysical experiments on human observers and physiological measurements on Pacinian corpuscles (PCs) isolated from cat mesentery were performed to explain certain discrepancies in the psychophysical-physiological model (Bolanowski et al., 1988) for the sense of touch in the vibrotactle Pacinian (P) channel. The model was based on correlations among the psychophysical frequency response obtained on human glabrous skin and physiological frequency-response functions measured on two PC preparations: PC fibers innervating human glabrous skin (Johansson et al., 1982) and PCs isolated from cat mesentery. The three frequency-response functions were qualitatively similar. However, the low-frequency slope for the human PC fibers differed from the slopes for the psychophysical and cat mesentery PC functions by being 3 dB/octave less steep. This discrepancy can be explained theoretically by differences in methodology involving the effect of stimulus duration and the property of temporal summation known to exist in the P channel (i.e., a 3-dB increase in sensitivity per doubling of stimulus duration). To test this, experiments were performed using two methods of stimulation: (1) a constant stimulus duration for different test frequencies, as generally used in this laboratory; and (2) a constant number of stimulus cycles (n = 5) for each test frequency as used by Johansson et al. The method of least squares was used to calculate the low-frequency (50 to 150-Hz) slopes of individual psychophysical and physiological functions. The mean slopes that resulted from using the two methods of stimulation were consistent with the theoretical expectations.

Semi-Serial Electron-Micrographic Reconstruction of Putative Transducer Sites in Pacinian Corpuscles

The Pacinian corpuscle (PC) is composed of an afferent neurite surrounded by an accessory capsule formed by concentric layers of lamellae. Projecting from the neurite, which is elliptical in cross-section, are "filopodia" or axonal, spike-like extensions. These filopodia are the putative sites of transduction. It has been proposed that two populations of filopodia organized in morphofunctional opposition exist, and that this arrangement is responsible for the bidirectional sensitivity of PCs as seen in receptor potential recordings. In order to explore this possibility, PCs obtained from cat mesentery were processed for electron microscopy, and semiserial reconstructions were made. We evaluated the extensions' (n > 110) locations, inclusions, shapes, and sizes. The filopodia were found to project along the major elliptical axis of the neurite, their density being approximately 2.8 per micron. The filopodia were found to contain filaments, vesicles, and amorphous ground substance, and dense accumulations of mitochondria were found at their bases. Measurements of their size (i.e., length, width, and height) suggest that there are two different types of filopodia. No other obvious relations among filopodial type, location along the neurite, and landmarks for transduction were found. The presence of the two filopodial types may be the basis for the bidirectional sensitivity of the PC.

Leukocyte-induced vascular protein leakage in cat mesentery

The overall objective of this study was to determine whether leukocyte adherence and/or emigration is a prerequisite for the increased vascular protein leakage associated with acute inflammation. An in vivo preparation was used to monitor intestinal vascular protein leakage as well as polymorphonuclear leukocyte (PMN) adhesion and emigration in feline mesenteric microvessels exposed to platelet-activating factor (PAF) and leukotriene B4 (LTB4). Local intra-arterial infusion of PAF (4 ng/min) produced a fourfold increase in vascular protein leakage. A 50-fold higher concentration of LTB4 had no effect on vascular protein efflux. LTB4, however, did potentiate the PAF-induced vascular protein leakage. Both inflammatory mediators caused leukocytes to adhere to endothelial cells in postcapillary venules; however, leukocyte emigration was observed only in the presence of PAF. PAF-induced leukocyte adhesion and emigration and the increased vascular protein leakage were inhibited by a monoclonal antibody (MoAb IB4) directed against the common beta-subunit of the adhesive glycoprotein complex CD11/CD18. MoAb IB4 also prevented LTB4-induced leukocyte adhesion. Both PAF and LTB4 caused degranulation of cat PMNs in vitro, yet superoxide production was stimulated by PAF only. The data derived from these in vivo and in vitro studies indicate that leukocyte adhesion per se does not necessarily lead to increased vascular protein leakage and leukocyte emigration. Adhesion-dependent PMN functions such as emigration and superoxide production may play an important role in producing the alterations in vascular integrity observed in inflamed microvessels.

Role of CD11/CD18 in shear rate-dependent leukocyte-endothelial cell interactions in cat mesenteric venules.

In vivo microscopy was used to assess the relationships among shear rate (and shear stress), leukocyte rolling velocity, and leukocyte adherence in a cat mesentery preparation. Shear rate in individual venules and arterioles of 25-35 microns diameter were varied over a wide range by graded occlusion of an arterial loop. There was a linear decline in leukocyte rolling velocity (Vwbc) as red cell velocity (Vrbc) was reduced. The ratio Vwbc/Vrbc remained constant despite variations in shear stress from 5-25 dyn/cm2. A reduction in shear stress was associated with an increased leukocyte adherence, particularly when Vwbc was reduced below 50 microns/s. Reduction in wall shear rate below 500 s-1 in arterioles allowed 1-3 leukocytes to adhere per 100 microns length of vessel, while venules exposed to the same shear rates had 5-16 adherent leukocytes. In arterioles, leukocyte rolling was only observed at low shear rates. At shear rates less than 250 s-1 leukocyte rolling velocity was faster in arterioles than venules, and the ratio Vwbc/Vrbc for arterioles was 0.08 +/- 0.02, which was fourfold higher than the ratio obtained in venules at similar shear rates. Pretreatment with the CD18-specific antibody (mAb) IB4 increased leukocyte rolling velocity in venules by approximately 20 microns/s at red cell velocities below 2,000 microns/s. mAb IB4 largely prevented the leukocyte adherence to arterioles and venules, and increased the ratio Vwbc/Vrbc observed in venules at low shear elicit a CD18-dependent adhesive interaction between leukocytes and microvascular endothelium, and that differences in shear rates cannot explain the greater propensity for leukocyte rolling and adhesion in venules than arterioles.

Ethanol enhances leukocyte-endothelial cell interactions in mesenteric venules

In vivo studies have implicated neutrophils in the gastric mucosal injury produced by intraluminal administration of ethanol. However, in vitro studies indicate that ethanol inhibits various neutrophil functions such as adherence, chemotaxis, and degranulation. The aim of the present study was to assess whether ethanol, at clinically relevant concentrations, is proinflammatory in vivo. Ethanol (0.2, 1.0, 2.0, and 4.0%) was applied to the surface of the cat mesentery, and neutrophil adherence to venules (30 microns diam) and extravasation into the interstitium were quantitated using intravital microscopy. Hemodynamic parameters were also measured (venular diameter, red blood cell velocity, and leukocyte rolling velocity) or calculated (venular blood flow and wall shear stress). In this model ethanol produced a dose-dependent increase in neutrophil adherence and extravasation. The increase in leukocyte-endothelial cell interactions could not be attributed to alterations in hemodynamic factors. Pretreatment of animals with a monoclonal antibody (MoAb IB4) directed to the neutrophil CD11/CD18 adherence complex completely prevented the ethanol-induced neutrophil adherence and extravasation. Pretreatment with a leukotriene B4 (LTB4)-receptor antagonist (SC 41930) or a platelet-activating factor (PAF)-receptor antagonist (WEB 2170) did not alter the ethanol-induced neutrophil-endothelial interactions. We conclude that ethanol is proinflammatory at concentrations which may be achieved in the mucosal interstitium during acute alcohol intoxication. The ethanol-induced leukocyte adherence and extravasation is dependent on the expression of adhesive glycoproteins. The inflammatory mediators, PAF and LTB4, do not appear to play an important role in the leukocyte-endothelial cell interactions initiated by ethanol.

Adenosine inhibits ischemia-reperfusion-induced leukocyte adherence and extravasation

Ischemia and reperfusion (I/R) of the small intestine initiates a series of events that result in neutrophil-mediated microvascular injury. Recent reports suggest that adenosine possesses anti-inflammatory properties by virtue of its ability to inhibit neutrophil (PMN) superoxide (O2-.) and hydrogen peroxide (H2O2) production and to interfere with PMN adherence to cultured endothelium. In an attempt to further characterize the anti-inflammatory properties of adenosine in vivo we assessed the influence of exogenous adenosine on 1) I/R-induced PMN-mediated microvascular injury in the feline small intestine, 2) feline PMN superoxide production, and 3) I/R-induced PMN adherence to feline mesenteric venular endothelium. We found that intra-arterial administration of adenosine (2 microM) significantly attenuated the I/R-induced increases in intestinal capillary permeability. This protective effect of adenosine could not be explained entirely on its ability to inhibit PMN O2-. (or H2O2) production, since adenosine was effective in inhibiting feline PMN O2-. production by only 20%. Using intravital microscopic techniques in cat mesentery, we found that adenosine did not alter the responses of venular blood flow, shear rate, leukocyte rolling velocity, and leukocyte adherence to I/R when compared with control animals. However, the number of extravasated leukocytes during the ischemic period was significantly reduced by adenosine. Adenosine reduced the number of adherent leukocytes by 25% at 10 and 60 min of reperfusion while leukocyte extravasation was reduced by 65-70% during the same period. Our data indicate that the adenosine-induced suppression of leukocyte extravasation cannot be explained solely by an attenuation in leukocyte adherence to venular endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Identifying possible neural codes for vibrotaction using the theory of temporal summation

The theory of temporal summation refers to the psychophysical phenomenon in which threshold decreases with increasing stimulus duration. The effect is found in audition and is central. Vibrotactile thresholds mediated by the Pacinian-corpuscle (PC) population (the “P” channel) also exhibit temporal summation. Assuming that the tactile summator is also central, it may be possible to determine the neural code for threshold used by the P channel. Theoretically, temporal summation predicts a decrease in threshold at a rate of −3 dB/doubling of duration from 10 to 100 ms. Thus by integrating the response from single fibers for various response criteria, those not having the potential for temporal summation can be rejected as possible coding schemes. PCs isolated from cat mesentery were stimulated with bursts of vibrations (300 Hz) having durations from 10 to 1000 ms, the intensity of the stimuli adjusted for fixed criterion responses of 1, 2, and 4 impulses/burst and 1 impulse/cycle. Data were sampled over the entire burst duration, in effect analyzing the response with an ideal summator. The decreases in intensity for increases in duration from 10 to 100 ms were −0.9, −1.2, −2.3, and −0.2 dB/doubling, respectively, with neither the 1 impulse/burst nor the impulse/cycle criteria showing significant summation. The other two criteria show modest summation, indicating that they have the potential for being the neural code for threshold in the P channel. [Work supported by NS23933.]

In vivo determination of the force of leukocyte-endothelium adhesion in the mesenteric microvasculature of the cat.

Quantitative estimates of the force of adhesion between leukocytes and endothelium were obtained from in vivo hemodynamic measurements in small venules of cat mesentery during topical application of the chemotactic compound N-formyl-methionyl-leucyl-phenylalanine (FMLP). Simultaneous measurements of upstream to downstream pressure drop, red cell velocity, microvessel hematocrit, and vessel diameter and length permitted application of the principles of momentum conservation to calculate the forces acting upon a leukocyte during adhesion to the endothelium. For venules ranging in diameter from 23 to 49 micron, the ratio of force (acting in the vessel axial direction) to wall shear stress on the endothelium fell from 14.6 X 10(-6) in small venules to 2.3 X 10(-6) dynes per dyne/cm2 in large venules; reflecting the larger pressure drops and forces attendant to greater lumen obstruction in the smaller venules. The equilibrium force representative of a balance between fluid shear stresses on the leukocyte and those at its site of contact with the endothelium ranged from 1.1 to 76.1 X 10(-5) dynes for wall shear stress ranging from 2 to 25 dynes/cm2; with venules with greater wall shear stresses having the greater leukocyte-endothelium shear force. Within individual venules, however, the force acting on a single leukocyte varied inversely with wall shear stress, most likely due to white blood cell deformation, which leads to a lessening of shear stress on the surface of the white blood cell.

Elevated ambient oxygen does not affect autoregulation in cat mesentery.

The purpose of this study was to determine whether oxygen plays a role in the autoregulation of blood flow in the isolated mesentery of the cat. Arteriolar diameter and red cell velocity were measured at normal arterial pressure and during 2 min of pressure reduction to 80 and 40 mmHg under ambient levels of 0, 10, and 20% oxygen in nitrogen. Autoregulatory responses during pressure reductions to 80 and 40 mmHg were not significantly different under 0% oxygen compared with those under 10 or 20% oxygen. Also, no significant difference was found in the control state between the mean diameters, linear velocities, or volume flows under 10 and 20% oxygen compared with 0% oxygen. We also determined oxygen levels just under the mesentery with different ambient oxygen levels. These values were the same as in the ambient gas mixture, suggesting that tissue oxygen levels in mesentery are determined by those in the external environment. Oxygen levels in the abdominal cavity averaged 67 mmHg, indicating that mesentery is normally exposed to a high-oxygen environment. We conclude that a change in tissue oxygen tension is not an essential factor in the mechanism of blood flow autoregulation in cat mesentery.

Specializations of plasma membranes in Pacinian corpuscles: implications for mechano-electric transduction.

Pacinian corpuscles of cat mesentery were studied with freeze-fracture and thin sectioning methods after chemical fixation. Intramembranous particles (IMPs) exhibit differences in both density and pattern of distribution between the axolemma of the smooth short axis (x-axis) region and that of the axonal spine region of the long axis (y-axis) of the axon terminal. The axolemma of the x-axis has IMPs at a density of 2687 +/- 581 per micron2 (mean +/- S.E.M.), and these particles are 9.0 +/- 1.7 nm (mean +/- S.D.) in diameter. In contrast, the axolemma of the y-axis has a higher density of IMPs (3607 +/- 612 per micron2) which are larger (diameter, 10.0 +/- 1.7 nm). The particle distribution is not homogeneous in x-axis membranes as there are small patchy areas devoid of particles scattered throughout the entire surface. The E-face of the axolemma has a low density of IMPs (approximately 200 per micron2 in both x- and y-axes). However, IMPs in the E-face are smaller (approximately 9 nm) in the x-axis than in the y-axis (approximately 10 nm). The inner core lamellar cells have IMPs at a density of 3276 +/- 739 per micron2 and 553 +/- 169 per micron2 in the P- and E-faces, respectively. The particles are about 10 nm in diameter in both faces. Many gap junctions occur between lamellar cells especially near the clefts, suggesting that hemilamellae of each inner core half are kept at the same electrotonic potential. The outer core lamellar cells have IMPs at a density of 2239 +/- 403 per micron2 and 536 +/- 123 per micron2 in their P- and E-faces, respectively. The particles are approximately 10 nm in diameter in both faces. A noteworthy finding is that tight junctions are prominent at cell-to-cell appositions within individual lamellae, especially in the first and second (or sometimes third) innermost lamellae of the outer core. These tight junctions are considered to be a barrier to the leakage of fluid and/or ions between interlamellar spaces as well as between inner and outer cores. An intermediate cell layer is identified between the inner and outer cores. The connective tissue space of this cell layer corresponds to the endoneurium, indicating that intermediate layer cells are comparable to endoneurial fibroblasts.(ABSTRACT TRUNCATED AT 400 WORDS)

Leukocyte-endothelium adhesion: Microhemodynamics in mesentery of the cat

The effects of leukocyte-endothelium adhesion on microhemodynamics were studied in cat mesentery under control conditions and following tissue suffusion with the chemotactic agent N-formyl-methionyl-leucyl-phenylalanine (FMLP). The results indicate that under normophysiological conditions there is little or no leukocyte-endothelium adhesion in arterioles and venules. Tissue suffusion with FMLP significantly increases the number of adhering leukocytes in venules, but not in arterioles. Analysis of the number of adhering leukocytes (in venules) as a function of wall shear rate suggested that increased adhesion of leukocytes was primarily due to elevated adhesive forces and not the result of decreases in dispersal forces, i.e., wall shear stress. From measurements of upstream to downstream pressure drop, red cell velocity, and microvessel hematocrit in 16 unbranched venules, no significant changes in diameter (mean of 39.9 ± 7.8 (SD) μm), intravascular pressure gradient (0.59 ± 0.40 × 10 −2 cm H 2O/μm), nor microvessel hematocrit (31.0 ± 9.8%) occurred in response to FMLP. There were significant decreases in upstream pressure (8%) and estimated bulk flow (28%) as well as significant increases in the number of adhering leukocytes, from 1.5 ± 2.8 to 11.4 ± 8.3 cells/100 μm, and vessel resistance (81%). Changes in hemodynamics were found to be more pronounced in venules with small diameters. The observed response to FMLP suggests that changes in hemodynamics during leukocyte-endothelium adhesion can be accounted for by a decrease in the effective diameter due to obstruction of the lumen by WBCs, and that adhesive interactions between WBCs and endothelium are a major determinant of blood flow resistance in the microcirculation.

Microbubble dynamics visualized in the intact capillary circulation

The potential for the use of contrast echocardiography to study myocardial perfusion has generated efforts to develop standardized echo contrast agents. The two methods used in this laboratory to generate microbubbles in solutions serving as contrast agents included the widely used hand-agitation method and the newer ultrasonic microcavitation (sonication) method. The latter has been demonstrated to generate smaller and more uniform microbubbles in an in vitro system. The present study was designed to observe, by direct microscopic examination of a cat mesentery preparation, the behavior and fate of the microbubbles in an in vivo system. The in vivo mesentery observations confirm the critical role of microbubble size in its unhindered passage through the capillary vasculature. The smaller and more uniform sonicated microbubbles passed rapidly through the microcirculation along with the red blood cells, whereas the larger microbubbles were observed to coalesce and interrupt the flow of blood and subsequently collapse or shrink.

Blood-nerve barrier in the Vater-Pacini corpuscle of cat mesentery.

Correlated thin-section, freeze-fracture and tracer examinations were used to examine the blood-nerve barrier of the Vater-Pacini corpuscles in cat mesentery. A laminar inner core and a multilayered outer core enfolded the terminal nerve fiber of the corpuscle. The lamellar cells of both cores were characterized by numerous vesicular membrane invaginations. Freeze-fracture images and tracer experiments employing lanthanum nitrate proved that these invaginations are static structures mediating in neither active pinocytosis nor the transcellular transport of metabolites. In both inner and outer cores, lamellar cells were connected to one another by tight junctions of either the zonula or the fascia type, that occurred between lamellar-cell processes within the lamella and between the cells of adjacent lamellae. Intravascularly applied lanthanum lay at the outermost regions of the corpuscles without entering their internal zones, apparently because lamellar-cell tight junctions hindered further penetration. The results of our investigations suggest strongly that the Vater-Pacini corpuscle lamellae enfolding the nerve terminal form an effective diffusion barrier against the permeation of tissue fluids, thus preserving the corpuscle internal circumference.

Intensity and frequency characteristics of pacinian corpuscles. II. Receptor potentials.

Intensity characteristics that relate receptor- (generator) potential amplitude to vibration amplitude and frequency characteristics that relate either the stimulus intensity required for a criterion response or the phase angle between the stimulus and the receptor potential to vibration frequency have been obtained from isolated pacinian corpuscles removed from cat mesentery. The intensity characteristics of signal-averaged receptor potentials in response to sinusoidal displacements were found to be linear at low stimulus levels and to saturate at higher ones. At the higher levels, an asymmetric full-wave rectification was often found, the degree of which varied among receptors. The receptor-potential waveforms showed a time-dependent hysteresis in response to every stimulus cycle at moderate and high stimulus levels. An average intensity characteristic is given. The measured amplitude-frequency characteristics for a constant magnitude of the receptor potential below the neural spike threshold were found to be U-shaped functions. The averaged (n = 7) amplitude-frequency characteristic generated at a constant criterion response had a best frequency of 370 Hz and a bandwidth of Q3 dB equal to 0.8. The phase-frequency characteristics of the receptor potentials below spike threshold exhibited two populations of responses. Both populations underwent phase changes of about 300 degrees as the vibration frequency was increased from 20 Hz to 1.0 kHz but were separated by 180 degrees. An average (n = 8) phase-frequency characteristic is shown. For a constant neural firing rate, the relationship between receptor-potential amplitude and stimulus frequency was also U-shaped. Several qualitative physiological models are presented in relation to previously reported anatomical evidence (14, 18, 19, 32, 45). For the intensity domain, it is suggested that the cytoplasmic extensions that protrude from the unmyelinated portion of the corpuscle axon into the hemilamellar clefts are responsible for the asymmetric full-wave rectification and the response polarity in the phase-frequency characteristics. It is the asymmetric full-wave rectification and consequent receptor-potential waveforms that produce the 2 spikes/stimulus cycle plateaus in the characteristics relating firing rate to stimulus intensity described in the preceding paper (5). An additional model, based on the recovery of spike threshold, suggests how the plateaus in the firing rate-intensity characteristics (5) are produced. For the frequency domain, three filters in cascade can account for the frequency characteristic obtained with a constant firing rate criterion (see Ref. 5).(ABSTRACT TRUNCATED AT 400 WORDS)

Intensity and frequency characteristics of pacinian corpuscles. I. Action potentials.

The mechanisms by which pacinian corpuscles, isolated from cat mesentery, transduce mechanical stimuli have been measured for directly applied sinusoidal deformations. Stimulus-response relationships were measured as follows: intensity characteristics, which relate the receptor-potential magnitude or the neural firing rate to stimulus intensity; amplitude-frequency characteristics, which relate the stimulus amplitude to stimulus frequency for a given response criterion; and phase-frequency characteristics, which relate the phase angle between the stimulus and the receptor response to stimulus frequency. This report, the first in a series of three, deals with the characteristics reflected in the neural firing rate. The two reports that follow deal with the receptor potential, which, if of sufficient amplitude, generates the propagated action potential. In the majority of the pacinian corpuscles investigated, the intensity characteristics for neural firing rates were steep at low stimulus intensities and plateaued at submultiples and multiples of the stimulus frequency as stimulus intensity was increased. Poststimulus time and interval histograms reveal that the plateaus occur as a result of phase locking to the stimulus. The submultiples and multiples of stimulus frequency at which phase locking was found and the length of the plateaus depended on stimulus frequency. These plateaus were eliminated with the use of narrow-band noise stimuli. The amplitude-frequency characteristics obtained with either a criterion of constant firing rate or that of a constant number of neural spikes per stimulus cycle were U-shaped functions. Their positions along both the intensity and frequency continua are affected by response criterion. For example, the mean (n = 19) amplitude-frequency characteristic generated with a constant firing rate criterion of 1 spike/s has a maximum sensitivity of about -37.0 dB re 1-micron peak and a best frequency (BF, stimulus frequency where maximum sensitivity occurs) of 465 Hz. The bandwidth, measured by Q3 dB, is 1.02. Alternatively, the average (n = 16) amplitude-frequency characteristic obtained with a response criterion of 1 spike per stimulus cycle has a maximum sensitivity of about -25.0 dB re 1-micron peak, a BF of 270 Hz and Q3 dB value of 1.16. Spontaneous activity (SPA; activity in the absence of controlled stimuli) was found in 13.6% of the pacinian corpuscles. Intensity characteristics and frequency characteristics of these corpuscles show features similar to those of corpuscles without spontaneous activity except that the intensity characteristics asymptote to SPA levels at low stimulus intensities.(ABSTRACT TRUNCATED AT 400 WORDS)