VASOCONSTRICTOR PEPTIDES AND COLD INTOLERANCE IN PATIENTS WITH STABLEANGINA-PECTORIS

Background-The exact mechanism that explains the phenomenon of cold in tolerance in patients with angina remains controversial. Although the response to the effects of a cold environment has been examined in the se patients, their response to cold air inhalation has produced confli cting results. In addition, the possible role of vasoactive peptides i n the pathophysiology has not been explored. Objectives-The aims of th is study were to examine the response of patients with stable angina t o the effects of cold air inhalation during exercise testing, and to i nvestigate the possible role played by the vasoconstrictor peptides en dothelin-1 (ET-1) and angiotensin-II (AT-II) in the pathophysiology. M ethods-In a randomised order, 12 men with stable angina, whose medicat ion had been stopped, underwent two separate symptom limited treadmill exercise tests. At one visit the patients exercised while breathing r oom air and at the other visit they exercised while breathing cold air from a specially adapted freezer. Serial peripheral venous blood samp les were taken for ET-1 and AT-II estimations during each visit. Resul ts-Cold air inhalation resulted in a significant reduction in the mean time to angina (232.7 (20.4) a v 274.1 (26.9) s, P = 0.04) and the me an total exercise time (299.5 (27.0) s v 350.3 (23.9) s, P = 0.008), b ut no significant change in the time to 1 mm ST depression (223.3 (29. 0) s v 241.3 (29.2) s, P = 0.25). There was no significant difference between the rate-pressure products at the onset of angina (P = 0.13) a nd the time to 1 mm ST depression (P = 0.85), but at peak exercise the rate-pressure product was significantly lower inpatients breathing co ld air as opposed to room air (P = 0.049). There was an equivalent sig nificant decrease in ET-1 concentrations at peak exercise compared wit h that at rest at both visits (room air 5.0 (0.7) pmol/l v 4.3 (0.7) p mol/l, P = 0.03; cold air 4.4 (0.6) pmol/l v 3.8 (0.5) pmol/l, P = 0.0 2). There was a significant increase in AT-II concentrations 10 min af ter peak exercise in patients breathing roam air (39.2 (6.1) pmol/l v 32.1 (4.8) pmol/l, P = 0.01) which was not repeated during cold air in halation (36.6 (3.4) pmol/l v 28.3 (3.4) pmol/l, P = 0.07). Conclusion s-Cold air inhalation in patients with stable angina results in an ear lier onset of angina and a reduction in exercise capacity. Both periph eral and central reflex mechanisms appear to contribute to the phenome non of cold intolerance. Peripheral ET-1 and AT-II do not appear to pl ay a significant role in the pathophysiology.