PATHOPHYSIOLOGY AND NATURAL HISTORY

Peripheral vascular resistance (PVR) and thromboxane A2(TxA2) synthesis after the cold pressor test were investigated in different subsets of patients with angina (10 with stable effort angina, 36 with resting angina [24 in an active phase and 12 in an inactive phase], and five with Prinzmetal's variant angina) and in 41 control subjects of equivalent age and risk factors. Left ventricular end-diastolic pressure, ejection fraction, extent of coronary angiographic lesions, and baseline PVR were not significantly different among the various patient groups. In all patient groups, except those with variant angina, the cold pressor test resulted in a higher increase in PVR than in the control subjects (p < .001 for all groups). In patients with variant angina the vasoconstrictor response was increased only in proximity (about 1 hr) to ischemic attacks. In patients with active resting angina the vasoconstrictor response was on the average four times longer than that in patients with effort angina and with inactive resting angina (p < .001). This exaggerated vasoconstrictor response was associated with elevated TxA2 resting levels in plasma and with increased TxA2 synthesis after the cold pressor test. A linear relationship was found between the area of the vascular response and the area of TxA2 production after the cold pressor test in patients with active resting angina (r = .87, p < .001). The increased TxA2 synthesis and the inappropriate increase of peripheral vascular response to sympathetic stimulation revert back to normal in the inactive phase. These alterations might contribute to the occurrence of inappropriate vasoconstriction and of the abnormal vascular responsiveness to various stimuli frequently found in patients with unstable angina. Circulation 73, No. 3, 409-417, 1986. SPONTANEOUS anginal attacks at rest have often been found to be associated with relative increases in heart rate and arterial blood pressure, which precede the onset of pain or ST segment depression in many patients1-7 and may play an important role in triggering and/or worsening myocardial ischemia. Because of the increases in heart rate and/or blood pressure before the onset of pain or ST segment depression, it has been suggested that angina at rest may be caused by an autonomically mediated sympathetic discharge with consequent increases in systemic vascular resistance.8 Furthermore, continuous monitoring of patients has shown that with continuing pain there is a tendency From Clinica Medica I, University of Florence, Italy. Supported by grants 82.02255. 56 and 82.01082. 83 from the Italian National Research Council, Project Atherosclerosis. Address for correspondence: Gian Gastone Neri Semeri, M.D., Clinica Medica I dell' Universita', Viale Morgagni, 85, 50134 Florence, Italy. Received July 31, 1984; revision accepted Nov. 7, 1985. Vol. 73, No. 3, March 1986 toward a secondary sympathetically induced increase in arterial blood pressure and heart rate, which can trigger a feedback mechanism increasing myocardial oxygen demand.2' 5' Thus, in anginal patients the vascular responsiveness both to resting sympathetic flow and to reflexively increased sympathetic activity may play an important role in the occurrence and/or worsening of myocardial ischemic attacks. Sympathetic activation is able to induce thromboxane A2 (TxA2) synthesis by vessel wall.9 Because of its direct vasoconstrictor activity, TxA2 is reported to potentiate the vasoconstrictor effect of norepinephrine and angiotensin II1° 11 and thus might play a role in an abnormally enhanced vascular response to sympathetic stimulation. The aim of this study was therefore to investigate peripheral vascular responsiveness to sympathetic stimulation such as the cold pressor test in different subsets of anginal patients and to correlate peripheral vascular responses to TxA2 production.