Characteristics of peak aerobic capacity in symptomatic and asymptomatic subjects with left ventricular dysfunction. The Studies of Left Ventricular Dysfunction (SOLVD) Investigators.

Expired gas analysis was used to determine the aerobic exercise performance of subjects with depressed left ventricular (LV) systolic function and congestive heart failure (CHF). To determine whether subjects with no or minimal CHF have better aerobic exercise performance than do those with overt CHF, oxygen consumption (VO2) at anaerobic threshold (AT) and peak exercise was measured in 184 subjects with LV ejection fraction less than or equal to 0.35 who participated in the Studies of Left Ventricular Dysfunction. Subjects were divided into those with overt CHF needing treatment (treatment trial; n = 20) and those who had neither overt CHF nor treatment for CHF (prevention trial; n = 164). Treatment trial subjects had a lower LV ejection fraction (0.25 +/- 0.07) than did prevention trial ones (0.29 +/- 0.05; p = 0.001), but there were no differences in age, gender, body weight, resting heart rate and blood pressure. Treadmill exercise testing was performed after 2 to 3 weeks of placebo (no angiotensin-converting enzyme inhibitor) treatment. Treatment trial subjects exercised for a shorter time (493 +/- 160 seconds) and attained a lower peak VO2 (13 +/- 4 ml/kg/min) and VO2 at AT (11 +/- 4 ml/kg/min) than did prevention trial ones (842 +/- 277 seconds, and 20 +/- 6 and 16 +/- 5 ml/kg/min, respectively). Analysis of covariance showed that the differences in peak VO2 and VO2 at AT were statistically significant between the 2 trials after adjusting for age, gender, LV ejection fraction and New York Heart Association functional class.(ABSTRACT TRUNCATED AT 250 WORDS)     

Controlled trial of physical training in chronic heart failure. Exercise performance, hemodynamics, ventilation, and autonomic function.

BACKGROUND. Many secondary abnormalities in chronic heart failure (CHF) may reflect physical deconditioning. There has been no prospective, controlled study of the effects of physical training on hemodynamics and autonomic function in CHF. METHODS AND RESULTS. In a controlled crossover trial of 8 weeks of exercise training, 17 men with stable moderate to severe CHF (age, 61.8 +/- 1.5 years; left ventricular ejection fraction, 19.6 +/- 2.3%), increased exercise tolerance (13.9 +/- 1.0 to 16.5 +/- 1.0 minutes, p less than 0.001), and peak oxygen uptake (13.2 +/- 0.9 to 15.6 +/- 1.0 ml/kg/min, p less than 0.01) significantly compared with controls. Training increased cardiac output at submaximal (5.9-6.7 l/min, p less than 0.05) and peak exercise (6.3-7.1 l/min, p less than 0.05), with a significant reduction in systemic vascular resistance. Training reduced minute ventilation and the slope relating minute ventilation to carbon dioxide production (-10.5%, p less than 0.05). Sympathovagal balance was altered by physical training when assessed by three methods: 1) RR variability (+19.2%, p less than 0.05); 2) autoregressive power spectral analysis of the resting ECG divided into low-frequency (-21.2%, p less than 0.01) and high-frequency (+51.3%, p less than 0.05) components; and 3) whole-body radiolabeled norepinephrine spillover (-16%, p less than 0.05). These measurements all showed a significant shift away from sympathetic toward enhanced vagal activity after training. CONCLUSIONS. Carefully selected patients with moderate to severe CHF can achieve significant, worthwhile improvements with exercise training. Physical deconditioning may be partly responsible for some of the associated abnormalities and exercise limitation of CHF, including abnormalities in autonomic balance.     

Failure of plasma norepinephrine to consistently reflect sympathetic activity in humans

To determine whether venous plasma norepinephrine concentrations consistently reflect changes in sympathetic nervous activity, the influence of mental arithmetic, static handgrip, and submaximal bicycle exercise on intra-arterial blood pressure, heart rate, and plasma norepinephrine was studied in 51 subjects with untreated essential hypertension (mean age, 46 years; range, 16-69 years). At rest, plasma norepinephrine was unrelated to age or blood pressure. Mental arithmetic increased mean arterial pressure from 108 +/- 18 to 127 +/- 18 mm Hg (mean +/- S.D.; p less than 0.001) and heart rate from 69 +/- 7 to 93 +/- 13 beats/min (p less than 0.001) but not plasma norepinephrine (547 +/- 297 to 518 +/- 250 pg/ml). Isometric exercise raised mean arterial pressure from 115 +/- 18 to 148 +/- 21 mm Hg (p less than 0.001) and heart rate from 76 +/- 9 to 95 +/- 13 beats/min (p less than 0.001) but not plasma norepinephrine (683 +/- 253 to 741 +/- 253 pg/ml). Bicycle exercise increased mean arterial pressure from 114 +/- 20 to 146 +/- 26 mm Hg (p less than 0.001), heart rate from 77 +/- 9 to 128 +/- 19 beats/min (p less than 0.001), and plasma norepinephrine from 645 +/- 228 to 1151 +/- 462 pg/ml (p less than 0.001). Both the maximum mean arterial pressure and the peak heart rate attained during bicycle exercise were related to the exercise plasma norepinephrine level (r = 0.33, p less than 0.02 and r = 0.28, p less than 0.03, respectively). Increases in plasma norepinephrine with exercise were not greater in older or more hypertensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Peak exercise left ventricular performance in normal subjects and in athletes assessed by first-pass radionuclide angiography.

The role of Frank-Starling law of the heart in determining the increase in cardiac output during exercise in humans is still controversial (e.g., the mechanisms responsible for the enhancement of left ventricular [LV] filling during the shortened diastolic interval). Ten weight lifters, 12 swimmers and 12 sedentary subjects who underwent maximal upright bicycle exercise testing were studied. First-pass radionuclide angiography was performed both at rest and at peak exercise using a multicrystal gamma camera. Compared with resting values, heart rate and cardiac index at peak exercise increased by 101 +/- 16 beats/min (p less than 0.001) and 6.7 +/- 2.8 liters/min/m2 (p less than 0.001) in weight lifters, by 96 +/- 9 beats/min (p less than 0.001) and 9.5 +/- 2 liters/min/m2 (p less than 0.001) in swimmers, and by 103 +/- 9 beats/min (p less than 0.001) and 7.3 +/- 1.8 liters/min/m2 (p less than 0.001) in sedentary subjects. Stroke volume increased by 20.5 +/- 9.8 ml/m2 (p less than 0.001) in swimmers only. End-diastolic volume at peak exercise did not change in weight lifters and in swimmers; it decreased by 8.2 +/- 8.6 ml/m2 (p less than 0.01) in sedentary subjects. A significant correlation was found between the decrease in end-systolic volume and the increase in peak rapid filling rate at peak exercise in all 3 groups (r = 0.65, p less than 0.05 in weight lifters; r = 0.59, p less than 0.05 in swimmers; r = 0.67, p less than 0.05 in sedentary subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Characterization of lymphocyte beta-adrenergic receptors at rest and during exercise in ambulatory patients with chronic congestive heart failure

To investigate beta-adrenergic receptor dysfunction in congestive heart failure (CHF), the density of lymphocyte beta receptors and adenylate cyclase activity was measured at rest and at peak exercise in 30 patients with CHF and 7 age-matched control subjects. At rest, patients with CHF had reduced beta-receptor density (normals 33 +/- 2; CHF 21 +/- 2 fmol/mg protein; p less than 0.01) and isoproterenol-stimulated adenylate cyclase activity (normals 50 +/- 9; CHF 28 +/- 4 pmol/mg protein/min; p less than 0.05). Sodium fluoride-stimulated adenylate cyclase activity was also reduced (normals 98 +/- 17; CHF 48 +/- 12 pmol/mg protein/min; p less than 0.01). In the patients with CHF, there was no significant correlation between receptor density and peak exercise VO2, ejection fraction or resting plasma catecholamines. In the normal subjects, maximal exercise increased beta-receptor density by 100% (rest 33 +/- 2; exercise 67 +/- 7 fmol/mg protein) and isoproterenol-stimulated adenylate cyclase activity by 66% (rest 50 +/- 9; exercise 83 +/- 18 pmol/mg protein/min (both p less than 0.01]. In contrast, patients with CHF exhibited only a 58% increase in beta-receptor density (rest 20 +/- 3; exercise 32 +/- 6 fmol/mg protein; p less than 0.01) and no significant change in isoproterenol-stimulated adenylate cyclase activity (rest 27 +/- 5; exercise 24 +/- 5 pmol/mg protein/min).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of metoprolol in chagasic patients with severe congestive heart failure

BACKGROUND: Beta-blockers are the most effective and promising treatment for congestive heart failure secondary to left ventricular dysfunction and sympathetic activation. METHODS: Since chagasic patients with severe congestive heart failure have left ventricular systolic dysfunction and neurohormonal activation, we administered metoprolol to nine chagasic patients who were in severe congestive heart failure. Metoprolol (5 mg p.o. daily) was uptitrated on a weekly basis. RESULTS: Patients were receiving digitalis, diuretics and angiotensin converting enzyme inhibitors and had left ventricular dilatation (6.77+/-0.89 cm), depressed ejection fraction (0.20+/-0.06), low systolic blood pressure (93+/-11 mm Hg), sinus tachycardia (115+/-17 beats/min) and sympathetic activation 400+/-246 pg/ml). One patient was in New York Heart Association Functional class III and eight patients were in functional class IV. At the end of the fifth week of treatment (metoprolol 25 mg), seven patients were in functional class III and two were in functional class II. Heart rate decreased to 85+/-15 beats/min (P<0.05) and the systolic blood pressure increased to 108+/-18 mm Hg (P<0.01). There were no significant changes in left ventricular ejection fraction. By the end of the tenth week of treatment (metoprolol 50 mg), four patients were now in functional class I and five were in functional class II. Left ventricular ejection fraction increased to 0.27+/-0.05 (P<0.01) and the left ventricular systolic diameter decreased from 6.38+/-0.90 at baseline to 5.89+/-0.59 and 5.76+/-0.96 after 25 and 50 mg of metoprolol treatment, respectively (P<0.04). Plasma norepinephrine decreased non-significantly to 288+/-91 pg/ml. CONCLUSION: Beta-blockers improve the clinical status and the left ventricular function of chagasic patients with severe congestive heart failure.     

Dissociation of sympathetic responses to baroreceptor loading and unloading in compensated congestive heart failure secondary to ischemic or nonischemic dilated cardiomyopathy.

This study tested the hypothesis that abnormalities of baroreceptor-mediated suppression of sympathetic activity may persist in chronic congestive heart failure (CHF) despite pharmacologic treatment and clinical stability. Plasma norepinephrine and norepinephrine kinetics (using 3HNE infusions) were measured during head-up and head-down tilt in 8 patients with chronic CHF and 6 normal control subjects. In response to upright tilt, normal subjects increased plasma norepinephrine (270 +/- 45 to 413 +/- 60 pg/ml, p less than 0.001) and norepinephrine spillover (540 +/- 103 to 781 +/- 124 ng/min, p less than 0.001). Patients also increased plasma norepinephrine (436 +/- 105 to 600 +/- 112 pg/ml, p less than 0.05) and norepinephrine spillover (802 +/- 180 to 1,037 +/- 370 ng/min). During head-down tilt, plasma norepinephrine decreased in normal subjects (from 413 +/- 60 to 256 +/- 26 pg/ml, p less than 0.001). The decrease was due entirely to a decrease in norepinephrine spillover (781 +/- 124 to 466 +/- 40 ng/min, p less than 0.001). In contrast, there was no significant change in norepinephrine spillover (1,037 +/- 370 to 949 +/- 338 ng/min) during head-down tilt in patients with CHF. These data suggest that suppression of sympathetic activity during baroreceptor loading may be defective in CHF despite relative preservation or correction of the response to baroreceptor unloading.     

Elevation of plasma neuropeptide Y levels in congestive heart failure

PURPOSE: Our objectives were to assess whether plasma neuropeptide Y (NPY) levels are elevated in patients with congestive heart failure (CHF) and whether or not NPY levels can serve as a reliable indicator of sympathetic activity in CHF. PATIENTS AND METHODS: Plasma levels of the sympathetic neurotransmitters norepinephrine and epinephrine and of the sympathetic co-transmitter NPY were measured in 17 patients with CHF and 14 healthy control subjects at rest and after maximal exercise. RESULTS: Under resting conditions, plasma NPY and norepinephrine levels were elevated in patients with CHF compared with control subjects (551 +/- 48 pg/ml versus 311 +/- 22 pg/ml, p less than or equal to 0.001 for NPY, and 306 +/- 73 pg/ml versus 124 +/- 22 pg/ml, p less than or equal to 0.02 for norepinephrine). Plasma NPY correlated better with plasma norepinephrine than with epinephrine, indicating its origin from sympathetic nerve terminals. Acute stimulation of sympathetic activity by dynamic exercise increased plasma norepinephrine levels in control subjects and patients with CHF, but did not significantly alter the mean plasma NPY value in the latter group. CONCLUSION: NPY may play a role in the pathophysiology of CHF.     

Effect of intravenous metoprolol on left ventricular performance in Q-wave acute myocardial infarction

To determine the effects of intravenous metoprolol on left ventricular (LV) function in acute myocardial infarction (AMI), 16 patients were studied within 48 hours of Q-wave AMI (mean ejection fraction 47 +/- 6%, mean pulmonary artery wedge pressure 22 +/- 6 mm Hg) with high fidelity pressure and biplane cineventriculography before and after intravenous metoprolol (dose 12 +/- 4 mg). Heart rate decreased from 90 +/- 13 to 74 +/- 11 beats/min (p less than 0.001), pulmonary arterial wedge pressure and LV end-diastolic pressure were unchanged (22 +/- 6 to 21 +/- 6 and 27 +/- 8 to 26 +/- 8 mm Hg, respectively), despite impaired LV relaxation (P = Poe-t/T) after intravenous metoprolol (T from 59 +/- 13 to 72 +/- 12 ms, p less than 0.001). Peak systolic circumferential LV wall stress decreased after beta-adrenergic blockade (330 +/- 93 to 268 +/- 89 g/cm2, p less than 0.05) and LV contractility decreased (dP/dtmax from 1,480 +/- 450 to 1,061 +/- 340 mm Hg/s, p less than 0.001). The ejection fraction decreased (48 +/- 7 to 43 +/- 7%, p less than 0.05) due to an increase in LV end-systolic volume (85 +/- 19 to 93 +/- 19 ml, p less than 0.05) since LV end-diastolic volume was unchanged (161 +/- 30 to 163 +/- 30 ml, difference not significant). In patients with Q-wave AMI, intravenous metoprolol reduces the major determinants of myocardial oxygen demand including heart rate, contractility and peak systolic wall stress. Further, despite decreased heart rate, (+)dP/dtmax, ejection fraction, isovolumic relaxation, LV end-diastolic pressure and end-diastolic volume remain unchanged.     

Acute inotropic stimulation with dopamine in severe congestive heart failure: beneficial hemodynamic effect at rest but not during maximal exercise

Hemodynamic and metabolic effects of dopamine were studied at rest and during maximal exercise in 13 patients with severe chronic congestive heart failure (CHF). During exercise before the administration of dopamine, the stroke volume index increased from 17.1 +/- 5.2 ml/m2 at rest to 28.1 +/- 10.9 ml/m2 (p less than 0.001) at exhaustion, while pulmonary capillary wedge (PCW) pressure increased from 22.7 +/- 12.7 to 43.9 +/- 11.9 mm Hg (p less than 0.001). The arteriovenous oxygen difference increased from 8.9 +/- 2.3 ml/100 ml to 12.4 +/- 2.0 ml/100 ml (p less than 0.001) and oxygen uptake increased from 3.5 +/- 0.6 0.6 to 11.9 +/- 2.5 ml/kg/min (p less than 0.001). At rest, dopamine increased the stroke volume index to 23.3 +/- 8.1 ml/m2 (p less than 0.001) and reduced the PCW pressure to 20.5 +/- 1.1 mm Hg (p less than 0.05). However, during maximal exercise, the stroke volume index and PCW pressure were not changed by dopamine: 28.1 +/- 10.9 versus 28.6 +/- 10.2 ml/m2 (difference not significant [NS]) and 43.9 +/- 11.9 versus 42.5 +/- 11.2 mm Hg (NS), respectively. In contrast, the maximal heart rate achieved during exercise was significantly higher with dopamine, 140.3 +/- 29.3 versus 136.0 +/- 29.7 beats/min (p less than 0.05), which contributed to a slight augmentation in the maximal cardiac index, 3.82 +/- 1.13 versus 3.64 +/- 1.17 liters/min/m2 (p less than 0.05). Nonetheless, neither peak arteriovenous oxygen difference nor maximal oxygen uptake were significantly changed by dopamine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immediate effects of milrinone on metabolic and sympathetic responses to exercise in severe congestive heart failure

A randomized, double-blind, placebo-controlled protocol was used to determine whether milrinone exerts an immediate effect on exercise performance in patients with severe congestive heart failure. In each of 14 patients with New York Heart Association class III or IV congestive heart failure, intravenous milrinone (mean 57 +/- 5 micrograms/kg) and placebo were randomly administered just before maximal progressive upright cycle ergometry. The duration of exercise was significantly longer with milrinone than with placebo treatment (placebo 11.0 +/- 0.6 minutes, milrinone 12.5 +/- 0.9 minutes, p = 0.01). Compared with placebo, milrinone caused a higher peak oxygen uptake (placebo 10.8 +/- 0.6 ml/kg/min, milrinone 12.4 +/- 0.7 ml/kg/min, p = 0.001) and oxygen uptake at the anaerobic threshold (placebo 7.8 +/- 0.4 ml/kg/min, milrinone 9.2 +/- 0.4 ml/kg/min, p = 0.001). At peak exercise intensity, systolic blood pressure (placebo 119 +/- 5 mm Hg, milrinone 131 +/- 5 mm Hg, p = 0.001) and heart rate (placebo 114 +/- 5 beats/min, milrinone 126 +/- 6 beats/min, p = 0.001) were both increased with milrinone. Likewise, at matched submaximal exercise intensities, heart rate (placebo 111 +/- 19 beats/min, milrinone 117 +/- 20 beats/min, p less than 0.05) and systolic blood pressure (placebo 116 +/- 19 mm Hg, milrinone 121 +/- 19 mm Hg, p = 0.04) were higher with milrinone; plasma norepinephrine (placebo 1,692 +/- 208 ng/liter, milrinone 1,320 +/- 216 ng/liter, p = 0.05) and blood lactate concentrations (placebo 2.2 +/- 0.2 mM, milrinone 1.9 +/- 0.2 mM, p less than 0.05) were lower.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sympathetic responses of patients with congestive heart failure to cold pressor stimulus

Studies in patients with congestive heart failure (CHF) demonstrate blunting of sympathoexcitatory responses to baroreflex perturbation. Whereas experimental and limited clinical evidence suggests impairment of baroreflex mechanisms as the etiology of these attenuated responses, an alternative mechanism would be an inability of patients with CHF to increase sympathetic neural outflow above markedly elevated baseline levels. Hemodynamic and sympathetic neural responses (peroneal microneurography) were therefore compared of normal subjects (n = 10) and patients with CHF (n = 10) during the non-baroreflex sympathoexcitatory stimulus of the cold pressor test. The cold pressor stimulus produced increases in arterial pressure and heart rate in both groups. During hand immersion in ice water, normal subjects demonstrated significant increases in muscle sympathetic nerve activity expressed as burst frequency (20 +/- 2 to 28 +/- 3 bursts/min, p less than 0.01), total integrated nerve activity (224 +/- 41 to 342 +/- 62 U/min, p less than 0.05), and total activity corrected for accompanying changes in heart rate (375 +/- 81 to 538 +/- 118 U/100 heart beats, p less than 0.05). Similarly, despite elevated control levels of sympathetic activity, patients with CHF also demonstrated significant sympathoexcitatory responses to the cold pressor stimulus, with increases in muscle sympathetic nerve burst frequency (60 +/- 7 to 67 +/- 7 bursts/min, p less than 0.01) total integrated nerve activity (818 +/- 159 to 1,015 +/- 191 U, p less than 0.001), and total activity corrected for accompanying changes in heart rate (1,008 +/- 178 to 1,173 +/- 201 U/100 heart beats, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of aerobic training on exercise tolerance and echocardiographic dimensions in untrained postmenopausal women

The cardiovascular effects of physical training were evaluated in a controlled trial involving 32 healthy, untrained, postmenopausal women. The subjects were randomly assigned to an aerobic exercise training program or a control group. The exercise group participated in at least three 40-minute supervised sessions per week for 8 months. Twenty-five subjects completed the study: eight in the control group and 17 in the training group. The training group had a significant increase over the training period in maximal oxygen consumption (27.3 +/- 4.6 ml/kg/min vs 30.8 +/- 5.4 ml/kg/min, p less than 0.05) and maximal treadmill exercise duration (9.8 +/- 2.6 minutes vs 11.3 +/- 2.2 minutes; p less than 0.05). The control group had no significant change in maximal treadmill exercise duration (9.0 +/- 1.2 minutes vs 9.2 +/- 1.4 minutes) but had a slight increase in maximal oxygen consumption (23.7 +/- 3.4 ml/kg/min vs 24.4 +/- 4.1 ml/kg/min, p less than 0.05). The training group had significant increases in M-mode echocardiographic left ventricular end-diastolic dimension (4.6 +/- 0.6 cm vs 4.8 +/- 0.4 cm, p less than 0.05) and calculated left ventricular ejection fraction (0.66 +/- 0.14 vs 0.74 +/- 0.12, p less than 0.05). M-mode echocardiograms demonstrated no significant change in left ventricular dimensions or wall thickness in the control group. In this group of untrained postmenopausal women, a training effect was associated with enhanced resting left ventricular ejection fraction and increased resting left ventricular end-diastolic dimension.     

Left ventricular systolic response to exercise in patients with systemic hypertension without left ventricular hypertrophy

Supine exercise radionuclide angiography was performed in 367 men to assess left ventricular (LV) systolic response to exercise; 58 had systemic hypertension without LV hypertrophy on a resting electrocardiogram and 309 were normotensive. All patients met the following criteria defining a low pretest likelihood of coronary artery disease: age less than 50 years; normal electrocardiographic response to exercise; absence of typical or atypical chest pain; and exercise heart rate greater than 120 beats/min. Patients taking beta-receptor blockers were excluded. There were no significant differences between hypertensive and normotensive groups in peak exercise heart rate, workload or exercise duration. However, hypertensive patients had significantly higher peak exercise systolic blood pressures and peak exercise rate-pressure products. There were no differences between patients with and without hypertension in resting ejection fraction, peak exercise ejection fraction (hypertensive patients 0.71 +/- 0.01, normotensive patients 0.70 +/- 0.05) or change in ejection fraction at peak exercise (hypertensive patients 0.07 +/- 0.01, normotensive patients 0.07 +/- 0.04). Diastolic and systolic ventricular volumes tended to be smaller in the hypertensive patients, but the difference was not statistically significant. The change in systolic volume with exercise was similar in the 2 groups (hypertensive -10 +/- 3 ml/m2, normotensive -10 +/- 1 ml/m2). In the absence of electrocardiographic evidence of LV hypertrophy, systemic hypertension does not influence LV systolic response to exercise.     

Association of decreased myocardial beta-receptors and chronotropic response to isoproterenol and exercise in pigs following chronic dynamic exercise

The effects of chronic dynamic exercise on myocardial beta-adrenergic and muscarinic cholinergic receptors and chronotropic sensitivity to isoproterenol were studied in 5 Yucatan miniswine. Right atrial and left ventricular biopsies, heart rate responses to isoproterenol, and maximal exercise treadmill testing were obtained before and after 10-19 weeks of treadmill running. Radioligand studies using 125I-iodocyanopindolol (ICYP) and 3H-quinuclidinyl benzilate (QNB) were used to determine the number of beta-adrenergic and muscarinic cholinergic receptors. Maximal oxygen consumption increased from 52 +/- 5 to 65 +/- 7 ml/kg/min (mean +/- SD; p less than 0.02), maximal workload from 530 +/- 111 to 1,074 +/- 179 KPM/min (p less than 0.01), resting heart rate decreased from 91 +/- 13 to 62 +/- 4 beats/min (p less than 0.01), heart rate at 75% of pretraining maximal workload decreased from 253 +/- 15 to 196 +/- 12 beats/min (p less than 0.01), and maximal exercise heart rate decreased from 273 +/- 6 to 254 +/- 9 beats/min (p less than 0.01). Decreased heart rate responsiveness to adrenergic stimulation was observed following chronic exercise. Maximal isoproterenol-stimulated heart rate decreased from 225 +/- 13 to 185 +/- 28 beats/min (p less than 0.05) and the slope of the isoproterenol dose-response relation decreased from 63 +/- 16 to 40 +/- 16 (p less than 0.05). Radioligand studies revealed a decrease in beta-receptor number in the right atrium following chronic exercise (61 +/- 9 vs. 34 +/- 8 fmol/mg; p less than 0.02), but receptor number in membranes from the left ventricle did not change (60 +/- 9 vs. 62 +/- 4 fmol/mg).(ABSTRACT TRUNCATED AT 250 WORDS)     

The acute response of plasma norepinephrine, renin activity, and arginine vasopressin to short-term nitroprusside and nitroprusside withdrawal in patients with congestive heart failure

Activation of the sympathetic nervous system, manifested by an increase in heart rate and circulating plasma norepinephrine, can occur in normal subjects when they are given vasodilators. The extent to which this activation occurs in patients with congestive heart failure (CHF) and whether this activation could account for the hemodynamic rebound sometimes observed following abrupt withdrawal of nitroprusside in such patients are unclear. We prospectively and retrospectively studied the effects of nitroprusside on plasma norepinephrine in 38 patients with CHF to determine if acute vasodilator therapy activates this vasoconstrictor system during or following such treatment. Thirty-six of these patients also had plasma renin activity (PRA) measured and plasma arginine vasopressin was measured in 12 patients. Baseline supine plasma norepinephrine (714 +/- 72 pg/ml, +/- SEM), PRA (15 +/- 2 ng/ml/hr), and arginine vasopressin (10 +/- 1 pg/ml) were increased at least twofold in the CHF patients. Nitroprusside (96 +/- 11 micrograms/min) was infused for 63 +/- 5 minutes after achieving an optimal hemodynamic response: cardiac index increased (2.01 +/- 0.08 to 2.67 +/- 0.1 L/min/m2, p less than 0.001), pulmonary artery wedge pressure decreased (25 +/- 1 to 16 +/- 1 mm Hg, p less than 0.001), mean arterial pressure decreased (83 +/- 1 to 72 +/- 1 mm Hg, p less than 0.001), and heart rate was unchanged. Plasma norepinephrine (632 +/- 43 pg/ml), PRA (18 +/- 3 ng/ml/hr), and arginine vasopressin (11 +/- 1 pg/ml) did not change significantly for the group during peak effect of the vasodilator.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of orthotopic heart transplantation on sympathetic control mechanisms in congestive heart failure

Abnormal sympathetic nervous system activity in severe congestive heart failure (CHF) was studied in 14 patients before and 3 to 6 months after orthotopic heart transplantation. Before transplantation plasma norepinephrine (NE) levels at rest were elevated (909 +/- 429 pg/ml, p less than 0.01 compared with normal, 185 +/- 60 pg/ml). No reflex activation of the sympathetic nervous system was seen with infusion of sodium nitroprusside despite a significant decrease in arterial pressure. The response to orthostatic tilt also was blunted in the patients before transplantation. Exercise capacity was reduced in these patients and plasma NE increased promptly at low exercise loads. After cardiac transplantation plasma NE levels returned to normal (319 +/- 188 pg/ml) and the sympathetic response to the stresses of orthostatic tilt (320 +/- 196 to 419 +/- 197, p less than 0.002) and nitroprusside infusion (255 +/- 94 to 555 +/- 130, p less than 0.001) normalized within 6 months after transplantation. Exercise capacity increased and the increase in plasma NE levels at various exercise loads was reduced for any given workload. Therefore, abnormal adrenergic activity in patients with severe CHF results mostly from the reduction in left ventricular pump function and is reversible if adequate pump function is restored.     

Isometric exercise in patients with chronic advanced heart failure: hemodynamic and neurohumoral evaluation

We evaluated the hemodynamic effects of isometric exercise in 53 patients with congestive heart failure (CHF) and compared them with those found in 10 normal subjects. In both groups, isometric exercise increased heart rate and blood pressure. Systemic resistance increased in patients with CHF (1862 +/- 520 vs 2126 +/- 642 dyne-sec-cm-5; p less than .001) but not in normal subjects (1359 +/- 268 vs 1380 +/- 252 dyne-sec-cm-5). Cardiac index and stroke volume index increased mildly but not significantly in the normal subjects (2.8 +/- 0.5 vs 3.1 +/- 0.7 liters/min/m2 and 46 +/- 8 vs 47 +/- 7 ml/m2) and showed a significant fall in the patients with CHF (2.1 +/- 0.6 to 1.9 +/- 0.6 liters/min/m2, p less than .01 and 23 +/- 7 vs 20 +/- 7 ml/m2, p less than .01). Mean pulmonary arterial wedge pressure increased in patients with CHF from 26 +/- 7 to 30 +/- 8 mm Hg (p less than .001). Although no significant change was found in mean value for stroke work index (21 +/- 9 vs 20 +/- 9 g-m/m2), the individual changes were variable, with marked decrease (greater than 15%) in 17 of the patients. This hemodynamic deterioration could not be predicted from resting hemodynamics, left ventricular ejection fraction, or functional classification. Isometric exercise resulted in no significant change in circulatory catecholamine levels or plasma renin concentration in our 10 normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of metoprolol CR/XL on exercise tolerance in chronic heart failure - a substudy to the MERIT-HF trial

BACKGROUND: Beta-blockade usually causes a slight reduction in exercise capacity among healthy subjects, while more variable results have been observed in chronic heart failure (CHF), probably related to patients studied, methods and agent used. The effect of metoprolol controlled release/extended release (CR/XL) on peak oxygen uptake (peak VO(2)) in this patient population has not previously been investigated. AIMS: We examined the effect of long-term treatment with the selective beta(1)-receptor blocker metoprolol CR/XL once daily on exercise capacity in patients with CHF. METHODS: Ninety-four patients (70 males and 24 females; mean age 63.6+/-10.6 years) with chronic symptomatic heart failure in New York Heart Association (NYHA) functional class II-IV, and with ejection fraction 相似文献   

Hemodynamic, renal, and hormonal responses to brain natriuretic peptide infusion in patients with congestive heart failure

BACKGROUND. This study was designed to examine the hemodynamic, renal, and hormonal effects of brain natriuretic peptide (BNP) infusion in patients with congestive heart failure (CHF) and in control subjects. METHODS AND RESULTS. We infused synthetic human BNP at a rate of 0.1 micrograms/kg/min. BNP infusion decreased pulmonary capillary wedge pressure (control, from 5 +/- 1 to 2 +/- 1 mm Hg, p less than 0.01; CHF, from 21 +/- 3 to 14 +/- 4 mm Hg, p less than 0.05) and systemic vascular resistance (control, from 1,264 +/- 75 to 934 +/- 52 dyne.sec.cm-5; CHF, from 2,485 +/- 379 to 1,771 +/- 195 dyne.sec.cm-5; p less than 0.01, respectively) and increased stroke volume index (control, from 49.9 +/- 2.7 to 51.5 +/- 2.3 ml/m2, p = NS; CHF, from 25.6 +/- 3.8 to 32.0 +/- 3.9 ml/m2, p less than 0.01). BNP infusion significantly increased urine volume (control, from 2.3 +/- 0.7 to 7.5 +/- 1.9 ml/min; CHF, from 0.8 +/- 0.2 to 5.3 +/- 1.0 ml/min; p less than 0.01, respectively), excretion of sodium (control, from 79.2 +/- 21.6 to 332.8 +/- 70.9 microEq/min; CHF, from 77.4 +/- 20.8 to 753.5 +/- 108.0 microEq/min; p less than 0.01, respectively), and excretion of chloride (control, from 72.5 +/- 18.4 to 256.0 +/- 43.3 microEq/min; CHF, from 74.0 +/- 19.6 to 708.8 +/- 103.3 microEq/min; p less than 0.01, respectively). Urinary excretion of sodium and of chloride in response to BNP infusion was higher in patients with CHF than in control subjects (p less than 0.01, respectively). BNP infusion increased the levels of plasma atrial natriuretic peptide (control, from 65 +/- 11 to 84 +/- 14 pg/ml; CHF, from 262 +/- 65 to 301 +/- 62 pg/ml; p less than 0.05, respectively) and decreased plasma aldosterone concentrations in both groups (control, from 43.3 +/- 12.1 to 27.3 +/- 7.1 pg/ml; CHF, from 91.1 +/- 34.3 to 66.3 +/- 27.2 pg/ml; p less than 0.05, respectively). CONCLUSIONS. We conclude that BNP infusion improves left ventricular function in patients with CHF by vasodilation and prominent natriuretic action.