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SUMMARYThe present study was undertaken to investigate the relationship between the extent of impaired chronotropic response and cardiac output during exercise, and exercise tolerance in patients with chronic heart failure. The subjects consisted of 24 patients (mean 60.1 ± 14.0 years) who had mild chronotropic incompetence. Cardiopulmonary exercise testing was performed in all patients, and heart rate (HR), anaerobic threshold (AT), maximum oxygen uptake (peak VO 2 ), slope of the regression line relating the ventilatory equivalent to carbon dioxide output (VE/VCO 2 slope), and exercise time were measured. Cardiac output (CO) was measured by a thoracic bioimpedance method and cardiac index (CI) was calculated. Plasma norepinephrine (NE) was measured at rest and immediately after the exercise test. The changes in HR, NE, and CI from the resting state to immediately after exercise were calculated as ∆HR, ∆NE, and ∆CI, respectively. The ∆NE was converted to a logarithmic scale and ∆HR/log∆NE was used as a parameter of HR response to sympathetic nerve stimulation. The results were as follows: HR and NE in the resting state had no correlation with AT and with peak VO 2 . ∆HR/log∆NE correlated positively with both AT and peak VO 2 , and negatively with the VE/VCO 2 slope. ∆HR/ log∆NE correlated positively with peak CI, %∆CI, and ∆CI/exercise time. The data suggest that one of the mechanisms of low exercise tolerance in chronic heart failure patients was due to an inadequate increase in CO response against exercise caused by an impaired HR response to increased NE. (Jpn Heart J 2003; 44: 515-525)

In general practice, BNP levels predicted the risk of cardiovascular events other than coronary heart disease events and of death.

SUMMARYThis study was undertaken in acute myocardial infarction (AMI) patients with noninsulin-dependent diabetes mellitus (type 2 DM) to investigate their impaired chronotropic response to exercise. Seventy-one AMI subjects entered the study, 30 with type 2 DM and 41 age-and body mass index-matched non-DM (control) patients. One month after the onset of AMI, these patients underwent cardiopulmonary exercise testing on a treadmill under a ramp protocol. Anaerobic threshold (AT) and peak oxygen uptake (peak VO 2 ) were determined as indicators of exercise capacity. Plasma norepinephrine (NE) concentration was measured in blood samples obtained at 2 time points: during pre-exercise rest and immediately after peak exercise. The change in NE concentration during exercise, as an index of sympathetic nervous activity, was calculated as a percentage: ∆NE = [(NE during exercise)-(resting value)]/(resting value) × 100. The change in heart rate (HR) during exercise was calculated as a simple difference: ∆HR = [(peak HR) -(rest HR)]. Index of chronotropic response to exercise was then quantified as the ∆HR/∆NE during exercise. No significant intergroup differences in ejection fraction at rest or HR at peak exercise were observed. However, VO 2 at AT, peak VO 2 , ∆HR, and ∆HR/∆NE were significantly lower in the type 2 DM group than in the non-DM group. ∆HR correlated with VO 2 at AT (r = 0.49, P < 0.001) and with peak VO 2 (r = 0.53, P < 0.001) in all subjects. Also, ∆HR/∆NE correlated with VO 2 at AT (r = 0.42, P < 0.001) and with peak VO 2 (r = 0.44, P < 0.001) in all subjects. AMI patients with type 2 DM had impaired cardiopulmonary responses to maximal and submaximal exercise testing and impaired chronotropic response to exercise, even though their cardiac function at rest was similar to that of non-DM AMI patients. The data suggest that one mechanism of impaired cardiopulmo-

The aim of this study was to clarify the mechanism of impaired exercise tolerance in chronic sleep-restricted conditions by investigating variables related to heart-rate (HR) response to sympathetic nervous stimulation. Sixteen healthy men (mean age 21.5 years) were tested in a control state, acute sleep-loss state, and chronic sleep-restricted state. Participants underwent cardiopulmonary exercise testing in each state. Their norepinephrine (NE) concentration was measured before and immediately after exercise. Intracellular magnesium (Mg) concentration was measured in a resting state. Exercise duration was shorter and the ratio of HR response to the percentage increase in NE was higher in the chronic sleep-restricted state than in the control state. Intracellular Mg gradually decreased from control to chronic sleep restriction. There was a negative correlation between peak exercise duration and the ratios of HR response to the rate of increase in NE. Intracellular Mg was positively correlated with the ratios of HR response to the increase in NE both in control and in acute sleep loss. The authors conclude that the impaired exercise tolerance in a chronic sleep-restricted state is caused by hypersensitivity of the HR response to sympathetic nervous stimulation, which showed a compensation for decreased intracellular Mg concentration.

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Endothelin-1 (ET-1) is a potent vasoconstrictor peptide produced by vascular endothelial cells. However, the role of ET-1 in exercise-induced physiological responses is still to be investigated. The purpose of the present study was to investigate in healthy volunteers whether the ET-1 plasma concentration in nonworking muscles is changed by exercise and to investigate the physiological role of ET-1 during exercise. Bicycle ergometer cardiopulmonary exercise tests were performed in 36 healthy men (mean age, 22.5 years). Blood samples for measuring ET-1 were drawn from the cubital vein during rest and immediately after the exercise test. The ET-1 change ratio was calculated as ET-1 immediately following exercise/ET-1 during the resting state. Cardiac output (CO) was measured during the exercise test by the impedance method. Arterial venous oxygen difference (AVO2D) when CO reached 10L/min or 15L/min was calculated as AVO2D = VO2/CO. Results were as follows: (1) the ET-1 change ratio correlated inversely with exercise time at the anaerobic threshold (r = -0.37, p = 0.03) and peak exercise time (r = -0.35, p = 0.04); (2) the ET-1 change ratio tended toward an inverse correlation with deltaVO2/deltawork rate (r = -0.29, p = 0.09); (3) the ET-1 change ratio correlated positively with AVO2D when CO reached 10L/min (r = 0.42, p = 0.02) and tended toward a positive correlation with AVO2D when CO reached 15 L/min (r = 0.32, p = 0.08). These results indicate that an increase in ET-1 in nonworking muscles may participate in the exercise-induced redistribution of blood flow and in increasing the blood flow to working muscles.

rain natriuretic peptide (BNP) secretion from the left ventricle increases after the occurrence of a myocardial infarction (MI). Its plasma level may reflect the degree of left ventricular dysfunction given the negative correlation between ejection fraction and BNP secretion and also the positive correlation between left ventricular end diastolic pressure and BNP secretion. [1][2][3] The plasma level of BNP, measured during an exercise test, has been shown to increase in patients with MI, 4 but the influence of exercise training on BNP secretion in patients in the chronic phase of MI is still unknown. A great concern of exercise therapy in the chronic phase of MI is its aggravation of left ventricular function. Jugdutt et al reported that patients with left ventricular asynergy of 18% or more had significant topographic abnormalities, with marked regional shape distortion, and showed topographic deterioration with low-level exercise training in the chronic phase of MI. 5 The purpose of the present study was to investigate the influence of aerobic exercise training on left ventricular function, using the plasma level of BNP as a parameter of left ventricular function in patients in the chronic phase of MI. Methods Study SubjectsEighty-four consecutive patients hospitalized for acute MI (AMI) who completed the routine 4-week cardiac rehabilitation program for AMI during hospitalization were assigned alternately to a training group (42 patients) and a nontraining group (42 patients) (non-blind randomized study). Over the course of the study, 7 patients dropped out of the training group and 7 patients refused repeat exercise testing in the nontraining group. Ultimately, the study consisted of 70 patients with a mean age of 62.0±11.3 years (± SD), 40 diagnosed as having anterior MI and 30 as having inferior MI. They were divided into 4 groups, comprising 2 groups that underwent exercise training (group 1, 20 with anterior MI, and group 2, 15 with inferior MI) and two groups that did not undergo exercise training (group 3, 20 with anterior MI, and group 4, 15 with inferior MI). Patients with severe heart failure showing a functional classification of NYHA III or more, angina pectoris, uncontrolled arrhythmia, uncontrolled diabetes mellitus, or who had had coronary artery bypass surgery were excluded. The diagnosis of AMI was made on the basis of chest pain persisting for at least 30 min, an ST-segment elevation of at least 0.1 mV in at least 2 contiguous leads, and elevation of serum creatine kinase-MB (CK-MB) to more than twice the upper limit of the normal range. (1) 20 patients with an anterior MI and exercise training; (2) 20 patients with an anterior MI and no exercise training; (3) 15 patients with an inferior MI and exercise training; and (4) 15 patients with an inferior MI and no exercise training. The training groups performed aerobic exercise 3 times a week for 2 months. Exercise intensity was defined as a heart rate of anaerobic threshold (AT), derived from the treadmill cardiopulmonary exercise testing at ...