SYMPATHETIC NERVOUS RESPONSE RELATIVE TO THE ADENOSINE-TRIPHOSPHATE SUPPLY-DEMAND IMBALANCE DURING EXERCISE IS AUGMENTED IN PATIENTS WITH HEART-FAILURE

Objective: Increase in plasma hypoxanthine (HX) (purine nucleotide deg radation product from working muscle) reflects insufficiency of adenos ine triphosphate (ATP) supply during exercise, and the exercise-induce d increase in plasma norepinephrine (NE) can be an index of sympatheti c nerve activity. The aim of this study was to investigate the relatio nship between plasma NE and plasma HX during exercise in patients with heart failure (HF) according to its severity. Methods: Blood lactate, plasma IM, and plasma NE were measured at rest and after symptom-limi ted cardiopulmonary exercise test in 54 patients with HF (New York Hea rt Association [NYHA] classes I:18, II:20, III:16) and 19 normal subje cts. Results: Peak work rate and peak oxygen uptake decreased as the N YHA functional class increased. Blood lactate and plasma HX levels at rest were comparable, but peak blood lactate (normal, NYHA I, II, III: 6.4 +/- 0.3, 5.6 +/- 0.4, 5.3 +/- 0.3, 3.5 +/- 0.2 mmol/L) and peak p lasma HX (3.6 +/- 0.4, 3.0 +/- 0.5, 2.4 +/- 0.3, 1.4 +/- 0.1 mu mol/L) were progressively smaller as HF worsened. Resting plasma NE (137 +/- 15, 180 +/- 29, 201 +/- 21, 318 +/- 55 pg/mL) was significantly highe r in NYHA class III HF, but peak plasma NE (2,235 +/- 356, 2,021 +/- 3 26, 2,188 +/- 292, 2,210 +/- 316 pg/mL) was not different among groups . The ratio of the exercise increments in plasma NE to the increments in plasma HX during exercise (Delta plasma NE/Delta plasma HX: 666 +/- 96, 1,083 +/- 229, 1,252 +/- 222, 2,260 +/- 351) increased according to the severity of HF. Conclusion: These data suggest that plasma leve ls of HX after maximal exercise are smaller as HF worsened, and sympat hetic responsiveness to the imbalance of ATP supply-demand during exer cise is augmented according to the severity of HF.