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Study objectives: In patients with pulmonary hypertension (PH) secondary to congestive heart failure, inhaled nitric oxide (NO) increases pulmonary vascular smooth-muscle intracellular cyclic guanosine monophosphate (cGMP) concentration, thereby decreasing pulmonary vascular resistance (PVR) and increasing cardiac index (CI). However, these beneficial effects of inhaled NO are limited in magnitude and duration, at least in part due to cGMP hydrolysis by the type 5 isoform of phosphodiesterase (PDE5). The goal of this study was to determine the acute pulmonary and systemic hemodynamic effects of the selective PDE5 inhibitor, sildenafil, administered alone or in combination with inhaled NO in patients with congestive heart failure and PH. Design: Single center, case series, pharmacohemodynamic study. Setting: Cardiac catheterization laboratory of a tertiary care academic teaching hospital. Patients: We studied 11 patients with left ventricular systolic dysfunction due to coronary artery disease or idiopathic dilated cardiomyopathy who had PH. Interventions: We administered oral sildenafil (50 mg), inhaled NO (80 ppm), and the combination of sildenafil and inhaled NO during right-heart and micromanometer left-heart catheterization. Measurements and results: Sildenafil administered alone decreased mean pulmonary artery pressure by 12 ± 5%, PVR by 12 ± 5%, systemic vascular resistance (SVR) by 13 ± 6%, and pulmonary capillary wedge pressure by 12 ± 7%, and increased CI by 14 ± 5% (all p <0.05) 11± SEMI. The combination of inhaled NO and sildenafil decreased PVR by 50 ± 4%, decreased SVR by 24 ± 3%, and increased CI by 30 ± 4% (all p < 0.01). These effects were greater than those observed with either agent alone (p < 0.05). In addition, sildenafil prolonged the pulmonary vasodilator effect of inhaled NO. Administration of sildenafil alone or in combination with inhaled NO did not change systemic arterial pressure or indexes of myocardial systolic or diastolic function. Conclusions: PDE5 inhibition with sildenafil improves cardiac output by balanced pulmonary and systemic vasodilation, and augments and prolongs the hemodynamic effects of inhaled NO in patients with chronic congestive heart failure and PH. [ABSTRACT FROM AUTHOR]

Objectives: To test the hypothesis that patients with well-documented diastolic dysfunction (DD) in the setting of normal systolic function will have inspiratory muscle weakness when compared to normal control subjects, and will experience dyspnea and tachypnea during exercise. Background: Respiratory muscle weakness has been described in patients with (systolic) congestive heart failure; however, whether or not patients with DD may present with the findings of congestive heart failure is not known. Methods: We selected for study 14 patients with DD previously referred for cardiopulmonary evaluation whose diagnosis had been confirmed by data obtained at cardiac catheterization. Seven control subjects matched for age, sex, and weight were recruited from the hospital community. Subjects performed both basic pulmonary function tests and tests of muscle strength: handgrip strength (Hgr), and maximal subatmospheric static inspiratory muscle pressure (PImax). Subjects then performed a graded exercise test on a bicycle ergometer. Minute ventilation, oxygen consumption, carbon dioxide production, and heart rate were monitored continuously. Echocardiography was performed three times: before exercise, at a selected submaximal exercise level (20% of a predicted maximal workload), and at maximal exercise. Subjects rated their degree of dyspnea using the Borg scale at the same three time intervals. Results: PImax was - 102 ± 17 cm H2O in control subjects, and - 77 ± 19 cm H2O in patients with DD (p = 0.013) [mean ± SD]. Hgr was similar between the groups. At the selected submaximal exercise level, patients with DD rated dyspnea to be 2.6 ± 2.2 Borg scale units (control subjects, 0.5 ± 0.8 Borg scale units). Hey plots described a rapid, shallow breathing pattern in patients with DD during exercise. Patients with DD and control subjects achieved similar maximal work loads. Conclusion: Patients with DD have diminished PImax, adopt a rapid, shallow breathing pattern during exercise, and experience dyspnea at low work loads when compared to matched control subjects. [ABSTRACT FROM AUTHOR]