NITRIC-OXIDE PRODUCTION DURING EXERCISE IN CHRONIC HEART-FAILURE

In chronic heart failure (CHF), the ventilatory response is increased compared with normal. This response is, in part, caused by reduced per fusion to ventilated lung. Nitric oxide (NO) is a potent vasodilator a nd may have an important role in pulmonary vasodilatation during exerc ise. NO is present in exhaled air. The amount of NO in exhaled air, wh en breathing NO-free compressed air, is known to increase in normal su bjects during exercise. In this study, we quantified NO output in exha led air in patients with CHF during exercise. Six patients with CHF (N ew York Heart Association Class II and III; two with dilated cardiomyo pathy, three with ischemic heart disease, and one with hypertensive he art disease) and six normal subjects were studied with a symptom-limit ed incremental exercise test on a cycle ergometer. Oxygen uptake ((V) over dot(2)), carbon dioxide output ((V) over dotCO(2)), and minute ve ntilation ((V) over dotE) were measured breath by breath with a mass s pectrometer, flow meter, and computer. The NO concentration was contin uously measured in mixed expired air by chemiluminescence. Peak exerci se work rate was lower in patients with CHF than in normal subjects (7 1.3 +/- 41.6 W vs 257.0 +/- 49.7 W; p < 0.01). Patients with CHF showe d a higher (V) over dotE/(V) over dotCO(2) level at peak exercise than normal subjects (CHF, 47.0 +/- 10.7; normal subjects, 35.6 +/- 5.2; p < 0.01). NO concentration of exhaled air at rest was lower in CHF pat ients than in normal subjects (4.0 +/- 2.2 ppb vs 10.5 +/- 6.2 ppb, re spectively; p < 0.05). NO output from the respiratory tract ((V) over dotNO) was significantly lower in patients with CHF compared with norm al subjects at rest (45.3 +/- 24.3 nl/min, 117.5 +/- 60.1 nl/min, resp ectively, p < 0.05), and although it increased during exercise, it did not increase in patients with CHF as much as in normal subjects (75.3 +/- 43.4 nl/min vs 512.9 +/- 253.6 nl/min, respectively; p < 0.01). T he increase above rest (exercise/rest) was smaller in patients with CH F than in normal subjects (2.10 +/- 1.92 vs 4.81 +/- 2.67, p < 0.05). These data support the concept that the smeller increase in NO product ion ((V) over dotNO) during exercise may be responsible for a blunted vasodilation in patients with CHF, resulting in a smaller reduction in dead space/tidal volume and (V) over dotE/(V) over dotCO(2) at the la ctic acidosis threshold than normal. This finding may play a role in t he abnormally high ventilatory response to exercise in patients with C HF.