Validation of double vascular occlusion method for Pc,i in lung and skeletal muscle

Capillary pressures in isogravimetric lung and skeletal muscle measured with the double vascular occlusion technique (Pdo) were compared to those measured using the traditional gravimetric technique (Pc,i). Pressures were measured using both techniques in isolated blood-perfused canine lungs (n = 18), blood-perfused rat hindquarters before (n = 8) and after (n = 6) maximal dilatation with papaverine and in rat hindquarters perfused with an artificial plasma (n = 6). In both organs, regardless of vascular tone, the double vascular occlusion isogravimetric pressure was the same as the gravimetric Pc,i, and the two measurements were highly correlated. Lung: Pdo = -0.22 + 1.06 Pc,i (r = 0.85, P less than 0.01); hindquarter: Pdo = -1.03 + 0.99 Pc,i (r = 0.91, P less than 0.01). In addition, Pdo was the same at every combination of isogravimetric arterial and venous pressures tested. The results indicate that the more rapidly applied double vascular occlusion pressure yields an accurate measure of isogravimetric capillary pressure in isolated organs over a wide range of isogravimetric pressures.     

Evaluation of Starling forces in the equine digit

A pump-perfused extracorporeal digital preparation was used to evaluate blood flow, arterial pressure, venous pressure, isogravimetric capillary filtration coefficient, capillary pressure, and vascular compliance in six normal horses. From these data, pre- and postcapillary resistances and pre- and postcapillary resistance ratios were determined. Vascular and tissue oncotic pressures were estimated from plasma and lymph protein concentrations, respectively. By use of the collected and calculated data, tissue pressure in the digit was calculated using the Starling equation. In the isolated equine digit, isogravimetric capillary pressure averaged 36.7 mmHg, plasma and lymph oncotic pressures averaged aged 19.12 and 6.6 mmHg, respectively, interstitial fluid pressure averaged 25.6 mmHg, and the capillary filtration coefficient averaged 0.0013 ml.min-1.mm-1.100 g-1. Our results indicate that digital capillary pressure in the laterally recumbent horse is much higher than in analogous tissues in other species such as dog and human. However, the potential edemagenic effects of this high digital capillary pressure are opposed by at least two mechanisms: 1) a high tissue pressure and 2) a low microvascular surface area for fluid exchange and/or a low microvascular permeability to filtered fluid.     

Comparison of isogravimetric and venous occlusion capillary pressures in isolated dog lungs

Venous occlusion capillary pressures (Pcv) were simultaneously compared with isogravimetric capillary pressures (PcI) in the same isolated perfused dog lung preparations. For 26 determinations, PcI averaged 1.23 +/- 0.22 (SE) mmHg higher than Pcv. However, the two measurements of capillary pressure were highly correlated (r = 0.99), and the following regression equation was obtained: Pcv = 1.12 PcI - 2.1. Pcv could be easily measured several times in the same preparation, either by total venous occlusion or regional venous occlusion using a Swan-Ganz balloon catheter. In addition, Pcv did not require an isogravimetric state for its determination. These data suggest that the major sites of filtration and vascular capacitance in the pulmonary circulation reside in the microvessels and that the more easily determined Pcv is an adequate measure of the average capillary filtration pressure in the lungs.     

Metabolic and myogenic factors in local regulation of the microcirculation.

Patterns of flow were recorded from individual capillaries of mesentery and muscle during autoregulation and reactive hyperemia. In cat mesentery at normal arterial pressure capillary blood flow was often periodic in nature. When arterial pressure was reduced periodicity was abolished and in certain cases mean flow increased. Elevation of venous pressure at this time caused restoration of flow periodicity and simultaneously a large fall in mean flow. Vasomotion and autoregulation in mesentery appear to be dependent on intravascular pressure per se. In cat sartorius muscle substantial increase in flow was seen in most capillaries during reactive hyperemia. In certain capillaries the pattern resembled the gross flow pattern while others showed a brief hyperemia and then a period of flow arrest that is presumably due to a strong precapillary vasoconstriction. The latter response is suggestive of a myogenic control while the former may be due to accumulation of metabolites. In frog pectoralis muscle reactive hyperemia was very prolonged in comparison to cat sartorius muscle. The general pattern of flow was consistent with the notion of a strong metabolic control mechanism. The three tissues studied provide examples of strong myogenic, strong metabolic, and combined metabolic and myogenic control of the microcirculation.     

Changes in the respiratory muscles and their microcirculatory bed during exposure of the body to chronic hypoxia and its aftereffects

Changes of the respiratory muscles have been studied under the effect of a rarefied atmosphere when the pressure is 560 mm Hg (2,500 m), 405 mm Hg (5,000 m), 286 mm Hg (7,500 m) and during the period of their aftereffect. The experimental group consists of 260 and the control group--of 130 white rats. Adaptation of the respiratory muscles to the effect of the rarefied atmosphere at the pressure of 560 mm Hg takes place mainly at the expense of certain functional changes of the microcirculatory bed and hypertrophy of the muscle fibers. The period of aftereffect is characterized with normalization of these phenomena. Adaptation of the respiratory muscles at the pressure of 405 mm Hg takes place at the expense of hypertrophy of the muscle fibers, small destructive changes and a complex rearrangement of the microcirulatory bed. During the period of aftereffect, by the 40th day no destructive changes are noted in the muscle tissue. The capillary bed undergoes some rearrangements by the 42d -56th day with increasing quantitative indices per area unit. This results in improvement of the muscles nutrition. In the respiratory muscles at the pressure 286 mm Hg, atrophic changes in the muscle fibers take place at certain stages of the experiment. Essential destructive changes are observed, rearrangement of the microcirculatory bed with decreasing convolution of the longitudinal capillaries and a decreasing number of the transversal capillaries are noted by the end of the experiment. During the period of aftereffect, by the 56th day, the external and internal intercostal muscles completely restore their structure, and in the diaphragm the destructive changes remain. By the same time, the microcirculatory bed becomes more rare at the expense of decreasing capillarization of the muscle fibers and a decreasing number of the transversal capillaries.     

Intramuscular pressures during exercise: an evaluation of a fiber optic transducer-tipped catheter system

The efficacy of a modified fibre optic transducer-tipped catheter system for measuring intramuscular pressures during exercise was determined. A microcapillary infusion technique using a catheter was employed as the standard of comparison due to its established dynamic properties. Pressures were measured in the tibialis anterior muscle of six healthy adults at rest before exercise, during isometric and concentric exercise, and at rest after exercise. The fibre optic system measured contraction pressures equal to the microcapillary infusion technique during all phases of the exercise protocols but recorded a lower relaxation pressure during isometric exercise and a lower rest pressure following 20 min of concentric exercise. Negative relaxation pressures were recorded by the fibre optic system for two subjects during continuous concentric exercise. It is hypothesized that a piston effect, due to the sliding of muscle fibres at the catheter tip following a contraction, rendered falsely low pressures during relaxation and that this artefact was reflected in the subsequent rest pressure following exercise. The larger volume (157 mm3) and area (3.49 mm2) of the fibre optic catheter in the muscle made it more prone to this effect than the conventional catheter (39 mm3 and 0.87 mm2, respectively). The fibre optic system may be preferred when recording the muscle contraction pressures during complex limb movements but should not be used when assessing the relaxation pressures or the pressure at rest following exercise.     

Tissue pressures and fluid dynamics in the kidney.

The kidney has several characteristics which make renal pressures and fluid dynamics unique when compared to other organs. Renal blood flow is roughly 100 times that of skeletal muscle. The renal circulation consists of two distinct capillary beds in series: a high pressure system in the glomerulus that favors filtration and a low pressure system in the peritubule network that favors reabsorption. The hydrostatic pressure in the glomerular capillary is 4-6 times higher than the hydrostatic pressure in the peritubule capillary so that approximately 25% of the plasma is filtered. The bulk of the filtrate is subsequently reabsorbed by the peritubule capillary network. Micropuncture techniques have been used to obtain quantitative measurements of the pressures and fluid dynamics of the peritubule microcirculation. The net force for uptake of all the fluid reabsorbed by a single proximal tubule up to the point of micropuncture is 21 mm Hg acting over a capillary bed with a permeability surface area product of 2 nl/min per mm Hg. In contrast to subcutaneous tissue and muscle, the renal interstitial fluid pressure is positive. The consequence of a positive interstitial fluid pressure is that normal lymph flow is relatively high and changes in interstitial fluid pressure have relatively little effects on lymph flow.     

Electrical resistance of a capillary endothelium

The electrical resistance of consecutive segments of capillaries has been determined by a method in which the microvessels were treated as a leaky, infinite cable. A two-dimensional analytical model to describe the potential field in response to intracapillary current injection was formulated. The model allowed determination of the electrical resistance from four sets of data: the capillary radius, the capillary length constant, the length constant in the mesentery perpendicular to the capillary, and the relative potential drop across the capillary wall. Of particular importance were the mesothelial membranes covering the mesenteric capillaries with resistances several times higher than that of the capillary endothelium. 27 frog mesenteric capillaries were characterized. The average resistance of the endothelium was 1.85 omega cm2, which compares well with earlier determinations of the ionic permeability of such capillaries. However, heterogeneity with respect to resistance was observed, that of 10 arterial capillaries being 3.0 omega cm2 as compared with 0.95 omega cm2 for 17 mid- and venous capillaries. The average in situ length constant was 99 micrometers for the arterial capillaries and 57 micrometers for the mid- and venous capillaries. It is likely that the ions that carry the current must move paracellularly, through junctions that are leaky to small solutes.     

Endotracheal cuff pressure and tracheal mucosal blood flow: endoscopic study of effects of four large volume cuffs.

Large volume, low pressure endotracheal tube cuffs are claimed to have less deleterious effect on tracheal mucosa than high pressure, low volume cuffs. Low pressure cuffs, however, may easily be overinflated to yield pressures that will exceed capillary perfusion pressure. Various large volume cuffed endotracheal tubes were studied, including Portex Profile, Searle Sensiv, Mallinkrodt Hi-Lo, and Lanz. Tracheal mucosal blood flow in 40 patients undergoing surgery was assessed using an endoscopic photographic technique while varying the cuff inflation pressure. It was found that these cuffs when overpressurised impaired mucosal blood flow. This impairment of tracheal mucosal blood flow is an important factor in tracheal morbidity associated with intubation. Hence it is recommended that a cuff inflation pressure of 30 cm H2O (22 mm Hg) should not be exceeded.     

Intramuscular fluid pressure during isometric contraction of human skeletal muscle

Intramuscular fluid pressures were recorded in the vastus medialis of seven healthy male volunteers. Pressures were measured simultaneously at three different sites in the muscle by a catheter-tip transducer with extremely low volume-displacement characteristics and by two extracorporeal transducers connected to slit catheters. All three recording systems gave qualitatively similar results provided the catheters had inner diameters exceeding 0.53 mm and allowed measurement of pressures lasting as short as 1 s. Wick catheters yielded slower responses than slit catheters. At any position intramuscular fluid pressure increased linearly with force up to maximal voluntary contraction (MVC). However, slopes of these curves varied greatly mainly because the pressure was also a linear function of the distance from the fascia. The highest recorded pressure was 570 Torr. At prolonged submaximal contractions intramuscular fluid pressure oscillated independent of contraction force. The linearity of both the pressure-force relationship and the pressure-depth relationship is compatible with a simple model based on the law of Laplace because the muscle fibers are curved during contraction in this muscle. It is hypothesized that blood flow is first compromised deep in the muscle where pressure is highest and in general at lower stress or tension in short bulging muscles with great curvature of the fibers compared with long slender ones.     

Osmotic reflection coefficient for total plasma protein in lung microvessels

The osmotic reflection coefficient (sigma) for total plasma proteins was estimated in 11 isolated blood-perfused canine lungs. Sigma's were determined by first measuring the capillary filtration coefficient (Kf,C in ml X min-1 X 100g-1 X cmH2O-1) using increased hydrostatic pressures and time 0 extrapolation of the slope of the weight gain curve. Kf,C averaged 0.19 +/- 0.05 (mean +/- SD) for 14 separate determinations in the 11 lungs. Following a Kf,C determination, the isogravimetric capillary pressure (Pc,i) was determined and averaged 9.9 +/- 0.5 cmH2O for all controls reported in this study. Then the blood colloids in the perfusate were either diluted or concentrated. The lung either gained or lost weight, respectively, and an initial slope of the weight gain curve (delta W/delta t)0 was estimated. The change in plasma protein colloid osmotic pressure (delta IIP) was measured using a membrane osmometer. The measured delta IIP was related to the effective colloid osmotic pressure (delta IIM) by delta IIM = (delta W/delta t)0/Kf,C = sigma delta IIP. Using this relationship, sigma averaged 0.65 +/- 0.06, and the least-squares linear regression equation relating Pc,i and the measured IIP was Pc,i = -3.1 + 0.67 IIP. The mean estimate of sigma (0.65) for total plasma proteins is similar to that reported for dog lung using lymphatic protein flux analyses, although lower than estimates made in skeletal muscle using the present methods (approximately 0.95).     

Estimation of capillary density in human skeletal muscle based on maximal oxygen consumption rates

A previously developed Krogh-type theoretical model was used to estimate capillary density in human skeletal muscle based on published measurements of oxygen consumption, arterial partial pressure of oxygen, and blood flow during maximal exercise. The model assumes that oxygen consumption in maximal exercise is limited by the ability of capillaries to deliver oxygen to tissue and is therefore strongly dependent on capillary density, defined as the number of capillaries per unit cross-sectional area of muscle. Based on an analysis of oxygen transport processes occurring at the microvascular level, the model allows estimation of the minimum number of straight, evenly spaced capillaries required to achieve a given oxygen consumption rate. Estimated capillary density values were determined from measurements of maximal oxygen consumption during knee extensor exercise and during whole body cycling, and they range from 459 to 1,468 capillaries/mm2. Measured capillary densities, obtained with either histochemical staining techniques or electron microscopy on quadriceps muscle biopsies from healthy subjects, are generally lower, ranging from 123 to 515 capillaries/mm2. This discrepancy is partly accounted for by the fact that capillary density decreases with muscle contraction and muscle biopsy samples typically are strongly contracted. The results imply that estimates of maximal oxygen transport rates based on capillary density values obtained from biopsy samples do not fully reflect the oxygen transport capacity of the capillaries in skeletal muscle.     

CHANGES IN HEPATIC STRUCTURE IN RATS PRODUCED BY BREATHING PURE OXYGEN

The livers of rats exposed to pure oxygen were examined electron microscopically to study toxic effects of oxygen in a metabolically sensitive organ. Pressures of 1/3 (258 mm Hg), 1 (760 mm Hg), and 3 (2280 mm Hg) atmospheres were used, with exposures up to 90 days with the lowest pressures. The first changes in the hepatocytes were loss of glycogen and enlargement of mitochondria with development of mitochondria with bizarre shapes which were seen after 3 days at 258 mm, 1 day at 760 mm, and 3 hours at 2280 mm. These changes were followed by formation of increased numbers of cristae, membranes surrounding mitochondria, autophagic vacuoles, and polyribosome clusters. After 2 weeks at 258 mm, which is the pressure of the atmosphere of space cabins, numerous mitochondrial myelin figures appeared but the mitochondrial enlargement had begun to regress. After 90 days at 258 mm, the liver cells appeared almost normal except that many pigment granules had accumulated in the pericanalicular zones. The changes were non-specific and seemed to parallel biochemical alterations recorded elsewhere. They are not considered the result of toxicity but rather of adaptation. These atmospheres, which are used in clinical medicine and in space travel, appear to have no permanent deleterious effects on the liver in rats under the conditions of this experiment.     

Early effects of tobacco smoke exposure on vascular dynamics in the microcirculation.

The purpose of these studies is to examine the early effects of chronic tobacco smoke exposure on vascular dynamics in the mesenteric microcirculation. Female rats were exposed daily to tobacco smoke from five reference cigarettes for a period of 2 mo. At the end of this period the smoke-treated rats had gained 12 g less than sham-treated controls, and arterial blood pressure in the smoke-treated animals was slightly less than pressure in the sham-treated animals. These are characteristic effects of tobacco smoke exposure on rats. Following the treatment period, red blood cell (RBC) velocity in single mesenteric capillaries and microvascular pressures in arterioles and venules were measured in accordance to established methods. There was no significant difference in pressure distribution on the arterial side of the mesenteric vascular network, but pressure in the venules of the smoke-treated animals was significantly higher than that of the sham-treated group. In association with the higher venular pressure in the smoke-treated animals, capillary RBC velocity (an index of capillary flow) was significantly lower. The reduction in velocity was in proportion to the decrease in pressure drop (arteriole-venule) across the capillary network.     

Arterial blood pressure response to heavy resistance exercise

The purpose of this study was to record the blood pressure response to heavy weight-lifting exercise in five experienced body builders. Blood pressure was directly recorded by means of a capacitance transducer connected to a catheter in the brachial artery. Intrathoracic pressure with the Valsalva maneuver was recorded as mouth pressure by having the subject maintain an open glottis while expiring against a column of Hg during the lifts. Exercises included single-arm curls, overhead presses, and both double- and single-leg presses performed to failure at 80, 90, 95, and 100% of maximum. Systolic and diastolic blood pressures rose rapidly to extremely high values during the concentric contraction phase for each lift and declined with the eccentric contraction. The greatest peak pressures occurred during the double-leg press where the mean value for the group was 320/250 mmHg, with pressures in one subject exceeding 480/350 mmHg. Peak pressures with the single-arm curl exercise reached a mean group value of 255/190 mmHg when repetitions were continued to failure. Mouth pressures of 30-50 Torr during a single maximum lift, or as subjects approached failure with a submaximal weight, indicate that a portion of the observed increase in blood pressure was caused by a Valsalva maneuver. It was concluded that when healthy young subjects perform weight-lifting exercises the mechanical compression of blood vessels combines with a potent pressor response and a Valsalva response to produce extreme elevations in blood pressure. Pressures are extreme even when exercise is performed with a relatively small muscle mass.     

Der O2-Austausch zwischen Capillaren und Gewebe

Summary The distribution of oxygen concentration or oxygen partial pressure (=po₂) in models with different capillary arrangements is calculated. The capillaries form homogeneously perfused concurrent and countercurrent systems or inhomogeneously perfused capillary mesh systems with different velocities of blood flow on the inside of the capillaries. The question arises as to what extent the distribution of the po₂ in the tissue and the capillaries depends on the differences in streaming velocities and directions of the blood. The results show, that the greatest gradients in the po₂ distribution are to be found in the capillary mesh system. A typical example with a set of constants after Thews (1960) shows that the differences between the venous po₂ and the lowest po₂ in the tissue is 32 mm Hg in the case of the capillary network, 9 mm Hg in the case of the concurrent and 3 mm Hg in that of the countercurrent system.     

Recruitment in networks of pulmonary capillaries.

To improve our understanding of the pressure-flow characteristics of pulmonary capillaries, we analyzed by means of computer stimulation a theoretical model composed of 50 interconnected nonlinear elements. Each element required a critical pressure across it before flow occurred and there was a subsequent linear pressure-flow region whose slope, or resistance, could be related to the transmural pressure of the element ("distensibility"). The critical pressures and resistances of each element of the network were randomly chosen from distributions. We found that recruitment (i.e., onset of flow) occurred over a large range of network upstream or "arterial" pressures, and that relatively high arterial pressures were required before all elements had no distensibility. Intermittent and reverse flow were commonly seen in some elements as the arterial pressure was raised in steps. These flow reversals were particularly common when the critical pressures and resistances of the elements were inversely related. The critical pressures required for such behavior in the capillary segments of the pulmonary microcirculation were calculated to be extremely small, of the order of 0.02 cmH2O. Pressures of this magnitude might result from sticking of red cells to capillary walls or to each other. The properties of such a network may explain the patchiness of flow in the pulmonary microcirculation and the large range of arterial pressures over which recruitment is observed to occur.     

Screening for hypertension in a high school population.

Of 15 594 high school students (ages, 15 to 20) whose blood pressure was measured in a screening program, 350 (2.2%) has hypertensive readings (150 mm Hg or more systolic, or 95 mm Hg or more diastolic, or both). The mean blood pressure for the boys was 125.0 plus or minus 12.1/71.8 plus or minus 10.9 mm Hg, and for the girls, 119.8 plus or minus 10.2/72.3 plus or minus 9.2 mm Hg. The parents of the students with hypertensive readings were advised to send their children to a physician. By 6 months, of the 232 who were followed up, 156 (67.2%) has visited a physician and in 19 cases (12.2%) the physician had confirmed the hypertensive readings. Only one student, an asymptomatic 17-year-old boy whose hypertension had not previously been detected, was found to have secondary hypertension, which was relieved surgically. Of the 18 hypertensive students 4 are currently receiving antihypertensive medication and 8 continue to have their blood pressure monitored. The mean blood pressures recorded in the physicians'' offices averaged 23.7/11.1 mm Hg less than those recorded in the schools. One reason for this was that none of the physicians used pediatric cuffs, but these were required by 62.4% of the students at the screening. Hence, the intravascular blood pressure was probably underestimated in a number of cases in the physicians'' offices.     

Redistribution of intestinal microcirculatory oxygenation during acute hemodilution in pigs.

Acute normovolemic hemodilution (ANH) compromizes intestinal microcirculatory oxygenation; however, the underlying mechanisms are incompletely understood. We hypothesized that contributors herein include redistribution of oxygen away from the intestines and shunting of oxygen within the intestines. The latter may be due to the impaired ability of erythrocytes to off-load oxygen within the microcirculation, thus yielding low tissue/plasma Po(2) but elevated microcirculatory hemoglobin oxygen (HbO(2)) saturations. Alternatively, oxygen shunting may also be due to reduced erythrocyte deformability, hindering the ability of erythrocytes to enter capillaries. Anesthetized pigs underwent ANH (20, 40, 60, and 90 ml/kg hydroxyethyl starch; ANH group: n = 10; controls: n = 5). We measured systemic and mesenteric perfusion. Microvascular intestinal oxygenation was measured independently by remission spectrophotometry [microcirculatory HbO(2) saturation (muHbO(2))] and palladium-porphyrin phosphorescence quenching [microcirculatory oxygen pressure in plasma/tissue (muPo(2))]. Microcirculatory oxygen shunting was assessed as the disparity between mucosal and mesenteric venous HbO(2) saturation (HbO(2)-gap). Erythrocyte deformability was measured as shear stress-induced cell elongation (LORCA difractometer). ANH reduced hemoglobin concentration from 8.1 to 2.2 g/dl. Relative mesenteric perfusion decreased (decreased mesenteric/systemic perfusion fraction). A paralleled reduction occurred in mucosal muHbO(2) (68 +/- 2 to 41 +/- 3%) and muPo(2) (28 +/- 1 to 17 +/- 1 Torr). Thus the proposed constellation indicative for oxygen off-load deficits (sustained muHbO(2) at decreased muPo(2)) did not develop. A twofold increase in the HbO(2)-gap indicated increasing intestinal microcirculatory oxygen shunting. Significant impairment in erythrocyte deformability developed during ANH. We conclude that reduced intestinal oxygenation during ANH is, in addition to redistribution of oxygen delivery away from the intestines, associated with oxygen shunting within the intestines. This shunting appears to be not primarily caused by oxygen off-load deficit but rather by oxygen/erythrocytes bypassing capillaries, wherein a potential contributor is impaired erythrocyte deformability.     

The villi contribute to the mechanics in the guinea pig small intestine

Previous studies have shown that intestinal mucosa is compressed in vivo. The present study investigated the contribution of the mucosal villi to the biomechanical properties in circumferential direction in the guinea pig jejunum. Eight 20-cm-long jejunal segments were excised and each separated into two 10-cm-long segments. The mucosal villi were scraped off from half the segments. The segments were pressurized in vitro with Krebs solution from 0-10cmH(2)O using a ramp distension protocol with simultaneous diameter recordings. Circumferential stresses and strains were computed from the diameter, pressure and the zero-stress state data. Removing the villi resulted in small opening angles (139+/-16 degrees vs 189+/-27 degrees with villi) and small absolute values of residual strain (inner: -0.05+/-0.03 vs -0.33+/-0.06 with villi; outer: 0.11+/-0.04 vs 0.33+/-0.08 with villi) (P<0.001). The outer diameter as a function of the pressure did not differ between jejunal segments with villi and without villi. The average mid-wall stress-strain curve without villi was shifted to the left compared to the segment with villi, indicating the wall was stiffer without villi. However, if the stress-strain computation for the segments with villi was referenced to the zero-stress state of the segments without villi, the curve was only partly shifted to the left. In conclusion, this paper provides the first direct experimental evidence that the villi are important for the biomechanical properties of guinea pig small intestine in circumferential direction, because the villi not only affect the zero-stress state configuration but also partially affect the stress-strain distribution in the intestinal wall. Therefore, the villi should be taken into account in the analysis of biomechanical properties of the intestinal wall.