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European Journal of Heart Failure 2004 6(7):917-926; doi:10.1016/j.ejheart.2004.02.010
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© 2004 European Society of Cardiology

Biomechanical efficiency is decreased in heart failure during low-level steady state and maximal ramp exercise

Wayne C. Levya,*, Barbara A. Maichelb, Natalie P. Steelea, Kenneth M. Leclercc and John R. Strattonb

a University of Washington Box 356422, 1959 NE Pacific Street, Seattle, WA 98195, USA
b VA Puget Sound Health Care System USA
c Brooke Army Medical Center San Antonio, TX, USA

* Corresponding author. Tel.: +1-206-221-4507; Fax: +1-206-221-6835. E-mail address: levywc{at}u.washington.edu


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusions
 References
 
Background: Previous studies of biomechanical efficiency (external work/energy input – Watt/O2 consumed) in heart failure (HF) using cardiopulmonary exercise testing (CPET) and magnetic resonance spectroscopy (MRS) have had discordant results with increased efficiency by CPET and decreased efficiency by MRS.

Aims: Compare biomechanical efficiency of HF subjects and normal controls during steady state (SS=35 W for 6 min) and ramp cycle ergometer exercise. The hypothesis was that HF subjects would have impaired biomechanical efficiency that correlated with HF symptoms.

Methods: Biomechanical efficiency used the actual VO2 during exercise and recovery. Gross (VO2 above zero), Net (VO2 above the resting VO2) and Work (VO2 above the unloaded pedaling VO2) efficiencies were calculated.

Results: HF subjects had an 18% higher VO2 during SS exercise (P=0.029). Biomechanical efficiency was reduced during SS exercise (gross –15%, P=0.019, net –15%, P=0.062, and work –35%, P=0.002). Gross Efficiency during SS exercise had the strongest correlation with HF symptoms (r=0.55). During ramp exercise gross (–26%), net (–10%) and work (–8%) biomechanical efficiency were all reduced (all P<0.05). The slope of the VO2/Watt relationship during ramp exercise had the best correlation with HF symptoms (r=0.46).

Conclusions: HF subjects have an increased O2 cost/Watt during SS and ramp exercise that correlates with HF symptoms of fatigue and breathlessness. Methods to improve biomechanical efficiency in HF subjects by exercise training or medications may improve the symptoms and the impaired exercise capacity associated with HF.

Key Words: Abbreviations • HF, Heart failure • SS, Steady state • MLWHF, Minnesota living with HF questionnaire • VO2, oxygen consumption • CPET, cardiopulmonary exercise testing • MRS, magnetic resonance spectroscopy • VT, ventilatory threshold

Received August 20, 2003; Revised January 26, 2004; Accepted February 25, 2004


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 5. Conclusions
 References
 
Systolic HF is a syndrome that has as its hallmark impaired exercise capacity. The etiology of the impaired exercise capacity is multifactorial including a reduction in cardiac output, neurohormonal/cytokine activation, and changes in skeletal muscle fiber type [1]. Histologic studies have demonstrated a decrease in the efficient skeletal muscle Type I highly oxidative fibers (metabolize lactate/pyruvate during exercise), a decrease in the oxidative enzymes and mitochondrial density, with an increase in the inefficient Type IIb glycolytic fibers (produce lactate during exercise) as well as muscle atrophy [1–3]. Type II fibers require twice the amount of oxygen as Type I fibers to perform the same work [4,5]. Magnetic resonance spectroscopy have shown HF patients have a greater decrease in phosphocreatine (PCr) stores and a ~50% higher ATP consumption [6] primarily due to a decrease in skeletal muscle ‘metabolic’ efficiency [7]. These changes probably represent the ‘metabolic’ inefficiency due to skeletal muscle fiber type changes that occurs in HF, favoring the less aerobically efficient type IIb fibers [7]. This ~50% higher ATP consumption should translate into a HF patient walking at 2 MPH having a similar ATP consumption and oxygen consumption as a normal subject walking at 3 MPH. This ‘metabolic’ efficiency would further compound the reduced peak VO2 in HF. However, the oxygen cost of exercise (oxygen consumption/Watt) has been reported to be lower is severe HF which has been interpreted as an increase in efficiency during cardiopulmonary exercise testing (CPET) [8–10]. The discordant results obtained from MRS (decreased efficiency) and CPET (increased efficiency) in HF patients have not previously been explained.

Physiologists define biomechanical efficiency as the energy output/energy input. Biomechanical efficiency has been measured during steady state (SS) low-level exercise in which the oxygen consumption is assumed to reach a plateau (Fig. 1). Biomechanical efficiency can be estimated with CPET in which the energy output is known (Watts) and the energy input is estimated by the oxygen consumed (1 l of O2 consumed produces ~4700–5000 calories of energy depending on the energy source) [11].


Figure 1
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  		Fig. 1 The O2 deficit method for calculating gross, net and work biomechanical efficiency is illustrated in a–c. The VO2 within the dotted box is summated. The O2 debt method is illustrated in d–e.

 
During ramp exercise, an O2 deficit develops during exercise that is repaid as an O2 debt during the 5–10 min of recovery after exercise [12]. To obtain an accurate measure of biomechanical efficiency, this additional O2 cost of exercise must be measured [13,14]. Several studies have examined the slope of VO2 vs. Watts (O2/Watt) during ramp exercise in normals and obtained a value of ~10–10.5 ml O2/Watt or ~27–29% efficiency [8,10]. HF subjects have generally had a lower slope of the VO2 vs. Watts than normals. However, failure to account for the higher O2 debt in determining the total O2 cost of exercise would make HF subjects appear to be more efficient than the normal subjects during exercise due to a greater O2 debt that must be repaid after exercise [13–16].

Biomechanical efficiency in isolated skeletal muscle is the product of the oxidative phosphorylation ({cong}64%) and the mechanical coupling of the skeletal muscle (conversion of ATP to muscle contraction {cong}41%) resulting in a net biomechanical efficiency of ~27%, similar to the values obtained using CPET using SS exercise [17].

In this study we sought to determine if (1) patients with HF have reduced biomechanical efficiency using low level steady state (SS) and ramp exercise compared with matched normal controls; (2) whether ramp exercise testing that incorporates oxygen consumption measures during recovery from exercise can also be used to measure biomechanical efficiency with equivalent results; and (3) whether measures of biomechanical efficiency would correlate with HF symptoms measured by the MLWF.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 5. Conclusions
 References
 
2.1. Subjects
HF subjects were recruited from the University of Washington End Stage HF clinic. Entry criteria included EF ≤35%, NYHA functional class II–III for ≥3 months, ACE inhibitors for ≥3 months (one subject was on losartan 75 mg/day). Subjects with pacemakers or use of β blockers (except amiodarone) were excluded as most subjects were entering a 3 month trial of clonidine TTS2 patch. Twenty-four HF subjects and 15 age/sex/weight matched normal control subjects were studied. Fifteen HF subjects and all control subjects had both a SS and maximal ramp exercise test. Nine HF had only a maximal ramp test. Symptoms were assessed by the MLWHF [18]. All subjects signed an informed consent form approved by the Human Subjects Committee at the University of Washington. All tests were in the morning after an overnight fast. Subjects took their usual medicines on the day of testing.

2.2. SS Exercise
After rest data, pedaling at 60 rev./min for 2 min was followed by 6 min of exercise at 35 W. The subjects did not pedal during recovery.

2.3. Ramp exercise
Subjects who had a SS exercise test rested for 30 min and then underwent maximal testing. The ramp was a 10 W/min in all HF subjects and 10–20 W/min (average 15 W) in the normal subjects. The protocols were designed to have a similar duration of exercise in both groups. VO2 measurements were continued after the completion of exercise until the respiratory exchange ratio was <1.0 for 30 s to estimate the O2 debt [13].

2.4. SS Gas analysis
Data was obtained with a Medigraphics metabolic cart and a cycle ergometer. Resting VO2 was a two minute average. For the SS test, linear regression was performed using the VO2 from 3 to 6 min of exercise [19]. VO2 during recovery above the resting VO2 was used to determine the O2 debt [12].

2.5. Ramp exercise gas analysis
Calculation of the O2 debt used all VO2 during recovery above the resting VO2 until the RER was <1.0 for 30 s. The slope of the VO2/Watt relationship was calculated using all data points during exercise.

2.6. Measures of biomechanical efficiency
To calculate efficiency the external work performed (Watts) is divided by the energy input (oxygen consumption) using SS VO2 as previously described [11]. The respiratory exchange ratio (RER) at the end of 6 min of exercise was used to estimate the caloric equivalents of VO2 (k) from the equation: k=calories/l of VO2=3840+1180xRER [11]. Subjects who had a RER>1 at the end of exercise were assigned a RER of 1.0. We examined a new method of measuring SS biomechanical efficiency using the sum of the actual VO2 during exercise and during recovery (O2 debt) rather than the estimated O2 deficit. It is calculated by substituting the actual VO2 during exercise (rather than the theoretical SS VO2) and the measured O2 debt (Fig. 1d–f). This method should be applicable to both SS exercise and ramp exercise.


Formula


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O2 debt and O2 deficit are expressed as a % of the total O2 utilized above the resting VO2 during exercise and recovery (Net VO2) as illustrated in Fig. 1b [15]. Statistics are by unpaired t test and linear regression using StatView 5 (Abacus Concepts, Berkeley, CA). Significance was defined as P=0.05.


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 5. Conclusions
 References
 
3.1. Baseline characteristics
The HF subjects and controls were well matched (see Table 1) (all P=ns). All HF subjects were symptomatic with a mean NYHA functional class of 2.7 and a mean MLWHF score of 47.


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  		Table 1 Demographics and medications

 
All HF subjects were on ACE inhibitors (mean 39 mg/day of enalapril or equivalent). Most HF subjects also received diuretics and digoxin. No subjects were on beta blockers as most of these subjects were entering a randomized trial of clonidine TTS2 patch vs. placebo.

3.2. 35 Watts SS exercise
At the end of 6 min of 35 W of SS exercise, the HF subjects had a significant 18–19% higher VO2 (Table 2, Fig. 2) and a higher RER. The O2 deficit and debt were approximately doubled for the HF subjects at this relatively low workload. The gross, net and work VO2/Watt were increased in the HF subjects (Table 2, Fig. 3a). The 18–19% higher SS VO2 translated into significantly decreased gross, net, and work (–16%, –16%, and –36%) biomechanical efficiency by both the O2 deficit method and the O2 debt method (–15, –15 and –35%, 5 of 6 measures, P<0.05, Fig. 3b). There was a strong correlation between the three different measures of biomechanical efficiency using the O2 deficit and the O2 debt method with no mean difference (Fig. 4, r=0.99, standard error of the estimate=1.05 ml O2/Watt).


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  		Table 2 Steady state exercise

 


Figure 2
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  		Fig. 2 (a) The VO2 for the normal and CHF subjects during SS exercise is illustrated. At the end of exercise the VO2 was 144 ml/min higher in the HF subjects. All three estimations of biomechanical efficiency are reduced in the HF subjects. (b) The O2 cost for each Watt of exercise above unloaded pedaling during SS exercise is shown above using the average of mono-exponential fitting of the VO2 data. The normal subjects had an O2 cost of 9.9±0.8 ml/min/W, consistent with previously published data. However, the HF subjects had a 50% increase in the O2 cost (14.8±1.3, P=0.004) in comparison to the normal subject with a prolonged VO2 time constant.

 


Figure 3
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  		Fig. 3a) During 35 W SS exercise, the HF subjects had a 50% increase in the work VO2/Watt (a) and a 35% decrease in work efficiency (b).

 


Figure 4
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  		Fig. 4 The Gross, Net and Work VO2/Watt using the O2 deficit method vs. the new O2 debt method is shown above.

 
The ventilatory threshold from the ramp protocol was 48±11 W in the HF subjects and 92±36 W in the controls. The SS VO2 at 35 W expressed as a % of the peak VO2 was 67±16% in the HF subjects and 32±12% in the controls. Only 1 HF and one control had a ventilatory threshold during the ramp exercise below 35 W. However, due to the circulatory time delay, the SS VO2 exceeded the VO2 at the ventilatory threshold during ramp exercise in 11 HF and one control subject, consistent with exercise above VT as shown in Fig. 5. The work VO2/Watt below the ventilatory threshold in normal subjects was 9.5 ml/min/W. whereas the CHF subjects had an elevated value of 11.5. The work VO2/Watt above the VT was markedly elevated at 16.0 in the heart failure subjects.


Figure 5
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  		Fig. 5 The work VO2/Watt during 35 W steady state exercise vs. the ratio of the steady state VO2 to the VO2 at the ventilatory threshold during ramp exercise (VT) is shown above. The work VO2/Watt in the normal subjects below the ventilatory threshold was 9.5 ml/min. The CHF subjects below the VT had an elevated VO2/Watt of 11.5. The work VO2/Watt above the VT was markedly elevated at 16.0 ml/min.

 
3.3. Ramp exercise
At peak exercise the HF subjects, compared to controls, had a 12% lower peak heart rate, a 46% lower peak VO2 (ml/kg/min), and a 53% lower peak workload (Table 3). All the three measurements of biomechanical efficiency were significantly decreased in the HF subjects during ramp exercise (gross –26%, net –10%, and work –8%, all P<0.05). This was not due to a higher O2 cost during exercise as the slope of the VO2/Watt and the exercise VO2/Watt are similar in the HF subjects and the normal controls. The HF subjects accumulated a greater O2 deficit during exercise (which cannot be measured) resulting in a 20% higher O2 debt. The recovery VO2/Watt was 38% higher in the HF subjects (Fig. 6).


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  		Table 3 Ramp exercise

 


Figure 6
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  		Fig. 6 The VO2 during recovery from exercise has been normalized to match different peak VO2. 100% is the peak VO2 and 0% is the resting VO2 prior to exercise. The HF subjects had a time delay of 16 s before the VO2 started to decrease. The time for the VO2 to decrease to 1/2 of the peak value (T1/2) was 56% greater in the HF subjects. The O2 debt was 20% higher in the HF subjects.

 
Lower ejection fractions correlated with higher O2 debt (r=–0.55, P=0.006). There was an inverse correlation between the O2 debt and the exercise VO2/Watt in all subjects (r=–0.414, P=0.02) and in the HF subjects (r=–0.58, P=0.02). HF subjects with a low exercise VO2/Watt relationship appeared to be more aerobically efficient (lower O2 requirement during exercise for the same workload), but actually had a greater reliance on anaerobic metabolism, reflected by a greater O2 debt and a higher total O2 cost of exercise. The higher the % predicted peak VO2 the lower the O2 debt in all subjects (r=–0.51, P=0.001) and the HF subjects (r=–0.49, P=0.02). The HF subjects with a lower% predicted peak VO2 relied to a greater extent on anaerobic metabolism with a lower exercise VO2/Watt (r=+0.67, P=0.007) and a greater O2 debt and recovery Net VO2/Watt. This reiterates the necessity of measuring both the exercise VO2/Watt and recovery VO2/Watt to determine the total O2 cost during ramp exercise.

We compared biomechanical efficiency during ramp exercise to 35 W SS exercise. There were only modest but significant correlations between gross (r=0.52, P=0.003), net (r=0.36, P=0.05) and work (r=0.42, P=0.02) VO2/Watt.

3.4. HF Symptoms
The MLWHF had a significant positive correlation with weight and NYHA class (Table 4). There were trends for a negative correlation with the 6 min walk distance and mean blood pressure. HF subjects with a higher VO2/Watt slope during exercise had more symptoms. Neither peak VO2 expressed as milliliter per kilogram or as percent of predicted peak VO2 correlated with symptoms.


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  		Table 4 MLWHF correlation with clinical and exercise variables

 
The 35 W SS exercise data had much stronger correlations with HF symptoms than the ramp exercise data. The VO2 during unloaded pedaling, gross efficiency, and the SS VO2 @ 35 W all had significant correlations with the MLWHF score. The more symptomatic HF subjects had a lower gross efficiency during SS exercise (higher VO2 for the 35 W workload) and a higher VO2/Watt slope during ramp exercise (higher VO2 for the same workload).


   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
5. Conclusions
 References
 
This study is the first to report that HF subjects are biomechanically inefficient (a lower energy output for the energy input) during low level SS and maximal ramp exercise as measured by CPET. The biomechanical inefficiency has potential important clinical implications since it occurs in the workload range of activities of daily living (~11 ml O2/kg) and correlates with HF symptoms. For example, a control subject walking at 3 MPH would have a similar oxygen consumption as a HF subject walking at 2 MPH during steady state exercise. Thus, the HF subject not only has a markedly reduced peak VO2 but also can perform less work for the same VO2 during steady state exercise.

Both the O2 debt and the O2 deficit method used to estimate SS biomechanical efficiency provided similar results. In subjects with more severe HF, it is probable that 6 min of exercise is not sufficient to reach a true SS [14]. In these subjects, using the recovery phase data (O2 debt method) may provide a more accurate estimate of biomechanical efficiency than the O2 deficit method. Unfortunately, the ramp exercise efficiency measurements do not have a high correlation with the SS measurements and thus cannot be easily substituted for SS exercise.

4.1. Biomechanical efficiency
Biomechanical efficiency is unrelated to gender, age or physical training and is 27–30% in normals [9,20]. Efficiency is decreased during SS exercise above the VT with a VO2/Watt of ~9.5 below VT and ~11.5 above the VT [21]. Certainly, some of the increase in SS VO2 in the HF subjects was because many were exercising above the VT, even at this low 35 W workload. However, the HF subjects above VT had a VO2/Watt of ~16 vs. an anticipated value of ~11.5 above the VT.

4.2. Previous investigators
Previous investigators have generally reported that CHF patients have a lower VO2 at a given workload suggesting that HF subjects were more efficient than normals [9,10] contrary to the results in this study. Some investigators have reported a higher VO2 in HF subjects (~10%) than controls at the end of 20 [22], 25 and 60 W [23] of SS exercise although the differences were not significant. However, the O2 debt and the recovery VO2/Watt were not measured in most previous studies. The recovery VO2/Watt was modestly increased in our HF subjects, but can double the estimated total O2 cost of exercise, in severe HF subjects [15]. We have previously reported a 14% increase in the work VO2/Watt with ramp exercise in 45 heart failure patients [15], similar to the 9% increase seen in the current study during ramp exercise. Hayashida et al. [16] showed that the recovery time constant had a strong (r=0.88) inverse correlation with the VO2/Watt slope during exercise. We found a similar, although weaker, correlation between the exercise VO2/Watt with the O2 debt in the HF subjects (r=–0.58). The current study suggest that a low exercise VO2/Watt or a low VO2/Watt slope, rather than implying increased efficiency, reflects an excessive reliance on anaerobic metabolism that must be repaid after exercise as an O2 debt.

Larsen et al. reported that exercise training in HF subjects increased the peak workload by 45% with only a 6% increase in peak VO2, suggesting that exercise training in heart failure may improve biomechanical efficiency [24]. HF medications like angiotensin II receptor blockers or ACEIs, which improve skeletal muscle blood flow, increase the exercise VO2/Watt relationship [25], and may decrease O2 debt. Thus, exercise training and possibly HF medications may improve biomechanical efficiency and thus exercise capacity in HF even if the peak VO2 is unchanged.

Wilson et al. found no correlation of symptoms with central hemodynamics during ramp exercise, with VT having a weak correlation (r=0.37) [26]. In the current study, gross efficiency during SS exercise had a good correlation with symptoms supporting the hypothesis that peripheral manifestations of HF are important in the generation of symptoms.

4.3. Skeletal muscle fiber type changes in HF
Skeletal muscle fiber type changes in HF include a decrease in the efficient Type I highly oxidative fibers, oxidative enzymes, and mitochondrial density, and an increase in the inefficient Type IIb glycolytic fibers as well as muscle atrophy [1]. It is quite likely that these skeletal muscle fiber type changes are the primary cause of the biomechanical inefficiency in HF. For example, the O2 consumption in Type II fibers is twice that of Type I fibers performing the same work [4,5,27]. Thus, substitution of a Type II fiber for a Type I fiber, as occurs in HF, would double the amount of oxygen necessary to perform the same work (biomechanical inefficiency). The exact mechanism of the higher efficiency in type I fibers is unknown. However, Type I fibers produce three ATP for each oxygen molecule utilized using the NADH pathway (ATP/O=3) whereas Type IIb produce ~2.4 ATP for each oxygen molecule due to greater utilization of the FAD linked pathway (ATP/O=2).

The reason that HF subjects have a decrease in Type I fibers and an increase Type II fibers are unknown. However, chronic β2 stimulation with clenbuterol will decrease Type I fibers and increases Type IIb fibers, similar to the changes seen in HF [28]. Skeletal muscle fiber type changes can be partially reversed with ACEI, angiotensin receptor blockers, or β blockers [29,30].

4.4. Skeletal muscle fiber type recruitment and blood flow during exercise
Another potential cause of the biomechanical inefficiency in HF would be diversion of skeletal muscle blood flow from Type I to II fibers. During low levels of exercise, Type I fiber utilization predominates and lactate levels are relatively low. At levels of exercise above the VT Type II glycolytic fibers are recruited and lactate production occurs [24]. Type I fibers are more sensitive then Type II to the norepinephrine mediated vasoconstriction [31]. In HF, high sympathetic activity would divert skeletal muscle blood flow from the efficient Type I fibers to inefficient Type IIb fibers.

4.5. Sympathetic activation in HF
Sympathetic activation in HF is an independent predictor of mortality [32]. Acute reduction of sympathetic activity with clonidine in HF subjects increases leg blood flow, decreases lactate levels, and decreases VO2 at matched workloads, all consistent with improved biomechanical efficiency [33]. We have shown that an acute infusion of norepinephrine decreases biomechanical efficiency in HF subjects but not in normal adults [11].

Thus, the elevated sympathetic drive in HF may mediate the following changes observed in HF and are likely the major contributors to the biomechanical inefficiency seen in this study: (1) a decrease in efficient Type I fibers; (2) an increase in inefficient Type IIb fibers; and (3) dysregulation of muscle recruitment/blood flow by reducing exercise blood flow to Type I fibers.


   5. Conclusions
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusions
References
 
During both SS and ramp exercise HF subjects had decreased biomechanical efficiency. The mechanism of the biomechanical inefficiency is uncertain, but is likely mediated by changes in skeletal muscle fiber types and/or utilization during exercise. These changes may be mediated by chronic sympathetic activation. Mechanisms to improve skeletal muscle efficiency via exercise training or medications, may improve symptoms and exercise capacity in HF subjects even if the peak oxygen consumption is unchanged.


   Acknowledgements
 
Supported in part by the American Heart Association, Washington Affiliate, Seattle, WA, VA Puget Sound Health System, and Lilly Research Laboratories. Dr Levy is supported by a NIH K12 AG00503. Potential Conflict of Interest—WCL was a steering committee member of the Eli Lilly trial MOXCON (Moxonidine in Congestive Heart Failure).


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusions
 References
 

  1. Clark A.L., Poole-Wilson P.A., Coats A.J. Exercise limitation in chronic heart failure: central role of the periphery. J Am Coll Cardiol (1996) 28:1092–1102.[Abstract]
  2. Sullivan M.J., Green H.J., Cobb F.R. Skeletal muscle biochemistry and histology in ambulatory patients with long-term heart failure. Circulation (1990) 81:518–527.[Abstract/Free Full Text]
  3. Mancini D.M., Coyle E., Coggan A., et al. Contribution of intrinsic skeletal muscle changes to 31P NMR skeletal muscle metabolic abnormalities in patients with chronic heart failure. Circulation (1989) 80:1338–1346.[Abstract/Free Full Text]
  4. Awan M.Z., Goldspink G. Energy utilization by mammalian fast and slow muscle in doing external work. Biochim Biophys Acta (1970) 216:229–230.[Medline]
  5. Coyle E.F., Sidossis L.S., Horowitz J.F., Beltz J.D. Cycling efficiency is related to the percentage of Type I muscle fibers. Med Sci Sports Exerc (1992) 24:782–788.[Web of Science][Medline]
  6. Massie B.M., Conway M., Rajagopalan B., et al. Skeletal muscle metabolism during exercise under ischemic conditions in congestive heart failure. Evidence for abnormalities unrelated to blood flow. Circulation (1988) 78:320–326.[Abstract/Free Full Text]
  7. Kemp G.J., Thompson C.H., Stratton J.R., et al. Abnormalities in exercising skeletal muscle in congestive heart failure can be explained in terms of decreased mitochondrial ATP synthesis, reduced metabolic efficiency, and increased glycogenolysis. Heart (1996) 76:35–41.[Abstract/Free Full Text]
  8. Hansen J.E., Sue D.Y., Oren A., Wasserman K. Relation of oxygen uptake to work rate in normal men and men with circulatory disorders. Am J Cardiol (1987) 59:669–674.[CrossRef][Web of Science][Medline]
  9. Itoh H., Taniguchi K., Koike A., Doi M. Evaluation of severity of heart failure using ventilatory gas analysis. Circulation (1990) 81:II31, II37.
  10. Solal A.C., Chabernaud J.M., Gourgon R. Comparison of oxygen uptake during bicycle exercise in patients with chronic heart failure and in normal subjects. J Am Coll Cardiol (1990) 16:80–85.[Abstract]
  11. Leclerc K.M., Steele N.P., Levy W.C. Norepinephrine alters exercise oxygen consumption in heart failure patients. Med Sci Sports Exerc (2000) 32:2029–2034.[CrossRef][Web of Science][Medline]
  12. Whipp B.J., Seard C., Wasserman K. Oxygen deficit-oxygen debt relationships and efficiency of anaerobic work. J Appl Physiol (1970) 28:452–456.[Free Full Text]
  13. Cohen Solal A., Laperche T., Morvan D., Geneves M., Caviezel B., Gourgon R. Prolonged kinetics of recovery of oxygen consumption after maximal graded exercise in patients with chronic heart failure. Analysis with gas exchange measurements and NMR spectroscopy. Circulation (1995) 91:2924–2932.[Abstract/Free Full Text]
  14. Cross A.M. Jr, Higginbotham M.B. Oxygen deficit during exercise testing in heart failure. Relation to submaximal exercise tolerance. Chest (1995) 107:904–908.[Abstract/Free Full Text]
  15. Mitchell S.H., Steele N.P., Leclerc K.M., Sullivan M., Levy W.C. Oxygen cost of exercise is increased in heart failure after accounting for recovery costs. Chest (2003) 124:572–579.[Abstract/Free Full Text]
  16. Hayashida W., Kumada T., Kohno F., et al. Post-exercise oxygen uptake kinetics in patients with left ventricular dysfunction. Int J Cardiol (1993) 38:63–72.[CrossRef][Web of Science][Medline]
  17. Pahud P., Ravussin E., Jequier E. Energy expended during oxygen deficit period of submaximal exercise in man. J Appl Physiol (1980) 48:770–775.[Abstract/Free Full Text]
  18. Rector T.S., Johnson G., Dunkman W.B., et al. Evaluation by patients with heart failure of the effects of enalapril compared with hydralazine plus isosorbide dinitrate on quality of life. V-HeFT II. The V-HeFT VA Co-operative Studies Group. Circulation (1993) 87:VI71, VI77.
  19. Whipp B.J., Wasserman K. Oxygen uptake kinetics for various intensities of constant-load work. J Appl Physiol (1972) 33:351–356.[Free Full Text]
  20. Wasserman K., Whipp B.J. Excercise physiology in health and disease. Am Rev Respir Dis (1975) 112:219–249.[Web of Science][Medline]
  21. Barstow T.J., Casaburi R., Wasserman K. O2 uptake kinetics and the O2 deficit as related to exercise intensity and blood lactate. J Appl Physiol (1993) 75:755–762.[Abstract/Free Full Text]
  22. Chelimsky Fallick C., Stevenson L.W., Lem V., Whipp B.J. Excessive oxygen deficit during low-level exercise in heart failure. Am J Cardiol (1995) 76:799–802.[CrossRef][Web of Science][Medline]
  23. Sietsema K.E., Ben Dov I., Zhang Y.Y., Sullivan C., Wasserman K. Dynamics of oxygen uptake for submaximal exercise and recovery in patients with chronic heart failure. Chest (1994) 105:1693–1700.[Abstract/Free Full Text]
  24. Segal S.S., Kurjiaka D.T. Co-ordination of blood flow control in the resistance vasculature of skeletal muscle. Med Sci Sports Exerc (1995) 27:1158–1164.[Web of Science][Medline]
  25. Guazzi M., Palermo P., Pontone G., Susini F., Agostoni P. Synergistic efficacy of enalapril and losartan on exercise performance and oxygen consumption at peak exercise in congestive heart failure. Am J Cardiol (1999) 84:1038–1043.[CrossRef][Web of Science][Medline]
  26. Wilson J.R., Rayos G., Yeoh T.K., Gothard P., Bak K. Dissociation between exertional symptoms and circulatory function in patients with heart failure. Circulation (1995) 92:47–53.[Abstract/Free Full Text]
  27. Goldspink G. Energy Turnover during contraction of different types of muscle. In: Biomechanics VI-A—Amussen E., Jorgensen K., eds. (1978) Baltimore: University Park Press. 27–39.
  28. Criswell D.S., Powers S.K., Herb R.A. Clenbuterol-induced fiber type transition in the soleus of adult rats. Eur J Appl Physiol (1996) 74:391–396.[CrossRef][Web of Science]
  29. Sabbah H.N., Shimoyama H., Sharov V.G., et al. Effects of ACE inhibition and beta-blockade on skeletal muscle fiber types in dogs with moderate heart failure. Am J Physiol (1996) 270:H115–H120.[Web of Science][Medline]
  30. Vescovo G., Serafini F., Dalla Libera L., et al. Skeletal muscle myosin heavy chains in heart failure: correlation between magnitude of the isozyme shift, exercise capacity, and gas exchange measurements. Am Heart J (1998) 135:130–137.[CrossRef][Web of Science][Medline]
  31. Gray S.D. Responsiveness of the terminal vascular bed in fast and slow skeletal muscles to adrenergic stimulation. Angiologica (1971) 8:285–296.[Web of Science][Medline]
  32. Francis G.S., Cohn J.N., Johnson G., Rector T.S., Goldman S., Simon A. Plasma norepinephrine, plasma renin activity, and congestive heart failure. Relations to survival and the effects of therapy in V-HeFT II. The V-HeFT VA Co-operative Studies Group. Circulation (1993) 87:IV40, IV48.
  33. Lang C.C., Rayos G.H., Chomsky D.B., Wood A.J., Wilson J.R. Effect of sympathoinhibition on exercise performance in patients with heart failure. Circulation (1997) 96:238–245.[Abstract/Free Full Text]

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