Lower limb blood flow, oxygen uptake, and femoral vein 02 content were measured at rest and during maximal bicycle exercise, performed with two legs and one leg, in four normal subjects and in five patients with severe congestive heart failure. While in normal subjects femoral vein blood flow and lower limb vascular conductance were significantly greater during one-leg exercise than during two-leg exercise (6084 + 745 vs 5370 + 803 ml/min, p < .05, and 52.3 8.0 vs 45.1 + 8.2 U x 1o3, p < .05, respectively), in patients with severe congestive heart failure these values were similar during the two forms of exercise (1082 ± 459 vs 1053 ± 479 m/min and 9.6 ± 3.7 vs 9.4 + 3.5 U x 103, respectively). In five additional patients, one-leg maximal bicycle exercise was performed before and after administration of phentolamine into the femoral artery of the active leg. Regional a-adrenergic blockade with phentolamine did not alter maximal oxygen uptake attained during one-leg bicycle exercise (9.8 ± 1.5 vs 10.3 ± 1.9 ml/kg). Lower limb blood flow and femoral vein 02 content attained during maximal one-leg exercise were also similar before and after phentolamine. Thus, in contrast with normal subjects, patients with severe congestive heart failure were unable to further increase limb blood flow during one-leg bicycle exercise. Moreover, local a-adrenergic blockade does not augment blood flow to the active limb during maximal one-leg bicycle exercise. This suggests that the ability of the muscular vasculature to vasodilate during exercise is impaired and may be a limiting factor to maximal exercise capacity in such patients. Circulation 74, No. 2, 245-251, 1986. PATIENTS with congestive heart failure, when compared with normal subjects, have a reduced metabolic arteriolar vasodilative response after restoration of flow to an ischemic limb.1 They also do not have an adequate increase in forearm blood flow in response to rhythmic handgrip exercise of increasing intensity.2 Thus, an inability of the peripheral muscle vasculature to dilate appropriately during dynamic exercise may be a limiting factor to maximal exercise capacity in patients with severe congestive heart failure.In normal subjects, during graded exercise involving 40% or more of the total muscle mass, such as bicycling with two legs, maximal functional capacity, i.e., oxygen uptake, is limited by the ability of the heart to increase its output. In contrast, when graded exercise involves a smaller percentage of the total mus- Received Jan. 9, 1986; revision accepted May 5, 1986. cle mass, such as bicycling with one leg, maximal exercise capacity is attained before maximal cardiac output or V02 max is reached, suggesting that a lack of output by the heart is no longer the limiting factor. Of interest, when the effects of one-leg vs two-leg bicycle exercise are compared in normal subjects, the maximal workload per leg is greater during one-leg exercise than during two-leg exercise, suggesting that peak blood flow to the active limb during two-leg exer...

Systemic oxygen uptake and deep femoral vein oxygen content were determined at peak exercise in 53 patients with chronic heart failure with impaired systolic function (mean left ventricular ejection fraction 0.18; n = 41) or preserved systolic function (mean left ventricular ejection fraction 0.70; n = 12) and in 6 age-matched sedentary normal subjects. At peak exercise, deep femoral vein oxygen content in heart failure patients with impaired systolic function and preserved systolic function were similar, both significantly lower than that of normal subjects (2.5 +/- 0.1, 2.9 +/- 0.2, and 5.0 +/- 0.1 ml/100 ml, respectively; P < 0.05). Deep femoral venous oxygen content was lower in patients with the greater impairment of aerobic capacity, regardless of the underlying systolic function (r = 0.72, P < 0.01). Fractional oxygen extraction in the skeletal muscle at peak exercise is enhanced in patients with chronic heart failure when compared with normal subjects, in proportion to the degree of aerobic impairment.

No abstract

produced substantial symptomatic improvement and increased maximal oxygen uptake at 1 week. Patients were further improved after 4 weeks of WIN 47203, and maximal oxygen uptake increased from 9.0 ± 1.9 to 11.6 ± 2.5 ml/kg/min (p < 0.01 vs control). No overt clinical or laboratory manifestations of toxicity were observed. Withdrawal of WIN 47203 in two patients in whom clinical benefit was not sustained resulted in clinical and hemodynamic deterioration, which was reversed by reinstitution of the drug. Therefore, this study demonstrates the acute and sustained cardiotonic efficacy of WIN 47203 in man. If long-term administration remains well tolerated and without side effects, this drug appears to be very promising for treatment of chronic severe congestive heart failure.PATIENTS with congestive heart failure become increasingly symptomatic as the severity of the disease progresses. In the advanced stage of the disease, patients are severely incapacitated despite optimal therapy with diuretics, digitalis and vasodilators.'-3 Amrinone, a nonglycosidic, nonadrenergic cardiotonic agent, improves ventricular performance and reduces symptoms at rest and during exertion.7 However, amrinone therapy is complicated by various side effects, e.g., thrombocytopenia, gastrointestinal intolerance, hepatotoxicity and fever. congestive heart failure. Methods SubjectsTherapy with WIN 47203 was offered to 11 patients with chronic congestive heart failure who were severely incapacitated despite treatment with diuretics, digitalis and nitrates. Eight of the patients had not benefited from therapy with arteriolar vasodilators, which were therefore discontinued. The severity of the functional impairment was confirmed by a maximal oxygen uptake below 12 ml/kg/min in every patient (average 9.0 ml/kg/min, range 6-11.2 ml/kg/min). The nature, benefits and risks of the study were fully explained and all patients gave informed consent. The protocol was approved by the Committee on Clinical

Cardiopulmonary exercise testing refers to the noninvasive measurement of respiratory gas exchange and air flow, together with heart rate, blood pressure, and the electrocardiogram. These data, obtained during an incremental exercise test, can be used to derive the aerobic capacity or Vo_2max, which is an objective measure of the severity of chronic cardiac and circulatory failure, as well as to predict the maximum cardiac output response to exercise. The additional monitoring of minute ventilation and arterial oxygen saturation can be used to distinguish ventilatory from cardiac or circulatory causes of exertional dyspnea. Finally, this information serves as an objective measure of functional capacity which can be monitored over time to assess the natural history of disease as well as its response to medical therapy.