Exercise Training In Chronic Heart Failure Research Articles

Effects of Exercise Training on Cardiac and Skeletal Muscle Functions in Patients with Chronic Heart Failure.

The primary symptom in patients with chronic heart failure (CHF) is exercise intolerance. Previous studies have reported that reduced exercise tolerance in CHF can be explained not only by cardiac output (a central factor) but also by reduced skeletal muscle aerobic capacity (a peripheral factor). Although exercise training in CHF improves exercise tolerance, few studies have evaluated the effects of exercise training on each specific central and peripheral factor in CHF. The aim of this study was to investigate the central and peripheral aerobic functions in CHF and the effects of exercise training in CHF on cardiac output and skeletal muscle deoxygenation during exercise. We assessed peak oxygen uptake (VO2) during cardiopulmonary exercise testing, peak cardiac output (CO) using noninvasive hemodynamic monitoring, and muscle oxygen saturation (SmO2) using near-infrared spectroscopy (NIRS). Patients with CHF were trained for 12weeks and performed ramp cycling exercise until exhaustion before and after the exercise training. Peak VO2, peak CO, and SmO2 changes from rest to peak exercise (ΔSmO2) were significantly lower in CHF than those in healthy subjects. As a result of exercise training, peak oxygen uptake in patients with CHF was improved and positively associated with change in ΔSmO2. In contrast, there was no change in peak cardiac output. The results of this study indicate that both cardiac and skeletal muscle functions in patients with CHF were lower than those in healthy subjects. Further, the results suggest that the improvement of exercise capacity in patients with CHF by exercise training was related to the improved utilization of oxygen (a peripheral factor) in skeletal muscle.

Exercise training in chronic heart failure: improving skeletal muscle O2 transport and utilization.

Chronic heart failure (CHF) impairs critical structural and functional components of the O2 transport pathway resulting in exercise intolerance and, consequently, reduced quality of life. In contrast, exercise training is capable of combating many of the CHF-induced impairments and enhancing the matching between skeletal muscle O2 delivery and utilization (Q̇mO2 and V̇mO2 , respectively). The Q̇mO2 /V̇mO2 ratio determines the microvascular O2 partial pressure (PmvO2 ), which represents the ultimate force driving blood-myocyte O2 flux (see Fig. 1). Improvements in perfusive and diffusive O2 conductances are essential to support faster rates of oxidative phosphorylation (reflected as faster V̇mO2 kinetics during transitions in metabolic demand) and reduce the reliance on anaerobic glycolysis and utilization of finite energy sources (thus lowering the magnitude of the O2 deficit) in trained CHF muscle. These adaptations contribute to attenuated muscle metabolic perturbations (e.g., changes in [PCr], [Cr], [ADP], and pH) and improved physical capacity (i.e., elevated critical power and maximal V̇mO2 ). Preservation of such plasticity in response to exercise training is crucial considering the dominant role of skeletal muscle dysfunction in the pathophysiology and increased morbidity/mortality of the CHF patient. This brief review focuses on the mechanistic bases for improved Q̇mO2 /V̇mO2 matching (and enhanced PmvO2 ) with exercise training in CHF with both preserved and reduced ejection fraction (HFpEF and HFrEF, respectively). Specifically, O2 convection within the skeletal muscle microcirculation, O2 diffusion from the red blood cell to the mitochondria, and muscle metabolic control are particularly susceptive to exercise training adaptations in CHF. Alternatives to traditional whole body endurance exercise training programs such as small muscle mass and inspiratory muscle training, pharmacological treatment (e.g., sildenafil and pentoxifylline), and dietary nitrate supplementation are also presented in light of their therapeutic potential. Adaptations within the skeletal muscle O2 transport and utilization system underlie improvements in physical capacity and quality of life in CHF and thus take center stage in the therapeutic management of these patients.

Effects of Exercise Training on Autonomic Function in Chronic Heart Failure: Systematic Review.

Objectives. Cardiac autonomic imbalance accompanies the progression of chronic heart failure (CHF). It is unclear whether exercise training could modulate autonomic control in CHF. This study aimed to review systematically the effects of exercise training on heart rate recovery (HRR) and heart rate variability (HRV) in patients with CHF. Methods. Literatures were systematically searched in electronic databases and relevant references. Only published randomized controlled trials (RCTs) focusing on exercise training for CHF were eligible for inclusion. Outcome measurements included HRR and HRV parameters. Results. Eight RCTs were eligible for inclusion and provided data on 280 participants (186 men). The participants were 52–70 years of age with New York Heart Association functional class II-III of CHF. Each study examined either aerobic or resistance exercise. Two trials addressed outcome of HRR and six HRV among these studies. Two RCTs showed that moderate aerobic exercise could improve HRR at 2 minutes after exercise training in CHF. Five of six RCTs demonstrated positive effects of exercise training on HRV which revealed the increments in high frequency (HF) and decrements in LF (low frequency)/HF ratio after training. Conclusion. Participation in an exercise training program has positive effects on cardiac autonomic balance in patients with CHF.

Central mechanisms for exercise training-induced reduction in sympatho-excitation in chronic heart failure.

The control of sympathetic outflow in the chronic heart failure (CHF) state is markedly abnormal. Patients with heart failure present with increased plasma norepinephrine and increased sympathetic nerve activity. The mechanism for this sympatho-excitation is multiple and varied. Both depression in negative feedback sensory control mechanisms and augmentation of excitatory reflexes contribute to this sympatho-excitation. These include the arterial baroreflex, cardiac reflexes, arterial chemoreflexes and cardiac sympathetic afferent reflexes. In addition, abnormalities in central signaling in autonomic pathways have been implicated in the sympatho-excitatory process in CHF. These mechanisms include increases in central Angiotensin II and the Type 1 receptor, increased in reactive oxygen stress, upregulation in glutamate signaling and NR1 (N-methyl-D-aspartate subtype 1) receptors and others. Exercise training in the CHF state has been shown to reduce sympathetic outflow and result in increased survival and reduced cardiac events. Exercise training has been shown to reduce central Angiotensin II signaling including the Type 1 receptor and reduce oxidative stress by lowering the expression of many of the subunits of NADPH oxidase. In addition, there are profound effects on the central generation of nitric oxide and nitric oxide synthase in sympatho-regulatory areas of the brain. Recent studies have pointed to the balance between Angiotensin Converting Enzyme (ACE) and ACE2, translating into Angiotensin II and Angiotensin 1-7 as important regulators of sympathetic outflow. These enzymes appear to be normalized following exercise training in CHF. Understanding the precise molecular mechanisms by which exercise training is sympatho-inhibitory will uncover new targets for therapy.

Central command dysfunction in rats with heart failure is mediated by brain oxidative stress and normalized by exercise training.

Sympathoexcitation elicited by central command, a parallel activation of the motor and autonomic neural circuits in the brain, has been shown to become exaggerated in chronic heart failure (CHF). The present study tested the hypotheses that oxidative stress in the medulla in CHF plays a role in exaggerating central command-elicited sympathoexcitation, and that exercise training in CHF suppresses central command-elicited sympathoexcitation through its antioxidant effects in the medulla. In decerebrate rats, central command was activated by electrically stimulating the mesencephalic locomotor region (MLR) after neuromuscular blockade. The MLR stimulation at a current intensity greater than locomotion threshold in rats with CHF after myocardial infarction (MI) evoked larger (P < 0.05) increases in renal sympathetic nerve activity and arterial pressure than in sham-operated healthy rats (Sham) and rats with CHF that had completed longterm (8–12 weeks) exercise training (MI + TR). In the Sham and MI + TR rats, bilateral microinjection of a superoxide dismutase (SOD) mimetic Tempol into the rostral ventrolateral medulla (RVLM) had no effects on MLR stimulation-elicited responses. By contrast, in MI rats, Tempol treatment significantly reduced MLR stimulation-elicited responses. In a subset of MI rats, treatment with Tiron, another SOD mimetic, within the RVLM also reduced responses. Superoxide generation in the RVLM, as evaluated by dihydroethidium staining, was enhanced in MI rats compared with that in Sham and MI + TR rats. Collectively, these results support the study hypotheses. We suggest that oxidative stress in the medulla in CHF mediates central command dysfunction, and that exercise training in CHF is capable of normalizing central command dysfunction through its antioxidant effects in the medulla.

Körperliches Training bei Herzinsuffizienz

In patients with chronic but stable heart failure (HF) exercise training is a recommended and widely accepted adjunct to an evidence-based management involving pharmacological and non-pharmacological therapies. Various pathophysiological mechanisms, such as central hemodynamics, vasculature, ventilation, skeletal muscle function as well as neurohormonal activation and inflammation are responsible for exercise intolerance described in HF patients. There is sufficient and growing evidence that exercise training in HF with reduced (HFrEF) and with preserved ejection fraction (HFpEF) is effective in improving exercise capacity, HF symptoms and quality of life. The positive effects of exercise training in HF are mediated by an improvement of central hemodynamics, endothelial function, inflammatory markers, neurohumoral activation, as well as skeletal muscle structure and function. In contrast to convincing data from a large meta-analysis, the large HF-ACTION study (Heart Failure-A Controlled Trial Investigating Outcomes of exercise TraiNing) only demonstrated a modest improvement of all cause mortality and hospitalizations in HFrEF. Outcome data in HFpEF are lacking. Whether interval training incorporating variable and higher intensities or the addition of resistance exercise to a standard aerobic prescription is superior in improving clinical status of HF patients is currently being examined. Despite increasing validation of the potential of exercise training in chronic HF, challenges remain in the routine therapeutic application, including interdisciplinary management, financing of long-term exercise programs and the need to improve short-term and long-term adherence to exercise training.

RbAp48 and 46 Disassociate GATA4 from p300 and Inhibit Hypertrophy-responsive Gene Transcription in Cardiomyocytes

cardiovasculature of rats with chronic heart failure (CHF). Methods and Results: Male Sprague-Dawley rats underwent left coronary artery ligation (LCAL) to induce CHF, and were randomly assigned to sedentary or treadmill exercise groups at 4 weeks after the LCAL. Exercise training for 4weeks improved cardiac and renal function in CHF rats, as indicated by echocardiographic data, plasma brain natriuretic peptide (BNP) and creatinine clearance. The NOS activity and expression of eNOS, nNOS protein were significantly decreased in the left ventricle, renal cortex, outer medulla and inner medulla of CHF rats, and exercise training markedly increased the NOS activity and expressions in those tissues of CHF rats. Conclusion: Exercise training improves cardiac and renal function in CHF rats through upregulating the NOS activity and eNOS, nNOS expressions in the kidney in addition to in the cardiovasculature. The beneficial effects of exercise training in CHF may be mediated in part by upregulation of the NOS in the kidney.

Trainingstherapie bei kardiologischen Patienten (Sportkardiologie)

Clinical application of physical exercise has developed into an evidence-based therapeutic option for cardiovascular diseases, especially coronary artery disease (CAD) and chronic heart failure (CHF). In CAD regular physical exercise training partially corrects endothelial dysfunction and leads to an economization of left ventricular function. Meta-analyses have shown a reduction of angina pectoris symptoms and a decrease of total and cardiovascular mortality by regular aerobic exercise training. Endurance training for CHF reduces cardiac afterload by correcting peripheral endothelial dysfunction und leads to a better left ventricular function. In addition exercise training reduces the adrenergic tone and the stimulation of the renin-angiotensin-aldosterone system in CHF. Exercise training provides positive effects on the metabolism and function of skeletal muscle (e.g. reduced inflammation and oxidative stress). Supervised regular physical exercise training in CHF is safe and has improved the morbidity in clinical studies. Thus aerobic exercise training is an important component of therapeutic management of stable CAD and CHF with a class 1a recommendation in the current guidelines.

Parallel Changes in Neuronal AT1R and GRK5 Expression Following Exercise Training in Heart Failure

Although exercise training (ExT) is an important therapeutic strategy for improving quality of life in patients with chronic heart failure (CHF), the central mechanisms by which ExT is beneficial are not well understood. The angiotensin II type 1 receptor (AT1R) plays a pivotal role in the development of CHF and is upregulated in a number of tissues owing, in part, to transcription factor nuclear factor kappa B (NF-κB). In addition, AT1R is marked for internalization and recycling via G-protein-coupled receptor kinase (GRK) phosphorylation. Because previous studies have shown that the beneficial effects of ExT in CHF rely on a reduction in angiotensin II, we hypothesized ExT would decrease AT1R, GRK5, and NF-κB protein expression in the paraventricular nucleus and rostral ventrolateral medulla of CHF rats. Following infarction by coronary artery ligation, animals were exercised 4 weeks postsurgery on a treadmill at a final speed of 25 miles per minute for 60 minutes, 5 days per week for 6 weeks. Western blot analysis of paraventricular nucleus and rostral ventrolateral medulla micropunches revealed an upregulation of AT1R, GRK5, and NF-κB in the infarcted group that was reversed by ExT. Furthermore, the relative expression of phosphorylated AT1R and AT1R/GRK5 physical association was increased in the CHF sedentary group and reversed by ExT. Overexpression of GRK5 in cultured CATH.a neurons blunted angiotensin II-mediated upregulation of AT1R and NF-κB; conversely, silencing of GRK5 exacerbated angiotensin II-mediated AT1R and NF-κB upregulation. Taken together, increased GRK5 may regulate AT1R expression in CHF, and ExT mitigates AT1R and its pathway components.

Exercise training prevents skeletal muscle afferent sensitization in rats with chronic heart failure

An exaggerated exercise pressor reflex (EPR) contributes to exercise intolerance and excessive sympathoexcitation in the chronic heart failure (CHF) state, which is prevented by exercise training (ExT) at an early stage in the development of CHF. We hypothesized that ExT has a beneficial effect on the exaggerated EPR by improving the dysfunction of muscle afferents in CHF. We recorded the discharge of mechanically sensitive (group III) and metabolically sensitive (group IV) afferents in response to static contraction, passive stretch, and hindlimb intra-arterial injection of capsaicin in sham+sedentary (Sed), sham+ExT, CHF+Sed, and CHF+ExT rats. Compared with sham+Sed rats, CHF+Sed rats exhibited greater responses of group III afferents to contraction and stretch, whereas the responses of group IV afferents to contraction and capsaicin were blunted. ExT prevented the sensitization of group III responses to contraction or stretch and partially prevented the blunted group IV responses to contraction or capsaicin in CHF rats. Furthermore, we investigated whether purinergic 2X (P2X) and transient receptor potential vanilloid 1 (TRPV1) receptors mediate the altered sensitivity of muscle afferents by ExT in CHF. We found that the upregulated P2X and downregulated TRPV1 receptors in L4/5 dorsal root ganglia of CHF rats were normalized by ExT. Hindlimb intra-arterial infusion of a P2X antagonist attenuated the group III response to contraction or stretch in CHF rats to a greater extent than in sham rats, which was normalized by ExT. These findings suggest that ExT improves the abnormal sensitization of muscle afferents in CHF at least, in part, via restoring the dysfunction of P2X and TRPV1 receptors.

Developing the model of pulmonary rehabilitation for chronic heart failure

Patients with chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) commonly suffer from exertional symptoms of breathlessness and fatigue. The similar systemic manifestations of the conditions, including skeletal muscle dysfunction, are a major contributing factor to the limitation in exercise capacity. A period of exercise training has been shown to improve exercise performance and health-related quality of life for both conditions. Exercise training is a key component of pulmonary rehabilitation (PR) which is now a standard of care for patients with COPD and is symptom based. Although it may be assumed that patients with CHF could be incorporated into cardiac rehabilitation, this is predominantly a secondary prevention programme for patients who are largely asymptomatic. It has been shown that patients with CHF can be successfully trained together with patients with COPD by the same therapists within PR. There are comparable outcome measures that can be used for both COPD and CHF. Many patients with CHF still do not have access to an exercise rehabilitation programme and incorporating them into the PR model of care could be one solution. This article reviews the (1) similar symptoms, mechanisms and consequences between COPD and CHF, (2) rationale and evidence for exercise training in CHF, (3) model of PR, (4) safety of exercise training in CHF, (5) evidence for combined exercise rehabilitation for CHF and COPD, (6) adaptations necessary to include patients with CHF into PR, (7) the chronic care model and (8) summary.

Effect and Safety of Combination of Waon Therapy and Exercise Training in Patients with Chronic Heart Failure

Background: Exercise training or Waon therapy is effective in patients with chronic heart failure (CHF). However, the efficacy of combination of Waon therapy and exercise training in CHF has not been elucidated. Objective: To elucidate the effect and safety of combination of Waon therapy and exercise training in CHF. Method: Twenty eight patients with CHF were enrolled [only Waon therapy group: 17 patients, combined therapy group (Waon therapy and exercise training): 11 patients]. In both groups, Waon therapy was started immediately after admission. In combined therapy group, exercise training was started at the steady state. BNP and exercise capacity evaluated by cardiopulmonary exercise testing were measured in all patients before and after the study. Results: In only Waon therapy group, log BNP tended to decrease by Waon therapy, but exercise capacity did not change. On the other hand, in combined therapy group, log BNP tended to decrease, and peak VO2 and VE/VCO2 slope were significantly improved by combined therapy of Waon therapy and exercise training. In addition, there is no patient with deterioration of symptom or dropout in both groups. Conclusion: Combined therapy of Waon therapy and exercise training in CHF is effective and safety.

Exercise training reverses adiponectin resistance in skeletal muscle of patients with chronic heart failure

BackgroundResistance to the insulin-sensitising adipocytokine, adiponectin, has been described at the level of the skeletal muscle in patients with chronic heart failure (CHF).ObjectiveTo investigate whether exercise training (ET) would improve...

Exercise training improves function of circulating angiogenic cells in patients with chronic heart failure

Alterations in circulating angiogenic cells (CAC) and endothelial progenitor cells (EPC), known to contribute to endothelial repair, could explain the reversal of endothelial function in response to exercise training. Moreover, training-induced vascular remodeling might affect the acute response of EPC and CAC following a single exercise bout. We studied the impact of exercise training on CAC function and numbers of CD34(+)/KDR(+) EPC in patients with chronic heart failure (CHF) and we assessed the effect of acute exercise on CAC and EPC in sedentary and trained patients. Twenty-one sedentary CHF patients underwent 6-month exercise training and were compared to a non-trained control group (n = 17) and 10 healthy age-matched subjects. At baseline and follow-up, flow-mediated dilation was assessed and graded exercise testing (GXT) was performed. Before and immediately after GXT, CAC migratory capacity was assessed in vitro and circulating CD34(+)/KDR(+) EPC were quantified using flow cytometry. At baseline, CAC migration was significantly impaired in sedentary CHF patients but normalized acutely after GXT. Training corrected endothelial dysfunction, which coincided with a 77% increase in CAC migration (P = 0.0001). Moreover, the GXT-induced improvement detected at baseline was no longer observed after training. Numbers of CD34(+)/KDR(+) EPC increased following 6-month exercise training (P = 0.021), but were not affected by GXT, either prior or post-training. In conclusion, the present findings demonstrate for the first time that exercise training in CHF reverses CAC dysfunction and increases numbers of CD34(+)/KDR(+) EPC, which is accompanied by improvement of peripheral endothelial function. The acute exercise-induced changes in CAC function wane with exercise training, suggesting that repetitive exercise bouts progressively lead to functional endothelial repair.

Impact of exercise training on myostatin expression in the myocardium and skeletal muscle in a chronic heart failure model

In late-stage chronic heart failure (CHF), elevated cytokines and cachexia are often observed. Several studies have shown that exercise training exerts beneficial effects on skeletal muscle in this setting. Furthermore, it has been shown that the expression of myostatin, a key regulator of skeletal muscle mass, is increased in a variety of cachectic states. This study aimed to investigate the expression of myostatin in CHF, the influence of exercise training on myostatin levels, and regulation of myostatin by tumour necrosis factor-alpha (TNF-alpha). In an animal model of CHF (LAD-ligation model), protein expression of myostatin was elevated 2.4-fold in the skeletal muscle and more than four-times in the myocardium, compared with control (Co). Exercise training on a treadmill over 4 weeks led to a significant reduction in myostatin protein expression in the skeletal muscle and the myocardium of CHF animals, with values returning to baseline levels. In differentiated C2C12 cells, TNF-alpha induced the expression of myostatin through a p38MAPK-dependent pathway involving nuclear factor kappa-B (NF-kappaB). The increased TNF-alpha mRNA levels in the skeletal muscle of CHF animals correlated significantly with myostatin expression. These alterations in myostatin expression in the skeletal and heart muscle following exercise training could help to explain the beneficial anti-catabolic effects of exercise training in CHF.

Effect of Exercise Training on Autonomic Derangement and Neurohumoral Activation in Chronic Heart Failure

In chronic heart failure (CHF), persistent autonomic derangement and neurohumoral activation cause structural end-organ damage, decrease exercise capacity, and reduce quality of life. Beneficial effects of pharmacotherapy and of exercise training in CHF have been documented at various functional and structural levels. However, pharmacologic treatment can not yet reduce autonomic derangement and neurohumoral activation in CHF to a minimum. Various studies suggest that exercise training is effective in this respect. After reviewing the available evidence we conclude that exercise training increases baroreflex sensitivity and heart rate variability, and reduces sympathetic outflow, plasma levels of catecholamines, angiotensin II, vasopressin, and brain natriuretic peptides at rest. Exercise training has direct and reflex sympathoinhibitory beneficial effects in CHF. The mechanism by which exercise training normalizes autonomic derangement and neurohumoral activation is to elucidate for further development of CHF-related training programs aimed at maximizing efficacy while minimizing workload.

Belastung und Belastbarkeit bei chronischer Herzinsuffizienz

Exercise intolerance in patients with chronic heart failure (CHF) shows no correlation to the degree of left ventricular dysfunction. This surprising finding has directed attention to peripheral changes in CHF. During the last years several different peripheral factors as determinants of exercise intolerance have been defined, i.e. abnormalities in ventilation, reduced endothelium-dependent vasodilatation of peripheral conduit and resistance vessels, and altered skeletal muscle metabolism. Skeletal muscle alterations are characterized by a reduced oxidative capacity, a catabolic state with reduced local IGF-I expression and muscle atrophy, chronic inflammation with local expression of the inducible isoform of nitric oxide synthase (iNOS) and an accelerated rate of programmed cell death (apoptosis). Physical exercise training has evolved as an important therapeutic approach to influence these non-cardiac causes of exercise intolerance. After the first studies documenting the effect of aerobic training on the peripheral causes of exercise intolerance in CHF the question was asked: Should we treat the heart or the periphery to improve exercise intolerance in CHF? Today, we have come closer to the answer: It is now clear that these two systems are not mutually exclusive. Exercise training in CHF has been shown to improve skeletal muscle metabolism and function, to avert muscle catabolism, to reduce neurohumoral overactivation, to reverse endothelial dysfunction and to contribute to the prevention of pathologic left ventricular remodeling. After 6 months of regular exercise training oxidative capacity of the working skeletal muscle increases by approximately 40%. Regular exercise training leads to a significant improvement of endothelium-dependent vasodilatory capacity of peripheral resistance vessels, thereby reducting peripheral resistance in particular during exercise. These beneficial training effects result in a small, but significant improvement of stroke volume and reduction in cardiomegaly. Although several questions regarding patient selection, optimal training protocol and training intensity remain unanswered, exercise training can been seen as an established adjunct to pharmacotherapy in CHF. We may soon reach the conclusion that by treating the periphery with exercise programs we are in fact treating the heart, as well. All exercise-induced adaptations converge to increase peak oxygen uptake by up to 2 ml/kg.min. For patients in stable CHF on optimal cardiac medication a combination of in-hospital and home-based aerobic endurance training in combination with local muscle strength training seems most promising. Although exercise training offers no causal treatment of CHF, it has great potentials as an adjunct therapy directed at improving exercise tolerance and expanding the physical limits of CHF patients.

Exercise training in heart failure

Chronic heart failure (CHF) is a common condition with a poor prognosis. It is associated with poor exercise tolerance and debilitating symptoms. These symptoms appear to be associated with pathophysiological changes that occur systemically in the patient with CHF. Exercise training in carefully selected patients has been shown to be safe and to improve exercise capacity. Many of the pathophysiological abnormalities of CHF are improved by training. Some studies have suggested a possible improvement in morbidity and mortality with training. This review analyzes the controlled clinical trials of exercise training in CHF published to date.

Impact of exercise training on ventricular properties in a canine model of congestive heart failure.

Exercise training improves functional class in patients with chronic heart failure (CHF) via effects on the periphery with no previously documented effect on intrinsic left ventricular (LV) properties. However, because methods used to evaluate in vivo LV function are limited, it is possible that some effects of exercise training on the failing heart have thus far eluded detection. Twelve dogs were instrumented for cardiac pacing and hemodynamic recordings. Hearts were paced rapidly for 4 wk. Six of the dogs received daily treadmill exercise (CHF(EX), 4.4 km/h, 2 h/day) concurrent with rapid pacing, while the other dogs remained sedentary (CHFs). Hemodynamic measurements taken in vivo at the end of 4 wk revealed relative preservation of maximum rate of pressure rise (2,540 +/- 440 vs. 1,720 +/- 300 mmHg/s, P < 0.05) and LV end-diastolic pressure (9 +/- 5 vs. 19 +/- 4 mmHg, P < 0.05) in CHF(EX) compared with CHFs. The hearts were then isolated and cross perfused for in vitro measurement of isovolumic pressure-volume relations; these results were compared with those of six normal dogs (N). Systolic function was similarly depressed in both groups of pacing animals [end-systolic elastance (Ees) values of 1.66 +/- 0.47 in CHFs, 1.77 +/- 0.38 in CHF(EX), and 3.05 +/- 0.81 mmHg/ml in N, with no changes in volume axis interceptors of the end-systolic pressure-volume relationship]. The diastolic myocardial stiffness constant, k, was elevated in CHFs and was normalized by exercise training (32 +/- 3 in CHFs, 21 +/- 3 in CHF(EX), 20 +/- 4 in N). Thus daily exercise training preserved in vivo hemodynamics during 4 wk of rapid cardiac pacing and was accompanied by a significant change in diastolic myocardial stiffness in vitro. These findings suggest that changes in heart function may contribute to the overall beneficial hemodynamic effects of exercise training in CHF by a significant effect on diastolic properties.