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1 Department of Kinesiology and Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas 66506-5802; 2 Department of Medicine, University of California, La Jolla, California 92093-0623; and 3 Department of Physiology, Kirksville College of Osteopathic Medicine, Kirksville, Missouri 63501
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Type I diabetes reduces
dramatically the capacity of skeletal muscle to receive oxygen
(
O2). In control (C;
n = 6) and streptozotocin-induced diabetic (D:
n = 6, plasma glucose = 25.3 ± 3.9 mmol/l
and C: 8.3 ± 0.5 mmol/l) rats, phosphorescence quenching was used
to test the hypothesis that, in D rats, the decline in microvascular PO2 [PmO2, which
reflects the dynamic balance between O2 utilization (
O2) and
O2] of the spinotrapezius muscle
after the onset of electrical stimulation (1 Hz) would be faster
compared with that of C rats. PmO2 data were
fit with a one or two exponential process (contingent on the presence
of an undershoot) with independent time delays using least-squares
regression analysis. In D rats, PmO2 at rest
was lower (C: 31.2 ± 3.2 mmHg; D: 24.3 ± 1.3 mmHg, P < 0.05) and at the onset of contractions decreased
after a shorter delay (C: 13.5 ± 1.8 s; D: 7.6 ± 2.1 s, P < 0.05) and with a reduced mean response
time (C: 31.4 ± 3.3 s; D: 23.9 ± 3.1 s,
P < 0.05). PmO2 exhibited a
marked undershoot of the end-stimulation response in D muscles (D:
3.3 ± 1.1 mmHg, P < 0.05), which was absent in C
muscles. These results indicate an altered
O2-to-O2
matching across the rest-exercise transition in muscles of D rats.
streptozotocin diabetes; oxygen uptake kinetics; exercise intolerance; muscle oxygen delivery; phosphorescence quenching
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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PULMONARY GAS
EXCHANGE DYNAMICS (i.e., oxygen uptake,
O2 kinetics) at exercise onset are
slowed profoundly in diabetic patients (5, 23). Slowed
O2 kinetics in response to a given
metabolic challenge will mandate generation of a greater O2
deficit and exacerbate intracellular perturbations of phosphocreatine,
free ADP, and Pi, for example, that accelerate
glycogenolysis and utilization of finite glycogen reserves
(33). This phenomenon is likely to contribute to the
reduced exercise tolerance that is present in the diabetic condition.
In healthy subjects, there is strong evidence that pulmonary
O2 kinetics closely reflect
the dynamics of O2 exchange at the muscle
(10). Moreover, it is known that streptozotocin-induced diabetes in rats elicits marked skeletal muscle structural (7, 19, 27), hemodynamic (8, 12, 19), and metabolic
perturbations (6, 7). For instance, streptozotocin-induced
diabetes causes marked muscle fiber atrophy (7, 19, 27),
slows arteriolar vasodilation and capillary red blood cell (RBC)
velocity (VRBC) (8, 12, 19), and
reduces citrate synthase activity (19) and
pyruvate-stimulated O2 consumption (6, 11).
Thus it appears that the ability to deliver O2 to muscle
(O2) as well as the capability of
muscle to utilize that O2
(O2) is impaired in diabetic rats.
During electrical stimulation, phosphocreatine concentration falls to a
greater extent in muscles of diabetic rats, and this is associated with
a reduced ability to maintain submaximal force production during
contractions (6). This finding is consistent with a lower
oxidative enzyme capacity (15) and a reduced
O2 availability to muscle mitochondria (13).
The technique of phosphorescence quenching measures
PO2 at the site of blood-tissue O2
exchange (i.e., predominantly within the microcirculation,
PmO2) and therefore provides information regarding the efficacy of the matching between muscle
O2 and O2. We adapted this technique to
monitor PmO2 in the rat spinotrapezius muscle
at rest and across the transition to muscle contractions (3). The purpose of this study was to test the hypothesis
that diabetes induces an impairment of the matching between muscle O2 and
O2 such that
PmO2 falls more rapidly and to a greater extent
during the transition from rest-exercise than in healthy controls.
Specifically, we hypothesized that in muscle of diabetic rats, after
initiation of contractions, PmO2 would fall
with little delay (the control response manifests a delay of 10-20
s) and would undershoot the steady-state level. If these responses are observed, they will provide evidence of a reduced ability of skeletal muscle in diabetes to adequately match
O2 and
O2 across the transition to an
increased energetic requirement. Such information would support the
notion that an impaired muscle O2 delivery, concomitant
with a decreased oxidative capacity, may be responsible for the slowed
O2 kinetics (large O2
deficit) and thus contribute to the poor muscle performance in the
diabetic population.
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METHODS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Experimental animals. Female Sprague-Dawley rats (n = 21, initial weight 244 ± 2 g) were utilized in this investigation. The rats were randomly divided into control (n = 9) and diabetic (n = 12) groups. All surgical procedures and handling of the rats were performed in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals, and the protocols were approved by the Animal Care and Use Committee of Kansas State University. Animals assigned to the diabetic group received a single intracardiac injection of streptozotocin (50 mg/kg) in sterile citrate-buffered saline (pH = 4.5) while under halothane anesthesia (2% in 95% O2-5% CO2). The onset of diabetes was verified 48 h later using urine glucose test strips (Diastix; Ames, IA). All diabetic rats had a urine glucose concentration >100 mmol/l. Experiments were conducted 8 wk after confirmation of the diabetic state.
Surgical preparation. All surgical procedures were performed under pentobarbital anesthesia (50 mg/kg ip to effect and supplemented as necessary). The left carotid artery was cannulated (polyethylene-50, Intra-Medic polyethylene tubing, Clay Adams Brands; Sparks, MD) to monitor arterial blood pressure (model 200, DigiMed BPA; Louisville, KY) as well as to allow infusion of the phosphorescent probe and blood sampling.
The spinotrapezius muscle preparation is employed routinely for intravital microscopy studies of microvascular function. In the present investigation, a U-shaped skin incision exposed the left spinotrapezius muscle for phosphorescence measurements of PmO2 and electrical stimulation. After reflection of overlying skin and fascia, the muscle surface was superfused with Krebs-Henseleit solution equilibrated with 5% CO2-95% N2 at 38°C. Body temperature was maintained at 38°C using a heating pad. Stainless steel plate electrodes (2.5 mm diameter) were attached to each muscle proximal to the motor point (cathode) and across the caudal end (anode) close to the spinal attachment to elicit indirect, bipolar muscle contractions.Experimental protocol. The phosphorescent probe R2 (30 mg/kg) was infused via the arterial cannula ~10 min before each experiment. An arterial blood sample was taken for analysis of blood glucose concentration (Accu-Check Advantage, Boehringer-Mannhiem), blood gases, pH (Nova Stat Profile M; Waltham, MA), and pre- and postmeasurement hematocrit. Following a 10- to 15-min stabilization period after surgery, twitch muscle contractions were elicited at 1 Hz for 3 min (4-5 V, 2-ms pulse duration) using a Grass S88 stimulator (Quincy, MA). PmO2 was determined at 2-s intervals at rest and after the rest-to-stimulation transition for 3 min. Mean arterial pressure (MAP) and body temperature were monitored continuously throughout the protocol. At the conclusion of each experiment, the rat was euthanized using an intra-arterial bolus of saturated KCl. The spinotrapezius muscle was dissected immediately and frozen for later analysis of citrate synthase activity.
Microvascular PO2 measurements. The oxygen dependence of the probe phosphorescence can be described quantitatively through the Stern-Volmer relationship (26). For the phosphorescent probe palladium meso-tetra(4-carboxyphenyl)porphyrin dendrimer (R2) bound to albumin at 38°C and pH 7.4, the quenching constant is 409 Torr/s and lifetime of decay in absence of O2 is 601 µs (20, 21). PmO2 was determined using a PMOD 1000 Frequency Domain Phosphorometer (Oxygen Enterprises; Philadelphia, PA) with the common end of the bifurcated light guide placed ~2-3 mm above the medial region of the spinotrapezius (i.e., superficial to dorsal surface). The PMOD 1000 uses a sinusoidal modulation of the excitation light (524 nm) at frequencies between 100 Hz and 20 kHz, which allows phosphorescence lifetime measurements from 10 µs to ~2.5 ms. In the single frequency mode, 10 scans (100 ms) were used to acquire the resultant lifetime of the phosphorescence (700 nm) and repeated every 2 s (for a review, see Ref. 30). The phosphorescence lifetime was obtained by taking the logarithm of the intensity values at each time point and by fitting the linearized decay to a straight line by the least-squares method (4).
Citrate synthase activity. The citrate synthase activity within the spinotrapezius was determined spectrophotometrically at 30°C as described by Srere (28).
Statistical analysis.
Curve fitting was accomplished using nonlinear regression (KaleidaGraph
3.5, Synergy software; Reading, PA) and was performed on the
PmO2 values using the following monoexponential
function
![Pm<SUB>O<SUB>2</SUB>(<IT>t</IT>)</SUB> = Pm<SUB>O<SUB>2</SUB>(b)</SUB> − &Dgr;Pm<SUB>O<SUB>2</SUB>(es)</SUB> [1 − <IT>e</IT><SUP>−(<IT>t</IT>−TD)<IT>/&tgr;</IT></SUP>]](/content/vol283/issue3/fulltext/H926/img001.gif)
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![Pm<SUB>O<SUB>2</SUB>(<IT>t</IT>)</SUB> = Pm<SUB>O<SUB>2</SUB>(b)</SUB> − &Dgr;Pm<SUB>O<SUB>2</SUB>(primary)</SUB> [1 − <IT>e</IT><SUP>−(<IT>t</IT>−TD<SUB>1</SUB>)&tgr;<SUB>1</SUB></SUP>]](/content/vol283/issue3/fulltext/H926/img002.gif)
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![+ &Dgr;Pm<SUB>O<SUB>2</SUB>(secondary)</SUB> [1 − <IT>e</IT><SUP>−(<IT>t</IT>−TD<SUB>2</SUB>)/&tgr;<SUB>2</SUB></SUP>]](/content/vol283/issue3/fulltext/H926/img003.gif)
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PmO2(es) are
PmO2 at time t, baseline (i.e.,
precontraction) PmO2, and the decrease in
PmO2 from baseline to the end-stimulation
values, respectively. For the more complex double-exponential model,
PmO2(primary) and PmO2(secondary) designate the
asymptotic value to which that component of the
PmO2 is projecting. 
1 and
2 are the time constants, and TD1 and
TD2 are the independent time delays of the respective
responses. Magnitude of the "undershoot" was assessed from the
PmO2 response independent of the curve-fitting model utilized. 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 baseline
(precontracting), nadir, and end-stimulation PmO2 were analyzed using a one-way
repeated-measures ANOVA. When differences were detected by ANOVA,
where these differences lie was determined using a Student-Newman-Keuls
post hoc analysis. Differences between model parameter estimates
[i.e., TD, , mean response time (MRT), etc.] were determined by an
unpaired t-test. Significance was accepted at
P < 0.05.
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RESULTS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Animals in which MAP fell below 60 mmHg and/or arterial PO2 fell below 80 mmHg (control: n = 3; diabetic: n = 6) were rejected, and their data were omitted from further analysis. By these criteria, successful experiments were completed in six control and six diabetic rats.
Animal data.
Blood glucose was significantly elevated and body weight and
spinotrapezius muscle weight were less in the diabetic rats compared with control rats (Table 1).
Spinotrapezius muscle weight-to-body weight ratio was lower in diabetic
rats, reflecting marked muscle atrophy (Table 1). Diabetes resulted in
a reduction in citrate synthase activity in the spinotrapezius muscle
(Table 1). MAP during experiments, systemic hematocrit measured before
(pre) and after (post) the experiments, pH, and arterial
PO2 were not different in control and diabetic
animals (Table 1).
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Spinotrapezius PmO2 response.
Baseline PmO2 in the resting state was lower in
diabetic compared with control muscles (control: 31.2 ± 3.2 mmHg;
diabetic: 24.3 ± 1.3 mmHg, P < 0.05; Table
2). The PmO2
at end-stimulation (i.e., 1 + 2) was
less in diabetic than control muscles (control: 15.7 ± 2.4 mmHg;
diabetic: 8.8 ± 1.4 mmHg, P < 0.05). In
addition, whereas the end-stimulation PmO2
values were not different between groups (control: 15.5 ± 2.4 mmHg; diabetic: 15.2 ± 2.3 mmHg), the
PmO2 nadir was significantly lower in diabetic
muscle (diabetic: 10.8 ± 1.6 mmHg; control: 15.5 ± 2.4 mmHg, P < 0.05). As depicted in Figs.
1 and 2,
the profile of PmO2 at the onset of
contractions was substantially different in control vs. diabetic
muscles. Specifically, in spinotrapezius muscles of control rats,
PmO2 remained at baseline levels for an average
of ~14 s before decreasing monoexponentially to the end-stimulation
value (Fig. 1). In contrast, in diabetic animals,
PmO2 decreased either immediately at the onset
of contractions or with a reduced delay (average about one-half of that
seen in control muscles; Fig. 2, Table 2). Furthermore, in diabetic
muscles, there was a consistent and significant undershoot (i.e.,
endcontracting minus absolute nadir value) of
PmO2 (3.3 ± 1.1 mmHg), followed by a
subsequent slow increase to a value at which
PmO2 was not different between control and
diabetic muscles (control: 15.5 ± 2.4 mmHg; diabetic: 15.2 ± 2.3 mmHg, P > 0.05) at 3 min of
stimulation.
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Modeled PmO2 responses.
A simple monoexponential model fit the
PmO2 responses observed in muscle of
control rats well (r2 = 0.985 ± 0.006, 
2 = 27.8 ± 8.6; Fig. 1), and,
consequently, a more complex model was not considered. As evident from
Figs. 2 and 3, the more complex double-exponential model provided a substantially better fit to the
PmO2 response in diabetic muscles, as confirmed
by significantly lower 2-error values (monoexponential:
129.9 ± 49.1; double exponential: 61.7 ± 17.9, P < 0.05).
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1 was not different in control vs. diabetic muscles
(Table 2). The MRT (i.e., TD1 + 1) for
the primary response was less in diabetic rats (control: 31.4 ± 3.3 s; diabetic: 23.9 ± 3.1 s, P < 0.05). The time necessary from the initiation of contractions for
PmO2 to fall to 63% of the difference between
baseline and the nadir of the response (T63),
i.e., a model-independent estimate of the MRT, was also less in
diabetic muscles (control: 32.0 ± 3.3 s; diabetic: 22.8 ± 3.6 s, P < 0.05).
For the control muscles, there was no evidence of a significant
PmO2 undershoot. In contrast, there was a
consistent and marked PmO2 undershoot in the
diabetic muscles that ranged up to 7 mmHg (average ~3.5 mmHg; Table
2). In diabetic muscles, the double-exponential model identified a
secondary increase in PmO2 after a time delay (TD2) of 85.4 ± 18.6 s with a 2
of 85.4 ± 40.9 s (Fig. 2 and Table 2).
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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The results presented herein demonstrate that at rest and across
the transition from rest to contractions, diabetes alters the dynamic
relationship between O2 and
O2. The decreased PmO2 at rest is consistent with microvascular
studies that have documented a reduced capillary RBC flux in muscles of
diabetic rats (19). Moreover, across the
rest-to-contractions transition, the accelerated fall of
PmO2 and subsequent undershoot are indicative of a comparatively sluggish O2
response. Thus both conductive (O2)
and diffusive (driving pressure for blood-tissue O2
exchange, PmO2) elements of O2
delivery and exchange are impaired in muscles of diabetic rats. The
early reduction in PmO2 would be expected to
occur concomitant with a lower intramuscular
PO2, which has been linked mechanistically with
slower O2 kinetics (9). Accordingly, the present findings offer a putative mechanistic basis
for the slowed pulmonary O2 kinetics
that is symptomatic of diabetic patients (2, 23).
Phosphorescence quenching measurement of
PO2.
Oxygen is transported by bulk flow from the lungs to the skeletal
muscle capillaries and by diffusion from the capillaries to the
myocytes according to Fick's Law. In the plasma, the content of oxygen
is a function of pressure and solubility (which is very low, 0.003 ml
O2 · 100 ml
1 · mmHg1), such that the overall
oxygen-carrying capacity of plasma is trivial compared with that of
hemoglobin or myoglobin. The location of the plasma between these two
principal O2 carriers is such that plasma
PO2 (measured via phosphorescence quenching)
(26) provides a sensitive indicator of the matching
between muscle O2 (i.e., myocyte
O2 uptake) and O2.
Therefore, as intracellular PO2 falls as a
result of increased mitochondrial
O2, a greater extraction from the
adjacent capillaries is expected based on Fick's Law. It is these
changes that are reflected by the prevailing PmO2. As evident from Fick's Law, for any
given intramyocyte PO2, a fall in
PmO2 will reduce the pressure gradient driving
the diffusive movement of O2 from the blood into the
myocyte and, given a finite muscle O2-diffusing capacity,
will serve to limit blood-muscle O2 transfer (i.e.,
O2) (14, 24, 31).
Diabetes model.
Streptozotocin-induced diabetes leads to marked alterations in skeletal
muscle morphology and hemodynamics that significantly impact the
structural and functional capacity of the muscle to transport,
exchange, and utilize O2 at rest and during metabolic challenges (e.g., exercise). One of the most obvious changes induced by
diabetes is a pronounced muscle fiber atrophy, which is associated with
a decreased oxidative enzyme capacity (7, 19, 27) and
maximal O2.
Interpretation of data.
At the onset of muscle contractions, ATP demand increases almost
instantaneously. However, the time delay (TD1) preceding the decrease of PmO2 at the onset of muscle
contractions need not imply that both
O2 or
O2 are stagnant, but rather that they increase in concert such that there is little or no change in the
O2-to-O2
ratio and therefore PmO2. Accordingly, the results of the present investigation (i.e., reduced TD before PmO2 falling in diabetic muscle) demonstrate
that across the rest-contractions transition, the duration for which
the
O2-to-O2
ratio is unaltered is attenuated in diabetic compared with control
muscle (Figs. 1 and 2). The resultant overall faster kinetics
(expressed by MRT and T63) and undershoot in
PmO2 observed in the muscle of diabetic rats
are consistent with an attenuated or slower muscle blood flow response
(increased O2) across the
rest-contractions transition. In marked contrast to the control
response, after a secondary delay (TD2) that averaged
85 s, PmO2 subsequently increased toward
the end-stimulation level. Because a marked reduction of
O2 at 80-90 s of contractions
is highly unlikely, this response is consistent with the presence of a
delayed rise in blood flow (and thus
O2) in the diabetic muscle that is
necessary to elevate the PmO2 to a value
commensurate with that found in control muscle at the end of
stimulation. The suddenness of this response suggests an abrupt
arterial vasodilation at a time when the rate of
O2 increase is relatively slow. It
is also possible that, had the diabetic muscles been stimulated for >3
min, the PmO2 may have risen above that seen
for the control steady-state condition. Indeed, a reduced muscle
O2-diffusing capacity [as suggested from morphometric and
intravital microscopy examination of diabetic muscle (19,
27)] would mandate an elevated
PmO2-to-intramyocyte PO2 gradient at any given
O2.
O2-to-O2
ratio in diabetes at any given time point across the transition is also
apparent through the increased periodicity and magnitude of
oscillations in PmO2, which is quantified by
the 2-values (diabetic: 61.7 ± 17.9; control:
27.8 ± 8.6, P < 0.05) of the model used (i.e.,
the magnitude of oscillations around the model fit). These data suggest
that there is an inability to regulate and match
O2 to
O2 precisely within the
microvasculature (i.e., as reflected in the oscillations around the
model fit shown in Figs. 2 and 3) and is consistent with the reported
impairment in myogenic reactivity of arterioles in diabetic rats
(8, 12). In addition, the reduced deformability of RBCs in
diabetic rats coupled with the decreased capillary luminal diameter
(19, 27) would be expected to both reduce blood flow
capacity and to alter the distribution of RBCs within the capillary bed
of contracting muscle (19). Deficits in
O2 in concert with reduced
intramuscular myoglobin content (17) would further reduce
the muscle O2-buffering capacity and therefore shorten the
TD that precedes the decrease in PmO2, as
observed in the present study. This rationale is strengthened by the
presence of a decreased muscle oxidative capacity (7, 11, 19,
27), which would act to reduce the speed of the O2 response (for a
review, see Ref. 22). That PmO2
(i.e., O2-to-O2
ratio) falls more rapidly in diabetic muscle despite O2 dynamics that are expected to be
slower strengthens our conclusion that the
O2 response across the
rest-contractions transition must be slowed. The direct consequence of
impaired O2 and reduced PmO2 across the transition is that
blood-myocyte O2 exchange will be reduced compared with
that of the control in diabetic muscle. This condition will mandate
exacerbation of intracellular perturbations (e.g., greater decrease in
intracellular phosphocreatine, increase in free ADP, enhanced
glycogenolysis) needed to support the energetic demand of the muscle
(34). Such a rationale is consistent with the observations
of Challiss et al. (6), who demonstrated a greater
decrease in muscle phosphocreatine levels in diabetic rat muscle
compared with control rats working at the same intensity.
Preparation considerations.
The results presented herein must be considered within the context and
limitations of the model used. For example, electrical stimulation
recruits all muscle fiber types simultaneously in contrast to a
physiological ordered recruitment pattern. In addition, the combination
of the depressant effects of anesthesia on cardiovascular function and
electrical muscle stimulation may slow the
O2 response compared with voluntary
muscle contractions (3). Notwithstanding this
consideration, it is evident that the control and diabetic rat muscles
exhibited a profoundly different PmO2 profile
with evidence for a O2 limitation to
O2 transfer in diabetic rat muscles but not in their
control counterparts. It is pertinent that there was a tendency for MAP
to be lower in the diabetic rats due possibly to their greater
sensitivity to the anesthesia. However, correlation analyses revealed
no significant relationship between MAP and either the
PmO2 TD or the magnitude of the
PmO2 undershoot found within the diabetic
muscles. This analysis supports the notion that the differential
pattern of the PmO2 response found in diabetic
rat muscles was not induced secondary to any effects of anesthesia on MAP.
Relevance.
Patients with Type 2 diabetes evidence slowed pulmonary
O2 kinetics at the onset of moderate
intensity (i.e., sublactate threshold) exercise and a reduced maximum
O2 (23). The slowed O2 kinetics arise from 1) a
prolonged phase I (cardiodynamic phase) attributable to a sluggish
cardiovascular response (16, 18, 23, 25); and
2) slowed phase II kinetics thought to reflect limitations
in VO2 at the exercising muscle (2,
10). The present investigation provides the first empirical
evidence that the dynamic relationship between muscle
O2 and
O2 is altered across the
rest-contractions transition in diabetic muscle. Thus, consistent with
a delayed increase of O2 (relative
to O2), PmO2
falls more rapidly, and this effectively reduces the pressure gradient
for blood-myocyte O2 diffusion. The presence of a
PmO2 undershoot and secondary rise in diabetic
but not control muscle indicates that
O2 may take substantially longer to
reach endstimulation levels in diabetic rat muscle. Thus the slowed pulmonary O2 kinetics and increased
O2 deficit incurred at exercise onset (5, 23)
would be expected to arise from impaired conductive and diffusive
O2 transport within skeletal muscle. Given the
deterministic role of skeletal muscle in setting pulmonary
VO2 kinetics and the data presented herein, it
is quite possible that the training-induced speeding of pulmonary
VO2 kinetics in diabetic patients demonstrated by Brandenburg et al. (5) is driven by improvements in
microvascular function and O2 exchange and possibly
increases in oxidative enzymes within the active skeletal muscle.
However, this notion remains to be tested.
O2-to-O2
ratio across the transition to contractions that must arise from
comparatively sluggish O2 kinetics,
which impairs conductive O2 delivery and diffusive
blood-myocyte O2 exchange within contracting muscle. This
behavior at the microvascular level concomitant with a reduced oxidative capacity offers a putative mechanistic explanation for the
slowed pulmonary O2 kinetics observed in
diabetic patients that causes an increased O2 deficit and
is associated with a reduced exercise tolerance.
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ACKNOWLEDGEMENTS |
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We thank Troy E. Richardson and Janet K. Bailey for excellent technical support.
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FOOTNOTES |
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This work was funded in part by National Heart, Lung, and Blood Institute Grant HL-50306 (to D. C. Poole) and by the Heartland Affiliate of the American Heart Association (to W. L. Sexton).
Address for reprint requests and other correspondence: D. C. Poole, Dept. 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.
May 16, 2002;10.1152/ajpheart.00059.2002
Received 23 January 2002; accepted in final form 7 May 2002.
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REFERENCES |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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