Multiple compensatory mechanisms operate to preserve exercise tolerance in patients with left ventricular failure. Exercise capacity of most patients with chronic heart failure is limited by dyspnea or fatigue, or both. Maximal stress testing with direct assessment of peak O2 uptake is an essential measurement in planning exercise conditioning programs, which are now attracting patients with chronic heart failure. The biochemical and histologic patterns of skeletal muscle changes seen in chronic heart failure patients are consistent with the effects of long-term exercise deconditioning in normal subjects. Recent studies have suggested beneficial effects of training in subjects with moderate or even severe left ventricular dysfunction by showing increased exercise tolerance or peak O2 consumption, anaerobic threshold, peak leg blood flow, peak central arteriovenous oxygen difference and decreased lactate accumulation. However, a number of questions remain unanswered. Exercise training for the treatment of chronic heart failure should be determined on an individual basis and used with caution.

Although the pathophysiology of exercise intolerance in patients with chronic heart failure (CHF) is not fully understood, it appears that the cardiac output response plays an important role in limiting exercise in this disorder. Although previous studies have demonstrated that peak VO2 is not related to left ventricular (LV) ejection fraction, studies have consistently identified peak exercise cardiac output as an important predictor of peak VO2. It is likely that a reduced cardiac output to work rate relationship in CHF causes hypoperfusion of both working skeletal muscle and visceral organs, which leads to early anaerobic metabolism and fatigue. Several factors may influence the cardiac output response in patients with severe systolic LV dysfunction, including heart rate, diastolic LV function, and the mitral regurgitation fraction. Although stroke volume increases through use of the Frank-Starling mechanism in many patients with severe systolic LV dysfunction, some patients with this disorder may not increase stroke volume during exercise due to diastolic LV dysfunction or pericardial constraint. The finding that this latter group has more severe exercise intolerance suggests that diastolic dysfunction may further decrease peak VO2 in this disorder. Variations in the mitral regurgitation fraction also have been found to have an important effect on exercise stroke volume in some patients with CHF. Therefore, the finding that LV ejection fraction at rest or during exercise is not related to peak VO2 in patients with systolic LV dysfunction does not necessarily indicate that central hemodynamics do not play a role in exercise intolerance. Rather, it is likely that variability in the LV ejection fraction with exercise, which does not take variable increases in LV end-diastolic volume or mitral regurgitation into account, plays only a modest role in determining the stroke volume and cardiac output response to exercise in patients with severe systolic dysfunction.

Work by a number of laboratories over the last decade has revealed that skeletal muscle in patients with congestive heart failure (CHF) exhibits altered metabolism, biochemistry, and histology. These alterations appear to be at least in part independent of systemic hemodynamic abnormalities and they lead to abnormal muscle function. Furthermore, muscle dysfunction may play a role in limiting exercise capacity. While blood flow to exercising muscle may be impaired in CHF, both the functional and metabolic changes are, to some degree, independent of the changes in blood flow. Deconditioning and muscle atrophy may be responsible for some of these functional metabolic alterations in muscle, but other factors appear to be operating as well. Finally, the finding that many of the changes in skeletal muscle associated with CHF can be reversed by exercise training suggests that activity should be encouraged in patients with CHF.

The factors that contribute to the symptoms of breathlessness and fatigue, and that limit exercise capacity in patients with chronic heart failure are poorly understood. Recent evidence suggests that the major mechanism is not related to central hemodynamics but to a reduction of skeletal muscle mass and diminished blood flow to skeletal muscle on exercise.

Although several studies have shown that physical training lowers blood pressure values both in normotensives and in hypertensives, the mechanisms accounted for this effect are not clearly elucidated. It has been reported that the decrease in blood pressure and heart rate that accompanies physical training is associated not only with an increase in vagal tone but also with a reduction in plasma norepinephrine levels. Whether this reduction really means a decrease in sympathetic neural discharge is unknown, however. To clarify this issue, we have performed in 7 normotensives direct recording of postganglionic muscle sympathetic nerve activity from the peroneal nerve by microneurography before and after 10 weeks of an endurance training which increased oxygen consumption by 10%. It was shown that the blood pressure lowering effect of the training program was accompanied by a marked reduction in resting sympathetic nerve activity. These data provide the first direct evidence that in man, the blood pressure reduction induced by physical training is mediated by the neural sympathetic mechanisms.

The majority of US patients with clinical evidence of coronary heart disease are elderly. Appropriately prescribed and designed exercise training can improve physical and psychologic functional status and encourage maintenance of an independent life-style. Exercise testing, in addition to helping identify elderly coronary patients at high risk of recurrent events who warrant added therapies, can guide the recommendations for their exercise regimen.

The main hemodynamic abnormality in COPD is raised pulmonary vascular resistance and pulmonary hypertension. This is particularly evident when the vascular bed is stressed as in exercise; the absence of reserve collateral vessels prevents the normal reduction in pulmonary vascular resistance, and hence, pressure increases with flow. The increased afterload reduces right ventricular ejection fraction and stroke volume, but cardiac output is maintained by a relative tachycardia. Although most patients have a ventilatory limitation to exercise, in the later stages of the disease, hemodynamic factors may contribute. Studies of the effects of physical training on pulmonary hemodynamics have been few but none has shown any significant improvement. Occasionally there may be an increase in arteriovenous oxygen difference, accounting for the increase in symptom-limited oxygen consumption seen in some patients. The absence of hemodynamic effects of training may be due to insufficient training intensity. The often impressive increases in work tolerance after training may be due in part to an increase in muscular coordination and technique, as well as to metabolic training effects and psychologic factors.

In assessing the effectiveness of lower-limb and upper-limb nonspecific physical training, we have considered 3 objectives in this study: (1) determination of clinical and functional actual state in patients with chronic airway obstruction (CAO), before and after training; (2) determination of the tests, level of work, and duration of the session training as well as how to increase the training load throughout the training program; and (3) the "particular" upper-limb exercise training in patients with CAO. Many personal factors such as psychologic (personality, degree of patient motivation), alcohol and smoking habits, physical activity, malnutrition, as well as routine tests, at rest and maximal exercise, including the control of metabolic acidosis (lactate) and arterial blood gases (or at least of SaO2), should be considered. Exercise training has the potential to improve exercise tolerance in those who develop metabolic acidosis. The pattern of lactates during exercise represents a good criterion on the selection of patient's training. Two ergospirometric strategies, at high intensity exercise, established from the anaerobic threshold (AT) are described: (a) the above AT 45 min constant exercise (high work rate), at 60% of the difference between AT and maximum VO2 or 80% of the maximal tolerated power (MTP), and (b) the "45 min square-wave endurance exercise test" (SWEET), simulating an interval training session, established from the MTP and the AT. To the SWEET's base (% MTP from AT or aerobic training), a peak of 60 s at MTP (anaerobic training) is added every 5 min. While those 2 protocols, after 6 to 8 weeks of training, lactate and ventilation were lower for identical work rate. In addition, endurance (time in "a" and total physical work in "b") increased up to 60%. Further, maximal exercise ventilation and maximum VO2 increased after SWEET training. Roughly every 7 training sessions, a 10% to 15% reduction in heart rate (HR), during the training program, allows the patient to increase the work rate of the sessions. Evaluation of training the upper limb in patients with CAO requires measurements of MTP and maximum VO2. With the upper limb (wheelchair ergometer), Wmax, maximum VO2, and HR represent 30%, 65%, and 95%, respectively, of the lower limb (ergometer). Further, some expiratory and inspiratory accessory muscles show electromyographic fatigue at the MTP upper-limb level. This may contribute to the rationale for training respiratory muscles.(ABSTRACT TRUNCATED AT 400 WORDS)

Design of exercise programs that are part of pulmonary rehabilitation programs should be founded on an appreciation of the principles of exercise training of healthy subjects. Training produces structural and biochemical changes in the muscles that exercise which increase the ability of the trained muscle to perform aerobic exercise. After training, a given level of heavy exercise engenders lower levels of blood lactate. This is associated with a lower requirement for oxygen uptake, carbon dioxide output, and ventilation. Although the precise mechanism by which training produces changes in the exercising muscles is unknown, characteristics of an effective training program have been defined. Healthy subjects must train for at least 30 min per day, 3 to 5 days per week for 4 to 8 weeks to achieve a physiologic training effect. More controversial is whether a critical training intensity exists. Further, it is not clear which yardstick to apply to quantitate training intensity. Finally, after a training effect has been achieved, regular exercise must be continued or the gains will be lost.

Right ventricular ejection fraction (RVEF), a measure of systolic pump performance of the right ventricle, is frequently depressed at rest or during exercise in patients with chronic obstructive pulmonary disease (COPD). The most common cause of reduced RVEF in COPD is augmentation of right ventricular afterload, namely an increase in pulmonary artery pressure and pulmonary vascular resistance. Therapy with agents that decrease the afterload on the right ventricle have the potential to improve the systolic performance of this chamber. Oxygen, vasodilators such as hydralazine and nifedipine, theophylline, and sympathomimetics all may augment RVEF in part by reducing pulmonary vascular resistance and, in some cases, pulmonary artery pressures in patients with COPD and cor pulmonale. However, only oxygen therapy has been shown to improve survival.

Because of the additive effects of impaired ventilatory muscle function on the one hand and the increased ventilatory load on the other, increasing attention is now directed at therapies to improve ventilatory muscle function. Three main approaches are being used: (1) reduction in load; (2) increase in intrinsic ventilatory muscle function; and (3) reduction in dyspnea perception. While promising results have been achieved, additional investigative work is required to resolve outstanding questions.

The measurement of dyspnea during an exercise task provides an opportunity to simulate daily physical activities that lead to breathing difficulty in patients with lung disease. Although the exact stimulus for the sensation of breathlessness is unknown, it is possible to measure dyspnea during exercise by applying the principles of psychophysics to the analysis of various stimulus-response relationships. It is logical to consider that the exercise task, ie, work or power production, causes both physiologic and perceptual responses. A 0 to 10 category scale with ratio properties developed by Borg and a visual analogue scale are the most commonly used instruments for rating the severity of dyspnea during exercise. The ratings of breathlessness are generally reliable over time and are sensitive to evaluate an acute intervention in patients with stable respiratory disease. The exercise intensity-dyspnea relationship appears to be the most appropriate stimulus-response relationship for quantifying dyspnea during exercise.

Both neural and humoral systems participate in the control of blood flow to various organs. Exercise places the greatest demands on the circulation. At rest, in humans, skeletal muscle receives somewhere between 15% and 20% of cardiac output, while during maximal exercise, this percentage reaches a value of 80% to 90%. The active human muscles have a high-flow capacity that exceeds the capacity of the heart to pump blood. Measurements in single human muscle have indicated that blood flow may be inhomogenous, that is, probably depending on variations of the vasomotor tone of the muscle mediated by humoral and neural factors. Exercise raises cardiac output and coronary blood flow, which rise linearly with increases in heart rate. In normal young men, coronary blood flow averages 280 ml/min/100 g of the left ventricle and reaches as high as 390 ml/min during moderately severe exercise, requiring about 85% of maximal heart rate. In nonexercising organs, the blood flow decreases at about 20% to 40% of the resting values, being the net result of competing vasoconstrictor and vasodilator drives.

We introduce our recent approach to study autonomic nervous system control of heart rate during exercise by means of heart rate variability (HRV) spectral analysis with special reference to its relationship to ventilatory threshold (Tvent). The rationale for the study was that HRV has been shown to reflect (cardiac) parasympathetic and sympathetic nervous system (PNS and SNS, respectively) activity, together with the underlying complexity of cerebral autonomic system in terms of fractal dimension (DF) of HRV time series. The experimental results showed that PNS was markedly reduced below Tvent, that the rate of change in sympathoadrenal activity indicators (plasma norepinephrine and epinephrine concentrations and SNS indicator) was enhanced above Tvent, and that these changes in PNS and SNS indicators were associated with the appearance of the low-dimensional (low DF) dynamics that might reflect less complex autonomic activity. These findings have been considered with respect to implication for clinical cardiology.

The weak relationship between left ventricular function and exercise capacity in heart failure has stimulated interest in neurohumoral mechanisms as possibly contributing to exercise intolerance. Although chronic activation of neuroendocrine systems is characteristic of heart failure and is accompanied by impaired reflex responsiveness to physiologic stimuli, data from clinical trials do not support the hypothesis that the abnormal neurohumoral state is directly related to exercise intolerance. Thus, these systems may play an important role in the natural history of the disease and its high mortality, but they may not be critical to the impaired exercise capacity.

A 19-year-old woman with a childhood history of cavitating left upper lobe pneumonia presented with persistent weight loss, fever, cough and roentgenographic evidence of right upper lobe pneumonia resistant to antibiotic therapy. An open lung biopsy led to the diagnosis of botryomycosis. Neutrophil function studies including flow cytometric evaluation of oxidative burst, bacterial killing and evaluation of neutrophil cytosolic proteins required for oxidase activation were consistent with chronic granulomatous disease. This is the first case report of primary pulmonary botryomycosis as a clinical manifestation of CGD. Other recent cases of immunodeficiency states associated with botryomycosis are reviewed.

Fibrinolytic therapy has an expanding role in the treatment of many thromboembolic disorders. Four fibrinolytic drugs are currently marketed: streptokinase, anisoylated plasminogen-streptokinase activator complex, urokinase, and recombinant human tissue-type plasminogen activator. All 4 of these drugs activate the fibrinolytic system by converting plasminogen to the active enzyme, plasmin. Plasmin present in the confines of a thrombus degrades fibrin and dissolves the thrombus. Plasmin free in the circulation degrades fibrinogen and other coagulation factors. All 4 of the currently available fibrinolytic agents are capable of initiating thrombus dissolution and, at doses currently recommended, cause degradation of fibrinogen and predispose to bleeding complications. Differences in the mechanisms of plasminogen activation among the available agents provide a theoretical basis for postulating the superiority of one agent over another in clinical practice. However, the relative roles of these agents in treatment of thromboembolic disorders depend on the outcome of properly designed and executed clinical trials.

Many clinicians who practiced in the early and mid-1970s remember PE thrombolysis as an extraordinary enterprise that consumed hospital resources and physicians' time around the clock for at least several days. Indeed, more than 1 in every 4 patients suffered a major hemorrhagic complication when a 24-h dosing regimen was utilized. This unfavorable experience soured some physicians, who have been reluctant to reconsider PE thrombolysis in the 1990s. Fortunately, recently completed clinical trials have taught us many ways to make thrombolytic therapy safer, more streamlined, and more economical (Fig 1).