Development of a Human Model for the Study of Effects of Hypoxia, Exercise, and Sildenafil on Cardiac and Vascular Function in Chronic Heart Failure.

BACKGROUND: Pulmonary hypertension is associated with poor outcome in patients with chronic heart failure (CHF) and may be a therapeutic target. Our aims were to develop a noninvasive model for studying pulmonary vasoreactivity in CHF and characterize sildenafil's acute cardiovascular effects. METHODS AND RESULTS: In a crossover study, 18 patients with CHF participated 4 times [sildenafil (2 × 20 mg)/or placebo (double-blind) while breathing air or 15% oxygen] at rest and during exercise. Oxygen saturation (SaO2) and systemic vascular resistance were recorded. Left and right ventricular (RV) function and transtricuspid systolic pressure gradient (RVTG) were measured echocardiographically. At rest, hypoxia caused SaO2 (P = 0.001) to fall and RVTG to rise (5 ± 4 mm Hg; P = 0.001). Sildenafil reduced SaO2 (-1 ± 2%; P = 0.043), systemic vascular resistance (-87 ± 156 dyn·s·cm; P = 0.034), and RVTG (-2 ± 5 mm Hg; P = 0.05). Exercise caused cardiac output (2.1 ± 1.8 L/min; P < 0.001) and RVTG (19 ± 11 mm Hg; P < 0.0001) to rise. The reduction in RVTG with sildenafil was not attenuated by hypoxia. The rise in RVTG with exercise was not substantially reduced by sildenafil. CONCLUSIONS: Sildenafil reduces SaO2 at rest while breathing air, this was not exacerbated by hypoxia, suggesting increased ventilation-perfusion mismatching due to pulmonary vasodilation in poorly ventilated lung regions. Sildenafil reduces RVTG at rest and prevents increases caused by hypoxia but not by exercise. This study shows the usefulness of this model to evaluate new therapeutics in pulmonary hypertension.

Effects of reducing inspired oxygen concentration for one hour in patients with chronic heart failure: implications for air travel.

AIMS: The objective of this study was to establish the acute effects of hypoxia on clinical, spirometric, haemodynamic, and echocardiographic variables. Reducing inspired oxygen to 15%, as experienced during commercial air travel, decreases arterial oxygen saturation, increases respiratory rate and pulmonary artery pressure in healthy subjects. The effect on patients with chronic heart failure is unknown. METHODS AND RESULTS: Seventy-two patients with chronic heart failure and an LVEF <40%, in NYHA functional class II (74%) or III (26%), on stable treatment were studied and compared with 18 age-matched controls (65 ± 11 vs. 62 ± 12 years, respectively). Clinical, spirometric, haemodynamic, and echocardiographic measurements were performed in patients and controls before and after one hour inspiring 15% oxygen. Inspired 15% oxygen for 1 h was tolerated in all subjects and caused no worsening of symptoms. Arterial oxygen saturation decreased to a similar extent in patients (from 97 ± 2% to 86 ± 4%) and controls (from 97 ± 2% to 86 ± 3%). Mean arterial pressure increased from 81 ± 13 mmHg to 87 ± 12 mmHg in patients, but did not change in controls. There was no effect on heart rate, but systolic pulmonary artery pressure rose from 30.2 ± 14.0 mmHg to 34.0 ± 15.2 mmHg in patients, and from 22.4 ± 5.5 mmHg to 24.1 ± 6.9 mmHg in controls. CONCLUSIONS: Inspiring 15% oxygen was tolerated and caused no worsening of symptoms despite reductions in arterial oxygen saturation and increases in mean arterial pressure and systolic pulmonary artery pressure.