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

Abstract

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...

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

“…Disease-induced decreases in O 2 delivery relative to muscle O 2 demands have been found to accelerate and amplify rest-toexercise decrements in PO 2mv and to slow its recovery after exercise (8,12,24,25). This is physiologically equivalent to faster and heightened on-exercise increases in microvascular fractional O 2 extraction (ϳ[deoxy-Hb ϩ Mb], the mirror image of PO 2mv ) and slower postexercise [deoxy-Hb ϩ Mb] recovery (9,10,18,37). Moreover, fractional O 2 extraction transiently overshoots the subsequent steady-state value (Fig.…”

“…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 concomitantly assessed the rate of change in phase II ("muscle") V O 2 (39) and intramuscular fractional O 2 extraction {ϳdeoxygen-ated hemoglobin ϩ myoglobin ([deoxy-Hb ϩ Mb]) by nearinfrared spectroscopy (NIRS)} (18) to gain insight into the dynamic matching of O 2 delivery to utilization (9,10,37). This analysis is based on the widely accepted concept that PO 2mv and changes thereof reflect the delivery/utilization ratio, i.e., V O 2 /microvascular O 2 delivery (Q O 2mv ) as deoxygenation (18).…”

“…This analysis is based on the widely accepted concept that PO 2mv and changes thereof reflect the delivery/utilization ratio, i.e., V O 2 /microvascular O 2 delivery (Q O 2mv ) as deoxygenation (18). In fact, decreases in O 2 delivery relative to O 2 needs speeded (and heightened) on-exercise [deoxy-Hb ϩ Mb] kinetics but slowed postexercise [deoxy-Hb ϩ Mb] recovery in patients with CHF (9,10,37). The therapeutic potential of increasing NO bioavailability to improve the dynamic coupling of Q O 2mv to V O 2, thereby accelerating V O 2 kinetics and enhancing exercise tolerance, however, remains unexplored in these patients.…”

Divergent skeletal muscle mitochondrial phenotype between male and female patients with chronic heart failure

“…Pacemaker requirement was sick sinus syndrome, heart block, or cardiac arrest (implantable cardioverter defibrillator patients). All HFrEF patients undertook a peak symptom‐limited CPX test to volitional exhaustion on a cycle ergometer for determination of pulmonary gas exchange (V̇O 2 and V̇CO 2 ) and ventilation (V̇ E ) . Control subjects were consecutive patients listed for device implantation of a permanent pacemaker without symptoms of heart failure.…”

Pulmonary Rehabilitation and Palliative Care for the Lung Cancer Patient

“…Exercise improves gas exchange by boosting oxygen transport, enhancing cellular uptake and utilization while enabling more efficient CO 2 elimination. 11 In so doing, exercise is the most effective means to resolve dyspnea from exertion over the long term. 12 In the early days of pulmonary rehabilitation, the mechanism for this improvement was unclear, since COPD patients were viewed as so limited by their lung disease that they were unable to exercise at a high enough work rate to achieve a training effect.…”