Journal of Applied Physiology Information on EB 2010
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

J Appl Physiol 96: 1039-1044, 2004. First published November 7, 2003; doi:10.1152/japplphysiol.00499.2003
8750-7587/04 $5.00
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow All Versions of this Article:
96/3/1039    most recent
00499.2003v1
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (9)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by McDonough, P.
Right arrow Articles by Poole, D. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by McDonough, P.
Right arrow Articles by Poole, D. C.

Recovery of microvascular PO2 during the exercise off-transient in muscles of different fiber type

Paul McDonough, Brad J. Behnke, Timothy I. Musch, and David C. Poole

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

Submitted 12 May 2003 ; accepted in final form 5 November 2003


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
The speed with which muscle energetic status recovers after exercise is dependent on oxidative capacity and vascular O2 pressures. Because vascular control differs between muscles composed of fast- vs. slow-twitch fibers, we explored the possibility that microvascular O2 pressure (PmvO2; proportional to the O2 delivery-to-O2 uptake ratio) would differ during recovery in fast-twitch peroneal (Per: 86% type II) compared with slow-twitch soleus (Sol: 84% type I). Specifically, we hypothesized that, in Per, PmvO2 would be reduced immediately after contractions and would recover more slowly during the off-transient from contractions compared with Sol. The Per and Sol muscles of six female Sprague-Dawley rats (weight = ~220 g) were studied after the cessation of electrical stimulation (120 s; 1 Hz) to compare the recovery profiles of PmvO2. As hypothesized, PmvO2 was lower throughout recovery in Per compared with Sol (end contraction: 13.4 ± 2.2 vs. 20.2 ± 0.9 Torr; end recovery: 24.0 ± 2.4 vs. 27.4 ± 1.2 Torr, Per vs. Sol; P <= 0.05). In addition, the mean response time for recovery was significantly faster for Sol compared with Per (45.1 ± 5.3 vs. 66.3 ± 8.1 s, Sol vs. Per; P < 0.05). Despite these findings, PmvO2 rose progressively in both muscles and at no time fell below end-exercise values. These data indicate that, during the recovery from contractions (which is prolonged in Per), capillary O2 driving pressure (i.e., PmvO2) is reduced in fast-compared with slow-twitch muscle. In conclusion, the results of the present investigation may partially explain the slowed recovery kinetics (phosphocreatine and O2 uptake) found previously in 1) fast- vs. slow-twitch muscle and 2) various patient populations, such as those with congestive heart failure and diabetes mellitus.

recovery from exercise; muscle fiber type; oxygen delivery; oxygen uptake

AFTER MUSCULAR CONTRACTIONS, the speed at which the cellular energetic status [i.e., concentrations of phosphocreatine (PCr), ADP, and creatine] can be restored to resting levels is dependent on muscle mitochondrial content and oxidative capacity (2, 21, 22). Thus diseases or conditions that reduce muscle oxidative capacity, such as chronic heart failure (44, 45), are associated with slowed PCr recovery kinetics (43). However, it has been demonstrated that the rate of PCr recovery after exercise is acutely dependent on O2 delivery (O2) and vascular O2 pressures (13, 20). Specifically, after isotonic contractions of the human gastrocnemius, inspired hypoxic gas slowed and hyperoxic gas speeded PCr recovery (13). Similar findings were reported for the perfused rat hindlimb, where PCr recovery was speeded in proportion to the elevated O2 after isometric contractions (20).

Microvascular O2 pressure (PmvO2) is proportional to the O2-to-O2 uptake (O2) ratio, both during and after contractions (5, 31). The theoretical basis for this relationship within skeletal muscle was developed by Roca et al. (39), who adapted the work (on the pulmonary system) of Piiper and Scheid (36) for use in skeletal muscle. Thus changes in O2/O2 are mirrored precisely by changes in PmvO2 (31), and the time course of changes in PmvO2 is dependent, therefore, on the relative temporal changes in O2 and O2 (3). In addition, we have recently demonstrated that PmvO2 is substantially lower in a contracting muscle composed predominantly of fast-twitch fibers [peroneal (Per)] compared with one composed of slow-twitch fibers [soleus (Sol)]. However, to our knowledge, the PmvO2 profile in such muscles has never been resolved during recovery. This information may provide a mechanistic basis for the slowed PCr recovery kinetics reported in muscles with a predominantly fast-compared with slow-twitch fiber profile (26), irrespective of their oxidative capacities per se. Moreover, because major chronic diseases (e.g., chronic heart failure and diabetes mellitus) result in a shift toward a greater percentage of fast-twitch fibers (30, 42), it is possible that this fiber-type shift (via its effect on PmvO2) may be responsible, in part, for the impaired muscle energetics and slowed recovery kinetics of O2, heart rate, and PCr that are symptomatic of these conditions (7, 8, 25, 41, 43).

PmvO2 dynamics during recovery from contractions have only been studied to date in the rat spinotrapezius muscle (31). In that investigation, a marked asymmetry was noted between the on- and off-transient, with the recovery PmvO2 dynamics being substantially slower that those of the on-transient response. Because the spinotrapezius is a mixed fiber-type muscle (41% type I, 24% type IIa and d/x, 35% type IIb; Ref. 9), it is impossible to know with certainty the impact that fiber type played in the slow off-transient response. However, because PmvO2 is reduced at the beginning of the exercise off-transient (5) and O2 is reduced at both 30 s and 3 min of recovery (1) from exercise in Per (~86% type II) compared with Sol (~84% type I; Ref. 9), it is likely that the temporal profile of the recovery PmvO2 response differs between these muscles. Indeed, in the 1920s, Hill and Lupton (14) noted that recovery processes should be intimately dependent on PmvO2, i.e., increasing in speed as PmvO2 is raised, and this has indeed been borne out by more recent experimental data (13). Thus we tested the hypothesis that the recovery kinetics of PmvO2 would be slower in the Per compared with the Sol and that this would result in a reduced capillary O2 driving pressure during recovery in Per.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
Surgical Preparation

All procedures were approved by the Kansas State University institutional animal care and use committee. Six female Sprague-Dawley rats (219 ± 4 g) were anesthetized with pentobarbital sodium (40 mg/kg ip to effect). The carotid artery was isolated and, with the use of an introducer, cannulated with PE-50 tubing to provide a route of access for infusion of the phosphorescent probe [palladium meso-tetra (4-carboxyphenyl) porphine dendrimer (R2); 15 mg/kg], blood pressure measurement (Digi-Med BPA model 200, Louisville, KY), and withdrawal of arterial blood for blood-gas measurement (Nova Stat Profile M, Waltham, MA).

The Sol is a postural muscle whose primary function is plantar flexion. Sol is composed of primarily slow-twitch fibers (84% type I, 7% type IIa, 9% type IId/x, and 0% type IIb), and its oxidative capacity (as measured by citrate synthase activity) is 21.3 µmol·g-1· min-1 (9). The Per muscle group is also a postural muscle whose primary actions are ankle eversion and plantar flexion. Per is composed primarily of fast-twitch muscle (14% type I, 19% type IIa, 22% type IId/x, and 45% type IIb), and its citrate synthase activity is 20.3 µmol·g-1·min-1 (9). Each muscle was exposed for PmvO2 measurements by using techniques described previously (5). The exposed tissue was superfused with a Krebs-Henseleit bicarbonate-buffered solution (38°C, equilibrated with 5% CO2-N2 balance), and body temperature was maintained at ~38°C by using a heating pad.

Principle and Measurement of Phosphorescence Quenching

The Stern-Volmer relationship (40) describes the quantitative relationship between probe phosphorescence and PmvO2

Rearranged to solve for PmvO2

Thus PmvO2 is dependent on the lifetime of the phosphorescence decay, where kQ is the quenching constant (Torr/s) and t and t0 are the phosphorescence lifetimes (in µs) at the prevailing PO2 and a PO2 of zero, respectively. For the phosphor R2, kQ is 409 Torr/s and t0 is 601 µs (28). The R2 probe has a-14-mV potential and binds strongly with albumin. Consequently, the probe is thought to remain predominantly within the vascular space, ensuring that the signal represents microvascular plasma PO2 (28). In the blood, O2 is the only molecule that quenches phosphorescence from R2, thereby facilitating an absolute measurement of PmvO2 (40).

PmvO2 was determined by using a PMOD 1000 frequency domain phosphorimeter (Oxygen Enterprises, Philadelphia, PA) with the common end of the bifurcated light guide placed ~2–4 mm above the medial portion of either muscle. With the use of the single-frequency mode, the excitation light (524 nm) is modulated sinusoidally within the range of frequencies between 100 Hz and 20 kHz, adequately covering phosphorescence lifetimes (wavelength: 700 nm) from 10 µs to 2.5 ms. The scan rate was preset at 10 (100 ms) to acquire data and repeated at 2-s intervals. The excitation light was focused on an ~2-mm-diameter circle of exposed muscle surface and samples blood within the microvasculature up to 500 µm deep. This being the case, it is crucial that sufficient capillaries are sampled that the PmvO2 measurement captures a "mean" response that is representative of the muscle and the physiological behavior of interest. Viewed in this context, the value of PmvO2 reflects principally an average PO2 of capillary blood, because this compartment constitutes the majority of intramuscular blood volume (38).

Experimental Protocol

The phosphor was infused via the arterial catheter ~15 min before the experimental protocol was begun. After this 15-min period, the Sol or Per was stimulated (stainless steel electrodes attached to the distal and proximal ends of the muscle) to contract at 1 Hz for 2 min (2–4 V, 2-ms pulse duration; i.e., on-transient) by using a Grass S48 stimulator (Quincy, MA). After the cessation of stimulation, recovery data were gathered for at least 3 min or until baseline values were reached. This contraction protocol has been shown in our laboratory to increase muscle blood flow (m) three- to fourfold, while not changing arterial acid-base status or elevating plasma lactate concentrations (5). Thus, in this regard, it resembles moderate-intensity exercise. Animals were euthanized with an overdose of pentobarbitol sodium (>80 mg/kg intra-arterial) after the conclusion of the experimental protocol.

m and O2 Measurements

Blood flow and O2 were determined as part of a larger study as described in Behnke et al. (5). Briefly, m was determined by using the radiolabeled microsphere technique (27, 34) and was measured at rest and 2 min after the onset of the contraction period in Sol and Per and expressed in milliliters per 100 g tissue per minute. Arterial (CaO2) and venous (CvO2) O2 content were calculated from the measured arterial and microvascular (PmvO2) PO2 values [PmvO2 used as an approximation of venous PO2 (31, 39) by using the rat O2 dissociation curve, and O2 was calculated via the Fick principle of mass balance, i.e., O2 = blood flow·(CaO2 - CvO2)].

Curve Fitting and Statistical Analysis

Curve fitting was accomplished by using KaleidaGraph software (version 3.5; Synergy Software, Reading, PA) and was performed on the off-transient by using a one-component model

and a more complex two-component model

where PmvO2(t) is the PmvO2 at any time t, PmvO2end-ex is the PmvO2 at the end of the stimulation protocol, {Delta}PmvO2fast and {Delta}PmvO2slow are the amplitudes of the fast and slow recovery components, TD1 and TD2 are the independent time delays, and {tau}1 and {tau}2 are the time constants for each component, respectively. Mean response time (MRT) was determined according to the methodology of MacDonald et al. (29). Briefly, a weighted sum of the time delay and time constant for each component were calculated as follows: MRT = ({Delta}1/{Delta}tot)· (TD1+{tau}1) + ({Delta}2/{Delta}tot)·(TD2+{tau}2). Goodness of fit was determined by three criteria: 1) the coefficient of determination (i.e., r2), 2) the sum of the squared residuals ({chi}2), and 3) visual inspection and analysis of the residual fit to a linear model. Differences between parameter estimates were determined by paired t-test. Pearson product-moment correlations were performed between select variables, and statistical significance was preselected to correspond to a P value of <=0.05.


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
Microvascular PmvO2 Dynamics During the Off-Transient in Sol and Per

After contractions, PmvO2 was reduced and remained lower throughout the recovery period in Per compared with Sol (Fig. 1; Table 1). However, at no point was there any evidence of a fall in capillary O2 driving pressure, because PmvO2 did not decrease further after stimulation ceased in either muscle. Rather, PmvO2 rose with a biphasic profile toward baseline values (Fig. 1; Table 1). In addition, MRT for the off-transient in the Per was significantly slower than that for Sol (Table 1; Fig. 2). This lengthening of MRT in Per was due to a significantly longer primary component time constant ({tau}1), because the TD1 was shorter for Per and neither {tau}2 nor TD2 were different between muscles (Table 1). In addition, the primary component delta ({Delta}1) was significantly greater for Per compared with Sol (Table 1). Therefore, although the absolute speed of recovery (i.e., MRT) was slowed for Per, the relative rate of recovery ({Delta}/{tau}; dPmvO2/dt) was similar between muscles for both the primary and secondary components of recovery (Table 1; Fig. 3).



View larger version (18K):
[in this window]
[in a new window]
  		Fig. 1. Comparsion of the recovery microvascular PO2 (PmvO2) responses for soleus (Sol) and peroneal (Per) muscles. Note the dual-exponential nature of the response in each muscle. Solid line, real data; hatched line, model fit. Inset: PmvO2 as a percentage of the final recovery value for the average model fits for Sol and Per.

 

View this table:
[in this window]
[in a new window]
  		Table 1. Microvascular PO2 kinetics during the on- and off-transient from stimulation

 


View larger version (12K):
[in this window]
[in a new window]
  		Fig. 2. Mean (±SE) response time (MRT) for the on- ({diamondsuit}) and off-transient (shaded squares) as a function of the percentage of fast-twitch fibers. Spino, spinotrapezius (Ref. 31). *Significantly different from Sol (P < 0.05). #Significantly different from on-transient (P < 0.05).

 


View larger version (14K):
[in this window]
[in a new window]
  		Fig. 3. Change in PmvO2 expressed relative to the time course of the response (dPmvO2/dt, rate of change in PmvO2 per unit time during the transient) for the on- and off-transient for Sol (solid bars) and Per (open bars). Note that, although the dPmvO2/dt is markedly faster for Per during the on-transient, the rate of the response is similar for Sol and Per throughout recovery. Values are means ± SE. *Significant difference between Sol and Per (P < 0.05). #Significant difference between slow and fast off-transient response (P < 0.05).

 

Asymmetry of the On- and Off-Transient Responses

After the contraction period, the temporal profile of PmvO2 during recovery was both qualitatively and quantitatively different than that observed during the on-transient (monoexponential for both Sol and Per; see Ref. 5). Indeed, recovery PmvO2 was better fit by the more complex dual-exponential (2-exp) than single exponential (1-exp) model for both Sol and Per. This was determined on the basis of significantly greater values for the coefficient of determination (r2: 1-exp: 0.993 ± 0.001; 2-exp: 0.996 ± 0.001; P < 0.05) and lower values for the sum of squared residuals ({chi}2: 1-exp: 9.3 ± 2.2; 2-exp: 4.7 ± 0.8; P < 0.05). In addition, the off-transient MRT was slower than that of the on-transient for Per but not for Sol (Table 1; Fig. 2).

Blood Gas, pH, and Lactate Values

Poststimulation values for blood gas and acid-base are as follows: arterial PO2, 93.1 ± 5.2 Torr; arterial PCO2, 42.1 ± 3.3 Torr; pH 7.38 ± 0.02; and lactate, 1.0 ± 0.4 mM.


   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
ACKNOWLEDGMENTS
 REFERENCES
 
The present study is the first to show that the recovery profile of PmvO2 is substantially different in muscles of contrasting fiber type but similar oxidative capacity. Specifically, PmvO2 (i.e., capillary O2 driving pressure) was reduced throughout recovery in fast-twitch (Per) compared with slow-twitch (Sol) muscle, which would either serve to reduce O2 exchange and/or lower intracellular PO2 according to Fick's law, and thus might be expected to prolong the recovery of high-energy phosphates (13), an event which relies almost entirely on oxidative metabolism (20, 22). In addition, the temporal profile of PmvO2 recovery was prolonged (i.e., longer MRT) in Per, which is likely due to a greater degree of metabolic disturbance (i.e., {uparrow} {Delta}PCr due to {downarrow} PO2; see Ref. 17) during the contraction period because the relative rate of recovery was similar in both muscles (Table 1; Fig. 3). However, at no point did PmvO2 decrease below end-contraction values in either muscle, which supports the contention that O2 per se is not likely to provide any greater limit to muscle O2 during the recovery from contractions than during the contraction period itself in either muscle (31, 50).

Determinants of the PmvO2 Response During Recovery

The dynamic profile of PmvO2 during recovery is determined by the proportionality of O2 and O2 and the temporal change in that proportionality (31). Notwithstanding the fact that PmvO2 is determined by O2/O2, PmvO2 can influence the O2 by impacting blood-myocyte O2 exchange. Specifically, in accordance with Fick's law, a reduced PmvO2 will reduce the O2 pressure head driving O2 into the myocyte. Thus, although O2 is a critically controlled variable, when a lowered O2 decreases PmvO2 such that blood myocyte O2 transfer is impaired, one consequence will be that O2 will decrease. The most likely mechanistic basis for the reduced O2 in Per compared with Sol is the reduced O2 and subsequent lowering of PmvO2 in Per. This limits convective and also diffusive O2 transport and hence restricts the O2 response to a small range (for review, see Ref. 46).

O2 response in Sol and Per. Per and Sol have similar oxidative capacities (as measured by citrate synthase activity; Ref. 9). Thus a similar m (and thus O2) during maximal exercise is predicted (37). However, O2 was markedly lower ({downarrow}~53%) during submaximal contractions (5) and after 30 s ({downarrow}~57%) and 3 min of recovery ({downarrow}~79%) in Per compared with Sol (1), which is in agreement with O2 data from our laboratory comparing Per and Sol at end contractions ({downarrow}~52%; see Table 2) and at 3 min of recovery ({downarrow}~89%; Table 2). Thus the above results suggest that intermuscle differences in either anatomic and/or functional control are likely to be responsible for the blunted O2 response noted within fast-twitch muscle. In addition, although a greater heterogeneity of capillary O2 flux and velocity may potentially exist within fast-compared with slow-twitch muscle, it is important to point out that the volume of tissue sampled in the present study presents a mean PmvO2 within many hundreds of microvessels and is, therefore, representative of the muscle as a whole (40). The PmvO2 values reported herein occur on the linear portion of the O2 dissociation curve, and, with the stimulation paradigm utilized (representing ~30–40% of muscle aerobic capacity), no appreciable acid-base disturbances are expected. Consequently, the measured PmvO2 will change as a direct function of the global O2/O2, irrespective of heterogeneities at the individual capillary level.


View this table:
[in this window]
[in a new window]
  		Table 2. O2 and O2 at rest, end contraction, and end recovery

 

Thus the most plausible mechanistic basis for the reduced recovery of O2 in Per compared with Sol is a reduced functional vasoreactivity in the vascular bed associated with muscles composed of fast-twitch fibers. Specifically, Williams and Segal (47) demonstrated that the feed artery reactivity (to sodium nitroprusside) of extensor digitorum longus (a fast-twitch muscle of similar oxidative capacity as Sol and Per; Ref. 9) was diminished compared with Sol. Furthermore, Wunsch et al. (49) noted that endothelium-dependent vasodilation (i.e., to acetylcholine) was of greater magnitude in slow-compared with fast-twitch muscle, and Woodman et al. (48) demonstrated that endothelial nitric oxide synthase expression was elevated in slow-compared with fast-twitch muscle. This later study corroborates the work of Hirai et al. (16), who showed that the absolute decrease of blood flow in response to the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester was linearly related to the sum of type I and IIa fibers. Taken together, these studies provide a functional basis for the reduced O2 and thus PmvO2 noted during recovery from contractions in Per compared with Sol.

O2 response in Sol and Per. Because O2 was lower during contractions and recovery in Per than in Sol (Table 2), O2 per se cannot explain the lower PmvO2 in Per. Given the similar oxidative capacities of Per and Sol, a different O2 response might not be expected. However, under the presiding conditions of a substantially lower O2, the O2/O2 ratio (and thus PmvO2) will be determined by the blood-tissue PO2 gradient and the O2 diffusing capacity as they determine O2. Consequently, the O2 response of Per will be limited to a small range of values that is determined by the diffusive and convective flux of O2 (for review, see Ref. 46).

O2/O2 sets the PmvO2 in both Sol and Per. It is pertinent that anatomic differences between Per and Sol exist that can explain the altered O2-to-O2 matching during the contraction and recovery periods (Refs. 1, 5, and present data). As an index of overall vascularity, capillary-to-fiber ratio is significantly lower in Per compared with Sol (i.e., 1.5 ± 0.1 and 2.9 ± 0.2 capillaries/fiber, respectively; see Ref. 5), which agrees with other studies comparing fast- and slow-twitch muscle (12, 19). As noted earlier, O2 is lower in Per compared with Sol during recovery from contractions (1). Thus Per is faced with a decreased convective (O2) and diffusive (DO2; related to lower perfused capillary surface area) O2 conductance. The reduced O2 mandates an elevated O2 extraction that effectively lowers PmvO2 (30 s of recovery: 16.8 ± 2.2 vs. 23.0 ± 1.2 Torr; 3 min of recovery: 24.0 ± 2.4 and 27.4 ± 1.2 Torr, Per vs. Sol), which in turn reduces the blood myocyte O2 driving pressure (according to Fick's Law), as discussed above. Thus it is likely that the anatomic differences between fiber types, in combination with functional differences in vasoreactivity, play a large role in determining PmvO2 dynamics during the recovery from contractions.

Differences Between the On- and Off-Transients

The off-transient response for both Sol and Per, in marked contrast to the on-transient response, was best described by using a dual-exponential model. We have noted this discrepancy between the on- and off-transient responses previously (31). Whereas both O2 and O2 increase virtually immediately during the on-transient (3), it is likely that the time courses of these variables are nonsynchronous during recovery (50). For example, O2 likely falls immediately with energetic demand, whereas O2 may exhibit a slower rate of fall, possibly due to the altered intracellular biochemical milieu and the continued presence of vasodilatory stimuli. This causes PmvO2 to rise rapidly (fast component). As the influence of metabolic vasodilation wanes, O2 will fall more rapidly, which slows the rate of rise in PmvO2 (slow component; Ref. 31).

Consequences of Reduced PmvO2 Response During Recovery

As mentioned above, a reduction in O2 (relative to O2) reduces mixed venous PO2, mean capillary PO2, and PmvO2 (5, 17, 18) and thus may limit oxidative metabolism through reductions in both convective (O2 = O2·O2 extraction) and diffusive O2 (O2 = DO2·PmvO2) flux. One major consequence of the reduced PmvO2 in Per during recovery would be a prolongation of the recovery of high-energy phosphates (13, 20), a process that relies almost entirely on oxidative metabolism (20, 22). In addition, the recovery of high-energy phosphates will be further prolonged by the greater {Delta}PCr noted in fast-twitch muscles during contractions (15), because the recovery of PCr is thought to conform to a linear first-order system that is a function of total creatine content (32, 33). In addition, it is plausible to consider that intracellular pH is likely to have been lower and recovered more slowly in Per after contractions. This alone would serve to slow the recovery of PCr and PmvO2 (2, 6, 13, 21). However, this effect was probably minor given the negligible changes in pH noted during 1-Hz contractions (45). Thus a larger and faster rate of fall in PmvO2 during the on-transient should result in a greater degree of substrate level phosphorylation and also in a longer time course of recovery. This is represented graphically in Fig. 2, where the on-transient response (as quantified by MRT) becomes progressively faster and recovery slower as the percentage of fast-twitch fibers within the individual muscle increases (Sol, Spino, Per; spinotrapezius data from Ref. 31). Thus recovery of PmvO2 after contractions in fast-twitch fibers is likely prolonged due to the greater metabolic disturbance (i.e., {Delta}PCr) during contractions, a reduced O2 and O2/O2 during the recovery period, and the finite recovery kinetics of PmvO2. This concept is explained nicely by Idstrom et al. (20), who demonstrated that the initial rate of PCr resynthesis is linearly dependent on O2. Because PmvO2 recovery is also dependent on O2 (through O2/O2), the present findings provide further evidence of a strong linkage between O2/O2 and both PCr and PmvO2 during recovery from work.

In summary, the present study demonstrates for the first time that differences in PmvO2 dynamics exist between muscles of different fiber types during the off-transient from contractions. Specifically, PmvO2 was lower during recovery (Fig. 1) and MRT prolonged in Per (Fig. 2), indicative of a reduced capillary O2 driving pressure during the recovery period from contractions in Per. Despite the reduced PmvO2 in Per, PmvO2 rose systematically with little delay after contractions in both Sol and Per (Fig. 1), suggesting that, in both fast- and slow-twitch muscles, the proportionality between O2 and O2 is maintained in a manner that ensures that the driving pressure for O2 diffusion from the capillary bed (although reduced in Per compared with Sol) is not compromised beyond that seen during contractions during recovery from muscular work. However, the degree of on-off asymmetry was greater in Per than in Sol, suggesting that metabolic and microvascular adjustments during the on-transient may impact the recovery process. These findings may also provide a conceptual frame-work for understanding the prolonged recovery dynamics that are seen in patients with chronic heart failure (41) and diabetes mellitus (8), which are marked by a profoundly reduced (24, 34) and more heterogeneous (23, 24) skeletal blood flow and altered PmvO2 dynamics (4, 11), as well as a shift from a slow- to a more fast-twitch fiber profile (10, 30).


   ACKNOWLEDGMENTS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
REFERENCES
 
The authors acknowledge the technical assistance and contributions of Holly Brown-Feltner, Kelly Brown, Janet Bailey, William Marshall, Jay Harper, and Dr. Casey Kindig.

GRANTS

This study was supported by National Institutes of Health Grants HL-50305, HL-531742, and AG-19228.


   FOOTNOTES
 

Address for reprint requests and other correspondence: P. McDonough, Dept. of Internal Medicine, Pulmonary & Critical Care Medicine, H8.130, Univ. of Texas Southwestern Medical Center, Dallas, TX 75390-9034 (E-mail: paul.mcdonough{at}utsouthwestern.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.


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 

  1. Armstrong RB and Laughlin MH. Blood flows within and among rat muscles as a function of time during high speed treadmill exercise. J Physiol 344: 189-208, 1983.
  2. Arnold DL, Matthews P, and Radda GK. Metabolic recovery after exercise and the assessment of mitochondrial function in vivo in human skeletal muscle by means of 31P NMR. Magn Reson Med 1: 307-315, 1984.
  3. Behnke BJ, Barstow TJ, Kindig CA, McDonough P, Musch TI, and Poole DC. Dynamics of oxygen uptake following exercise onset in rat skeletal muscle. Respir Physiol Neurobiol 133: 229-239, 2002.
  4. Behnke BJ, Kindig CA, McDonough P, Poole DC, and Sexton WL. Dynamics of microvascular oxygen pressure during rest-contraction transition in skeletal muscle of diabetic rats. Am J Physiol Heart Circ Physiol 283: H926-H932, 2002.
  5. Behnke BJ, McDonough P, Padilla DJ, Musch TI, and Poole DC. Oxygen exchange profile in muscles of contrasting fibre types. J Physiol 547: 597-605, 2003.
  6. Bylund-Fellenius AC, Walker PM, Elander A, Holm S, Holm J, and Schersten T. Energy metabolism in relation to oxygen partial pressure in human skeletal muscle during exercise. Biochem J 200: 247-255, 1981.
  7. Challiss RAJ, Vranic M, and Radda GK. Bioenergetic changes during contraction and recovery in diabetic rat skeletal muscle. Am J Physiol Endocrinol Metab 256: E129-E137, 1989.
  8. Crowther GJ, Milstein JM, Jubrias SA, Kushmerick MJ, Gronka RK, and Conley KR. Altered energetic properties in skeletal muscle of men with well-controlled insulin-dependent (Type 1) diabetes. Am J Physiol Endocrinol Metab 284: E655-E662, 2003.
  9. Delp MD and Duan C. Composition and size of type I, IIA, IID/X and IIB fibers and citrate synthase activity of rat muscle. J Appl Physiol 80: 261-270, 1996.
  10. Delp MD, Duan C, Mattson JP, and Musch TI. Changes in skeletal muscle biochemistry and histology relative to fiber type in rats with heart failure. J Appl Physiol 83: 1291-1299, 1997.
  11. Diederich ER, Behnke BJ, McDonough P, Kindig CA, Barstow TJ, Poole DC, and Musch TI. Dynamics of microvascular oxygen partial pressure in contracting skeletal muscle of rats with chronic heart failure. Cardiovasc Res 56: 479-486, 2002.
  12. Gute D, Fraga C, Laughlin MH, and Amann JF. Regional changes in capillary supply in skeletal muscle of high-intensity endurance trained rats. J Appl Physiol 81: 619-626, 1996.
  13. Haseler LJ, Hogan MC, and Richardson RS. Skeletal muscle phosphocreatine recovery in exercise-trained humans is dependent on O2 availability. J Appl Physiol 86: 2013-2018, 1999.
  14. Hill AV and Lupton H. Muscular exercise, lactic acid, and the supply and utilization of oxygen. Quart J Med 16: 135-171, 1923.
  15. Hintz CS, Chi MMY, Fell RD, Ivy JL, Kaiser KK, Lowry CV, and Lowry OH. Metabolite changes in individual rat muscle fibers during stimulation. Am J Physiol Cell Physiol 242: C218-C228, 1982.
  16. Hirai T, Visneski MD, Kearns KJ, Zelis R, and Musch TI. Effects of NO synthase inhibition on muscular blood flow response to treadmill exercise in rats. J Appl Physiol 77: 1288-1293, 1994.
  17. Hogan MC, Arthur PG, Bebout DE, Hochachka PW, and Wagner PD. Role of O2 in regulating tissue respiration in dog muscle working in situ. J Appl Physiol 73: 728-736, 1992.
  18. Hogan MC, Bebout DE, and Wagner PD. Effect of blood flow reduction on maximal O2 uptake in canine gastrocnemius in situ. J Appl Physiol 74: 1742-1747, 1993.
  19. Hudlicka O, Hoppeler H, and Uhlmann E. Relationship between the size of the capillary bed and oxidative capacity in various cat skeletal muscles. Pflügers Arch 410: 369-375, 1987.
  20. Idstrom JP, Subramanian VH, Chance B, Schersten T, and Bylund-Fellenius A-C. Oxygen dependence of energy metabolism in contracting and recovering rat skeletal muscle. Am J Physiol Heart Circ Physiol 248: H40-H48, 1985.
  21. Iotti S, Lodi R, Frassineti C, Zaniol P, and Barbiroli B. In vivo assessment of mitochondrial functionality in human gastrocnemius muscle by 31P MRS. The role of pH in the evaluation of phosphocreatine and inorganic phosphate recoveries from exercise. NMR Biomed 6: 248-253, 1993.
  22. Kemp GJ, Taylor DJ, and Radda GK. Control of phosphocreatine resynthesis during recovery from exercise in human skeletal muscle. NMR Biomed 6: 66-72, 1993.
  23. Kindig CA, Musch TI, Basaraba RJ, and Poole DC. Impaired capillary hemodynamics in skeletal muscle of rats in chronic heart failure. J Appl Physiol 87: 652-660, 1999.
  24. Kindig CA, Sexton WL, Fedde MR, and Poole DC. Skeletal muscle microcirculatory structure and hemodynamics in diabetes. Respir Physiol 111: 163-175, 1998.
  25. Koike A, Hiroe M, and Marumo F. Delayed kinetics of oxygen uptake during recovery after exercise in cardiac patients. Med Sci Sports Exerc 30: 185-189, 1998.
  26. Kushmerick MJ, Meyer RA, and Brown TR. Regulation of oxygen consumption in fast- and slow-twitch muscle. Am J Physiol Cell Physiol 263: C598-C606, 1992.
  27. Laughlin MH, Armstrong RB, White J, and Rouk K. A method for using microspheres to measure muscle blood flow in exercising rats. J Appl Physiol 52: 1629-1635, 1982.
  28. Lo LW, Vinogradov SA, Koch CJ, and Wilson DF. A new, water soluble, phosphor for oxygen measurements in vivo. Adv Exp Med Biol 411: 577-583, 1997.
  29. MacDonald M, Pedersen PK, and Hughson RL. Acceleration of O2 kinetics in heavy submaximal exercise by hyperoxia and prior high-intensity exercise. J Appl Physiol 83: 1318-1325, 1997.
  30. Marin P, Andersson B, Krotkiewski M, and Bjorntop P. Muscle fiber composition and capillary density in women and men with NIDDM. Diabetes Care 17: 382-386, 1994.
  31. McDonough P, Behnke BJ, Kindig CA, and Poole DC. Rat muscle microvascular PO2 kinetics during the exercise off-transient. Exp Physiol 86: 349-356, 2001.
  32. Meyer RA. A linear model of muscle respiration explains monoexponential phosphocreatine changes. Am J Physiol Cell Physiol 254: C548-C553, 1988.
  33. Meyer RA. Linear dependence of muscle phosphocreatine kinetics on total creatine content. Am J Physiol Cell Physiol 257: C1149-C1157, 1989.
  34. Musch TI and Terrell JA. Skeletal muscle blood flow abnormalities in rats with a chronic myocardial infarction: rest and exercise. Am J Physiol Heart Circ Physiol 262: H411-H419, 1992.
  35. Piiper J and Scheid P. Model for capillary-alveolar equilibration with special reference to O2 uptake in hypoxia. Respir Physiol 46: 193-208, 1981.
  36. Poole DC, Sexton WL, Behnke BJ, Ferguson CS, Hageman KS, and Musch TI. Respiratory muscle blood flows during physiological and chemical hyperpnea in the rat. J Appl Physiol 88: 186-194, 2000.
  37. Poole DC, Wagner PD, and Wilson DF. Diaphragm microvascular plasma PO2 measured in vivo. J Appl Physiol 79: 2050-2057, 1995.
  38. Roca J, Agusti AGN, Alonso A, Poole DC, Viegas C, Barbera JA, Rodriguez-Roisin R, Ferrer A, and Wagner PD. Effects of training on muscle O2 transport at O2 max. J Appl Physiol 73: 1067-1076, 1992.
  39. Rumsey WL, Vanderkooi JM, and Wilson DF. Imaging of phosphorescence: a novel method for measuring oxygen distribution in perfused tissue. Science 241: 1649-1651, 1988.
  40. Sietsema KE, Ben-Dov I, Zhang YY, Sullivan C, and Wasserman K. Dynamics of oxygen uptake for submaximal exercise and recovery in patients with chronic heart failure. Chest 105: 1693-1700, 1994.
  41. Simonini A, Massie BM, Long CS, Qi M, and Samarel AM. Alterations in skeletal muscle gene expression in the rat with chronic congestive heart failure. J Mol Cell Cardiol 28: 1683-1691, 1996.
  42. Tada H, Kato H, Misawa T, Sasaki F, Hayashi S, Takahashi H, Kutsumi Y, Ishizaki T, Nakai T, and Miyabo S.31P-nuclear magnetic resonance evidence of abnormal skeletal muscle metabolism in patients with chronic lung disease and congestive heart failure. Eur Respir J 5: 163-169, 1992.
  43. Thompson CH, Kemp GJ, Rajagopalan B, and Radda GK. Abnormal ATP turnover in rat leg muscle during exercise and recovery following myocardial infarction. Cardiovasc Res 29: 344-349, 1995.
  44. Thompson CH, Kemp GJ, Sanderson AL, and Radda GK. Skeletal muscle mitochondrial function studied by kinetic analysis of postexercise phosphocreatine resynthesis. J Appl Physiol 78: 2131-2139, 1995.
  45. Wagner PD. Gas exchange and peripheral diffusion limitation. Med Sci Sports Exerc 24: 54-58, 1992.
  46. Williams DA and Segal SS. Feed artery role in blood flow control to rat hindlimb skeletal muscles. J Physiol 463: 631-646, 1993.
  47. Woodman CR, Schrage WG, Rush JWE, Ray CA, Price EM, Hasser EM, and Laughlin MH. Hindlimb unweighting decreases endothelium-dependent dilation and eNOS expression in soleus not gastrocnemius. J Appl Physiol 91: 1091-1098, 2001.
  48. Wunsch SA, Muller-Delp J, and Delp MD. Time course of vasodilatory responses in skeletal muscle arterioles: role in hyperemia at onset of exercise. Am J Physiol Heart Circ Physiol 279: H1715-H1723, 2000.
  49. Yoshida T and Whipp BJ. Dynamic asymmetries of cardiac output transients in response to muscular exercise in man. J Physiol 480: 355-359, 1994.



This article has been cited by other articles:


Home page
 Exp PhysiolHome page
A. J. Harper, L. F. Ferreira, B. J. Lutjemeier, D. K. Townsend, and T. J. Barstow
Matching of blood flow to metabolic rate during recovery from moderate exercise in humans
Exp Physiol, October 1, 2008; 93(10): 1118 - 1125.
[Abstract] [Full Text] [PDF]

Home page
 Exp PhysiolHome page
P. McDonough, B. J. Behnke, D. J. Padilla, T. I. Musch, and D. C. Poole
Control of microvascular oxygen pressures during recovery in rat fast-twitch muscle of differing oxidative capacity
Exp Physiol, July 1, 2007; 92(4): 731 - 738.
[Abstract] [Full Text] [PDF]

Home page
 Exp PhysiolHome page
L. F Ferreira, A. J Harper, D. K Townsend, B. J Lutjemeier, and T. J Barstow
Kinetics of estimated human muscle capillary blood flow during recovery from exercise
Exp Physiol, September 1, 2005; 90(5): 715 - 726.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
P. McDonough, B. J Behnke, D. J Padilla, T. I Musch, and D. C Poole
Control of microvascular oxygen pressures in rat muscles comprised of different fibre types
J. Physiol., March 15, 2005; 563(3): 903 - 913.
[Abstract] [Full Text] [PDF]

Home page
 Exp PhysiolHome page
P. McDonough, B. J. Behnke, T. I. Musch, and D. C. Poole
Effects of chronic heart failure in rats on the recovery of microvascular PO2 after contractions in muscles of opposing fibre type
Exp Physiol, July 1, 2004; 89(4): 473 - 485.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow All Versions of this Article:
96/3/1039    most recent
00499.2003v1
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (9)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by McDonough, P.
Right arrow Articles by Poole, D. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by McDonough, P.
Right arrow Articles by Poole, D. C.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2004 by the American Physiological Society.