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J Appl Physiol 93: 227-232, 2002. First published January 18, 2002; doi:10.1152/japplphysiol.00735.2001
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Vol. 93, Issue 1, 227-232, July 2002

Dynamics of microvascular oxygen pressure in the rat diaphragm

Crystal M. Geer, Brad J. Behnke, Paul McDonough, and David C. Poole

Departments of Kinesiology, Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas 66506-5802


    ABSTRACT
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

The relative amplitudes and rates of increase of muscle blood flow (and O2 delivery) and O2 uptake responses determine the O2 pressure within the muscle microvasculature (PmO2) across the rest-to-contraction transition. Skeletal muscle function is a primary determinant of pulmonary O2 uptake kinetics; however, it has never been determined whether the dynamics of muscle PmO2 are faster in a highly oxidative muscle [e.g., diaphragm (Dia), citrate synthase activity of 39 µmol · min-1 · g-1] compared with less oxidative muscles [e.g., spinotrapezius (Spino), citrate synthase activity of 14 µmol · min-1 · g-1, male Sprague-Dawley rats; Delp MD and Duan C, J Appl Physiol 80: 261-270, 1996]. Phosphorescence quenching techniques (porphyrin dendrimer, R2) were used to determine PmO2 across the transition to electrically stimulated contractions (1 Hz) within the rat Dia. After a delay of 10.4 ± 1.3 (SE) s at the beginning of Dia contractions, PmO2 decreased close to monoexponentially from 42 ± 2 to 27 ± 3 Torr (P < 0.05) with an extremely fast time constant of 7.1 ± 1.1 s. Thus Dia PmO2 decreased with significantly (P < 0.05) faster kinetics than reported previously for the Spino muscle (delay, 19.2 ± 2.8 s; time constant PmO2, 21.7 ± 2.1 s; Behnke BJ, Kindig CA, Musch TI, Koga S, and Poole DC, Respir Physiol 126: 53-63, 2001). With the use of two specialized muscles with similar fiber-type composition but widely disparate oxidative capacities (Delp MD and Duan C, J Appl Physiol 80: 261-270, 1996), these data demonstrate that PmO2 kinetics are significantly faster in the highly oxidative Dia compared with the low-oxidative Spino muscle and that this effect is not dependent on muscle fiber-type composition.

oxygen uptake kinetics; spinotrapezius; microvascular oxygen exchange


    INTRODUCTION
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

AT THE TRANSITION TO A HIGHER metabolic rate, the dynamics of muscle O2 exchange determine the magnitude of the O2 deficit and thus impact intracellular energetics. In 1837, Magnus (see Ref. 38) demonstrated that the processes of O2 utilization and CO2 production occur within peripheral tissue, and yet it is only recently that muscle O2 uptake (VO2) kinetics have been characterized in humans (modeling, Ref. 3; measurement, Ref. 13). Specifically, for upright cycle ergometry, it has been demonstrated that, beyond the first 10-15 s of exercise (during which pulmonary VO2 may increase appreciably faster than muscle VO2 synonymous with phase I), the kinetics of pulmonary VO2 and muscle VO2 are matched closely (i.e., phase II; Refs. 1, 13). At the onset of dynamic exercise in the moderate (13) and severe (1) domains, fractional O2 extraction increases with a time course similar to that of muscle blood flow times O2 content (QO2) and VO2. Hence, measurement of microvascular PO2 (PmO2) dynamics may provide insight into the speed of O2 exchange processes within skeletal muscle and also the driving pressure that facilitates O2 diffusion from blood to muscle.

Among diverse species, such as humans [e.g., time constant (tau ) of primary VO2 response = 20-45 s; Refs. 2, 13, 20, 39, 40], horses (tau  = 10 s; Refs. 15, 20), and ghost crabs (tau  = 75-90 s; Ref. 11), it is evident that there is a broad range of speed for VO2 kinetics. In humans, pulmonary VO2 kinetics tend to be faster in more highly fit individuals (5, 14, 28, 37) and can be speeded with exercise training (5, 14, 25, 42). However, it is likely that cardiovascular dynamics (e.g., Ref. 36), neuromuscular recruitment patterns, and intracellular metabolic pathways (16), for example, are influenced by exercise training and, therefore, confound interpretation of the mechanistic bases for the training-induced responses.

To explore the dynamics of muscle O2 exchange across a broad range of oxidative capacities in the absence of cardiovascular, neuromuscular, or other training-related changes, phosphorescence quenching techniques have been adapted to measure PmO2 [which is representative of the dynamic VO2-to-QO2 ratio (VO2/QO2) within the microcirculation; Ref. 24] at the transition to electrically stimulated contractions in the diaphragm (Dia). At the on-transient to muscle contractions, O2 extraction will be determined principally by the relative tau  values for VO2 and QO2, as well as their degree of perturbation (Delta ) from resting or noncontracting values (43). Consequently, the change in PmO2 at time t will be dependent on the local VO2/QO2. Therefore, assuming mitochondrial PO2 is close to zero, the driving pressure for blood-muscle O2 exchange will be
Pm<SUB>O<SUB>2</SUB></SUB>(<IT>t</IT>)<IT>∝</IT>Ca<SUB>O<SUB>2</SUB></SUB>−Cv<SUB>O<SUB>2</SUB></SUB><IT>=</IT><FENCE><FR><NU><A><AC>V</AC><AC>˙</AC></A><SC>o</SC><SUB>2</SUB> (rest)+[&Dgr;<A><AC>V</AC><AC>˙</AC></A><SC>o</SC><SUB>2</SUB><IT> · </IT>1−<IT>e</IT><SUP><IT>−t/&tgr;</IT><A><AC>V</AC><AC>˙</AC></A><SC>o</SC><SUB>2</SUB></SUP>]</NU><DE><A><AC>Q</AC><AC>˙</AC></A><SC>o</SC><SUB>2</SUB> (rest)+[&Dgr;<A><AC>Q</AC><AC>˙</AC></A><SC>o</SC><SUB>2</SUB><IT> · </IT>1−<IT>e</IT><SUP><IT>−t/&tgr;</IT><A><AC>Q</AC><AC>˙</AC></A><SC>o</SC><SUB>2</SUB></SUP>]</DE></FR></FENCE>
where CaO2 and CvO2 denote arterial and venous O2 contents, respectively. Thus, after the time delay (TD), a monoexponential fall in PmO2 during exercise is expected, and the kinetic profile of PmO2 during the on-transient to stimulation is representative of the dynamic VO2/QO2. Indeed, this profile has been observed in the spinotrapezius (Spino) (4); however, the impact of an increased oxidative capacity (e.g., as in Dia) on the dynamics of this profile have yet to be determined.

In the rat, Dia possesses almost exactly the same fiber-type composition as the Spino (i.e., %Dia/Spino: type I, 44/41; IIa, 6/7; IID/x, 18/17; IIb, 32/35; Ref. 8). However, Dia has approximately a threefold greater citrate synthase activity and capillarity and a higher microvascular red blood cell (RBC) flux and hematocrit (at rest) than Spino (8, 17, 18). By comparison with data collected previously for Spino (4), we tested the hypotheses that 1) PmO2 would be higher in the Dia at rest compared with the Spino, and 2) across the transition to contractions, the Dia would elicit faster PmO2 dynamics than demonstrated for the low-oxidative Spino.


    METHODS
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Surgical Preparation

Ten female Sprague-Dawley rats, weighing 225-260 g, were anesthetized with pentobarbital sodium (40 mg/kg ip to effect). All procedures were approved by Kansas State University's Institutional Animal Care and Use Committee. The carotid artery was cannulated (PE-50 tubing, Intra Medic polyethylene tubing; Clay Adams, Sparks, MD) to facilitate measurement of arterial blood pressure [mean arterial pressure (MAP); model 200, Digi-Med BPA, Louisville, KY]; sampling of blood for analysis of blood gases, pH (Nova Stat Profile M, Waltham, MA), and hematocrit; as well as infusion of the phosphor [palladium meso-tetra(4-carboxyphenyl) porphyrin dendrimer (R2)] at 15 mg/kg body wt. Body temperature was maintained at ~38°C via a heating pad.

Each rat was tracheotomized and mechanically ventilated with a rodent ventilator (model 683; Harvard Apparatus, South Natick, MA). Breathing frequency and tidal volume were adjusted individually to maintain expired PCO2 in the range of 29-36 Torr (Micro-Capnometer, Columbus, OH) and prevent spontaneous Dia contractions. A laparotomy was performed to expose the liver and the abdominal surface of the Dia. The ligaments connecting the central tendon to the liver were severed, and the contents of the abdominal cavity were kept moist and covered with Saran Wrap (Dow, Indianapolis, IN). Stainless steel electrodes were sutured (6-0 silk; Ethicon, Somerville, NJ) to the right ventral costal (cathode) and the right dorsal costal (anode) Dia. A sagittal incision (1-2 mm) through the central tendon of the Dia was made for insertion of a rigid cylinder (1 mm diameter) along the thoracic surface of the right side of the Dia. This procedure minimized rostral movement of the Dia with contraction that would possibly have impaired PmO2 measurement.

Experimental Protocol

Heart rate (HR) and MAP were monitored throughout the experimental protocol. The phosphor R2 was injected 10-15 min before data collection. During all experiments, exposed tissues were superfused with 38°C Krebs-Henseleit bicarbonate-buffered solution, which was equilibrated with 5% CO2-95% N2. Electrically stimulated contractions of Dia (3-6 V) were induced at 1 Hz (2-ms pulse duration) with a Grass S88 stimulator (Quincy, MA) for 3 min. This stimulation protocol produces Dia contractions at a frequency close to that of the spontaneously breathing animal, and it also replicates that utilized previously for the Spino muscle (4). It is pertinent that muscles evidence similar force-velocity curves in response to twitch and tetanic stimulus paradigms (6). Use of a twitch rather than a tetanic stimulation protocol enables a blood flow response consistent with moderate-intensity exercise to be elicited (4). PmO2 was measured at 2-s intervals at rest and during electrically induced contractions.

Phosphorescence Quenching

Theory. The Stern-Volmer relationship describes the O2 dependence of phosphorescence (34)
T<SUB>0</SUB>/T<IT>=</IT>1<IT>+K</IT><SUB>Q</SUB> × T<SUB>0</SUB> × P<SC>o</SC><SUB>2</SUB>
where the quenching constant (KQ) is a second-order rate constant quantifying the collisions between O2 and the porphyrin in its excited triplet state and the probability of energy transfer as a result. The phosphorescence lifetimes in the absence of O2 and at a given PO2 are represented by T0 and T, respectively. With the use of the Stern-Volmer relationship, PmO2 is calculated as
Pm<SUB>O<SUB>2</SUB></SUB> (Torr) = (T<SUB>0</SUB>/T − 1)(<IT>K</IT><SUB>Q</SUB> × T<SUB>0</SUB>)<SUP>−1</SUP>
where T0 and T are expressed in µs and KQ in mmHg/s. Under the experimental conditions extant, i.e., 38°C and pH 7.4, KQ = 409 mmHg/s and T0 = 601 µs (22).

Measurement. The oxyphor R2 is a compound considered to bind completely to albumin in a 0.5% concentrated albumin solution (21). The concentration of albumin in rat serum is >3 g/dl (32), which is sixfold that necessary for complete binding. In addition, R2 has a net-negative charge (-14 mV), facilitating restriction to the vascular space. PmO2 was measured with a PMOD 1000 frequency domain phosphorometer (Oxygen Enterprises, Philadelphia, PA). The bifurcated light guide was positioned ~2-4 mm above the right medial costal Dia. The excitation light (524 nm) emitted from the light guide sampled blood within the microvasculature up to ~500 µm deep and from a circle ~2 mm in diameter. The value of PmO2 reflects principally that of capillary blood, which constitutes the principal intramuscular vascular space. The phosphorescence signal (700 nm) was averaged over 200 ms for each PmO2 measurement, which was made every 2 s.

Statistical Analysis

KaleidaGraph 3.5 allows for data analysis by fitting a user-defined function to the data by using an iterative least squares error method. Analysis of data was performed by using a monoexponential function with TD
Pm<SUB>O<SUB>2</SUB></SUB>(<IT>t</IT>)<IT>=</IT>Pm<SUB>O<SUB>2</SUB></SUB> (baseline) − {&Dgr;Pm<SUB>O<SUB>2</SUB></SUB> [<IT>e</IT><SUP><IT>−</IT>(<IT>t−</IT>TD)<IT>/&tgr;</IT></SUP>]}
where PmO2(t) is PmO2 at time t, Delta PmO2 is the decrease of PmO2 from resting baseline to steady state during contractions, and tau  is the time constant of the fitted PmO2 response. As previously reported, this model has been demonstrated to provide a superior fit compared with that afforded by an exponential without TD (4). Goodness of fit was determined by three criteria: 1) the coefficient of determination (i.e., r2); 2) the sum of the squared residuals; and 3) visual inspection and analysis of the residual fit to a linear model. Differences between parameter estimates [i.e., TD, tau , mean response time (MRT; TD + tau )] were determined by unpaired t-test. Significance was accepted at P <=  0.05.


    RESULTS
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Data were not analyzed for three rats because MAP fell <70 mmHg and/or there were complications related to effective electrical stimulation of the Dia. Thus data presented below are for those seven rats in which successful experiments were conducted. To maintain expired PCO2 values at 29-36 Torr, the rodent ventilator was set at an average breathing frequency of 68.5 ± 5.8 breaths/min and a tidal volume of 1.6 ±0.2 ml/breath. This corresponded to a mean arterial PCO2 value of 35.6 ± 2.5 Torr. Mean arterial PO2 was 92.9 ±6.8 Torr, and arterial pH and hematocrit were 7.45 ±0.03 and 39.7 ± 4.1%, respectively. MAP and HR remained stable during conditions of rest (MAP of 117.1 ± 9.6 mmHg, HR of 433 ± 28 beats/min) and contractions (MAP of 115.7 ± 10.1 mmHg, HR of 421 ± 30 beats/min).

On initiation of contractions, Dia PmO2 decreased by 15.2 ± 2.7 Torr from an average baseline value of 42.0 ± 1.6 to 26.8 ± 3.3 Torr during stimulation (P < 0.05). As evident from the representative Dia PmO2 profile shown in Fig. 1, at the onset of stimulation, a short delay (mean 10.4 ± 1.3 s) is discernable before the rapid exponential decrease of PmO2 (mean tau , 7.1 ± 1.1 s). Data for individual Dia are provided in Table 1. The monoexponential plus delay model provided a good fit across all data sets, yielding a mean correlation coefficient of 0.94 ± 0.03 and a chi 2 error value of 88.8 ± 21.4. Analysis of the data with a double-exponential model did not significantly improve the model fit. Therefore, all PmO2 data were analyzed with the single-exponential (with delay) model.


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  		Fig. 1.   Microvascular PO2 response to 1-Hz contractions initiated at time 0 for 1 representative diaphragm and spinotrapezius muscle.


                              
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  		Table 1.   Diaphragm microvascular PO2 at baseline and contractions and parameters of the on-transient response

In comparison to the Spino (4), Dia PmO2 decreased with significantly faster kinetics, eliciting an overall MRT (i.e., TD + tau ) of 17.7 ± 1.0 s compared with 40.9 ± 3.8 s for Spino (P < 0.01; Fig. 2). This occurred because of the significantly faster tau  (P < 0.05) rather than any significant shortening of TD (P > 0.05). Delta PmO2 from resting to the contracting steady state was not significantly different between the Dia and Spino muscles (P = 0.16).


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  		Fig. 2.   Comparison of diaphragm (time delay = 13.0 s) and a representative spinotrapezius muscle (time delay = 13.4 s; Ref. 4) microvascular PO2 (PmO2) dynamics at the onset of 1-Hz contractions with model fits. Responses are normalized to 100% of the decrease (Delta ) in PmO2 between baseline and contractions. tau , Time constant.


    DISCUSSION
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

This investigation has demonstrated that PmO2 in the noncontracting Dia is higher than that found in the Spino muscle. Moreover, at the onset of electrically induced contractions, the kinetics of PmO2 within the highly oxidative Dia is extremely rapid. Both tau  and the MRT for the Dia (i.e., tau , 7.1 ± 1.1; MRT, 17.7 ± 1.0 s) were significantly faster (P < 0.05) than those reported previously for the low-oxidative Spino muscle (i.e., tau , 21.7 ± 2.1; MRT, 40.9 ± 3.8 s; Ref. 4).

Nature of the PmO2 Signal

The PmO2 signal arises primarily from within the capillary bed, as this constitutes by far the greatest vascular volume within the sampled region of the spinotrapezius muscle. In addition, unlike mesentery and certain other tissues (e.g., tumors), the capillary endothelium is continuous (i.e., it lacks fenestrae), which facilitates a high-albumin reflection coefficient (12, 30, 31). This relative impermeability to albumin (which binds R2; Ref. 21) coupled with the negative charge of the phosphor inhibits or prevents R2 exudation from the vascular space, and thus contamination from extracellular compartments is avoided.

Interpretation of the PmO2 Profile

At any instant in time, PmO2 will reflect the instantaneous balance between muscle VO2 and QO2, and thus the relative magnitude (Delta ) and time course (TD, tau ) of change of VO2 and QO2 will determine the temporal profile of PmO2 such that (24)
Pm<SUB>O<SUB>2</SUB></SUB>(<IT>t</IT>)<IT> &agr; </IT><FR><NU>{<IT>&Dgr;</IT><A><AC>V</AC><AC>˙</AC></A><SC>o</SC><SUB>2</SUB><IT> · </IT>[1<IT>−e</IT><SUP><IT>−</IT>(<IT>t−</IT>TD)/&tgr;<A><AC>V</AC><AC>˙</AC></A><SC>o</SC><SUB>2</SUB></SUP>]}</NU><DE>{<IT>&Dgr;</IT><A><AC>Q</AC><AC>˙</AC></A><SC>o</SC><SUB>2</SUB><IT> · </IT>[1<IT>−e</IT><SUP><IT>−</IT>(<IT>t−</IT>TD)/&tgr;<A><AC>Q</AC><AC>˙</AC></A><SC>o</SC><SUB>2</SUB></SUP>]}</DE></FR>
Hence, across the rest-contraction transition [operating on the linear portion of the oxyhemoglobin dissociation curve and neglecting shifts in Hb-P50, which are estimated to rightshift the P50 < 1 Torr (where P50 is PO2 necessary to obtain 50% O2 saturation of Hb), given the acid-base status of these animals and assumed constant muscle temperature], the magnitude of the relative increases of VO2/QO2 will determine Delta PmO2, and the TD and tau  of PmO2 will be a function of the matching of tau VO2 to tau QO2.

The majority of evidence in vivo (e.g., Refs. 1, 7, 9, 13, 29, 35, 36) and within electrically stimulated (4, 23) muscle preparations indicates that arteriolar vasodilation and QO2 dynamics (i.e., tau QO2) are extremely fast relative to tau VO2. Indeed, in certain instances, effluent venous PO2 (1, 13) or PmO2 (30% of instances; Ref. 4) may rise for the first few seconds of contractions. This situation may be perceived as advantageous because elevating QO2 before VO2 will prevent a precipitous fall in PmO2 that may undershoot the steady state. According to Fick's law, maintenance of a higher PmO2 during the transition preserves a greater capillary-mitochondrial PO2 gradient to facilitate O2 diffusion into the myocyte and possibly limit perturbations of the intracellular physicochemical milieu by elevating intramyocyte PO2 (41).

The shape of the Dia PmO2 profile [i.e., a delay (TD) followed by a monoexponential decline to the steady state] is qualitatively similar to that demonstrated for the Spino muscle (4). The absence of an immediate fall in Spino PmO2 and no discernible undershoot in that model were interpreted as evidence that VO2 kinetics were not limited by those of QO2. In the present investigation, exactly the same case can be made for the Dia, albeit that the kinetics of PmO2 were far faster than observed in the Spino. Whereas neither VO2 nor QO2 were measured in separatum, the rapid Dia PmO2 dynamics are consistent with extraordinarily fast QO2 kinetics coupled with very fast VO2 kinetics (which are, nonetheless, comparatively slower than the QO2 kinetics, as evidenced by the delay in PmO2 fall and absence of PmO2 undershoot; Ref. 4). However, it is pertinent that Dia VO2 kinetics must have been substantially faster than those for the Spino, as the Dia PmO2 MRT was so short that it approximated the TD for the Spino, i.e., PmO2 for the Dia had reached >63% of its final response before Spino PmO2 had decreased below baseline.

Comparison of Dia vs. Spino Models

Because of anatomic location and function of Dia and Spino muscles, different experimental techniques were required. For the Dia preparation, the rat was placed supine, and a laparotomy was performed to access the abdominal surface of the Dia. The rat was then ventilated mechanically to achieve an expired PCO2 of 29-36 Torr (arterial PCO2, 36 ± 3 Torr) and prevent respiratory muscle contractions. Surgery for the Spino preparation was less extensive and consisted of a simple incision to expose the surface of the muscle with the rat placed prone. Muscle stimulation parameters were identical between Dia and Spino muscles. Despite Dia animals being ventilated and Spino animals breathing spontaneously, neither arterial blood gases and pH nor MAP was significantly different between groups (P > 0.1 for each). However, HR at rest and during contractions was significantly higher for the Dia preparation (Dia: rest 433 ± 28, contracting, 421 ± 30 beats/min; Spino: rest, 302 ± 9, contracting, 310 ± 6 beats/min; P < 0.05 for rest and steady-state contracting between Dia and Spino). To ensure that some feature of the preparation that resulted in the different HRs did not also produce the faster dynamics (i.e., tau ) for Dia, a regression analysis was performed between HR and tau  for Dia animals. No significant correlation was found (P > 0.05), and it is pertinent that (if the lower HR in Spino animals was indicative of a compromised cardiac output and thus QO2) this would have speeded tau PO2m (i.e., decreased the tau VO2/tau QO2 ratio) rather than slowed it. Thus our finding of faster PmO2 dynamics in Dia vs. Spino could not have been an artifact resulting from compromised QO2 in Spino.

Structure and Function of Dia vs. Spino

Dia structure and function are designed to facilitate higher O2 fluxes compared with Spino (7, 17, 18, 26). For example, the greater activity of the mitochondrial oxidative enzymes within Dia provides a substantial VO2 capacity during elevated metabolic demands. To supply O2, Dia possesses a rich microvascular supply characterized by a high-capillary volume density and surface area per fiber volume (26). Modeling studies suggest that the number of RBCs juxtaposed to the fiber (or fiber volume) at any given moment represents an important index of O2 transfer capacity (10). In this respect, the high capillary volume density (2.5-fold greater in Dia than Spino) and elevated capillary hematocrit at rest (Dia, 0.32 ± 0.02; Spino, 0.22 ± 0.03; P < 0.05; Ref. 18) provide for an extremely high muscle O2 diffusing capacity (DO2) in Dia vs. Spino. In addition, Dia also has a significantly greater percentage of capillaries with countercurrent flow (Dia, 29 ± 6%; Spino, 8 ± 6%; P < 0.05; Ref. 18), which may further increase the potential for blood-tissue O2 exchange (19).

Based on the morphometric and functional features of the Dia capillary bed compared with that of Spino, in concert with the sevenfold greater capillary RBC flux, Kindig and Poole (18) predicted that fractional O2 extraction by Dia would be lower, and thus effluent venous PO2 (and PmO2) would be higher in Dia vs. Spino at rest. This follows clearly from the relationship presented by Roca and colleagues (33)
O<SUB>2</SUB> extraction = <A><AC>V</AC><AC>˙</AC></A><SC>o</SC><SUB>2</SUB>/<A><AC>Q</AC><AC>˙</AC></A><SC>o</SC><SUB>2</SUB> = <A><AC>Q</AC><AC>˙</AC></A><SC>o</SC><SUB>2</SUB>(1<IT>−e</IT><SUP>−D<SC>o</SC><SUB>2</SUB>/&bgr;<A><AC>Q</AC><AC>˙</AC></A></SUP>)
where beta  is the slope of the O2 dissociation curve in the physiologically relevant range, and Q is blood flow. From this it can be seen that PmO2 will be inversely dependent on muscle DO2/beta Q and that this ratio will be lower at rest in Dia than in Spino.

Thus the present findings of a significantly higher PmO2 at rest in Dia vs. Spino (42.0 vs. 31.4 Torr) is consistent with theoretical predictions. Moreover, there was a strong tendency (P = 0.11) for PmO2 to be higher in Dia than in Spino during contractions, with 80% of Spino PmO2 values falling below the mean Dia PmO2. As alluded to above, a higher PmO2 in Dia, whether resulting from a lower DO2/beta Q, a greater countercurrent flow (18, 19), or other factors, would be beneficial for blood-tissue O2 flux. In addition, from Fick's law [VO2 = DO2 (PO2 capillary - PO2 intramyocyte)], if intracellular PO2 were raised, it would act to reduce the degree of intracellular perturbation necessary to achieve a given mitochondrial ATP flux (41). This feature would be of importance for reducing glycolytic flux and conservation of limited glycogen reserves, which may be especially critical for a muscle that contracts rhythmically throughout life.

In conclusion, it must be acknowledged that Dia and Spino represent two highly specialized muscles, and electrically induced muscle contractions recruit muscle fibers in a nonphysiological fashion. Notwithstanding this, PmO2 kinetics across the rest-contraction transition were substantially faster in the highly oxidative Dia than demonstrated previously for the low-oxidative Spino (4). This finding supports the notion that muscles with a very-high-oxidative capacity have fast O2 exchange dynamics. However, determination of whether oxidative capacity is the primary determinant of PmO2 dynamics must await systematic measurement of both variables in different muscles that span the range of oxidative capacities considered herein. Within such highly oxidative muscles as the rat Dia, it is likely that the coordinated capacities for a rapidly increased vascular O2 conductance, blood-tissue O2 diffusion, and mitochondrial O2 utilization each contribute to facilitate rapid O2 flux and lowering of PmO2 at exercise onset or across the transition to a higher metabolic rate.


    ACKNOWLEDGEMENTS

We thank Drs. Thomas J. Barstow, Craig A. Harms, Timothy I. Musch, and Casey A. Kindig for generous contributions to this work. In addition, Janet K. Bailey, Troy E. Richardson, and Rick Fels provided excellent technical support.


    FOOTNOTES

This work was funded, in part, by National Heart, Lung, and Blood Institute Grant HL-50306.

Address for reprint requests and other correspondence: D. C. Poole, Dept. of Anatomy and Physiology, College of Veterinary Medicine, Kansas State Univ., Manhattan, KS 66506-5802 (E-mail: poole{at}vet.ksu.edu).

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

First published January 18, 2002;10.1152/japplphysiol.00735.2001

Received 12 July 2001; accepted in final form 11 January 2002.


    REFERENCES
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

1.   Bangsbo, J, Krustrup P, Gonzalez-Alonso J, Boushel R, and Saltin B. Muscle oxygen kinetics at onset of intense dynamic exercise in humans. Am J Physiol Regulatory Integrative Comp Physiol 279: R899-R906, 2000.

2.   Barstow, TJ, Buchthal S, Zanconato S, and Cooper DM. Muscle energetics and pulmonary oxygen uptake kinetics during moderate exercise. J Appl Physiol 77: 1742-1749, 1994.

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