The role of exercise training for patients with heart failure.

Heart failure (HF) is characterized by dyspnea and fatigue leading to exercise intolerance. HF patients have been advised to avoid exercise because of concerns about detrimental cardiac effects. However, in many studies on the effects of exercise training HF patients have demonstrated beneficial outcomes. Furthermore, exercise training has been found to be safe. Recent studies have demonstrated that exercise training might reduce morbidity and mortality. Although these data are promising, confirmation is required from a large clinical trial powered to examine the effects of exercise training on mortality and morbidity. The "Heart Failure - A Controlled Trial Investigating Outcomes of Exercise TraiNing" (HF-ACTION) trial, a large randomized controlled clinical trial, will answer that question. Standardized guidelines for exercise training HF patients have not been established. Exercise training should be individualized according to the results of the exercise test. Ideally, the exercise program should be initiated in the setting of a supervised program followed by a home-based program. Each patient should have a tailored activity program based on a prescription for the frequency of each session, the intensity, duration of each session, and modalities to be used. Exercise training should involve aerobic exercise. Resistance exercise and interval training might be an acceptable method for HF patients; however, more studies are required for these types of exercise programs.

Acute cardiovascular responses to leg-press resistance exercise in heart transplant recipients.

BACKGROUND: Reduced skeletal muscle strength is characteristic of individuals following heart transplantation. Weight lifting exercise has been demonstrated as an effective means by which to increase muscular strength in other cardiac patients but the appropriateness of this form of exercise in heart transplant patients has not been investigated. The purpose of this study was to describe the cardiovascular responses of heart transplant patients to a single, prolonged bout of weight lifting training. METHODS: Twenty-three heart transplant recipients were stratified into early (Early; 3 months; n=6), intermediate (Intermediate; 1-3 years; n=7) and late (Late; 5-14 years; n=10) post transplant groups and studied in four experimental conditions: supine rest, upright rest, single leg-press exercise (28 repetitions over 2 min 20 s at 50% 1 repetition maximum) and recovery. Swan-Ganz catheterization allowed measurement of right heart pressures and cardiac output by thermodilution. Systemic arterial pressures and heart rate were measured continuously using a non-invasive finger cuff. RESULTS: Cardiac output increased by 30, 40 and 54% during exercise in Early, Intermediate and Late, respectively. Heart rate increased by 4.5% in Early compared to 11 and 16% increases in Intermediate and Late. At peak exercise, systolic blood pressures reached average values of 179+/-9, 180+/-14 and 176+/-8 mmHg in Early, Intermediate and Late, respectively. Average mean pulmonary artery pressure did not exceed 30 mmHg and average pulmonary wedge pressure did not exceed 15 mmHg in any group during the exercise. CONCLUSIONS: These observations indicate that a lengthened set of single leg-press exercise at a moderate lifting intensity can be performed within safe and acceptable physiological limits in patients following heart transplantation. To better address the specific rehabilitation needs of heart transplant recipients, future research should focus on developing training programs which include weight lifting exercise.

Acute precipitants of congestive heart failure exacerbations.

BACKGROUND: Few studies have prospectively and systematically explored the factors that acutely precipitate exacerbation of congestive heart failure (CHF) in patients with left ventricular dysfunction. Knowledge of such factors is important in designing measures to prevent deterioration of clinical status. The objective of this study was to prospectively describe the precipitants associated with exacerbation of CHF status in patients enrolled in the Randomized Evaluation of Strategies for Left Ventricular Dysfunction Pilot Study. METHODS: We conducted a 2-stage, multicenter, randomized trial in 768 patients with CHF who had an ejection fraction of less than 40%. Patients were randomly assigned to receive enalapril maleate, candesartan cilexetil, or both for 17 weeks, followed by randomization to receive metoprolol succinate or placebo for 26 weeks. Investigators systematically documented information on clinical presentation, management, and factors associated with the exacerbation for any episode of acute CHF during follow-up. RESULTS: A total of 323 episodes of worsening of CHF occurred in 180 patients during 43 weeks of follow-up; 143 patients required hospitalization, and 5 died. Factors implicated in worsening of CHF status included noncompliance with salt restriction (22%); other noncardiac causes (20%), notably pulmonary infectious processes; study medications (15%); use of antiarrhythmic agents in the past 48 hours (15%); arrhythmias (13%); calcium channel blockers (13%); and inappropriate reductions in CHF therapy (10%). CONCLUSIONS: A variety of factors, many of which are avoidable, are associated with exacerbation of CHF. Attention to these factors and patient education are important in the prevention of CHF deterioration.

Reliability, validity, and responsiveness of the six-minute walk test in patients with heart failure.

BACKGROUND: Our purpose was to evaluate the reliability, validity, and responsiveness of the 6-minute walk test (6MWT) in patients with heart failure (HF) enrolled in the Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) pilot study. METHODS: A total of 768 patients was enrolled in a multicenter randomized clinical trial evaluating the effect of candesartan, enalapril, and metoprolol on left ventricular ejection fraction (LVEF), 6MWT distance, neurohormones, and quality of life. The 6MWT was performed once at screening and twice at baseline, 18 weeks, and 43 weeks by a standardized method. RESULTS: Test-retest reliability at baseline (intraclass correlation coefficient [ICC] = 0.90), 18 weeks (ICC = 0.88), and 43 weeks (ICC = 0.91) was very good. Baseline 6MWT distance was weakly inversely correlated to the quality-of-life cumulative score (r = -0.26, P =.0001) and moderately inversely correlated to the New York Heart Association functional classification (NYHA-FC) (r = -0.43, P =.001). In the RESOLVD study, the 6MWT was not responsive to change when effect sizes and standardized response means were used. Disease-specific quality of life was responsive to change in patients treated with candesartan and enalapril and NYHA-FC was responsive to change in the candesartan and enalapril combination and for enalapril alone with small effect sizes. The 6MWT, NYHA-FC, and quality of life were not responsive to change during the metoprolol or placebo phase. CONCLUSIONS: The 6MWT is highly reproducible in patients with symptoms of HF. It is somewhat correlated to NYHA-FC and quality of life. Overall, quality of life was most responsive to change, whereas 6MWT and NYHA-FC were comparable but less responsive to change in the RESOLVD study.

Changes in exercise capacity and lipids after clinic versus home-based aerobic training in coronary artery bypass graft surgery patients.

PURPOSE: Despite the documented benefits of participating in rehabilitation programs, access to cardiac rehabilitation is limited for a large number of people with coronary artery disease (CAD). There is potential to increase participation in exercise training if home-based exercise were a viable option. METHODS: We conducted a retrospective database review of 1,042 patients who took part in exercise rehabilitation following coronary artery bypass graft surgery (CABGS) between 1992 and 1998. Of these, 713 patients took part in supervised exercise, and 329 were in an unsupervised, home-based group. All exercise protocols were based upon American College of Sports Medicine guidelines, and patients in both groups received exercise prescriptions that were similar in intensity, frequency, and duration. RESULTS: There were no differences between groups at baseline. Following 6 months of exercise training, there were substantial improvements in peak VO2, peak workload, and peak MET levels in both the supervised and unsupervised groups (P < 0.0001). Patients in the supervised group had significant improvements in both LDL and HDL-cholesterol, whereas the home-based group showed improvement in HDL-cholesterol only. When analyzed by sex, men performed better than women for all measures of exercise capacity; however, women in both groups showed approximate 20% improvements (P < 0.05) in exercise capacity as well as improvements in HDL-cholesterol. CONCLUSION: Stable post CABGS patients who receive a detailed exercise prescription to follow at home do as well as those in supervised rehabilitation.

Functional capacity in patients with congestive heart failure.

BACKGROUND: Six-minute walk distance (6MWd) is related to activities of daily living and is also an independent predictor of prognosis in patients with congestive heart failure (CHF). Therefore, it is important to determine factors that contribute to the variability of this test. METHODS AND RESULTS: We assessed the relationship between 6MWd and peak aerobic capacity (VO2) and dynamic muscle strength in 180 patients with CHF (age, 66+/-10 years; 146 men, 34 women; ejection fraction, .29+/-0.08). We also hypothesized that a measure of work performed during the walk test (6MWw) would be a better indicator of exercise capacity than 6MWd. The 6MWd had weak to moderate correlations with dynamic muscle strength (r = 0.33 to 0.41) and peak VO2 (r = 0.48). However, 6MWw was strongly related to dynamic muscle strength (r = 0.63 to 0.70) and peak VO2 (r = 0.77). Multivariate analysis indicated that a model combining dynamic muscle strength and peak VO2 explained 69% of the variance in 6MWw, more than with peak VO2 alone (R2 = 0.59). CONCLUSIONS: Compared with 6MWd, 6MWw correlates significantly better with peak VO2 and dynamic muscle strength, suggesting that 6MWw may be a better reflection of a patient's exercise capacity. Furthermore, these results suggest that an exercise program combining both aerobic and strength training in patients with CHF may improve 6MWw and therefore 6MWd.

Glucose and insulin abnormalities relate to functional capacity in patients with congestive heart failure.

AIMS: In addition to diabetes mellitus, less severe abnormalities of glucose and insulin metabolism may be related to functional status in patients with heart failure. We examined the relationship of hyperglycaemia (> or =6.1 mmol. l(-1)) and hyperinsulinaemia (> or =11.2 mU. l(-1)) to functional status and cardiac function in patients with heart failure. METHODS AND RESULTS: Fasting plasma glucose and insulin levels were obtained in 663 heart failure patients. The average left ventricular ejection fraction was 0.28+/-0.07, 63% were in New York Heart Association Functional Class (NYHA-FC) I/II and 37% were in NYHA-FC III/IV. Twenty seven percent had diabetes mellitus, but an additional 8% had undiagnosed diabetes mellitus (glucose > or =7 mmol. l(-1)) and 9% had glucose levels between 6.1 and 7 mmol. l(-1), so that a total of 43% (287) of patients had elevated glucose levels (> or =6.1 mmol. l(-1)). In general, more diabetic patients had NYHA-FC III/IV symptoms, shorter 6 min walk distances, but similar left ventricular ejection fractions compared to non-diabetic patients. The non-diabetic patients in NYHA-FC III/IV had higher glucose and insulin levels than patients in NYHA-FC I/II (6.3+/-0.2 vs 5.6+/-0.1 mmol. l(-1), P<0.001 and 19.6+/-2.3 vs 10. 2+/-0.6 mU. l(-1), P<0.001). Non-diabetic patients with elevated glucose levels had shorter 6 min walk distances compared to those with normal glucose levels (368.2+/-8 m vs 389.+/-4 m, P=0.02), however, left ventricular ejection fraction was similar. CONCLUSION: Glucose abnormalities are extremely common in heart failure patients (43% of patients). Diabetes mellitus and hyperglycaemia or hyperlinsulinaemia in non-diabetic patients were related to worse symptomatic status but not worsening left ventricular ejection fraction compared to patients with normal glucose and insulin levels.

Validity of predicting mean arterial blood pressure during exercise.

PURPOSE: Mean arterial blood pressure (mean arterial pressure (MAP)) at rest is conventionally estimated as the product of the diastolic pressure plus one-third of the pulse pressure. Since pulse wave forms and the duration of diastole change during exercise, one might question the validity of this prediction equation for the exercise state. Our purpose was to test this by directly measuring blood pressure over a wide range of exercise intensities. METHODS: Pressure was recorded by arterial catheterization in 29 subjects performing progressive exercise and/or constant-load exercise at different intensities. Actual MAP was measured by integrating the area under the pulse curve and compared it with the value which was predicted from systolic and diastolic measures over heart rates ranging from 100 to 200 beats x min(-1). RESULTS: Predicted values were quite close to actual MAP, and the accuracy of the prediction equation changed minimally with increased exercise intensity. CONCLUSION: This method provides a valid estimation of MAP during exercise.

The role of digitalis in the treatment of heart failure.

Over the past 200 years, digoxin has been commonly used to treat patients with congestive heart failure. Clinical trials have demonstrated the benefits of the use of digoxin on exercise tolerance, ejection fraction, and neurohormone production. The Digoxin Investigators Group trial has recently provided strong evidence for the long-term benefits of digoxin on morbidity for patients with heart failure. This article will review the evidence of the benefits of digoxin and its current role in the treatment of patients with congestive heart failure.

Comparison of candesartan, enalapril, and their combination in congestive heart failure: randomized evaluation of strategies for left ventricular dysfunction (RESOLVD) pilot study. The RESOLVD Pilot Study Investigators.

BACKGROUND: We investigated the effects of candesartan (an angiotensin II antagonist) alone, enalapril alone, and their combination on exercise tolerance, ventricular function, quality of life (QOL), neurohormone levels, and tolerability in congestive heart failure (CHF). METHODS AND RESULTS: Seven hundred sixty-eight patients in New York Heart Association functional class (NYHA-FC) II to IV with ejection fraction (EF) <0.40 and a 6-minute walk distance (6MWD) <500 m received either candesartan (4, 8, or 16 mg), candesartan (4 or 8 mg) plus 20 mg of enalapril, or 20 mg of enalapril for 43 weeks. There were no differences among groups with regard to 6MWD, NYHA-FC, or QOL. EF increased (P=NS) more with candesartan-plus-enalapril therapy (0.025+/-0.004) than with candesartan alone (0.015+/-0.004) or enalapril alone(0.015+/-0.005). End-diastolic (EDV) and end-systolic (ESV) volumes increased less with combination therapy (EDV 8+/-4 mL; ESV 1+/-4 mL; P<0.01) than with candesartan alone (EDV 27+/-4 mL; ESV 18+/-3 mL) or enalapril alone (EDV 23+/-7 mL; ESV 14+/-6 mL). Blood pressure decreased with combination therapy (6+/-1/4+/-1 mm Hg) compared with candesartan or enalapril alone (P<0.05). Aldosterone decreased (P<0.05) with combination therapy (23.2+/-5.3 pg/mL) at 17 but not 43 weeks compared with candesartan (0.7+/-7.8 pg/mL) or enalapril (-0.8+/-11. 3 pg/mL). Brain natriuretic peptide decreased with combination therapy (5.8+/-2.7 pmol/L; P<0.01) compared with candesartan (4. 4+/-3.8 pmol/L) and enalapril alone (4.0+/-5.0 pmol/L). CONCLUSIONS: Candesartan alone was as effective, safe, and tolerable as enalapril. The combination of candesartan and enalapril was more beneficial for preventing left ventricular remodeling than either candesartan or enalapril alone.

Community management of heart failure.

OBJECTIVE: To review therapies for treating patients with heart failure (HF). QUALITY OF EVIDENCE: Recommendations in this paper are mainly based on the results of randomized controlled trials. To a lesser extent, data from smaller, more physiologic studies are included. Where appropriate, recommendations are based on the results of a consensus conference. MAIN MESSAGE: Although pharmacologic therapy is the main strategy for treating HF patients, general measures, such as counseling and advice about regular physical activity, are an important component of management. Use of angiotensin-converting enzyme inhibitors (ACE-I) is central to treating HF patients, because these agents decrease mortality and morbidity significantly. Digoxin does not reduce mortality but does reduce morbidity. Angiotensin II antagonists, although found to provide clinical benefit equal to ACE-I, have not been found as yet to have similar effects on mortality and morbidity. Diuretics and nitrates are useful for treating these patients' symptoms. Calcium channel blockers should generally be avoided. CONCLUSIONS: Angiotensin-converting enzyme inhibitors are the therapy of choice for HF patients and should be used in all cases unless there are contraindications or clear evidence of intolerance. All other therapies are used mainly for symptom relief.

Muscle performance and enzymatic adaptations to sprint interval training.

Our purpose was to examine the effects of sprint interval training on muscle glycolytic and oxidative enzyme activity and exercise performance. Twelve healthy men (22 +/- 2 yr of age) underwent intense interval training on a cycle ergometer for 7 wk. Training consisted of 30-s maximum sprint efforts (Wingate protocol) interspersed by 2-4 min of recovery, performed three times per week. The program began with four intervals with 4 min of recovery per session in week 1 and progressed to 10 intervals with 2.5 min of recovery per session by week 7. Peak power output and total work over repeated maximal 30-s efforts and maximal oxygen consumption (VO2 max) were measured before and after the training program. Needle biopsies were taken from vastus lateralis of nine subjects before and after the program and assayed for the maximal activity of hexokinase, total glycogen phosphorylase, phosphofructokinase, lactate dehydrogenase, citrate synthase, succinate dehydrogenase, malate dehydrogenase, and 3-hydroxyacyl-CoA dehydrogenase. The training program resulted in significant increases in peak power output, total work over 30 s, and VO2 max. Maximal enzyme activity of hexokinase, phosphofructokinase, citrate synthase, succinate dehydrogenase, and malate dehydrogenase was also significantly (P < 0.05) higher after training. It was concluded that relatively brief but intense sprint training can result in an increase in both glycolytic and oxidative enzyme activity, maximum short-term power output, and VO2 max.

Comparative effects of losartan and enalapril on exercise capacity and clinical status in patients with heart failure. The Losartan Pilot Exercise Study Investigators.

OBJECTIVES: This study was designed to determine 1) whether 12-week oral administration of losartan, an angiotensin II receptor antagonist, in patients with heart failure is well tolerated; and 2) whether functional capacity and clinical status of patients with heart failure in whom treatment with an angiotensin-converting enzyme (ACE) inhibitor is replaced with losartan for 12 weeks will remain similar to that noted in patients in whom treatment with an ACE inhibitor is continued. BACKGROUND: Losartan is a specific, nonpeptide angiotensin II receptor antagonist. Although specific receptor blockade with losartan has certain theoretic advantages over nonspecific ACE inhibition, definitive demonstration of comparable effects in patients with congestive heart failure is lacking. METHODS: A double-blind, multicenter, randomized, parallel, enalapril-controlled study was conducted in 116 patients with congestive heart failure (New York Heart Association functional classes II to IV) and left ventricular ejection fraction < or = 45% previously treated with stable doses of ACE inhibitors and diuretic agents, with or without concurrent digitalis and other vasodilators. After a baseline exercise period, open-label ACE inhibitors were discontinued, and patients were randomly assigned to 12 weeks of therapy with losartan, 25 mg/day (n = 38); losartan, 50 mg/day (n = 40); or enalapril, 20 mg/day (n = 38). Drug efficacy was evaluated by changes in maximal treadmill exercise time (using a modified Naughton protocol), 6-min walk test, left ventricular ejection fraction and dyspnea-fatigue index. Safety was measured by the incidence of clinical and laboratory adverse experiences. RESULTS: The treadmill exercise time and the 6-min walk test did not change significantly after replacement of ACE inhibitor therapy with losartan. Similarly, a significant change was not observed in either the dyspnea-fatigue index or left ventricular ejection fraction at the end of double-blind period relative to baseline. CONCLUSIONS: Losartan was generally well tolerated and comparable to enalapril in terms of exercise tolerance in this short-term (12-week) study of patients with heart failure. The clinical effects of long-term angiotensin II receptor blockade compared with ACE inhibition remain to be studied.

Sprint training enhances ionic regulation during intense exercise in men.

1. This study investigated the effects of 7 weeks of sprint training on changes in electrolyte concentrations and acid-base status in arterial and femoral venous blood, during and following maximal exercise for 30 s on an isokinetic cycle ergometer. 2. Six healthy males performed maximal exercise, before and after training. Blood samples were drawn simultaneously from brachial arterial and femoral venous catheters, at rest, during the final 10 s of exercise and during 10 min of recovery, and analysed for whole blood and plasma ions and acid-base variables. 3. Maximal exercise performance was enhanced after training, with a 13% increase in total work output and a 14% less decline in power output during maximal cycling. 4. The acute changes in plasma volume, ions and acid-base variables during maximal exercise were similar to previous observations. Sprint training did not influence the decline in plasma volume during or following maximal exercise. After training, maximal exercise was accompanied by lower arterial and femoral venous plasma [K+] and [Na+] across all measurement times (P < 0.05). Arterial plasma lactate concentration ([Lac-]) was greater (P < 0.05), but femoral venous plasma [Lac-] was unchanged by training. 5. Net release into, or uptake of ions from plasma passing through the exercising muscle was assessed by arteriovenous concentration differences, corrected for fluid movements. K+ release into plasma during exercise, and a small net K+ uptake from plasma 1 min post-exercise (P < 0.05), were unchanged by training. A net Na+ loss from plasma during exercise (P < 0.05) tended to be reduced after training (P < 0.06). Release of Lac- into plasma during and after exercise (P < 0.05) was unchanged by training. 6. Arterial and venous plasma strong ion difference ([SID]; [SID] = [Na+] + [K+] - [Lac-] - [Cl-]) were lower after training (mean differences) by 2.7 and 1.8 mmol l-1, respectively (P < 0.05). Arterial and femoral venous CO2 tensions and arterial plasma [HCO3-] were lower after training (mean differences) by 1.7 mmHg, 4.5 mmHg and 1.2 mmol l-1, respectively (P < 0.05), with arterial plasma [H+] being greater after training by 2.2 nmol l-1 (P < 0.05). 7. The acute changes in whole blood volume and ion concentrations during maximal exercise were similar to previous observations: Arterial and femoral whole blood [K+] and [Cl-] were increased, whilst [Na+] was lower, across all observation times after training (P < 0.05). 8. Net uptake or release of ions by exercising muscle was assessed by arteriovenous whole blood concentration differences, corrected for fluid movements. A net K+ uptake by muscle occurred at all times, including exercise, but this was not significantly different after training. An increased net Na+ uptake by muscle occurred during exercise (P < 0.05) with greater Na+ uptake after training (P < 0.05). Net muscle Lac- release and Cl- uptake occurred at all times (P < 0.05) and were unchanged by training. 9. Sprint training improved muscle ion regulation, associated with increased intense exercise performance, at the expense of a greater systemic acidosis. Increased muscle Na+ and K+ uptake by muscle during the final seconds of exercise after training are consistent with a greater activation of the muscle Na(+) - K+ pump, reduced cellular K+ loss and the observed lesser rate of fatigue. The greater plasma acidosis found after sprint training was caused by a lower arterial plasma [SID] due to lower plasma [K+] and [Na+], and higher plasma [Lac-].

Enhanced pulmonary and active skeletal muscle gas exchange during intense exercise after sprint training in men.

1. This study investigated the effects of 7 weeks of sprint training on gas exchange across the lungs and active skeletal muscle during and following maximal cycling exercise in eight healthy males. 2. Pulmonary oxygen uptake (VO2) and carbon dioxide output (VCO2) were measured before and after training during incremental exercise (n = 8) and during and in recovery from a maximal 30 s sprint exercise bout by breath-by-breath analysis (n = 6). To determine gas exchange by the exercising leg muscles, brachial arterial and femoral venous blood O2 and CO2 contents and lactate concentration were measured at rest, during the final 10 s of exercise and during 10 min of recovery. 3. Training increased (P < 0.05) the maximal incremental exercise values of ventilation (VE, by 15.7 +/- 7.1%), VCO2 (by 9.3 +/- 2.1%) and VO2 (by 15.0 +/- 4.2%). Sprint exercise peak power (3.9 +/- 1.0% increase) and cumulative 30 s work (11.7 +/- 2.8% increase) were increased and fatigue index was reduced (by -9.2 +/- 1.5%) after training (P < 0.05). The highest VE, VCO2 and VO2 values attained during sprint exercise were not significantly changed after training, but a significant (P < 0.05) training effect indicated increased VE (by 19.2 +/- 7.9%), VCO2 (by 9.3 +/- 2.1%) and VO2 (by 12.7 +/- 6.5%), primarily reflecting elevated post-exercise values after training. 4. Arterial O2 and CO2 contents were lower after training, by respective mean differences of 3.4 and 21.9 ml l-1 (P < 0.05), whereas the arteriovenous O2 and CO2 content differences and the respiratory exchange ratio across the leg were unchanged by training. 5. Arterial whole blood lactate concentration and the net lactate release by exercising muscle were unchanged by training. 6. The greater peak pulmonary VO2 and VCO2 with sprint exercise, the increased maximal incremental values, unchanged arterial blood lactate concentration and greater sprint performance all point strongly towards enhanced gas exchange across the lungs and in active muscles after sprint training. Enhanced aerobic metabolism after sprint training may contribute to reduced fatigability during maximal exercise, whilst greater pulmonary CO2 output may improve acid-base control after training.

Effect of progressive incremental exercise and beta-adrenergic blockade on erythrocyte ion concentrations.

Ion concentrations in whole blood, plasma, and erythrocytes from arterialized venous blood were examined in eight healthy males performing incremental exercise tests to fatigue on an electrically braked cycle ergometer. Exercise was performed during control and low dose (LD) and high dose (HD) of propranolol (beta-blockade). The LD and HD resulted in a significant decrease in peak heart rate compared with control, while peak oxygen uptake during HD was significantly less than either control or LD. Plasma potassium concentration ([K+]) increased significantly during exercise for control, LD, and HD, while LD and HD plasma [K+] were both significantly greater than control. Erythrocyte [K+] increased significantly for control to 119.2 +/- 1.3 mmol/L, for LD to 116.9 +/- 2.0 mmol/L, and for HD to 117.7 +/- 1.2 mmol/L. Plasma lactate concentration ([Lac-]) increased significantly during exercise for control, LD, and HD. Erythrocyte [Lac-] increased significantly for control to 6.4 +/- 0.8 mmol/L, for LD to 6.4 +/- 0.6 mmol/L, and for HD to 5.0 +/- 0.5 mmol/L, with HD [Lac-] less than either control or LD. beta-Blockade did not significantly alter the percent change in mean corpuscular volume (% delta MCV) during exercise. The results indicate that incremental exercise produces an increase in erythrocyte [Lac-] and [K+]. Although beta-blockade increased plasma [K+] at peak exercise, there was no alteration in erythrocyte [K+] response. The treatment did not impair the ability of the erythrocyte to maintain MCV.