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(Circulation. 2000;102:987.)
© 2000 American Heart Association, Inc.

Clinical Investigation and Reports

Postexercise Ischemia Is Associated With Increased Neuropeptide Y in Patients With Coronary Artery Disease

Lars Gullestad, MD, PhD; Bjørn Jørgensen, MD; Thorvald Bjurø, MD, PhD; John Pernow, , MD, PhD; Jan M. Lundberg, MD, PhD; Corina-Dana Dota, MD; Christian Hall, MD, PhD; Svein Simonsen, MD, PhD; Bengt Åblad, MD, PhD

From the Department of Cardiology (L.G., B.J., S.S.) and Institute of Internal Medicine (C.H.), Rikshospitalet University Hospital, Oslo, Norway; Wallenberg Laboratory (T.B.), Gøteborg, Sweden; Department of Cardiology (J.P.), Karolinska Hospital, Stockholm, Sweden; Department of Physiology and Pharmacology (J.M.L.), Karolinska Institutet, Stockholm, Sweden; and AstraZeneca (C.D., B.Å.), Mölndal, Sweden.

Correspondence to Lars Gullestad, MD, PhD, Medical Department, Baerum Hospital, 1306 Baerum Postterminal, Norway. E-mail lagulles{at}online.no

Background—Neurohormones may influence vascular tone both during and after exercise. Neuropeptide Y (NPY), which is costored and released with norepinephrine (NE) during sympathetic activity, is a potent vasoconstrictor with a relatively long half-life. We therefore examined its possible association with the ischemic response to exercise in patients with coronary artery disease.

Methods and Results—Twenty-nine male patients with effort-induced angina pectoris underwent a symptom-limited exercise test. In addition to conventional ST-segment analysis, we examined ischemia on the basis of heart rate (HR)-adjusted ST-segment changes through calculation of the ST/HR slope during the final 4 minutes of exercise and of the ST/HR recovery loop after exercise. Blood samples were taken before, during, and after exercise for an analysis of several neurohormones. Mean ST-segment depression was -223±20.2 µV (P<0.0001) just before the termination of exercise, followed by a gradual normalization, but it remained significant after 10 minutes (-49±8.9 µV, P<0.0001). At the end of exercise, the ST/HR slope, which reflects myocardial ischemia, was -6.0±0.77 µV/HR. In most patients, ST-segment levels at a given HR were lower during recovery than during exercise, here referred to as ST "deficit." Exercise increased the plasma levels of NPY, NE, epinephrine, and N-terminal proatrial natriuretic peptide, but big endothelin remained unchanged. Although NE and epinephrine peaked at maximal exercise, the highest levels of NPY and N-terminal proatrial natriuretic peptide were observed 4 minutes after exercise. The maximal increase in the NPY correlated significantly with ST-segment depression at 3 minutes after exercise (r=-0.61, P=0.0005), the ST deficit at the corresponding time point (r=-0.66, P=0.0001), and the duration of ST-segment depression after exercise (r=0.42, P=0.02). In contrast, no such correlations were found for NE.

Conclusions—The present study has for the first time demonstrated a correlation between plasma NPY levels and the degree and duration of ST-segment depression after exercise in patients with coronary artery disease, which suggests that NPY may contribute to myocardial ischemia in these patients.

Key Words: coronary disease • exercise • ischemia • peptides

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