Discrepancy Between Cardiac and Physical Functional Reserves in Stroke

To develop appropriate therapies to improve everyday function and physical fitness, it is essential to understand the physiological limitations to exercise after stroke. Peak oxygen consumption (Vo₂) is the product of the capacity of the cardiovascular system to supply oxygen (ie, cardiac output [Q_T]) and the capacity of the skeletal muscles to use oxygen (ie, arterial–venous oxygen difference). In stroke survivors, peak oxygen consumption has found to be reduced by approximately 50%.¹

Cerebrovascular disease can alter cardiovascular and autonomic regulation and compromise left ventricular performance.^2,3 To date, limited information is available on measures of cardiac function and performance during exercise in stroke survivors.⁴ Cardiac power output, a direct and integrative measure of overall cardiac function (ie, cardiac pumping capability) that incorporates both pressure and flow domains of the cardiovascular system,⁵ has not been reported in stroke survivors yet. The aims of this study were to define (1) whether maximal aerobic capacity is limited by the cardiovascular system to supply oxygen or by the capacity of the skeletal muscles to use oxygen in these individuals; and (2) cardiac pumping capability in individuals after stroke.

Twenty-eight male stroke survivors were enrolled in 2010 (Table). The study was approved by Durham and Tees Valley Research Ethics Committee and participants provided written informed consent.

Expired gases (Metalyzer 3B; Cortex, Leipzig, Germany) and bioreactance Q_T (NICOM; Cheetah Medical) were collected at rest for 5 minutes followed by a maximal progressive exercise test using an electromagnetically controlled recumbent bicycle ergometer (Corival; Lode, Groningen, The Netherlands). The exercise protocol included a warm-up, cycling at 20 W for 3 minutes, followed by 10-W increments every minute until volitional exhaustion. The standard 12-lead electrocardiogram was continuously monitored and blood pressure recorded. Peak exercise was defined as the absence of a rise in oxygen consumption with further increase in exercise intensity, respiratory exchange ratio >1.05, or inability of the patient to continue. Additionally, Q_T (assessed by CO₂ rebreathing) and Vo₂ data at peak treadmill exercise were obtained from 25 male, age- and body weight-matched healthy participants who took part in a previous study.⁶

Cardiac power output, expressed in Watts, was calculated⁷: cardiac power output=(Q_T×MAP)×K, where MAP is mean arterial pressure in mm Hg and K is the conversion factor (2.22×10⁻³). Peak arterial–venous oxygen difference, expressed in mL O₂/100 mL of blood, was calculated as the ratio between Vo₂ and Q_T.

Independent-sample t tests were used for between-group comparison. The Pearson coefficient of correlation demonstrated relationships between variables. Statistical significance was indicated if P<0.05. All data are presented as means±SD unless otherwise indicated. Post hoc power analysis for the sample size of 28 demonstrated high power of the study (β=0.95).

Stroke participants completed the maximal exercise testing with no adverse events and they achieved 87% of their age-predicted maximal heart rate. The mean peak exercise respiratory exchange ratio and the Borg scale scores were 1.10±0.10 (range, 1.02–1.18) and 19.5±1.2, suggesting that the patients demonstrated a high level of exertion.

Peak Vo₂ was 31% lower in stroke participants (18.4±4.6 versus 26.8±5.5 mL/kg/min, P<0.01; Figure 1A) and was accompanied by a reduction in peak exercise arterial–venous oxygen difference of 26% (9.3±2.5 versus 12.6±1.9 mL O₂/100 mL of blood, P<0.01; Figure 1B). Peak cardiac power output was not significantly different (P=0.49) between control and stroke participants (Figure 1D) as were not Q_T (16.4±3.1 versus 17.1±2.5 L/min, P=0.41; Figure 1C) and mean arterial pressure (127±11 versus 125±14 mm Hg; P=0.97).

Peak Vo₂ highly correlated with Q_T in healthy subjects (r=0.84, P<0.01) and only moderately in stroke participants (r=0.42, P<0.05; Figure 2).

The 2 major findings of the present study suggest that in stroke participants (1) the ability of skeletal muscles to extract oxygen is diminished; and (2) cardiac pumping capability is maintained.

Our finding that peak exercise Vo₂ is severely compromised in stroke survivors is in line with previous reports.^4,8 The underlying physiological limitations of this finding have not been well defined, restricting the ability to target therapies. Some explanations include bedrest-induced deconditioning, concomitant left ventricular dysfunction, the associated severity of neurological involvement, and the increased aerobic requirements of walking.¹ Cardiac function, measured at rest, has been found to be impaired after stroke⁹ and cardiac dysfunction appears to be associated with severity of stroke.³ Resting central hemodynamics, however, do not reflect peak Vo₂ and pumping capability of the heart because they do not account for the reserve of cardiac function.¹⁰ Only 1 previous study has assessed Q_T during exercise in people with stroke.⁴ The authors argued that reduced peak Vo₂ is secondary to a decline in peak and reserve Q_T,⁴ which was assessed in only 4 patients and therefore needs to be considered with caution. The present study, however, suggests that peak cardiac function is not diminished, whereas maximal arterial–venous oxygen difference is reduced by 26% in stroke participants. This suggests that maximal aerobic capacity in people with stroke is likely due to reduced ability of the working muscles to extract oxygen. Only a moderate relationship between Vo₂ and Q_T suggests that factors other than cardiac (ie, muscle) play an important role in the determination of maximal Vo₂ in patients with stroke.

This study has several limitations. Patients with mild stroke were recruited and it remains to be elucidated whether cardiac pumping capability is preserved in those with severe residual disability. In contrast to our stroke participants, healthy control subjects performed a treadmill exercise test with CO₂ rebreathing cardiac output measurement. This may limit findings of the present study bearing in mind that the treadmill may elicit a 10% to 15% higher physiological response than cycling. However, this does not compromise our findings because peak Vo₂ was reduced in patients with stroke by 31%.

In conclusion, the ability of skeletal muscles to extract oxygen is diminished after stroke but cardiac function and pumping capability are maintained. Appropriate therapies targeting muscle oxygen uptake such as exercise rehabilitation may improve exercise capacity after stroke.

We thank our patients and the North East National Institute for Health Research Stroke Research Network.

This work was supported by the Newcastle Medical Research Council Centre for Brain Ageing and Vitality, the UK National Institute for Health Research (NIHR) Biomedical Research Centre for Ageing and Age-Related Disease award to the Newcastle upon Tyne Hospitals National Health Service Foundation Trust, and the Medical Research Council. M.I.T. and G.A.F. are supported by personal awards from the NIHR.