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Biomedical subjects

C G Ellis

Publications and source records attributed to C G Ellis.

At least 19 recordsLinked to original sources

The aortic valve blood supply.

BACKGROUND AND AIM OF THE STUDY: Normal valves are known to be metabolically active, yet the route of oxygen delivery is unclear. Although diffusion from the valve surface is the presumed source, the presence, distribution and importance of the aortic valve's vascular bed is unclear. METHODS: Seventeen porcine hearts (51 cusps) were obtained at slaughter. The coronary circulation was pressure-rinsed with a heparin solution and filled with an Aquablack solution at physiological pressure. The cusps were subsequently dissected and fixed for viewing with an inverted microscope. The anterior leaflet of the mitral valve was evaluated as a control for the vessel filling protocol. Using Adobe Photoshop and captured images, whole cusps were reconstructed, a grid was overlaid and vascular distribution evaluated. RESULTS: Of the 15 porcine aortic valves that filled, 32/45 (71%) of the cusps contained vessels. Nine valves had vasculature in all three cusps and two valves were completely avascular. Vessels were found predominantly in the basal third of the cusps and extended in from the commissures almost to the level of the free edge. There was a statistically significant difference (p<0.001) between the appearance of vessels in the basal region and in the mid and free edge regions of the valve. No difference in vascularization pattern was noted between the left, right or non-coronary cusps. CONCLUSIONS: The presence of a vasculature suggests that the metabolic activity of the cusp is greater than can be supported by diffusion from the cusp surface alone. The absence of functioning vessels might explain the failure associated with cryopreserved implants and may play a role in the durability problems faced by bioprosthetic valves. It will also be important to consider the role of this intrinsic circulation with the advent of tissue-engineered valves.

Animals↗

Effects of FI(O(2)) on hemodynamic responses and O(2) transport during RSR13-induced reduction in P(50).

Reduced Hb-O(2) affinity facilitates O(2) release to tissue but may impair pulmonary O(2) uptake, affecting cardiac output and systemic vascular resistance (SVR). We studied the effects of shifting the O(2)-dissociation curve (ODC) to the right with a continuous infusion of RSR13, an allosteric modifier of Hb, and of different inspired O(2) fractions (FI(O(2))) on arterial O(2) saturations (Sa(O(2))) in Hb and on hemodynamics in nonanesthetized rats. At an FI(O(2)) of 0.21, Sa(O(2)) fell during RSR13 from 95 to 81%. Elevation of FI(O(2)) to 0.30 returned Sa(O(2)) to baseline in the RSR13 group. The decrease in mean arterial pressure (MAP) was significantly greater in the control than in the RSR13 group at 30% O(2). Cardiac index (CI) increased only during RSR13 at 21% O(2) and returned to baseline at 30% O(2). In contrast, SVR decreased after RSR13 was infused at 21% O(2) but returned to baseline at 30%O(2), whereas controls showed the opposite, a sustained SVR. In the follow-up period, when 21 O(2)% was reestablished and mild anemia was present, MAP and SVR fell significantly more in controls, whereas CI only increased in controls. Lactate was significantly lower in the RSR13 than in the control group during RSR13 and the follow-up period. These results demonstrate that 1) continuous infusion of RSR13 produces a constant shift in the O(2) tension at which Hb is 50% saturated (P(50)), 2) FI(O(2)) of 0.30 compensates for the effects of increased P(50) on pulmonary O(2) loading, and 3) right-shifted ODC combined with supplemental O(2) may improve tissue O(2) availability.

Aniline Compounds↗

Effects of modest anemia on systemic and coronary circulation of septic sheep.

Although a lower transfusion trigger is generally recommended, little evidence is available about the physiological mechanisms of mild anemia in diseases with an imbalance between O2 supply and O2 demand such as sepsis. This study was undertaken to describe the systemic and coronary metabolic O2 reserve in an awake sheep model of hyperdynamic sepsis comparing two different hemoglobin levels. Twenty-four hours after sheep were rendered septic by cecal ligation and perforation (CLP), blood transfusion (n = 7, hemoglobin = 120 g/l) and isovolemic hemodilution (n = 8, hemoglobin = 70 g/l), respectively, were performed. Another 24 h later, we measured hemodynamics, organ blood flows, and systemic and myocardial O2 metabolism variables at baseline and through four stages of progressive hypoxia. Maximum coronary blood flow was 766.3 +/- 87.4 ml. min(-1). 100 g(-1) in hemodiluted sheep group versus 422.7 +/- 53.7 ml. min(-1). 100 g(-1) in the transfused sheep (P < 0.01). Myocardial O2 extraction was higher in the transfusion group (P = 0.03) throughout the whole hypoxia trial. In the hemodilution group, coronary blood flow increased more per increase in myocardial O(2) uptake than in transfused sheep (P < 0.01). This was accompanied by a lower left ventricular epicardial-to-endocardial flow ratio in hemodiluted sheep (1.13 +/- 0.07) than in transfused sheep (1.34 +/- 0.02, P < 0.05). We conclude that the lower coronary blood flow and greater myocardial O2 extraction in transfused septic sheep preserves transmyocardial O2 metabolism better in comparison to hemodiluted sheep.

Anemia↗

Fibroblast growth factor-2 potentiates vascular smooth muscle cell migration to platelet-derived growth factor: upregulation of alpha2beta1 integrin and disassembly of actin filaments.

Fibroblast growth factor-2 (FGF-2) has been implicated in vascular smooth muscle cell (SMC) migration, a key process in vascular disease. We demonstrate here that FGF-2 promotes SMC motility by altering beta1 integrin-mediated interactions with the extracellular matrix (ECM). FGF-2 significantly increased surface expression of alpha2beta1, alpha3beta1, and alpha5beta1 integrins on human SMCs, as assessed by flow cytometry. The greatest increase was for the collagen-binding alpha2beta1 integrin. Despite this, FGF-2 did not increase SMC adhesion to type I collagen but instead promoted SMC elongation and SMC motility. The latter was evaluated by using a microchemotaxis chamber and by digital time-lapse video microscopy. Although FGF-2 was not chemotactic for human SMCs, cells preincubated with FGF-2 displayed a 3.1-fold increase in migration to the undersurface of porous type I collagen-coated membranes and a 2.1-fold increase in migration speed on collagen. Furthermore, chemotaxis to platelet-derived growth factor-BB on collagen was significantly greater in SMCs exposed to FGF-2. FGF-2-induced elongation and migration on collagen were inhibited by a blocking anti-alpha2beta1 antibody; however, SMC adhesion to collagen was unaffected. SMC migration on fibronectin was also enhanced by FGF-2, although less prominently: migration through porous membranes increased 1.8-fold, and migration speed increased 1.3-fold. Also, FGF-2 completely disassembled the smooth muscle alpha-actin-containing stress fiber network contemporaneously with the change in integrin expression and cell shape. We conclude that (1) exogenous FGF-2 promotes SMC migration and potentiates chemotaxis to PDGF-BB; (2) the promigratory effect of FGF-2 is especially prominent on type I collagen and is mediated by upregulation of alpha2beta1 integrin; and (3) FGF-2 disassembles actin stress fibers, which may promote differential utilization of alpha2beta1 integrin for motility but not adhesion. This dynamic SMC-ECM interplay may be an important mechanism by which FGF-2 facilitates SMC motility in vivo.

Actin Cytoskeleton↗

Decreased capillary density in vivo in bowel mucosa of rats with normotensive sepsis.

Translocation of bacteria and endotoxin leading to sepsis occurs in animals subjected to burns or intestinal ischemia. This may be mediated in part by bowel mucosal microcirculatory dysfunction. However, the direct effect of sepsis on the mucosal microcirculation is unknown. The objective of this study was to develop a technique for intravital microscopy of the mucosa of the small bowel in an animal model of normotensive sepsis. We tested the hypothesis that normotensive sepsis induced by cecal ligation and perforation leads to a decrease in perfused capillaries in the small bowel mucosa at 24 hr. Twelve male Sprague-Dawley rats were hemodynamically monitored and randomly assigned to cecal ligation and perforation (CLP) or control laparotomy (sham). Twenty-four hours after initial surgery each animal was reanesthetized and the mucosal surface of the distal small bowel prepared for intravital microscopy. Laser doppler measurements of bowel wall blood flow were made immediately and repeated after a 30-min stabilization period. Intravital microscopy of the mucosal microcirculation of six villi per animal was performed and the images recorded on videotape (2 min/villus). The areas surrounded by perfused capillaries (intercapillary area) were then measured using video analysis software. Laser doppler flowmetry revealed a decrease in bowel wall blood flow during the stabilization period in the shams that did not occur in the CLP rats. The intercapillary areas were significantly greater in the CLP rats compared to sham rats (1329 +/- 316 microns2 vs 979 +/- 217 microns2, P = 0.044). The intercapillary areas were also more highly variable in the CLP group (median coefficient of variation 102 vs 83% in the sham group, P = 0.025). Intravital microscopy may be used to examine microcirculatory function of the small bowel mucosa. Sepsis induced by CLP leads to a decrease in the number of perfused capillaries in the small bowel mucosa.

Animals↗

Sepsis depresses the metabolic oxygen reserve of the coronary circulation in mature sheep.

This study was undertaken to describe the metabolic O2 reserve of the coronary circulation in an awake sheep model of hyperdynamic sepsis. Forty-eight hours after sheep were randomized to either a SHAM group (n = 8) or a cecal ligation and perforation (CLP) group (n = 8), we measured hemodynamics, organ blood flows, and systemic and myocardial O2 metabolism variables at baseline and through four stages of progressive hypoxia. A significant elevation in arterial lactate levels occurred at a higher O2 delivery in the CLP group (527 +/- 55 ml/min/m2) than in the SHAM group (357 +/- 29 ml/min/m2, p < 0.05). The heart's metabolic O2 reserve (difference in circulatory determinants of O2 availability between baseline and where O2 uptake could not be sustained) was exhausted at an O2 content of 56.9 +/- 4.2 ml O2/L in SHAM sheep and 79.6 +/- 7.2 ml O2/L (p < 0.05) in CLP sheep. An increase in coronary blood flow was three times greater in SHAM than in CLP animals. Myocardial O2 extraction increased in hypoxia in SHAM sheep (0.78 +/- 0.03 to 0.88 +/- 0.02, p < 0.05), but not in CLP sheep (0.79 +/- 0.02 to 0.80 +/- 0.04). We conclude that the metabolic O2 reserve of the coronary circulation is depressed in this model of hyperdynamic sepsis as the ability to increase both coronary blood flows and myocardial O2 extraction was significantly limited.

Animals↗

Chronic unhappiness. Investigating the phenomenon in family practice.

PURPOSE: To investigate the experience of chronic unhappiness as it presents in family practice. DESIGN: A descriptive, qualitative study of both patients and physicians using an existential phenomenologic approach. SETTING: Two village general practices in South Africa. PARTICIPANTS: Four patients who were difficult, "heartsink" patients, who gave their doctors an overwhelming feeling of exasperation and defeat. METHOD: We investigated the clinical records thoroughly and explored patients' relationships with others. Through interpretation and reflection, we tried to discover what role the doctor could play with these patients. FINDINGS: Chronic unhappiness was found to be not only a condition of life for the patients but also for the doctor. It was an important factor in the relationship they shared. Unhappiness was revealed in part by frequent visits by the patients, a constellation of negative feelings in the doctor, and difficult patient-doctor relationships. CONCLUSION: Chronic unhappiness is not "treatable" in the normal curative or therapeutic sense. This does not prevent our quest to diagnose and cure, but enlarges our horizons to recognizing and accepting our own human reactions to patients and understanding how we can meet their needs.

Attitude of Health Personnel↗

Measurement of tissue viability using intravital microscopy and fluorescent nuclear dyes.

Intravital microscopy used with fluorescent vital stains provides the opportunity to measure the temporal and spatial extent of tissue injury following disease processes. However, this assumes that prolonged exposure to such dyes does not alter microvascular perfusion or cellular viability. To test this hypothesis, the extensor digitorum longus (EDL) muscle in 24 male Wistar rats, anesthetized with sodium pentobarbital (Somnotal, 65 mg/kg, ip), were prepared for microscopy. The EDL was either bathed continuously (n = 6) in Krebs solution containing bisbenzimide (5 micrograms/ml; labels nuclei of all cells) and ethidium bromide (5 micrograms/ml; labels nuclei of injured cells) or had dyes topically applied 1 hr (n = 4) and 4 hr (n = 4) following dissection of the muscle. Noxious stimuli (i.e., hypoxia:FiO2 of 8-10% (n = 3), 95% ethanol (n = 3), and 2 hr ischemia followed by 90 min reperfusion (n = 4) were used to test the ability of ethidium bromide, when used in conjunction with intravital microscopy, to differentiate injured tissue. Video recordings at the surface of the EDL muscle were made every 30 min for 5 hr from which the number of perfused capillaries was counted (NCper). The numbers of bisbenzimide- and ethidium bromide-labeled nuclei were counted at the surface of the muscle and at two to three additional locations within the muscle (to a maximum depth of approximately 120-160 microns). The average NCper (19.05 +/- 1.7) remained constant over 5 hr, while the number of nuclei stained by bisbenzimide increased linearly with time from an initial value of 1218 +/- 125.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The erythrocyte as a regulator of vascular tone.

Local regulation of microvascular blood flow is a complex process in which the needs of the tissue must be communicated to the vasculature, enabling the appropriate matching of O2 supply to demand. We hypothesize that the red blood cell is not only the major O2 carrier but also serves as an O2 sensor and affecter of changes in O2 delivery via its release of ATP, which subsequently binds to P2y receptors on the vascular endothelium, altering vessel caliber. Using the hamster as a model, we determined that the efflux of ATP from red blood cells after exposure to low-PO2 (PO2 = 17 +/- 6 mmHg) and low-pH (pH = 7.06 +/- 0.07) solutions was significantly (P < 0.01) greater than that after exposure to normoxic, normal pH (PO2 = 87 +/- 4; pH = 7.38 +/- 0.04) solutions, indicating that two factors that are associated with an impaired O2 supply relative to demand increase the release of ATP from the red blood cell. To ascertain whether ATP alters vascular caliber, we applied 10(-6) M ATP intraluminally to arterioles of the retractor muscle, using a micropressure system. Vessel diameter increased 8 and 10%, 140 +/- 60 microns upstream of the site of infusion after 50- and 500-ms pulses, respectively. Application of ATP to arteriolar and venular capillaries induced a 31 and 81% increase in red blood cell supply rate, respectively. These results support our hypothesis that the red blood cell is more than just an O2 carrier and has a direct role in the regulation of vascular tone.

Adenosine Triphosphate↗

Heterogeneity of red blood cell perfusion in capillary networks supplied by a single arteriole in resting skeletal muscle.

Flow heterogeneity within capillary beds may have two sources: (1) unequal distribution of red blood cell (RBC) supply among arterioles and (2) unique properties of RBC flow in branching networks of capillaries. Our aim was to investigate the capillary network as a source of both spatial and temporal heterogeneity of RBC flow. Five networks, each supplied by a single arteriole, were studied in frog sartorius muscle (one network per frog) by intravital video microscopy. Simultaneous data on RBC velocity (millimeters per second), lineal density (RBCs per millimeter), and supply rate (RBCs per second) were measured continuously (10 samples per second) from video recordings in 5 to 10 capillary segments per network for 10 minutes by use of automated computer analysis. To quantify heterogeneity, mean values from successive 10-second intervals were tabulated for each flow parameter in each capillary segment (ie, portion of capillary between successive bifurcations), and percent coefficient of variation (SD/mean.100%) was calculated for (1) spatial heterogeneity among vessels (CVs) every 10 seconds and for the entire 10-minute sample and (2) temporal heterogeneity within vessels for every capillary segment and for the mean flow parameter. Analysis of these data indicates that (1) capillary networks are a significant source of both spatial and temporal flow heterogeneity, and (2) continuous redistributions of flow occur within networks, resulting in substantial temporal changes in CVs, although a persistent spatial heterogeneity of perfusion still exists on a 10-minute basis. In most networks, CVs decreased as supply rate within the network increased, thus indicating that rheology plays a significant role in determining the perfusion heterogeneity.

Animals↗

Relationship between capillary and systemic venous PO2 during nonhypoxic and hypoxic ventilation.

We evaluated the relationship between end-capillary and systemic venous PO2 values in the retractor muscle of 14 anesthetized hamsters during both nonhypoxic and hypoxic ventilation to ascertain whether the level of tissue oxygenation could be reliably estimated from the systemic parameter. End-capillary PO2 was estimated from measurements of oxygen saturation in capillaries at the venular end of the network obtained using in vivo video microscopy and computer-aided image-analysis techniques at three different levels of inspired oxygen (0.3, 0.21, and 0.1). Measurements of systemic arterial and venous blood gases were made in conjunction with these capillary determinations. In addition, in a portion of the study we utilized an oxygen microelectrode to determine the PO2 in the first-order venule draining the portion of the muscle containing the capillaries under study. We found that only when the animals were made acutely hypoxic was there any correspondence between the systemic venous and end-capillary PO2 values. In addition, these data provide support for the presence of arteriovenous shunting of oxygen during nonhypoxic ventilation.

Animals↗

Ischemia-reperfusion induced microvascular dysfunction in skeletal muscle: application of intravital video microscopy.

Video microscopy of red cell flow in capillaries at the surface of skeletal muscle provided the opportunity to quantitate ischemia-reperfusion (I-R) induced microcirculatory changes, in vivo. Extensor Digitorum Longus (EDL) muscles of 22 male Wistar rats (300-400 g), anesthetized with sodium pentobarbital (Somnotol, 65 mg kg,-1 IP), were used to measure the number of perfused capillaries (CDper: mm-1) crossing lines drawn perpendicular to the muscle axis, and red blood cell velocity (VRBC: mm/s) within individual capillaries from controls (n = 6), and after 2 hr (n = 4), 3 hr (n = 4), and 4 hr (n = 5) of no-flow ischemia with the muscle temperature maintained at its normal value of 32 degrees C. Ischemia was induced by tightening a tourniquet placed around the limb above the EDL muscle. Measurements were made after 30, 60, and 90 min of reperfusion. To test the usefulness of this skeletal muscle model for evaluating proposed interventions in I-R, the effect of hypothermia (24 degrees C) on the microcirculation following 4 hr ischemia (n = 3) was measured. Edema formation was estimated from the wet/dry weight ratio of the ischemic and contralateral control EDL muscles. Capillary perfusion at the surface of the control muscles was remarkably stable over the 5 hr period studied, while significant changes occurred following the ischemic periods. Significantly lower CDper was measured 30 min following all periods of normothermic ischemia. However, unlike the 2 and 4 hr ischemic periods 3 hr normothermic ischemia resulted in a progressive decline in CDper throughout the reperfusion period. VRBC showed evidence of a hyperemic response following 2 hr normothermic ischemia (control: 0.12 mm/s +/- 0.19 compared to 0.26 mm/s +/- 0.03 following 90 min reperfusion; mean +/- sem). However, no such hyperemia was measured following either 3 or 4 hr normothermic ischemia (i.e., 3 hr control: 0.24 mm/s +/- 0.01 compared to 0.07 mm s +/- 0.003 following 90 min reperfusion). In fact, VRBC was essentially zero 90 min following 4 hr normothermic ischemia (0.01 mm/s +/- 0.01). However, when the muscle was allowed to cool to 24 degrees C during 4 hr ischemia no significant change in either VRBC or CDper was measured compared to pre-ischemic controls. Evidence of edema was found after 3 and 4 hr normothermic ischemia. This study establishes a skeletal muscle model of I-R, which may be useful in testing hypotheses regarding mechanisms of I-R injury, and effectiveness of proposed treatments of I-R.

Animals↗

Application of image analysis for evaluation of red blood cell dynamics in capillaries.

We have devised a method to display and directly evaluate red blood cell (rbc) dynamics in capillaries using the same dual camera intravital video microscopy system employed to determine rbc oxygen saturation (Ellis et al., 1990). Capillary images are recorded on videotape and an interactive graphics system is used for analysis. Data are sampled once a frame for 60 sec using a window (one pixel wide (0.93 micron) and 100 pixels high) positioned along the axis of a capillary. The resulting data are displayed as sequential space-time images 100 pixels high by 300 pixels wide (10 sec). The space-time images thus created represent the dynamics of the rbc's in a single comprehensive static image in which the rbc's appear as dark, diagonal bands separated by light bands representing plasma gaps. From these images one can obtain information on velocity of individual rbc's (micron/sec), lineal density of rbc's (rbc/mm), and rbc supply rate (rbc/sec). This information can be used to delineate the temporal and spatial heterogeneity of hemodynamics in capillary networks. These data can then be combined with coincident data on red blood cell oxygenation to provide a complete picture of oxygen transport in capillaries or it can be used alone as a tool for the evaluation of basic in vivo and in vitro rheological questions.

Animals↗

Muscle capillary-to-fiber perimeter ratio: morphometry.

It is known that a substantial amount of capillary tortuosity is found in shortened muscles. However, the increased capillary length and surface area contributed by tortuosity and branching are seldom taken into account when capillarity is estimated and/or blood-tissue exchange is modeled in muscles. In this paper, we sought morphometric estimates of capillarity in transverse sections that incorporated data on capillary geometry. We derived equations to estimate capillary perimeter per fiber perimeter (i.e., capillary-to-fiber perimeter ratio) in transverse sections. We show how capillary-to-fiber perimeter ratio is related to capillary surface per fiber surface, i.e., to the amount of capillary surface available for exchange per muscle fiber surface area, and how it can be obtained by morphometry. Because capillary tortuosity and fiber perimeter are both a function of sarcomere length, the degree of extension or shortening of muscle samples obviously needs to be taken into account when capillary-to-fiber perimeter ratio is compared between muscles and/or samples. Using data currently available on capillary length and diameter with fiber shortening and extension, we show that it is a feature of capillary-to-fiber perimeter ratio to change relatively little with sarcomere length. As sarcomere length decreases from 2.80 to 1.58 microns in perfusion-fixed hindlimb muscles of rats, capillary and fiber perimeters in transverse sections increase substantially, whereas the ratio between the two variables, capillary-to-fiber perimeter ratio, changes only less than or equal to 10-15%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of sarcomere length on total capillary length in skeletal muscle: in vivo evidence for longitudinal stretching of capillaries.

It is generally assumed that when a muscle is shortened or extended the total length of capillaries does not change, implying that capillaries are nondistensible, longitudinally. On the basis of stereological estimates of capillary anisotropy versus sarcomere length, we propose that as long as capillaries are in a tortuous configuration muscle extension will merely decrease the tortuosity, leaving vessel length unaltered. Once capillaries have been pulled into a straight configuration, further extension of the muscle will cause the vessels to stretch. By means of intravital videomicroscopy we have demonstrated that stretching of individual capillaries does indeed occur over a sarcomere length range of 2.1 to 2.9 microns in rat extensor digitorum longus muscle. In vivo measurements of the lengths of six capillaries together with the sarcomere lengths of adjacent fibers were made in muscles positioned at various degrees of extension. Normalized data indicated that four capillaries stretched to the same degree as the muscle, one stretched more and another less. This may reflect differences in distensibility or tortuosity of capillaries in series with one another. The elastic stretching of capillaries during muscle activity may have important consequences in terms of shifts in permeability and increases in capillary surface area.

Animals↗

Determination of red blood cell oxygenation in vivo by dual video densitometric image analysis.

We have developed a new video microspectrophotometric system for the in vivo determination of oxygen saturation in red blood cells in striated muscle capillaries. This method allows one to quantify changes in the oxygenation of small groups of red blood cells as they traverse the capillary. Simultaneous images of a single microscopic field are recorded using two silicon-intensified target cameras and high-resolution video recorders. One image is recorded at an oxygen-dependent wave-length (431 nm) and the other at an isosbestic wavelength (420 nm). Light intensities from 10 adjacent pixels aligned along the axis of the capillary from identical 10-s segments of the video-tapes are digitized once per frame. Both sets of data are redisplayed simultaneously as two-dimensional images (10 pixels high x 300 frames wide) using a graphics system. These images show alternating bright and dark bands corresponding to plasma gaps and red blood cells. Light intensities in the presence and absence of red blood cells are determined by positioning a window over the appropriate region of the graphics image. Optical densities of single red blood cells at the two wavelengths, OD431 and OD420, are computed as is their ratio (OD431/OD420), which is linearly related to oxygen saturation. In vivo calibration studies in capillaries of the hamster retractor muscle indicate that the error in measuring oxygen saturation with this technique is approximately 2.7% saturation for a group of 10 cells.

Animals↗

Temporal distributions of red cell supply rate to individual capillaries of resting skeletal muscle, in frog and rat.

Microvascular red cell (RBC) supply in resting skeletal muscle fluctuates with time and varies from capillary to capillary. Our aim was to quantitate this heterogeneity in two species (frog, rat) with very different oxygen requirements. Video recordings were made of RBC flow in capillaries associated with superficial fibers of frog sartorius and rat gracilis muscles, for periods of 2-10 min. RBC supply rate (cell/s) to individual capillaries was computed as the product of RBC 'content' (measured as lineal density, cells/mm, by a video-densitometric method) and RBC velocity (mm/s, measured by a spatial correlation technique). The videotapes were analyzed at rates of 6 to 15 samples per second. Regression analysis of the mean data showed little or no correlation between RBC content and RBC velocity (r2: frog 0.095, rat 0.002), both parameters contributing equally to variations in RBC supply rate. Temporal distributions of the three supply parameters demonstrate (1) the wide range of values present within each capillary, and (2) the symmetry of the distributions at high mean values versus a pronounced skewness as mean values approached zero. The wide range of mean values of each parameter, found in both species, suggests considerable 'spatial' heterogeneity of RBC supply among capillaries in resting muscle. Temporal heterogeneity of RBC supply rate to individual capillaries increased markedly as either velocity or content (or both) approached zero (overall mean coefficient of variation: frog, 62%; rat, 100%). Both species show remarkably similar rates of convective transport of RBCs per capillary in resting muscle (e.g. mean supply rates 3.2 and 6.2 RBCs/s in frog and rat, respectively).

Animals↗