Lack of contribution of nitric oxide to basal vasomotor tone in heart failure.

Patients with heart failure have reduced forearm vasodilator responses when endothelial cell nitric oxide production is stimulated by muscarinic agonists. The aim of this study was to determine if activity of the nitric oxide pathway was also abnormal under basal conditions. Forearm blood flow (FBF) was measured with strain-gauge plethysmography in response to the intraarterial infusion of a subsystemic dose range of L-N-monomethylarginine (L-NMMA), a competitive inhibitor of nitric oxide synthase. In 18 normal subjects, the baseline FBF of 3.6 +/- 1.4 was decreased by 0.3 +/- 0.5 (p < 0.01), 1.0 +/- 0.7 (p < 0.01), 1.4 +/- 0.9 (p < 0.01), and 1.3 +/- 1.3 (p < 0.01) ml/min/100 ml forearm volume during infusions of 1, 4, 8, and 16 mumol/min of L-NMMA, respectively. In 10 patients with heart failure, the baseline FBF of 2.6 +/- 0.9 was decreased by 0.4 +/- 0.5 (p < 0.05), 0.4 +/- 0.5 (p < 0.05), 0.9 +/- 0.8 (p < 0.01), and 0.9 +/- 0.7 (p < 0.01) ml/min/100 ml forearm volume with the 4 doses of L-NMMA, respectively. There was no difference in the L-NMMA response between the 2 groups in terms of absolute flow, percent change, or with analysis of covariance to adjust for different baselines. The stable end products of nitric oxide (nitrite and nitrate) were measured in the forearm venous effluent. Nitrite and nitrate levels at baseline were not reduced in patients with heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Endothelium-dependent vasodilation of peripheral conduit arteries in patients with heart failure.

Endothelium-dependent vasodilation of peripheral resistance vessels is abnormal in patients with heart failure, but there are little in vivo data on endothelium-dependent vasodilation of peripheral conduit vessels. This study assessed endothelium-dependent vasodilation of forearm conduit and resistance vessels in normal subjects and patients with heart failure. The effects of intraarterial endothelium-dependent and endothelium-independent vasodilators on both forearm conduit (brachial artery) and resistance vessels were assessed in 9 patients with New York Heart Association class II-III heart failure and 11 normal subjects of similar age. Brachial artery diameter was measured by two-dimensional, moderate-frequency (8 MHz) ultrasound, and forearm blood flow was measured by strain gauge plethysmography. The endothelium-dependent vasodilator, methacholine (0.3 and 1.5 micrograms/min), increased brachial artery diameter by 7.6 +/- 1.3% and 12.2 +/- 1.5% in normal subjects as compared to 6.9 +/- 2.1% and 10.4 +/- 2.4% in patients with heart failure (P = NS, normal vs heart failure). The endothelium-independent vasodilator, nitroglycerin (0.15 microgram), also produced similar increases in brachial artery diameter in the two groups (8.2 +/- 1.3% in normal subjects vs 11.1 +/- 1.4% in patients with heart failure, P = NS). In contrast, forearm blood flow responses to methacholine were significantly (P < .05) greater in normal subjects (4.1 +/- 0.5 and 9.2 +/- 1.4 mL/min/100 mL forearm volume) than in patients with heart failure (2.0 +/- 0.8 and 5.1 +/- 1.3 mL/min/100 mL forearm volume). Forearm blood flow responses to the endothelium-independent vasodilator, sodium nitroprusside, were similar between the two groups. This study suggests that endothelium-dependent and endothelium-independent vasodilation of the brachial artery is not impaired in patients with class II-III heart failure. This finding contrasts with abnormal endothelium-dependent vasodilation of forearm resistance vessels. These data suggest that there are regional differences in endothelial function in patients with heart failure.

Effects of norepinephrine on endothelium-dependent vasodilation of forearm resistance vessels.

BACKGROUND: Endothelium-dependent dilatation of forearm resistance vessels is attenuated in patients with heart failure. Activation of the sympathetic nervous system could cause this abnormality by way of vasoconstriction and chemical inactivation of nitric oxide. METHODS AND RESULTS: The effects of concurrent intra-arterial norepinephrine infusions (25, 50 and 100 ng/min) on forearm blood flow responses to equipotent doses of an endothelium-dependent vasodilator, methacholine (0.3 and 1.5 micrograms/min), and an endothelium-independent vasodilator, nitroprusside (1 and 5 micrograms/min), were studied in 12 normal subjects. Norepinephrine infusions increased the mean plasma norepinephrine from 255 pg/ml at baseline to 460, 629, and 1089 pg/ml, respectively. Basal forearm blood flow was reduced from 2.9 to 1.6 ml/min/100 ml of forearm volume at the highest dose (p < 0.01). The average response to the lowest dose of methacholine (4.5 ml/min/100 ml) was not significantly reduced by concurrent infusion of norepinephrine (4.4, 4.2, and 4.3 ml/min/100 ml, respectively), whereas the response to the higher dose of methacholine (8.9 ml/min/100 ml) tended to be lower (7.2, 6.7, and 7.4 ml/min/100 ml, respectively) but did not attain statistical significance. Methacholine induced vasodilation was not more sensitive to norepinephrine than nitroprusside responses. Lower body negative pressure (-20 mm Hg) also significantly reduced baseline forearm flow and increased plasma norepinephrine but did not effect either methacholine or nitroprusside induced vasodilation. CONCLUSION: Sympathetic stimulation induced by infusion of norepinephrine or lower body negative pressure is not a potent antagonist to endothelium-dependent vasodilation of the forearm vasculature. These data suggest that sympathetic activation does not completely explain the abnormal endothelium-dependent vasodilation seen in patients with heart failure.

Pulmonary and peripheral vascular factors are important determinants of peak exercise oxygen uptake in patients with heart failure.

OBJECTIVES: This study was conducted to determine the relations among exercise capacity and pulmonary, peripheral vascular, cardiac and neurohormonal factors in patients with chronic heart failure. BACKGROUND: The mechanisms of exercise intolerance in heart failure have not been fully clarified. Previous studies have indicated that peripheral factors such as regional blood flow may be more closely associated with exercise capacity than cardiac function, whereas the role of pulmonary function has received less attention. METHODS: Fifty patients with stable heart failure underwent a comprehensive assessment that included a symptom-limited maximal cardiopulmonary exercise test, right heart catheterization, pulmonary function tests, neurohormonal levels, radionuclide ventriculography and forearm blood flow at rest and after 5 min of brachial artery occlusion. Univariate and stepwise linear regression analyses were used to relate peak exercise oxygen uptake to indexes of cardiac, peripheral vascular, pulmonary and neurohormonal factors both alone and in combination. RESULTS: The mean ejection fraction was 19% and peak oxygen uptake was 16.5 ml/min per kg in this group of patients. By univariate analysis, there were no significant correlations between peak oxygen uptake and rest cardiac output, pulmonary wedge pressure, ejection fraction and pulmonary or systemic vascular resistance. In contrast, even in the absence of arterial desaturation during exercise, the forced expiratory volume in 1 s (r = 0.55, p < 0.001), forced vital capacity (r = 0.46, p < 0.01) and diffusing capacity for carbon monoxide (r = 0.47, p < 0.01) were all significantly associated with peak oxygen uptake. Peak postocclusion forearm blood flow (r = 0.45, p < 0.01), the corresponding minimal forearm vascular resistance (r = -0.56; p < 0.01) and plasma norepinephrine level at rest (r = -0.45; p < 0.01) were also significantly correlated with peak oxygen uptake. By multivariate analysis, minimal forearm vascular resistance and forced expiratory volume in 1 s were shown to be independently related to peak oxygen uptake, with a combined R value of 0.71. Other two-variate models included forced expiratory volume and plasma norepinephrine (R = 0.67) and forced expiratory volume and diffusing capacity (R = 0.65). Because forced vital capacity was highly correlated with forced expiratory volume in 1 s, it could be combined with the same variables to yield similar R values. Addition of any third variable did not improve these correlations. CONCLUSIONS: In comparison with rest indexes of cardiac performance, measures of pulmonary function and peripheral vasodilator capacity were more closely associated with peak exercise oxygen uptake in patients with heart failure. Furthermore, the associations were independent of each other and together accounted for 50% of the variance in peak oxygen uptake. These data suggest that pulmonary and peripheral vascular adaptations may be important determinants of exercise intolerance in heart failure.

Effects of cardiac transplantation on endothelium-dependent dilation of the peripheral vasculature in congestive heart failure.

Patients with congestive heart failure demonstrate attenuated endothelium-dependent vasodilation of the peripheral vasculature, but there are no data regarding the effect of therapies on this abnormality or whether this abnormality is reversible. This study was performed to address the hypothesis that abnormalities in endothelium-dependent vasodilation in heart failure are improved by heart transplantation. Forearm blood flow responses to the intraarterial administration of a dose range of methacholine, an endothelium-dependent vasodilator, and nitroprusside, an endothelium-independent vasodilator, were examined in 2 separate protocols. In protocol 1, forearm blood flow responses to methacholine in 14 heart transplant recipients were 5.02 +/- 3.11, 11.55 +/- 7.20 and 11.61 +/- 10.24 ml/min/100 ml forearm volume. These responses were significantly greater than those in 10 patients with heart failure (2.23 +/- 1.22, 4.60 +/- 3.43 and 6.70 +/- 4.91 ml/min/100 ml forearm volume; p < 0.05). In contrast, the responses to nitroprusside were nearly identical in the 2 groups. In protocol 2, six patients were studied before and 4 months (range 1 to 11) after transplantation. Methacholine responses before transplantation were 2.5 +/- 1.3, 5.2 +/- 1.5 and 7.3 +/- 1.5 ml/min/100 ml forearm volume and were significantly improved after transplantation to 5.7 +/- 1.2, 12.1 +/- 3.0 and 14.2 +/- 2.2 ml/min/100 ml forearm volume (p < 0.05). Peak reactive hyperemia responses increased significantly from 19.0 +/- 3.7 to 44.8 +/- 6.4 ml/min/100 ml forearm volume (p < 0.01) after transplantation. These data demonstrate that heart transplantation was associated with a significant improvement in the forearm blood flow responses to methacholine.(ABSTRACT TRUNCATED AT 250 WORDS)

Reproducibility of treadmill exercise data in patients with atrial fibrillation.

Serial submaximal treadmill tests are often used to evaluate the efficacy of therapy in patients with atrial fibrillation. Since the response to serial tests can be influenced by a 'learning phenomenon', we performed maximal exercise tests on 9 patients (mean age 63 +/- 4 years) with chronic atrial fibrillation. Points of analysis for the initial and follow-up treadmill exercise tests were 3 mph/0% grade, the gas exchange anaerobic threshold, and maximal exertion. Significant (p less than 0.05) reductions in ventilation (l/min) and oxygen uptake (ml/kg/min) were observed on follow-up at a standard submaximal work load of 3.0 mph/0% grade and at the gas exchange anaerobic threshold. There was no significant alteration in these variables at maximal exertion. A reduction in heart rate was observed throughout exercise during the follow-up test with the most marked reduction (21 beats/min) occurring at 3.0 mph/0% grade. There were no differences in respiratory exchange ratio or systolic blood pressure at any point. The reduction in submaximal heart rate and gas exchange variables without a significant change in these variables at maximal exertion is consistent with a learning effect. Therefore, studies comparing consecutive submaximal exercise test responses in patients with atrial fibrillation can be misleading.

Burn contractures: incidence, predisposing factors, and results of surgical therapy.

An important element in the care of the burn victim is the prevention and treatment of burn wound contractures. Since limited objective quantitative information is available on the incidence of contractures after thermal injury, or on the factors that predispose individuals to their development, a review of all patients seen from July 1980 through January 1986 for surgical correction of burn wound contractures was conducted. Among the 53 patients selected for study, the incidence of contractures was higher in the pediatric patients, 7.8%, than in the adult patients, 2.0% (P less than 0.001), although burn wound size was comparable in these two groups. There was a direct relationship between wound size and number of contractures per patient (P = 0.003). The majority of contractures occurred at the hand, head, neck, and axilla. Surgical release of contractures of these central body regions (P = 0.056) and of fascially excised burns (P = 0.04), yielded the poorest operative results. Patient age and race, type of operation performed, and timing of surgery did not affect the operative results.