Kinetics analysis of muscle arterial–venous O2 difference profile during exercise

Barbosa, Priscila; Bravo, Daniela M.; Neder, J. Alberto; Ferreira, Leonardo F.

doi:10.1016/j.resp.2010.06.008

Cited by 13 publications

(30 citation statements)

References 47 publications

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“…We restrained our analysis to [deoxy-Hb ϩ Mb], as this variable is insensitive to blood volume changes, and its time course has been found to be remarkably equivalent to fractional O 2 extraction when muscle venous outflow is carefully isolated in animal preparations [as discussed at length in Barbosa et al (4) and Ferreira et al (17)]. A caveat particularly pertinent to the present study, however, is its inability to differentiate Hb from Mb with regard to light absorption.…”

Section: Discussionmentioning

confidence: 99%

Sildenafil improves microvascular O₂ delivery-to-utilization matching and accelerates exercise O₂ uptake kinetics in chronic heart failure

Sperandio

Oliveira

Rodrigues

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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Sperandio PA, Oliveira MF, Rodrigues MK, Berton DC, Treptow E, Nery LE, Almeida DR, Neder JA. Sildenafil improves microvascular O 2 delivery-to-utilization matching and accelerates exercise O 2 uptake kinetics in chronic heart failure. Am J Physiol Heart Circ Physiol 303: H1474 -H1480, 2012. First published September 28, 2012; doi:10.1152/ajpheart.00435.2012 can temporally and spatially match microvascular oxygen (O 2) delivery (Q O2mv) to O2 uptake (V O2) in the skeletal muscle, a crucial adjustment-to-exercise tolerance that is impaired in chronic heart failure (CHF). To investigate the effects of NO bioavailability induced by sildenafil intake on muscle Q O2mv-to-O2 utilization matching and V O2 kinetics, 10 males with CHF (ejection fraction ϭ 27 Ϯ 6%) undertook constant work-rate exercise (70 -80% peak). Breath-bybreath V O2, fractional O2 extraction in the vastus lateralis {ϳdeoxy-genated hemoglobin ϩ myoglobin ([deoxy-Hb ϩ Mb]) by nearinfrared spectroscopy}, and cardiac output (CO) were evaluated after sildenafil (50 mg) or placebo. Sildenafil increased exercise tolerance compared with placebo by ϳ20%, an effect that was related to faster onand off-exercise V O2 kinetics (P Ͻ 0.05). Active treatment, however, failed to accelerate CO dynamics (P Ͼ 0.05). On-exercise [deoxy-Hb ϩ Mb] kinetics were slowed by sildenafil (ϳ25%), and a subsequent response "overshoot" (n ϭ 8) was significantly lessened or even abolished. In contrast, [deoxy-Hb ϩ Mb] recovery was faster with sildenafil (ϳ15%). Improvements in muscle oxygenation with sildenafil were related to faster on-exercise V O2 kinetics, blunted oscillations in ventilation (n ϭ 9), and greater exercise capacity (P Ͻ 0.05). Sildenafil intake enhanced intramuscular Q O2mv-to-V O2 matching with beneficial effects on V O2 kinetics and exercise tolerance in CHF. The lack of effect on CO suggests that improvement in blood flow to and within skeletal muscles underlies these effects.sildenafil; blood flow; heart failure; hemodynamics; near-infrared spectroscopy; oxygen consumption; kinetics THE INABILITY TO MAINTAIN an adequate driving pressure for blood-myocite oxygen (O 2 ) diffusion [i.e., microvascular partial pressure of O 2 (PO 2mv )] is paramount to explain the slowness of exercise O 2 uptake (V O 2 ) kinetics in patients with chronic heart failure [CHF; as recently reviewed by Poole and colleagues (34)]. To keep a sufficiently high PO 2mv , however, O 2 delivery should be spatially and temporally matched to V O 2 of individual fibers. In this context, seminal studies found that intramuscular PO 2mv in rodents with CHF was critically low either at rest-to-contractions transition (7,14) or during early recovery (12), i.e., when V O 2 should be increasing or decreasing most rapidly, respectively. Importantly, it was demonstrated that reduced nitric oxide (NO) bioavailability exerted a key mechanistic role on on-and off-exercise O 2 delivery-toutilization uncoupling in these animal preparations (24,25).In intact humans with CHF, previous studies have concomitant...

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Section: Discussionmentioning

confidence: 99%

Sildenafil improves microvascular O₂ delivery-to-utilization matching and accelerates exercise O₂ uptake kinetics in chronic heart failure

Sperandio

Oliveira

Rodrigues

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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“…Therefore, the steadystate TOI (TOI ss) was measured from the average of the final 2 min of exercise, and the deoxygenation overshoot was measured as the difference between TOI min and TOIss. The area bounded by the deoxygenation overshoot (TOI os-area) was measured by integrating between the measured response and the steady-state value, from the time at which the steady state was first attained until end exercise (2). This method, in the presence of a deoxygenation overshoot, is suggested to provide a close correlate of the dynamics of muscle O 2 delivery: the greater the TOIos-area, the slower the dynamics of O2 delivery relative to the dynamics of V O2 (2).…”

Section: Methodsmentioning

confidence: 99%

The intramuscular contribution to the slow oxygen uptake kinetics during exercise in chronic heart failure is related to the severity of the condition

Bowen

Cannon²,

Murgatroyd³

et al. 2012

Journal of Applied Physiology

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Bowen TS, Cannon DT, Murgatroyd SR, Birch KM, Witte KK, Rossiter HB. The intramuscular contribution to the slow oxygen uptake kinetics during exercise in chronic heart failure is related to the severity of the condition. J Appl Physiol 112: 378 -387, 2012. First published October 27, 2011 doi:10.1152/japplphysiol.00779.2011The mechanism for slow pulmonary O2 uptake (V O2) kinetics in patients with chronic heart failure (CHF) is unclear but may be due to limitations in the intramuscular control of O2 utilization or O2 delivery. Recent evidence of a transient overshoot in microvascular deoxygenation supports the latter. Prior (or warm-up) exercise can increase O2 delivery in healthy individuals. We therefore aimed to determine whether prior exercise could increase muscle oxygenation and speed V O2 kinetics during exercise in CHF. Fifteen men with CHF (New York Heart Association I-III) due to left ventricular systolic dysfunction performed two 6-min moderate-intensity exercise transitions (bouts 1 and 2, separated by 6 min of rest) from rest to 90% of lactate threshold on a cycle ergometer. V O2 was measured using a turbine and a mass spectrometer, and muscle tissue oxygenation index (TOI) was determined by near-infrared spectroscopy. Prior exercise increased resting TOI by 5.3 Ϯ 2.4% (P ϭ 0.001), attenuated the deoxygenation overshoot (Ϫ3.9 Ϯ 3.6 vs. Ϫ2.0 Ϯ 1.4%, P ϭ 0.011), and speeded the V O2 time constant (V O2; 49 Ϯ 19 vs. 41 Ϯ 16 s, P ϭ 0.003). Resting TOI was correlated to V O2 before (R 2 ϭ 0.51, P ϭ 0.014) and after (R 2 ϭ 0.36, P ϭ 0.051) warm-up exercise. However, the mean response time of TOI was speeded between bouts in half of the patients (26 Ϯ 8 vs. 20 Ϯ 8 s) and slowed in the remainder (32 Ϯ 11 vs. 44 Ϯ 16 s), the latter group having worse New York Heart Association scores (P ϭ 0.042) and slower V O2 kinetics (P ϭ 0.001). These data indicate that prior moderate-intensity exercise improves muscle oxygenation and speeds V O2 kinetics in CHF. The most severely limited patients, however, appear to have an intramuscular pathology that limits V O2 kinetics during moderate exercise. muscle oxygenation; near-infrared spectroscopy; prior exercise CHRONIC HEART FAILURE (CHF) is a syndrome characterized by exercise intolerance due to breathlessness and fatigue in the presence of cardiac dysfunction. A treadmill or cycle-based symptom-limited peak exercise test, with pulmonary gas exchange measurement to determine peak O 2 uptake (V O 2peak ), is the most widely used measure of physiological limitation in CHF and provides objective information on aerobic capacity, symptomatology, and prognosis (35). However, activities of daily living rarely occur at or around V O 2peak . Therefore, the rate at which aerobic energy transfer adapts [O 2 uptake (V O 2 ) kinetics] to changing energy demands may provide an assessment that is more appropriate to daily exercise limitations in CHF than traditional measures (1, 52). Accordingly, initial evidence indicates that V O 2 kinetics are more strongly correlated to disease s...

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“…Assuming that a larger area under the D[deoxy-Hb ? Mb] OS would be conceptually similar to a greater ''undershoot'' in microvascular PO 2 (Kindig et al 1999;Ferreira et al 2006) and, as we recently demonstrate on a modelling study (Barbosa et al 2010), quantitatively related to impaired capillary blood flow (Ferreira et al 2005a), this variable was used as an index of impaired microvascular O 2 delivery. The AOS was calculated in arbitrary units (a.u.)…”

Section: Discussionmentioning

confidence: 87%

“…Similarly, the amplitude of the OS and s S were used as ancillary indexes of O 2 delivery-to-utilization mismatch (Barbosa et al 2010). Considering, however, that an OS would prevent P parameters to be used as valid indexes of fractional (av)O 2 difference (Barbosa et al 2010), only the S parameters were recorded in OS(?) patients (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Mb] have been reported in elderly subjects (DeLorey et al 2005), young detrained individuals (Murias et al 2010)-especially after prolonged bed rest (Porcelli et al 2010)-and patients with type II diabetes (Bauer et al 2007a, b), chronic obstructive pulmonary disease (Chiappa et al 2008), and CHF (Sperandio et al 2009). In fact, we recently showed on an in silico study that the area under the OS in fractional O 2 extraction after the onset of exercise was tightly and inversely related to muscle blood flow (Barbosa et al 2010). This issue, however, has not been previously addressed in patients with PAH.…”

Section: Introductionmentioning

confidence: 97%

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Kinetics of skeletal muscle O2 delivery and utilization at the onset of heavy-intensity exercise in pulmonary arterial hypertension

et al. 2011

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Impaired O(2) delivery relative to O(2) demands at the onset of exercise might influence the response profile of muscle fractional O(2) extraction (≅Δ[deoxy-Hb/Mb] by near-infrared spectroscopy) either by accelerating its rate of increase or creating an "overshoot" (OS) in patients with pulmonary arterial hypertension (PAH). We therefore assessed the kinetics of O(2) uptake [Formula: see text] Δ[deoxy-Hb/Mb] in the vastus lateralis, and heart rate (HR) at the onset of heavy-intensity exercise in 14 females with PAH (connective tissue disease, IPAH, portal hypertension, and acquired immunodeficiency syndrome) and 11 age- and gender-matched controls. Patients had slower [Formula: see text] and HR dynamics than controls (τ[Formula: see text] = 62.7 ± 15.2 s vs. 41.0 ± 13.8 s and t (1/2)-HR = 61.3 ± 16.6 s vs. 43.4 ± 8.8 s, respectively; p < 0.01). No study participant had a significant reduction in oxyhemoglobin saturation. In OS(-) subjects (6 patients and 7 controls), the kinetics of Δ[deoxy-Hb/Mb] relative to [Formula: see text] were faster in patients (p = 0.05). Larger area under the OS and slower kinetics (MRT) of the "downward" component indicated greater O(2) delivery-to-utilization mismatch in OS(+) patients versus OS(+) controls (477.4 ± 330.0 vs. 78.1 ± 65.6 a.u. and 74.6 ± 18.8 vs. 46.0 ± 17.0 s, respectively; p < 0.05). Resting pulmonary vascular resistance was higher in OS(+) than OS(-) patients (23.1 ± 12.0 vs. 10.7 ± 4.0 Woods, respectively; p < 0.05). We conclude that microvascular O(2) delivery-to-utilization inequalities slowed the rate of adaptation of aerobic metabolism at the start of heavy-intensity exercise in women with PAH.

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Kinetics analysis of muscle arterial–venous O2 difference profile during exercise

Cited by 13 publications

References 47 publications

Sildenafil improves microvascular O₂ delivery-to-utilization matching and accelerates exercise O₂ uptake kinetics in chronic heart failure

Sildenafil improves microvascular O₂ delivery-to-utilization matching and accelerates exercise O₂ uptake kinetics in chronic heart failure

The intramuscular contribution to the slow oxygen uptake kinetics during exercise in chronic heart failure is related to the severity of the condition

Kinetics of skeletal muscle O2 delivery and utilization at the onset of heavy-intensity exercise in pulmonary arterial hypertension

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Kinetics analysis of muscle arterial–venous O2 difference profile during exercise

Cited by 13 publications

References 47 publications

Sildenafil improves microvascular O2 delivery-to-utilization matching and accelerates exercise O2 uptake kinetics in chronic heart failure

Sildenafil improves microvascular O2 delivery-to-utilization matching and accelerates exercise O2 uptake kinetics in chronic heart failure

The intramuscular contribution to the slow oxygen uptake kinetics during exercise in chronic heart failure is related to the severity of the condition

Kinetics of skeletal muscle O2 delivery and utilization at the onset of heavy-intensity exercise in pulmonary arterial hypertension

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Sildenafil improves microvascular O₂ delivery-to-utilization matching and accelerates exercise O₂ uptake kinetics in chronic heart failure

Sildenafil improves microvascular O₂ delivery-to-utilization matching and accelerates exercise O₂ uptake kinetics in chronic heart failure