Anginal Threshold Research Articles

Double-blind, randomized, placebo-controlled study of molsidomine in patients with stable effort angina receiving beta-blocker therapy with atenolol

A randomized, double-blind, placebo-controlled trial was performed in 12 patients with chronic and stable effort angina to study the antianginal and anti-ischemic actions of a single dose of molsidomine in addition to long-term therapy with a long-acting beta-adrenergic blocker (100 mg of atenolol daily). Efficacy was assessed by meas of objective endpoints obtained by computer-assisted exercise testing. The mean exercise time to produce angina improved significantly from 330 ± 38 seconds (mean ± SEM) in patients after administration of atenolol and placebo to 420 ± 36 seconds after administration of atenolol and molsidomine. Similar significant improvements were seen in ST segment changes at an identical exercise duration, in maximal heart rate, and in maximal exercise duration. The increased anginal threshold and the reduced ischemic changes were not explained by changes in the rate-pressure product at submaximal levels. Thus molsidomine showed antianginal and anti-ischemic efficacy in the treatment of stable effort angina additional to the effect of long-term therapy with beta-adrenergic blockers.

Effect of high dose aspirin on coronary hemodynamics during pacing-induced myocardial ischemia

The effects of aspirin on coronary hemodynamics and transcardiac concentrations of thromboxane B2 (the stable metabolite of thromboxane A2) were determined at rest and during pacing-induced myocardial ischemia in 11 patients with coronary disease. Control coronary sinus pacing increased both arterial thromboxane B2 (331 +/- 70 to 623 +/- 132 pg/ml, p less than 0.02) and coronary sinus thromboxane B2 (184 +/- 3 to 403 +/- 156 pg/ml, p less than 0.05), but positive transmyocardial gradients developed in only three patients. After 650 mg of oral aspirin, more than 90% inhibition of in vitro thromboxane B2 production was demonstrated and circulating thromboxane B2 was undetectable at rest and during pacing in all patients. Despite these changes in thromboxane B2 concentrations, coronary blood flow was unchanged by aspirin at rest (107 +/- 14 versus 112 +/- 13 ml/min, p = NS) and during pacing (189 +/- 29 versus 181 +/- 25 ml/min, p = NS). Myocardial lactate extraction was also unchanged at rest (24 +/- 7 versus 19 +/- 5%, p = NS) and during pacing (5 +/- 6 versus 9 +/- 5%, p = NS). No change occurred in the anginal threshold. Thus, aspirin does not have the vasoconstrictive properties that have been reported with another cyclo-oxygenase inhibitor, indomethacin. These findings also suggest that thromboxane A2 production does not play a major role in the pathogenesis of stress-induced ischemia. Nonetheless, intracoronary thromboxane A2 production in some patients may potentiate platelet activation and coronary thrombosis. Such patients may benefit from long-term aspirin therapy and can be treated with aspirin without risk of adverse coronary hemodynamic effects.

Dynamic coronary obstruction as a cause of angina pectoris: Implications regarding therapy

The strong link demonstrated at autopsy between coronary atherosclerosis and angina pectoris led to the important concept that a fixed obstruction of 1 or more coronary arteries was the pathophysiologic cause of angina: myocardial ischemia and angina occurred when myocardial oxygen demand out-stripped the capacity of the diseased coronary artery to deliver oxygen. Therapeutic strategies were based on attempts to lower myocardial oxygen needs induced by physical and emotional stress. However, the finding that dynamic increases in coronary vascular resistance can also either precipitate ischemia or reduce the threshold of myocardial oxygen consumption (MVO 2) at which it occurs has profoundly altered our understanding of the pathophysiologic features of angina and, therefore, its treatment. Dynamic coronary obstruction can occur at the large-vessel level, causing Prinzmetal's or variant angina. It is also possible that in some patients a continuum of large-vessel coronary vasoconstrictor tone exists, causing the common clinical situation manifested by angina with variable thresholds of onset. Recent studies have demonstrated that increases in the resistance offered to flow by small coronary arteries too small to be imaged by angiography can also decrease anginal threshold. The fact that ischemia can be precipitated by dynamic increases in large- or small-vessel coronary resistance has important implications for the therapy of angina pectoris. In those persons who mostly have a dynamic component contributing to their coronary obstruction, primary intervention with vasodilator therapy, including nitrates and calcium-channel blocking agents, are probably most effective therapeutically. In those persons with fixed obstruction and little evidence of a dynamic component, the traditional therapeutic approach designed to reduce myocardial oxygen consumption would be most efficacious. This would include the use of nitrates and β blockers. On the other hand, those persons who have a combination of fixed and dynamic obstruction might benefit either from interventions designed either to lower MVO 2 or to relieve obstruction; some patients might require both approaches for optimal symptomatic control. The recognition that dynamic influences can profoundly exacerbate the degree of coronary obstruction at either the large- or small-vessel level should influence medical approaches to the alleviation of ischemic pain and result in more effective treatment of anginal syndromes.

Alterations in angina threshold with nifedipine during pacing induced angina.

Changes in coronary haemodynamics and angina threshold were determined during atrial pacing in 11 patients with fixed obstructive coronary artery disease with effort angina before and after the administration of 20 mg of oral nifedipine. Coronary vascular resistance decreased at resting and at "subangina" heart rates but not at "angina" rates. Primary coronary vasodilatation with nifedipine was also suggested by higher coronary sinus oxygen content whether at rest or at subangina or angina heart rates. After nifedipine angina occurred at a lower double product and lower myocardial oxygen consumption. These findings suggest that nifedipine is a coronary vasodilator, but angina can occur at a lower angina threshold in some patients with obstructive coronary artery disease.

Sequential changes in regional coronary flow during pacing-induced angina pectoris: Coronary flow limitation precedes angina

To investigate the sequence of changes in regional myocardial perfusion which precedes stress-induced angina, we measured great cardiac vein flow (GCVF), draining the anterior left ventricle, during incremental atrial pacing in 10 patients with normal anterior perfusion (group I) and in 11 patients with ≥ 50% diameter stenosis of the left main or proximal left anterior descending coronary artery (group II). Pacing produced angina in 11 of 11 and regional lactate production in 9 of 11 group II patients. Both groups had comparable resting GCVF (group I = 62 ± 7 ml/min vs group II = 76 ± 9 ml/min; p = NS) and both exhibited progressive increases in GCVF with pacing. However, the entire flow-demand relationship was displaced downward in group II, as evidenced by a reduction in the percent increase in GCVF both following the first 20-beat pacing increment (group I = 46 ± 6% vs group II = 16 ± 4%; p < 0.001) and at angina (group I = 113 ± 16% vs group II = 44 ± 9%; p < 0.001). The first 20-beat pacing increment increased the heart rate to only 77 ± 2 bpm in group II whereas angina and ECG changes did not occur until a pacing rate of 117 ± 6 bpm. These data indicate that regional flow abnormalities precede the onset of pacing-induced angina in patients with coronary disease (CAD) and that these flow abnormalities frequently are detectable at heart rates substantially below the anginal threshold.

Haemodynamic effects of intravenous cibenzoline in patients with coronary heart disease.

The effect of a single dose of cibenzoline ( (diphenyl 2,2 cyclopropyl)--2 imidazoline, Cipralan ), a new compound with antiarrhythmic properties was studied in 14 patients undergoing routine heart catheterization for suspected coronary artery disease. The effect of the drug on dP/dt, Vmax TP, Vce, negative dP/dt, heart rate (HR), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), cardiac index (CI) and systemic vascular resistance (SVR) was measured before and after drug administration. A significant decrease in left ventricular isometric contraction parameters was manifested immediately after injection, with its maximal effect 2 to 5 min after injection. An increase in HR, a decrease in LVSP, a decrease in CI and an increase in SVR were observed; LVEDP was not significantly altered, nor was negative dP/dt. The effect of the drug on Vmax TP and LVEDP was also examined during two atrial pacing stress tests ( APST ) done before and 10 to 20 min after drug administration. Although the negative inotropic action of the drug was apparent during the second APST , the effect was less pronounced at higher paced heart rates. No difference in the two tests was found between the maximal paced heart rate, nor was there a difference in the angina threshold. Finally the plasma level of the drug and the changes in certain parameters were compared. A positive correlation was found between the plasma level and dP/dt, Vmax TP and cardiac index.

Verapamil Administered Twice Daily in Stable Angina Pectoris

To assess whether verapamil taken orally twice daily (bd) was as effective as four times daily (qd) in patients with angina a placebo controlled double blind crossover trial was conducted in 12 patients. Each patient was randomized to verapamil, 160 mg bd, 80 mg qd, or corresponding placebo, each for three weeks. Patients were assessed subjectively and by treadmill exercise test. On both verapamil regimens, patients had less angina with delayed onset of ST segment depression during exercise compared to placebo, without any differences between the two regimens. On bd verapamil, patients could increase their exercise capacity as much as on qd without any increase in adverse effects. Angina threshold during exercise was increased by both regimens with a slightly higher threshold on qd verapamil compared to bd. Therefore, administration of verapamil twice daily is effective in patients with stable angina pectoris, with a similar efficacy to taking verapamil four times daily without any increase in adverse effects.

The effect of nitrate on the oxygen availability during exercise in effort angina pectoris.

Respiratory responses during exercise were observed to determine whether improvement of oxygen availability in working skeletal muscle is attributable to increased aerobic capacity after administration of nitrate in patients with effort angina. After isosorbide dinitrate (ISDN) administration, the aerobic capacity increased 3.3 ml/min/Kg (20%) as compared with the control test (p less than 0.001), but the anaerobic threshold (AT), a good indicator of oxygen availability, was unchanged, and the respiratory quotient at the peak of exercise was elevated. These findings suggest that oxygen availability in skeletal muscle was not altered after ISDN, and increased exercise load accompanied increased anaerobic glycolysis. It was concluded that the nitrate-induced increase in aerobic capacity was not dependent upon the change in oxygen availability in skeletal muscle but rather upon the elevated anginal threshold.

Effects of low-dose dobutamine on coronary hemodynamics, myocardial metabolism, and anginal threshold in patients with coronary artery disease.

Fourteen patients with coronary artery disease and normal or near-normal left ventricular function were studied at rest and during atrial pacing until the occurrence of angina (12 patients) before and during infusion of dobutamine (3.80 +/- 0.45 micrograms/kg/min). At rest, during the infusion, three patients developed chest pain, mean ST segment depression increased from 0.02 to 0.08 mV (p less than .001), and myocardial lactate extraction fell from +17.5% to -1.4% (p less than .05). These ischemic changes were associated with significant increases in arterial systolic pressure (134 to 149 mm Hg), heart rate (79 to 91 beats/min), coronary sinus flow (89 to 113 ml/min), and myocardial oxygen consumption (10.8 to 13.5 cc/min). In contrast, during atrial pacing, dobutamine did not reduce the pacing threshold or further increase myocardial oxygen consumption or ST segment changes; however, arterial mean and diastolic pressures were significantly lower with pacing during dobutamine infusion compared with control pacing. In the absence of heart failure, dobutamine in low doses can cause myocardial ischemia in patients with coronary artery disease. The absence of increased ischemia from dobutamine during pacing may reflect reversal of pacing-induced ventricular dysfunction.

Angina caused by reduced vasodilator reserve of the small coronary arteries

To study the mechanism of chest pain in patients vvith insignificant large vessel coronary artery disease, 22 patients underwent great cardiac vein flow, coronary resistance and lactate determinations at rest and with coronary sinus pacing followed by coronary arteriography. Nine patients experiencing chest pain with pacing demonstrated significantly lesser increase in flow from base-line values (45 ± 30versus86 ± 50% [mean ± standard deviation], p < 0.025), lesser decrease from baseline in resistance (-28 ± 18 versus -44 ± 11%, p < 0.001) and less lactate consumption (25.0 ± 23.6 versus 45.6 ± 19.0 mmol ml/min, p < 0.025) compared with the 13 patients without pacing-induced chest pain. Pacing conducted during the cold pressor test elicited similar abnormalities in those patients experiencing chest pain and those who did not: four of eight patients experiencing chest pain demonstrated a lowered or new anginal threshold compared with that of the control pacing study. Coronary arteriography during the cold pressor test revealed no significant change in epicardial coronary artery dimension. After administration of ergonovine, 0.15 mg intravenously, 2 of 20 patients experienced spontaneous chest pain, which was associated with the greatest decrease in flow ( - 13 and -21%, respectively) and increase in resistance ( + 26 and +39%, respectively) of any patient. Pacing resulted in chest pain in 10 of the remaining 18 patients, including 5 patients who had not experienced chest pain during the control pacing study. Although none of these patients exhibited significant epicardial coronary artery narrowing on arteriography, their flow increased less (38 ± 12 versus 126 ± 68%, p < 0.001), resistance decreased less ( -18 ± 4 versus -50 ± 13%, p < 0.001) and was associated with less lactate consumption (32.7 ± 25.2 versus 70.1 ± 29.4mmolml/min, p < 0.01) than in patients not experiencing chest pain. Eight of the 12 patients developing chest pain demonstrated a decreased or new anginal threshold compared with that elicited by pacing during the control study. These findings suggest that some patients with atypical chest pain have inappropriate coronary arteriolar or small coronary artery constriction with abnormal vasodilator reserve in response to atrial pacing. The abnormality can be unmasked or exacerbated in some patients by vasoconstrictor stimuli, but cannot be identified with standard angiographic assessment of “spasm” because abnormal vasoconstriction occurs in vessels too small to be visualized by angiography.

Serial exercise testing up to 6 years after coronary bypass surgery: Behavior of exercise parameters in groups with different degrees of revascularization determined by postoperative angiography

To evaluate the behavior of exercise parameters in patients with different angiographically defined degrees of revascularization, serial exercise tests were analyzed in 435 patients 1 to 6 years after coronary artery bypass grafting (CABG). All patients had undergone postoperative angiography 2 to 12 months after CABG to determine the degree of revascularization achieved. Revascularization was complete in 182 patients (all significantly stenosed arteries had patent grafts), sufficient in 176 patients (at least the dominant artery supplying the left ventricle had a patent graft) and incomplete in 57 patients (the dominant artery supplying the left ventricle had a closed graft). Twenty patients had all grafts occluded. Exercise tolerance, angina-free exercise tolerance (angina threshold), maximal double product, prevalence of ≥0.1 mV exerciseinduced S-T segment depression, and the prevalence of the combination of S-T segment depression plus angina pectoris were determined in serial exercise tests (average of 3.0 postoperative exercise tests per patient for a mean follow up of 3.5 years). Patients with complete, sufficient, and incomplete revascularization showed improvement of all exercise parameters for 6, 4, and 1 year after CABG, respectively. Patients with all grafts occluded had improvement of only some exercise parameters.Five years after CABG, exercise tolerance was improved by 24 W (p < 0.0005) and 21 W (p < 0.005) in patients with complete and sufficient revascularization, respectively, and not improved in patients with incomplete revascularization or with all grafts occluded. The angiographically determined completeness of revascularization correlates with the extent and the duration of improvement of exercise parameters after CABG.

Exercise in the rehabilitation of CHD patients

The author sets out to show why cardiac patients should follow an exercise regimen and that the important psychological benefits achieved by an exercise rehabilitation programme relate to the healing concept - to making the patient whole again. In addition, the capacity for physical work increases as does the “angina threshold". The safety of the patient is ensured by prescribing exercise based on results of the target heart rate concept. Finally, the author defends walking and jogging as the ideal mode of exercise.

Variable threshold exertional angina in patients with transient vasospastic myocardial ischemia: Repeat exercise test results and therapeutic implications

Thirty-five of 70 patients with vasospastic angina at rest complained of chest pain during exercise or during usual daily activity. In 22, the angina threshold was described as variable during exercise: that is, the amount of exertion that induced angina was not always the same. In 12 patients with variable threshold exertional angina, 3 exercise tests performed in the morning on different days yielded different results, because chest pain and ischemic electrocardiographic changes occurred at different work loads with a wide range in heart rate-systolic pressure product. Two patients, in whom great cardiac vein flow was measured during exercise before and after taking nifedipine, tolerated heavier work loads after receiving the drug, with a more marked increase in flow during exercise. It is concluded that variable threshold exertional angina can be objectively demonstrated by repeat exercise tests in patients with vasospastic angina. Variability of the angina threshold may be due to a functional mechanism that causes myocardial ischemia in addition to the increased myocardial metabolic requirements provoked by exercise. Because in such patients fluctuations in coronary arterial tone play an important role in determining the response to exercise, calcium antagonistic drugs, which lower coronary tone and prevent the occurrence of coronary spasm, are effective in increasing exercise capacity.

Mechanism of relief of pacing induced angina with oral verapamil: reduced oxygen demand.

To evaluate the influence of oral verapamil (80 and 120 mg) on angina threshold, coronary blood flow, myocardial oxygen consumption and left ventricular function, we subjected 13 patients with effort angina and fixed obstructive coronary artery disease to atrial pacing at progressively higher heart rates. After 120 mg of verapamil, the time to onset of angina and the heart rate at the onset of ST-segment depression increased by 18% (p less than 0.005) and 10% (p less than 0.001), respectively, without any change in the angina threshold (rate-pressure product at the onset of angina). The rate-pressure product, coronary blood flow and myocardial oxygen consumption were lower at rest and at pre-angina heart rates but not when the angina threshold was reached. Thus, the beneficial effect of verapamil was primarily due to decreased myocardial oxygen demand rather than to increased coronary blood flow. The decreased demand resulted from a lower arterial pressure at each pacing rate. In these patients without heart failure, left ventricular pump function did not deteriorate. This beneficial response was less with 80 mg of oral verapamil. These findings suggest that oral verapamil has a potential role in the management of patients with effort angina due to fixed obstructive coronary artery disease.

Acute Effects of Chewable Nifedipine on Hemodynamic Responses to Upright Exercise in Patients with Prior Myocardial Infarction and Effort Angina

To evaluate the hemodynamic effects of nifedipine on anginal patients during exercise in the upright position, a placebo (P) and 20 mg of nifedipine were administered in a double-blind random sequence to ten patients presenting with exertional angina and a healed myocardial infarction. All patients had previously undergone coronary angiography. The effects of nifedipine in the upright position at rest, at the anginal threshold, and at the maximal level of exercise were studied. Nifedipine decreased systemic vascular resistances in upright position and increased the cardiac index. It reduced the severity of angina and allowed a higher physical work capacity without anginal symptoms. The most important beneficial effect of nifedipine appears to be the reduction in afterload, but an improvement of left ventricular function cannot be ruled out.

Verapamil in stable effort angina: Effects on left ventricular function evaluated with exercise radionuclide ventriculography

A double blind placebo-controlled study was performed in 12 patients with stable angina pectoris to evaluate the effects of oral verapamil (320 mg/day) on left ventricular function, as measured at rest and during exercise with gated equilibrium radionuclide ventriculography. On verapamil, patients had a lower heart rate-blood pressure product at each work load than with placebo. Anginal threshold increased by 28 ± 19 watts (p < 3.005), and maximal exercise capacity increased by 20 ± 14 watts ( p < 0.001) with verapamil, but the rate-pressure product at the onset of angina and at maximal exercise was unchanged. Left ventricular ejection fraction at rest during verapamil therapy was the same as with placebo therapy. On exercise during placebo therapy, the ejection fraction decreased from 40 ± 9 to 35 ± 11 percent (p < 0.025) because end-systolic volume increased disproportionately compared with end-diastolic volume. On exercise during verapamil therapy, the ejection fraction did not decrease (44 ± 8 versus 45 ± 12 percent) and was significantly higher at identical work loads than on placebo because of a smaller increase in end-systolic volume. Oral verapamil is effective treatment for effort angina and may prevent the decrease in left ventricular ejection fraction due to exercise-induced ischemia.

Hemodynamic response to glyceryl trinitrate in a spray at rest and during exercise in a sitting position.

Glyceryl trinitrate (GNT, 0.8 mg) was administered in a spray to 15 coronary patients of whom 7 had a pulmonary wedge pressure (PWP) greater than 16 mm Hg on exercise (subgroup I) and the others (subgroup II) had a normal PWP at rest and during exercise. At rest, GNT increased heart rate and decreased cardiac output, systolic index, stroke work index, right atrial pressure, pulmonary wedge and mean systemic pressures in all patients. Peripheral resistances did not change. During exercise, GNT lowered PWP, systemic arterial pressure and peripheral resistances in all cases. It increased cardiac output as well as systolic and stroke work indices only in patients of subgroup I. In subjects with coronary disease, no overt cardiac failure but elevated PWP on exercise, GNT in a spray can quickly improve exercise capacity and hemodynamic reserves and increase anginal threshold.

Influence of nifedipine on left ventricular systolic and diastolic function: Relationships to manifestations of ischemia and congestive failure

In addition to the favorable effects of calcium antagonists on symptoms related to coronary spasm, we recently documented preclusion of ergonovine-induced coronary spasm angiographically in four patients with proved Prinzmetal's angina. To determine whether nifedipine has similar “relaxing” or negative inotropic actions on left ventricular myocardial function, we studied 19 patients with various degrees of left ventricular dysfunction before and after nifedipine (20 mg sublingually) during cardiac catheterization. Left ventricular afterload was reduced, with a significant (13 percent) decline in arterial pressure; left ventricular diastolic pressures were unchanged. Left ventricular ejection function was augmented, with significant increases in ejection fraction (14 percent), mean velocity of circumferential fiber shortening (41 percent), systolic ejection rate (25 percent), and end-systolic pressure volume ratio (19 percent). Cardiac index increased significantly by 16 percent. Early diastolic relaxation, diastolic pressure-volume relations and end diastolic stiffness remained unchanged after nifedipine. When patients were categorized (Group I: left ventricular end-diastolic volume ≤ 90 ml/m 2, end-diastolic pressure ≤ 20 mm Hg; Group II: end-diastolic volume > 90 ml/m 2, end-diastolic pressure > 20 mm Hg), highly pertinent differences were apparent. Nifedipine significantly reduced left ventricular preload and end-diastolic pressures in Group II but not in Group I patients. Enhancement of left ventricular ejection function in Group II patients was significantly more prominent than that in patients with normal baseline function. Although diastolic properties were insignificantly changed overall, the left ventricular diastolic pressure-volume relation was displaced downward by nifedipine in Group II, but not in Group I patients. Both systemic and pulmonary vascular resistance declined significantly more in Group II patients, whereas cardiac index was increased 25 percent compared with a negligible change in group I patients. These results indicate beneficial effects of nifedipine on myocardial oxygen requirements, particularly in patients with impaired left ventricular function in whom left ventricular preload and afterload were both significantly reduced, cardiac index augmented and the pressure-volume relation shifted downward. To confirm predicted symptomatic benefits in 13 other patients with fixed coronary, disease, incremental atrial pacing to anginal threshold was performed before and 30 minutes after nifedipine (20 mg sublingually). Mean paced heart rate at onset of angina increased 19.3 percent after nifedipine. Concomitantly, aortic pressure decreased significantly by 22.1 percent at the onset of angina; double product was unchanged at the anginal threshold. Thus, although left ventricular afterload was reduced by nifedipine, the anginal threshold was unchanged in terms of myocardial oxygen requirements. In concert, these results indicate that therapeutically effective influences of nifedipine in patients with fixed coronary disease are attributable basically to hemodynamic alterations consequent upon left ventricular afterload reduction. Nevertheless, such effects imply therapeutic benefit, the reduced afterload concomitantly permitting greater exercise-induced tachycardia before the anginal threshold is reached.

Respiratory Alkalemia during Exercise Reduces Angina Threshold

The effect of hyperventilation-induced alkalemia on angina threshold was evaluated in nine subjects who had a consistent pattern of chest pain and ST segment depression during exercise. For this study, the subjects performed graded bicycle exercise to angina during normal breathing and during hyperventilation. The maximum workload achieved was not significantly different between normal breathing and hyperventilation exercise. However, in five subjects who had arterial alkalemia during hyperventilation exercise (mean pH = 7.52), the heart rate X blood pressure product (HR X BP) at angina was 224 X 10(2) compared with 240 X 10(2) during normal breathing exercise (P less than 0.05). Four subjects appeared to hyperventilate, but were not alkalemic (mean pH = 7.40). Their HR X BP at angina was not significantly different between the two exercise periods (288 X 10(2) vs 284 X 10(2). In conclusion, the threshold for angina during exercise fell in the five patients in whom hyperventilation caused alkalemia. This finding suggests that the alkalemia interfered with myocardial oxygen supply.

Variable threshold of angina during exercise: A clinical manifestation of some patients with vasospastic angina

Two patients complained of chest pain while at rest and during physical activities. However there seemed to be no direct relation between exertional angina and an increasing level of work performed, indicating that these patients had a variable threshold of angina during exercise. In one patient spontaneous chest pain was associated with transient S-T segment changes in precordial leads, and during coronary arteriography the administration of ergonovine induced spasm of the left anterior descending coronary artery. The other patient showed S-T segment elevation in inferior leads during an ergonovine-induced anginal attack and coronary arteriography revealed a spontaneous spasm of the right coronary artery. In both patients repeated exercise tests yielded different results, because the chest pain and S-T segment depression occurred at different work loads with large differences in heart rate-systolic blood pressure product. It is concluded that a variable threshold of angina during exercise is a clinical manifestation in some patients with vasospastic angina and is probably due to the difference in coronary arterial tone at the onset of exercise.