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D C Poole

Publications and source records attributed to D C Poole.

At least 55 records · Page 3Linked to original sources
PubMed1997

Effect of pulmonary emphysema on diaphragm capillary geometry.

In emphysema, the diaphragm shortens by losing sarcomeres. We hypothesized that unless capillaries undergo a similar shortening, capillary geometry must be altered. Without quantifying this geometry, capillary length and surface area per fiber volume, which are critical measurements of the structural potential for blood-tissue exchange, cannot be resolved. Five months after intratracheal elastase (E) or saline (control; C) instillation, diaphragms from male Syrian golden hamsters were glutaraldehyde perfusion fixed in situ at reference lung positions (residual volume, functional residual capacity, total lung capacity) to provide diaphragms fixed over a range of sarcomere lengths. Subsequently, diaphragms were processed for electron microscopy and analyzed morphometrically. Emphysema increased lung volume changes from -20 to 25 cmH2O airway pressure (i.e., passive vital capacity) and excised lung volume (both P < 0.001). In each region of the costal diaphragm (i.e., ventral, medial, dorsal), sarcomere number was reduced (all P < 0.05). Capillary-to-fiber ratio increased (C = 2.2 +/- 0.1, E = 2.8 +/- 0.1; P < 0.01) and fibers hypertrophied (C = 815 +/- 35, E = 987 +/- 67 microns2; P < 0.05; both values at 2.5 microns sarcomere length). Capillary geometry was markedly altered by the loss of sarcomeres in series. Specifically, the additional capillary length derived from capillary tortuosity and branching was increased by 183% at 2.5 microns sarcomere length compared with C values (C, 359 +/- 43; E, 1,020 +/- 158 mm-2, P < 0.01). This significantly increased total capillary length (C, 3,115 +/- 173; E, 3,851 +/- 219mm-2 at 2.5 microns, P < 0.05) and surface area (C, 456 +/- 13; E, 519 +/- 24 cm-1, P < 0.05) per fiber volume. Thus emphysema substantially alters diaphragm capillary geometry and augments the capillary length and surface area available for blood-tissue exchange.

Animals↗
PubMed1997

VO2 kinetics in the horse during moderate and heavy exercise.

The horse is a superb athlete, achieving a maximal O2 uptake (approximately 160 ml . min-1 . kg-1) approaching twice that of the fittest humans. Although equine O2 uptake (VO2) kinetics are reportedly fast, they have not been precisely characterized, nor has their exercise intensity dependence been elucidated. To address these issues, adult male horses underwent incremental treadmill testing to determine their lactate threshold (Tlac) and peak VO2 (VO2 peak), and kinetic features of their VO2 response to "square-wave" work forcings were resolved using exercise transitions from 3 m/s to a below-Tlac speed of 7 m/s or an above-Tlac speed of 12.3 +/- 0.7 m/s (i.e., between Tlac and VO2 peak) sustained for 6 min. VO2 and CO2 output were measured using an open-flow system: pulmonary artery temperature was monitored, and mixed venous blood was sampled for plasma lactate. VO2 kinetics at work levels below Tlac were well fit by a two-phase exponential model, with a phase 2 time constant (tau1 = 10.0 +/- 0.9 s) that followed a time delay (TD1 = 18.9 +/- 1.9 s). TD1 was similar to that found in humans performing leg cycling exercise, but the time constant was substantially faster. For speeds above Tlac, TD1 was unchanged (20.3 +/- 1.2 s); however, the phase 2 time constant was significantly slower (tau1 = 20.7 +/- 3.4 s, P < 0.05) than for exercise below Tlac. Furthermore, in four of five horses, a secondary, delayed increase in VO2 became evident 135.7 +/- 28.5 s after the exercise transition. This "slow component" accounted for approximately 12% (5.8 +/- 2.7 l/min) of the net increase in exercise VO2. We conclude that, at exercise intensities below and above Tlac, qualitative features of VO2 kinetics in the horse are similar to those in humans. However, at speeds below Tlac the fast component of the response is more rapid than that reported for humans, likely reflecting different energetics of O2 utilization within equine muscle fibers.

Animals↗
PubMed1997

Determinants of oxygen uptake. Implications for exercise testing.

For exercise modalities such as cycling which recruit a substantial muscle mass, muscle oxygen uptake (VO2) is the primary determinant of pulmonary VO2. Indeed, the kinetic complexities of pulmonary VO2 associated with exercise onset and the non-steady state of heavy (> lactate threshold) and severe [> asymptote of power-time relationship for high intensity exercise (W)] exercise reproduce with close temporal and quantitative fidelity those occurring across the exercising muscles. For moderate (< lactate threshold) exercise and also rapidly incremental work tests, pulmonary (and muscle) VO2 increases as a linear function of work rate (approximately equal to 9 to 11 ml O2/W/min) in accordance with theoretical determinations of muscle efficiency (approximately equal to 30%). In contrast, for constant load exercise performed in the heavy and severe domains, a slow component of the VO2 response is manifest and pulmonary and muscle VO2 increase as a function of time as well as work rate beyond the initial transient associated with exercise onset. In these instances, muscle efficiency is reduced as the VO2 cost per unit of work becomes elevated, and in the severe domain, this VO2 slow component drives VO2 to its maximum and fatigue ensues rapidly. At pulmonary maximum oxygen uptake (VO2max) during cycling, the maximal cardiac output places a low limiting ceiling on peak muscle blood flow, O2 delivery and thus muscle VO2. However, when the exercise is designed to recruit a smaller muscle mass (e.g. leg extensors, 2 to 3kg), mass-specific muscle blood flow and VO2 at maximal exercise are 2 to 3 times higher than during conventional cycling. consequently, for any exercise which recruits more than approximately equal to 5 to 6kg of muscle at pulmonary VO2max, there exists a mitochondrial or VO2 reserve capacity within the exercising muscles which cannot be accessed due to oxygen delivery limitations. The implications of these latter findings relate to the design of exercise tests. Specifically, if the purpose of exercise testing is to evaluate the oxidative capacity of a small muscle mass (< 5 to 6kg), the testing procedure should be designed to restrict the exercise to those muscles so that a central (cardiac output, muscle O2 delivery) limitation is not invoked. It must be appreciated that exercise which recruits a greater muscle mass will not stress the maximum mass-specific muscle blood flow and VO2 but rather the integration of central (cardiorespiratory) and peripheral (muscle O2 diffusing capacity) limitations.

Exercise Test↗
PubMed1996

Blood flow response to treadmill running in the rat spinotrapezius muscle.

The rat spinotrapezius muscle has been utilized to investigate the microcirculatory consequences of exercise training. It was the purpose of this investigation to determine whether, and to what extent, this muscle is recruited during treadmill exercise. Radioactive 15-micron microspheres were used to measure blood flow to the spinotrapezius and hind limb musculature as well as to the abdominal organs of female Wistar rats. Blood flows were measured at rest and during two levels of treadmill-running exercise (i.e., 0% grade, 15 m/min and 10% grade, 24 m/min). As expected, exercise increased blood flow to the soleus, plantaris, red gastrocnemius, mixed gastrocnemius, and white gastrocnemius muscles, whereas blood flow to the stomach, intestines, pancreas, spleen, and kidneys was decreased (P < 0.05). However, contrary to our expectation, blood flow to the spinotrapezius muscle decreased from 61 +/- 6 ml.100 g-1.min-1 at rest to 39 +/- 2 ml.100 g-1.min-1 at 0% grade, 15 m/min and 46 +/- 4 ml.100 g-1.min-1 at 10% grade, 24 m/min (P < 0.05). These findings support the premise that treadmill running does not recruit the spinotrapezius muscle and suggest that previous training-induced arteriolar adaptations produced in this muscle may result from mechanisms unrelated to augmented exercise blood flow or muscle metabolism.

Animals↗
PubMed1996

Muscle O2 uptake kinetics in humans: implications for metabolic control.

Muscle O2 uptake (VO2) kinetics in response to an augmented energetic requirement (on-transition) has never been directly determined in humans. We have developed a constant-infusion thermodilution technique that allowed rapid measurements of leg blood flow (Qleg) and, in conjunction with frequent serial measurement of arteriovenous O2 content difference across the leg [(Ca - Cv)O2leg], permitted the determination of the VO2 of the leg (VO2leg) at 3- to 4-s time intervals. VO2leg kinetics during the on-transition was taken as a close approximation of muscle VO2 (VO2mus) kinetics. Alveolar VO2 (VO2A), Qleg, leg O2 delivery [(Q.CaO2leg)], (Ca - Cv)O2leg, and VO2leg kinetics were determined in six trained subjects [age 22.8 +/- 4.4 (SD) yr; maximal O2 uptake 59.1 +/- 5.3 ml.kg-1.min-1] during the transition from unloaded pedaling to a workload (loaded pedaling; LP) (183 +/- 20 W) well below the previously determined ventilatory threshold. For all variables, two distinct phases were recognized. During the first 10-15 s of loaded pedaling (phase I), VO2A, Qleg, and (Q.CaO2)leg increased rapidly, whereas VO2leg increased only slightly and (Ca - Cv)O2leg actually decreased. After phase I, all variables showed a monoexponential increase (phase II), with similar time courses [slightly faster for (Ca - CV)O2leg]. In a consideration of both phases, the half times of the responses among variables were not significantly different: 25.5 +/- 2.6 s for VO2A, 26.6 +/- 7.6 s for Qleg, 26.9 +/- 8.3 s for (Q.CaO2leg, 23.5 +/- 1.3 s for (Ca - Cv)O2leg, and 27.9 +/- 5.7 s for VO2leg. We conclude that during the on-transition the kinetics of VO2A and VO2leg, as measured by these methods, are similar. The analysis of the early phase (first 10-15 s) of the on-transition indicates that bulk delivery of O2 to the working muscles is not limiting VO2leg kinetics. However, the present results cannot discriminate between maldistribution of blood flow/VO2 vs. inertia the intracellular oxidative machinery as the limiting factor.

Adult↗
PubMed1996

Effect of inspired O2 concentration on leg lactate release during incremental exercise.

The normal rate of blood lactate accumulation during exercise is increased by hypoxia and decreased by hyperoxia. It is not known whether these changes are primarily determined by the lactate release in locomotory muscles or other tissues. Eleven men performed cycle exercise at 20, 35, 50, 92, and 100% of maximal power output while breathing 12, 21, and 100% O2. Leg lactate release was calculated at each stage of exercise as the product of femoral venous blood flow (thermodilution method) and femoral arteriovenous difference in blood lactate concentrations. Regression analysis showed that leg lactate release accounted for 90% of the variability in mean arterial lactate concentration at 20-92% maximal power output. This relationship was described by a regression line with a slope of 0.28 +/- 0.02 min/l and a y-intercept of 1.06 +/- 0.38 mmol/l (r2 = 0.90). There was no effect of inspired O2 concentration on this relationship (P > 0.05). We conclude that during continuous incremental exercise to fatigue the effect of inspired O2 concentration on blood lactate accumulation is principally determined by the rate of net lactate release in blood vessels of the locomotory muscles.

Adult↗
PubMed1996

Relationship between fiber capillarization and mitochondrial volume density in control and trained rat soleus and plantaris muscles.

OBJECTIVE: The majority of investigations have demonstrated a strong relationship between muscle capillarity and oxidative capacity. There is, however, evidence that the capacities for O2 supply and utilization can be dissociated. Also, metabolite removal rather than O2 supply may represent the predominant design constraint placed on the capillary bed in some muscles (i.e, fast-twitch glycolytic). Recent evidence suggests that the principal barrier to O2 diffusion in skeletal muscle resides between the red blood cell and the immediately subjacent sarcolemmal space. Consequently, if the primary design constraint placed on the capillary bed is to facilitate O2 exchange, we hypothesized that capillary surface per fiber surface should be correlated with the mitochondrial volume subserved. Thus, the purpose of this study was to investigate whether one single relationship would be found between the capillary-to-fiber surface ratio and fiber mitochondrial volume in slow- (soleus) and fast-twitch (plantaris) muscle and whether this relationship would be preserved after training. METHODS: Rats were exercise-trained on a motor-driven treadmill up to 60 min/day, 5 days/week for 4 weeks at an intensity calculated to elicit congruent to 75% VO2max. Following training, soleus (S) and plantaris (P) muscles were removed under deep anesthesia for citrate synthase analysis, and the contralateral limb was perfusion-fixed in situ with glutaraldehyde and analyzed morphometrically under light and electron microscopy. RESULTS: Training significantly (p < 0.05) increased citrate synthase activity and capillary-to-fiber ratio both in S and P muscles. For all muscles combined (i.e., S and P, control and trained), the capillary-to-fiber surface ratio significantly correlated with mitochondrial volume per unit fiber length (r = 0.64). CONCLUSIONS: Our finding of a single relationship between the capillary-to-fiber surface ratio and fiber mitochondrial volume across the muscles is consistent with the notion that the size of the capillary bed in muscles comprised principally of either slow-twitch oxidative or mixed fast-twitch oxidative glycolytic and fast-twitch glycolytic fibers is primarily designed to meet fiber requirements for O2 exchange, and that an important site for O2 diffusion resistance is at the capillary-fiber interface. In addition, capillary-to-fiber surface and fiber mitochondrial volume increased in similar proportions, i.e., the relationship between the two variables was preserved after endurance training.

Animals↗
PubMed1995

Costal diaphragm blood flow heterogeneity at rest and during exercise.

To gain insight into diaphragm functional heterogeneity, blood flow (expressed as ml.min-1 x 100 g-1) was measured using radiolabeled microspheres in the ventral, medial, and dorsal regions of the costal diaphragm and in the crural diaphragm of sedentary control (S) and exercise trained (ET) female Wistar-Kyoto rats at rest and during treadmill exercise. ET animals had performed moderate intensity exercise training on a motorized treadmill (22 m/min, 10% grade, 60 min/d) for 12 months, while S were cage-confined. The efficacy of exercise training was demonstrated by a 12% increase (P < 0.05) in ventricular weight-to-body weight ratio and increases (P < 0.05) in citrate synthase activity in hindlimb skeletal muscles of ET. At rest, blood flow in the ventral costal diaphragm (16 +/- 1) averaged approximately 61% of that in the medial (26 +/- 3) and dorsal (25 +/- 2) costal regions (P = 0.035), and crural diaphragm flow was 23 +/- 3. During treadmill exercise (5 min at 22 m/min, 10% incline), blood flow increased an average of 5-fold (P < 0.001) throughout the diaphragm, but the heterogeneous flow pattern persisted; i.e., blood flow remained lower (P = 0.003) in the ventral region (77 +/- 7) than either the medial (135 +/- 15) or dorsal (127 +/- 11) costal regions. Flow in the crural diaphragm during exercise was intermediate (105 +/- 9). Exercise training did not alter either the magnitude of blood flows or the flow distribution pattern within the diaphragm. Citrate synthase activity was two-fold that of the plantaris muscle and was uniform across the ventral, medial, and dorsal costal and the crural diaphragm of a second group of age-matched rats (P = 0.57). These data demonstrate that, although oxidative capacity is uniform throughout the diaphragm, there is a significant regional heterogeneity of blood flow within the rat diaphragm both at rest and during locomotory exercise. The greater flow in the medial and dorsal regions of the costal diaphragm suggests that these regions sustain a greater portion of the inspiratory work load at rest and during exercise compared to the ventral region.

Animals↗
PubMed1995

Determinants of maximal exercise VO2 during single leg knee-extensor exercise in humans.

Previously, a reduction in fractional inspired O2 (FIO2) during dynamic exercise of the human quadriceps muscles of one leg resulted in increased muscle blood flow (Q) and a fall in femoral venous O2 tension (PO2) but no change in peak O2 uptake (VO2). These data can be interpreted as reflecting an increase in muscle O2 diffusive capacity (DO2) in hypoxia or, alternatively, that maximum O2 uptake (VO2max) was not reached for these muscles when air was breathed, in which case the theory of diffusion limitation to VO2max is not applicable to these data. Therefore, the primary goal of this study was to test the hypothesis that VO2max would be reduced in hypoxia as a result of the decreased O2 supply and a constant diffusional conductance from blood to exercising muscle. To resolve this, five trained men were studied performing single leg incremental knee-extensor exercise to VO2max while breathing air (N) and again while breathing 12% O2 (H). The maximum work rate (WRmax) was 30-50 W greater and produced even greater associated maximum leg Q (N = 9.1 +/- 0.61 and H = 8.2 +/- 0.65 l/min, P < 0.05) and leg O2 than in previous studies. Hypoxia reduced quadriceps muscle VO2max (N = 1.4 +/- 0.1 and H = 1.1 +/- 0.1 l/min, P < 0.05). In the two conditions the relationships between 1) measured femoral venous PO2 (N = 18 +/- 0.5 and H = 13 +/- 0.5 Torr) and VO2max and 2) calculated mean capillary PO2 (N = 37 +/- 0.4 and H = 28 +/- 0.8 Torr) and VO2max were each one of proportionality.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Diaphragm thickness heterogeneity at functional residual capacity and total lung capacity.

One of the determinants of muscular force is the number of myofibrils in parallel, which is approximated by thickness. To better understand the heterogeneity of diaphragm thickness, we quantified the interregional and radial patterns of thickness of nine canine diaphragms rapidly perfusion fixed in situ with glutaraldehyde at functional residual capacity (FRC) (n = 6) and total lung capacity (TLC) (n = 3). Thickness was determined gravimetrically from punch biopsies radiating from the central tendon to rib cage insertion in ventral, middle, and dorsal costal and crural regions. For comparison, the contralateral unfixed hemidiaphragm was sampled in the same fashion. The findings of this investigation include the following. 1) The costal diaphragm exhibits the same pattern of interregional heterogeneity at FRC, TLC, and in the freshly excised state. 2) The costal diaphragm is significantly thinner at FRC in situ (0.17 +/- 0.01 cm) than is the freshly excised contralateral diaphragm (0.21 +/- 0.01 cm; P < 0.05), whereas there is no significant difference between thickness at TLC and the freshly excised state. 3) There is significant, previously underscribed, radial tapering from the rib cage attachment (0.24 +/- 0.02) to the central tendon insertion (0.15 +/- 0.01 cm; P < 0.05) that is exaggerated at TLC. 4) With passive inflation from FRC to TLC, the greatest increase in thickness occurs close to the rib cage attachment for the ventral and medial costal regions but close to the central tendon in the dorsal and crural regions. We conclude that the diaphragm at FRC and TLC exhibits radial thickness heterogeneity that cannot be predicted from dimensions of the freshly excised diaphragm.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Diaphragm microvascular plasma PO2 measured in vivo.

Phosphorescence quenching techniques measure microvascular PO2 without direct surgical manipulation of the tissue. At a given arterial PO2, microvascular PO2 reflects the local O2 uptake-to-O2 delivery ratio, i.e., VO2/QO2. We evaluated the potential of phosphorescence quenching to determine microvascular PO2 in the rat costal diaphragm (PdiaO2). PdiaO2 and arterial blood gases were monitored across transient changes of inspired O2 among 21, 10, and 100% and also during hypotensive states evoked by progressive phlebotomy. After a transit delay, PdiaO2 responded rapidly to alterations of inspired and thus arterial PO2, with half times of the response averaging 5-7 s for switches to a lower inspired O2 (i.e., from 21 to 10%, from 100 to 21%, and from 100 to 10%) and also from 10 to 21%. By comparison, half times of the 10 to 100% and 21 to 100% switches were longer [11 s (P = 0.085) and 21 s (P < 0.05), respectively]. Below a mean arterial blood pressure (BP) of 120-130 mmHg, PdiaO2 decreased as a linear function of BP, with these variables being significantly correlated in each instance (n = 5, r = 0.851-0.937, P < 0.01 for all animals). From these results, it appears feasible to measure PdiaO2 in the spontaneously breathing rat in vivo under steady-state and transient conditions. Also, during progressive hypotension, the fall in PdiaO2 is significantly related to falling BP, likely as a consequence of an increased metabolic demand (increased ventilation and diaphragm VO2) concomitant with decreased blood flow. We conclude that phosphorescence quenching techniques offer a powerful tool for assessing diaphragm physiology and pathophysiology.

Animals↗
PubMed1995

Temporal correlation between maximum tetanic force and cell death in postischemic rat skeletal muscle.

To gain insight into the mechanisms responsible for muscle dysfunction after ischemia-reperfusion, a rat spinotrapezius muscle preparation was developed which enabled sequential measurements of in vivo maximum tetanic force production and cell death assessed using digital microfluorographic determination of propidium iodide (PI) staining. After 60 min of no-flow ischemia, maximum tetanic force fell significantly during 90 min of reperfusion compared with control, nonischemic muscles. The most striking fall was evident within 30 min of reperfusion and occurred concomitant with an explosive increase in PI-positive myocyte nuclei. Treatment with the oxygen radical scavenger, dimethylthiourea, attenuated both the fall in force and increased PI staining. Indeed, the rise in PI-positive nuclei correlated closely (r= 0.728) with the reduction of maximum tetanic force developed following ischemia and reperfusion under all conditions. Superoxide dismutase also attenuated the rise in PI-positive nuclei. Assessment of mitochondrial inner membrane potential (deltapsi) using Rhodamine 123 fluorescence revealed that myocytes with the lowest initial mitochondrial membrane potential were subject to the greatest injury after 90 min of reperfusion (r= 0.828). These results support the hypothesis that myocyte injury, as visualized by PI-staining, reflects an impaired contractile function in fibers with a low oxidative potential which is likely mediated by oxygen radicals.

Animals↗
PubMed1995

Increased [lactate] in working dog muscle reduces tension development independent of pH.

The purpose of this work was to examine the effect of the lactate ion on the fatigue process in working muscle independent of muscle [H+]. L-(+)-lactate was infused, at a pH that did not change arterial pH, into the blood perfusing an isolated, in situ dog gastrocnemius (N = 5) working at a submaximal intensity (isometric contractions at 2 Hz) and compared with control (C) conditions without lactate infusion. Each muscle was stimulated to work for two 60-min periods (separated by 45 min rest), consisting of three 20-min time periods with either the high arterial lactate condition (high [La]) or C condition sequentially ordered within each 60-min work period. Blood flow and O2 delivery were held constant between the C and high [La] conditions. Arterial and venous blood measurements and muscle biopsies were taken (7 biopsies from each condition) during each condition. Lactate infusion significantly increased arterial [La] (C = 4.2 +/- 0.2 mM vs high [La] = 14.4 +/- 0.2; mean +/- SE) and muscle [La] (C = 8.1 +/- 0.8 mM w.w. vs high [La] = 12.0 +/- 1.4) while arterial and muscle pH were unchanged between conditions. Muscle tension development was significantly reduced (C = 94 +/- 2 N.100 g-1 vs high [La] = 80 +/- 3) during lactate infusion and muscle O2 uptake changed proportionally with tension. These findings support an effect of the lactate anion on tension development which is independent of pH.

Animals↗
PubMed1994

Red blood cell transit time in man: theoretical effects of capillary density.

These data indicate that through the reduction in exercise time and recruitment of trained subjects, the exercising muscle in the human dynamic knee-extension model can reach even higher work rates, VO2, and Q than previously reported (Andersen & Saltin, 1985; Andersen et al., 1985; Rowell et al., 1986). Despite these high muscle Q, the achievement of high O2 extractions is possible (Richardson et al., 1993). Previously, this was attributed almost exclusively to the elevated WRMAX, and it was therefore concluded that O2 extraction is not limited by the high Q to any greater extent than in conventional two legged cycle ergometry (Richardson et al., 1993). It is now apparent from the analysis of the data in this paper that it is possible that a difference in capillary density between the subjects in the original studies and the present research may have played a role in the increase in O2 extraction with increasing muscle Q. Although, it should be recognized that a) the capillary density necessary to reduce red cell transit time suitably to match the range of measured femoral venous hemoglobin saturation is high (Gayeski et al., 1988), however it is within the measured values for man (Brodal et al., 1977), and b) where comparable, during low WR knee-extensor exercise and whole body VO2MAX, subjects across the studies did not differ. This would be expected if capillary density differed greatly (Brodal et al., 1977). It can therefore be concluded that both the rapid protocol during knee-extensor exercise and the potential increased capillarity of the trained subjects in the present study may have combined to produce the amplified physiologic and WR responses.

Adult↗
PubMed1994

Microcirculatory structure-function relationships in skeletal muscle of diabetic rats.

The effects of streptozotocin-induced diabetes on microcirculatory structure-function relationships in skeletal muscle were studied in control (C) and diabetic (D; 65 mg/kg streptozotocin ip) rats 6-8 wk after injection. Capillary exchange capacity was determined from measurements of capillary filtration coefficient (CFC) and permeability-surface area product (PS) for 51Cr-labeled EDTA in maximally vasodilated (papaverine), isolated hindquarters of C (n = 9) and D (n = 12) rats. Capillary numerical density, length, surface area, capillary geometry, and muscle fiber cross-sectional area were determined using morphometric methods in perfusion-fixed plantaris muscles from a second series of C (n = 5) and D (n = 6) rats. Hindquarters of D rats (61 +/- 3 g) weighed less than C rats (90 +/- 3 g) because of marked muscle atrophy. Minimal total vascular resistance was lower in D rats (P < or = 0.05), indicating an increased flow capacity. CFC was not different in C and D rats (0.0282 +/- 0.0020 vs. 0.0330 +/- 0.0025 ml.min-1.mmHg-1 x 100 g-1, respectively). The relationship between PS and flow was depressed in D rats (P < or = 0.05) compared with C rats, which indicated a reduced capillary diffusing capacity. Plantaris muscle weight was 41% less in D rats (174 +/- 9 vs. 293 +/- 11 mg; P < or = 0.001). Morphometric analysis revealed that muscle fiber cross-sectional area was reduced 39% in D rats, which, despite a lower capillary-to-fiber ratio (1.59 +/- 0.04 vs. 2.12 +/- 0.13; P < or = 0.001), resulted in a 27% increase in capillary density in D rats. Capillary diameter was less in D rats (3.58 +/- 0.12 vs. 4.51 +/- 0.23 microns; P < or = 0.005). Total capillary surface area was reduced 42% in D rats; however, capillary surface area per muscle fiber volume was unchanged in D rats (231 +/- 34 vs. 237 +/- 16 cm-1). These data indicate that there is remodeling of the capillary bed in skeletal muscle of D rats, resulting in a reduction in total microvascular surface area. The reduction in capillary surface area is proportional to the degree of muscle atrophy in D rats such that functional microvascular surface area per tissue mass (e.g., CFC) is unchanged. The lower diffusing capacity (PS) in D rats suggests that either small solute permeability is reduced and/or there is greater perfusion heterogeneity in D rat skeletal muscle.

Animals↗