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.     

Nocturnal angina: precipitating factors in patients with coronary artery disease and those with variant angina

Factors precipitating nocturnal myocardial ischaemia were investigated in 10 patients with frequent daytime and nocturnal angina pectoris. Eight patients had fixed obstructive coronary artery disease or a low exercise threshold or both before the onset of ischaemia. Two patients had variant angina with normal coronary arteries and negative exercise tests. During sleep the electrocardiogram, electroencephalogram, electro-oculogram, electromyogram, chest wall movements, nasal airflow, and oxygen saturation were continuously measured. Forty two episodes of transient ST segment depression were recorded in the eight patients with coronary artery disease and 26 episodes of ST segment depression and elevation in the two patients with variant angina and normal coronary arteries. All episodes of ST segment depression in the former group of patients were preceded by an increase in heart rate as a result of arousal and lightening of sleep, bodily movements, rapid eye movement sleep, or sleep apnoea (one episode). In contrast, in the variant angina group no increase in heart rate, arousal, or apnoea preceded 23 of the 26 episodes of ST segment change. Thus increase in myocardial oxygen demand was important in precipitating nocturnal angina in patients with coronary artery disease and reduced coronary reserve. In the patients with coronary spasm these factors did not often precede the onset of nocturnal myocardial ischaemia.     

Nocturnal angina: precipitating factors in patients with coronary artery disease and those with variant angina.

Factors precipitating nocturnal myocardial ischaemia were investigated in 10 patients with frequent daytime and nocturnal angina pectoris. Eight patients had fixed obstructive coronary artery disease or a low exercise threshold or both before the onset of ischaemia. Two patients had variant angina with normal coronary arteries and negative exercise tests. During sleep the electrocardiogram, electroencephalogram, electro-oculogram, electromyogram, chest wall movements, nasal airflow, and oxygen saturation were continuously measured. Forty two episodes of transient ST segment depression were recorded in the eight patients with coronary artery disease and 26 episodes of ST segment depression and elevation in the two patients with variant angina and normal coronary arteries. All episodes of ST segment depression in the former group of patients were preceded by an increase in heart rate as a result of arousal and lightening of sleep, bodily movements, rapid eye movement sleep, or sleep apnoea (one episode). In contrast, in the variant angina group no increase in heart rate, arousal, or apnoea preceded 23 of the 26 episodes of ST segment change. Thus increase in myocardial oxygen demand was important in precipitating nocturnal angina in patients with coronary artery disease and reduced coronary reserve. In the patients with coronary spasm these factors did not often precede the onset of nocturnal myocardial ischaemia.     

Salutary effect of nifedipine in pacing-induced angina: relation to afterload reduction

To determine the mechanisms responsible for beneficial effects of nifedipine in pacing-induced angina pectoris, 20 patients undergoing diagnostic cardiac catheterization were studied. Following left ventriculography and coronary arteriography, right atrial pacing was performed before and 30 min after administration of 20 mg of nifedipine sublingually. Heart rate was increased by 10-beat-per-minute (bpm) increments every 90 sec until angina occurred. Electrocardiogram, central aortic pressure, and pulmonary arterial occlusive pressure were monitored continuously. Mean paced heart rate at the onset of angina was increased from 107 +/- 12.6 bpm to 140.6 +/- 19.9 (P less than .001) after nifedipine. Systolic arterial pressure at the time of angina declined from 143 +/- 20 mm Hg to 112 +/- 23 mm Hg (P less than .001). Consequently, the double product heart rate X systolic blood pressure was not changed significantly at the onset of chest pain (149 +/- 28 mm Hg X 10(-2) vs. 142 +/- 28 mm Hg X 10(-2) ). Pulmonary arterial occlusive pressure also did not change significantly (10.4 +/- 4.4 vs. 10.5 +/- 5.9 mm Hg). Thus, nifedipine decreased myocardial oxygen demand at a given heart rate by reducing left ventricular afterload, but did not increase the rate pressure product threshold for ischemic pain. These results indicate that peripheral arterial vasodilator effects of nifedipine, with a resultant decrease in myocardial oxygen requirements, account for its antianginal effect in this setting in patients with fixed obstructive coronary artery disease.     

Inpatient treatment of unstable angina: Clinical perspective and sequential management

In the last decade, increasing information has become available to the effect that an increase in coronary artery tone and coronary artery spasm play an important role in patients with various ischemic heart disease syndromes. Coronary spasm may be superimposed on a coronary vessel already severely obstructed by atherosclerosis. Conversely, spasm may occur in an artery that is only minimally involved with atherosclerosis. The majority of patients studied in the United States with both stable and unstable angina pectoris have underlying severe organic obstructive coronary artery disease. There has now emerged a considerable amount of information from several centers showing that the calcium-channel blockers or calcium-flux antagonists are highly effective in the treatment of stable and unstable angina pectoris. This report focuses on the uses and limitations of one of these agents, nifedipine, in patients with unstable angina and provides a sequential approach to their management.     

The efficacy of the addition of nifedipine in patients with mixed angina compared to patients with classic exertional angina: a multicenter, randomized, double-blind, placebo-controlled clinical trial

Episodes of myocardial ischemia in patients with coronary artery disease may be due to transient increases in coronary vasomotor tone superimposed on a fixed atherosclerotic obstruction. The purpose of this study was to determine whether identification of the clinical pattern of angina could predict the therapeutic response to the addition of nifedipine to a regimen of beta blockers and/or long-acting nitrates. Seventy-two patients with stable exertional angina were divided into two groups: "classic exertional angina" (17 patients), defined as exertional angina with a stable threshold; and "mixed angina" (55 patients), defined as exertional angina provoked by a variable threshold and/or at least two episodes of rest angina within the 3 months prior to screening. Patients were studied with nifedipine and placebo in a 6-week, double-blind, crossover design that used serial anginal diaries, exercise treadmill tests, and 24-hour ambulatory ECG monitoring. In patients with mixed angina, nifedipine reduced the frequency of angina compared to that during placebo treatment (13.1 vs 9.9 episodes/3 weeks, p less than 0.01) and reduced nitroglycerin consumption (11.7 vs 7.5 tablets/3 weeks, p less than 0.05); while in patients with classic exertional angina, nifedipine had no symptomatic effect (7.9 vs 6.8 anginal episodes/3 weeks, NS; 6.4 vs 5.8 nitroglycerin tablets/3 weeks, NS). Patients in both groups experienced a significant decrease in the manifestations of ischemia during exercise testing. Patients with mixed angina experienced a reduction in the daily frequency of painful episodes of ST segment depression during nifedipine treatment compared to placebo (0.6 vs 0.2 episodes, p less than 0.05), but there was no effect on the frequency of episodes of silent ischemia (4.2 vs 3.4 episodes, NS). In patients with classic exertional angina, the addition of nifedipine had no effect on any measure of ambulatory ischemia. We conclude that patients with mixed angina are more likely to benefit symptomatically from the addition of nifedipine therapy than patients with classic exertional angina. The lack of a consistently preferential response to nifedipine in patients with mixed angina, however, suggests that episodic coronary vasoconstriction may not be the only mechanism responsible for ischemia in these patients, and/or that nifedipine may not necessarily provide additional therapeutic benefit beyond that conferred by a regimen of beta blockers and/or nitrates.     

Aging, autonomic function, and the perception of angina.

OBJECTIVE--To determine the effects of age and autonomic function on the perception of angina. DESIGN--Prospective evaluation of the relations between anginal perceptual threshold, autonomic function, and systolic blood pressure in patients with symptomatic coronary artery disease. Statistical analysis was by non-parametric techniques. SETTING--Cardiology departments of a district general hospital and a post-graduate teaching centre. SUBJECTS--82 non-diabetic men with typical exertional angina and coronary artery disease confirmed by arteriography (n = 64) or a history of Q wave infarction (n = 18). MAIN OUTCOME MEASURES--Age, anginal perceptual threshold, autonomic function, and blood pressure. Anginal perceptual threshold was defined as the time from onset of 0.1 mV ST depression to the onset of angina during treadmill stress testing. Autonomic function was measured as the ratio of peak heart rate during the Valsalva manoeuvre to the minimum rate after release. RESULTS--Anginal perceptual threshold showed a weak but significant correlation with age, with older patients tending to have a longer interval between the onset of ST depression and the onset of angina. Comparison of patients in the upper and lower quartile age ranges showed a difference of 50 seconds between median threshold measurements. Blood pressure and heart rate responses to the Valsalva manoeuvre also correlated with age, but neither variable correlated with the anginal perceptual threshold. CONCLUSIONS--In non-diabetic men with coronary artery disease the perception of angina tends to deteriorate with advancing age. The mechanism is unclear but is not attributable solely to alterations in blood pressure or autonomic function.     

Aging, autonomic function, and the perception of angina.

OBJECTIVE--To determine the effects of age and autonomic function on the perception of angina. DESIGN--Prospective evaluation of the relations between anginal perceptual threshold, autonomic function, and systolic blood pressure in patients with symptomatic coronary artery disease. Statistical analysis was by non-parametric techniques. SETTING--Cardiology departments of a district general hospital and a post-graduate teaching centre. SUBJECTS--82 non-diabetic men with typical exertional angina and coronary artery disease confirmed by arteriography (n = 64) or a history of Q wave infarction (n = 18). MAIN OUTCOME MEASURES--Age, anginal perceptual threshold, autonomic function, and blood pressure. Anginal perceptual threshold was defined as the time from onset of 0.1 mV ST depression to the onset of angina during treadmill stress testing. Autonomic function was measured as the ratio of peak heart rate during the Valsalva manoeuvre to the minimum rate after release. RESULTS--Anginal perceptual threshold showed a weak but significant correlation with age, with older patients tending to have a longer interval between the onset of ST depression and the onset of angina. Comparison of patients in the upper and lower quartile age ranges showed a difference of 50 seconds between median threshold measurements. Blood pressure and heart rate responses to the Valsalva manoeuvre also correlated with age, but neither variable correlated with the anginal perceptual threshold. CONCLUSIONS--In non-diabetic men with coronary artery disease the perception of angina tends to deteriorate with advancing age. The mechanism is unclear but is not attributable solely to alterations in blood pressure or autonomic function.     

Dynamic coronary tone in precipitation, exacerbation and relief of angina pectoris

Until recently, understanding of the pathogenesis of angina pectoris was based primarily on the concept of a fixed stenosis of one or more coronary arteries: Myocardial ischemia and angina occurred when myocardial oxygen consumption (MVO2) outstripped the capacity of the diseased coronary artery to delivery oxygen. Therapeutic strategies focused on interventions designed to reduce MVO2. The concept of dynamic obstruction, first applied to coronary spasm induced at rest and more recently to spasm induced by exercise, adds an additional important pathophysiologic mechanism responsible for causing angina pectoris. This study deals with the possibility that the concept of "spasm," as commonly understood, is too narrowly defined. It develops the hypothesis that subcritical increases in large vessel coronary tone occur, either in a "normal" coronary artery or in one with an existing lesion, that augment the degree of large vessel coronary resistance but not enough to exceed the vasodilator reserve of the coronary arterioles. Hence, although total coronary resistance, and thereby coronary flow, is unaltered at rest, the impingement on arteriolar vasodilator reserve would diminish the capacity to augment flow in response to increases in MVO2. Such coronary constriction would not precipitate angina at rest but would increase anginal threshold. Conversely, dilatation of a stenotic coronary artery could decrease the degree of obstruction and increase anginal threshold. This concept of dynamic coronary obstruction in the presence of "normal" or diseased coronary arteries implies a direct role for coronary vasodilators in some patients with angina pectoris, even when frank coronary spasm is absent. Also implicit in this hypothesis is the concept that dynamic and fixed components to obstruction may contribute variably to the degree of obstruction in different patients. Some patients with largely fixed obstruction would benefit mainly from attempts to lower MVO2 with nitrates and beta blocking agents. Dynamic coronary obstruction may constitute the major mechanism responsible for angina in other patients. In these persons nitrates or calcium channel blocking agents might provide the most efficacious form of therapy. Both fixed and dynamic obstruction may play an important role in symptom production in yet other patients. In such persons attempts to decrease MVO2 and the magnitude of coronary obstruction might provide the most successful form of therapy.     

Complementary mechanisms of atenolol and diltiazem in the clinical improvement of patients with stable angina

The combination of atenolol with diltiazem has been shown to be useful in the treatment of patients with coronary artery disease. Eighteen patients with proven coronary artery disease, stable angina, and no previous myocardial infarction were studied before and after treatment with atenolol (100 mg/day) (9 patients) or diltiazem (180 mg/day) (9 patients). Ischemic threshold at stress test, pressure-rate product at ischemic threshold, direct oxygen consumption at ischemic threshold, and exercise ejection fraction were determined. There was a slight increase in the duration of exercise, maximal oxygen consumption, and ischemic threshold after treatment with each drug. Double product at ischemic threshold decreased from 20.9 to 19.8 (p = NS) with atenolol but increased from 20.1 to 21.9 (p = NS) with diltiazem. Conversely oxygen consumption at ischemic threshold increased with atenolol to nearly significant values from 17.2 to 23.6 (p = 0.067) but not with diltiazem (16.2 to 22.3; p = 0.16). Before treatment, exercise ejection fraction increased less than 10% or decreased from its resting values in all patients but 1 with atenolol and 1 with diltiazem, but exercise ejection fraction increased significantly after treatment with atenolol (60.6 to 67.5; p = 0.02) but not with diltiazem. This improvement was due to a significant reduction in end systolic volume (103.8 to 78.6; p = 0.019), despite a similar increase in heart rate and blood pressure in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of a slow-release nifedipine on 24-hour ambulatory blood pressure and ischemic changes on 24-hour ambulatory electrocardiogram in patients with severe coronary artery disease

Calcium antagonists have long been used as first-line drugs for hypertension and angina. However, deleterious effects have also been reported in patients treated with calcium antagonists. Thus, we evaluated the effect of a slow-release twice-daily formulation of nifedipine in 10 patients with severe coronary artery disease. Twenty-four-hour ambulatory electrocardiography (AECG) and blood pressure monitoring (ABPM) were performed simultaneously to detect any association between ischemic episodes on the ECG and changes in blood pressure (BP) and heart rate with and without nifedipine. Increased oxygen demand due to an increased systolic BP and heart rate was associated with ischemic episodes without nifedipine, while those with nifedipine were accompanied by a fall in diastolic BP and a rapid increase in heart rate. This slow-release twice-daily formulation of nifedipine may induce myocardial ischemia through a heart-rate increase and a decrease in coronary blood flow due to lower diastolic BP in patients with severe coronary artery disease. A once-daily formulation of nifedipine might be of great value for such patients.     

Usefulness of nicardipine for angina pectoris

Nicardipine treatment has been evaluated in patients with chronic stable effort angina or with angina at rest due to coronary spasm. Acute studies in patients with effort angina suggest a very favorable hemodynamic profile characterized by coronary vasodilatation and reduction in determinants of myocardial oxygen demand. Both open and controlled trials in patients with effort angina show that long-term oral administration increases exercise time and time to onset of 1 mm ST-segment depression and decreases angina frequency. With treatment for up to 6 months, antiischemic effects were maintained without serious adverse reactions. Other studies indicate that nicardipine is generally comparable to propranolol and nifedipine in prolonging exercise time and time to onset of ST-segment depression. Nicardipine, however, does not depress heart rate at rest, and maximal exercise workload is higher with nicardipine than with either placebo or propanolol. In a controlled study of patients with angina at rest due to coronary spasm, nicardipine decreased angina frequency and nitroglycerin consumption by approximately 80%. Episodes of symptomatic and asymptomatic ST-segment shift, as recorded by ambulatory electrocardiographic monitoring, showed a trend to decrease in number. Nicardipine appeared similarly effective in patients with coronary spasm superimposed on significant coronary disease and with spasm in the absence of significant coronary disease. Nicardipine appears to be safe and effective in the management of patients with angina pectoris.     

Myocardial catecholamine balance during angina: effects of calcium entry blockers, verapamil and nifedipine

To evaluate the effects of calcium entry blocking agents on cardiac sympathetic tone during angina pectoris, arterial and coronary sinus (CS) norepinephrine (NE) and epinephrine (E) concentrations and CS blood flow were determined at rest and during pacing-induced angina, both before and after verapamil in nine patients and after nifedipine in nine patients, all of whom had fixed obstructive coronary artery disease. Resting arterial NE and E concentrations and myocardial NE release and E uptake remained unchanged during angina before verapamil and nifedipine, suggesting unaltered systemic and cardiac sympathetic tone and myocardial E handling. Following verapamil and nifedipine, arterial NE and E concentrations remained unchanged. After verapamil, net myocardial NE release increased from 16,072 +/- 18,881 to 35,520 +/- 30,595 at preverapamil angina rate (p less than 0.01) and to 39,643 +/- 29,728 pg/min at postverapamil angina rate (p less than 0.01). NE release after nifedipine increased from -4207 +/- 8898 to 10,988 +/- 30,711 (p less than 0.05) at prenifedipine angina rate and to 19,942 +/- 26,644 pg/min (p less than 0.05) at postnifedipine angina rate. NE release was independent of changes in CS flow after verapamil or nifedipine. E uptake after verapamil and nifedipine remained unchanged. Although the precise mechanism is not known, myocardial alpha-adrenergic receptor blockage with verapamil and nifedipine remains a possible explanation for increased myocardial NE release.     

Safety of acute calcium antagonist withdrawal: studies in patients with unstable angina withdrawn from nifedipine

The acute effects of nifedipine withdrawal were studied in 81 patients with angina at rest who had completed a prospective, double-blind, randomized trial of nifedipine versus placebo. Thirty-nine of the 81 patients (group 1) were withdrawn from nifedipine or placebo at the time of coronary artery bypass surgery for uncontrolled angina or left main coronary artery disease. When the patients withdrawn from nifedipine were compared with those withdrawn from placebo, no significant differences were seen in the incidence of hypotension, myocardial infarction, significant arrhythmias or vasopressor or vasodilator requirements during the perioperative period. Forty-two patients (group 2) completed 2 years on a protocol consisting of nitrates and propranolol, in addition to nifedipine or placebo. These patients were hospitalized for a controlled withdrawal of the study drug (nifedipine or placebo), and no significant difference was noted in either exercise performance on serial treadmill testing or the number or duration of episodes of ischemic ST-segment changes during continuous electrocardiographic monitoring. Eight patients continued to experience occasional episodes of angina at rest. Angina at rest recurred during the withdrawal period in 5 of these 8 patients. Four of these 5 patients were withdrawn from nifedipine. Of the 34 stable patients in group 2 who were not experiencing angina at rest before withdrawal, none had angina at rest during the withdrawal study period. Thus, there were no early untoward effects of acute nifedipine withdrawal either in patients undergoing coronary bypass surgery or in stable patients on long-term medical therapy. However, patients with persistent symptoms of angina at rest may experience early recurrent ischemia upon withdrawal from nifedipine.     

Changes in angina threshold induced by administration of ergonovine maleate during pacing in patients with chronic exertional angina

It is widely accepted that the occurrence of chest pain and/or ST segment elevation during ergonovine testing is a hallmark of abnormal coronary constriction. However, the negativity of this test cannot be considered as an incontrovertible proof of the absence of coronary sensitivity to vasoconstriction. Indeed, it could only indicate that the resulting effect is inadequate to critically reduce coronary blood flow. To test this hypothesis we studied 12 patients with proven coronary artery disease and negative ergonovine test who had complained of chronic exertional angina pectoris and referred variable threshold for the occurrence of pain. They were submitted to atrial pacing (starting from 90 bpm, with 10 bpm increments every 2 min) before (control) and after ergonovine administration (total dose = 0.675 mg). Time, heart rate and rate pressure product were evaluated at the onset of angina and significant ischemia (0.1 mV ST segment depression). After ergonovine, angina was achieved earlier (405 +/- 173 vs 526 +/- 180 sec, p less than 0.005) than during control and at a lower heart rate (116 +/- 15 vs 131 +/- 15 bpm, p less than 0.001) and rate pressure product (15.8 +/- 2.0 vs 18.8 +/- 2.3 X 10(3) U, p less than 0.001). Changes in anginal threshold were widely variable among cases being that the time to onset of pain was dramatically reduced in certain patients but unchanged in one. Similar results were obtained when substituting the ischemic to the anginal threshold. Thus, negativity to ergonovine testing does not imply the absence of coronary constriction which may be revealed when increasing myocardial oxygen demand by atrial pacing.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of isradipine and nifedipine in chronic stable angina

Isradipine, a new dihydropyridine calcium antagonist, was compared to nifedipine in the treatment of 11 male patients with angina and coronary artery disease in a randomised, double-blind cross-over study. Patients received 5 mg nifedipine three times a day rising to 20 mg three times a day in three dosage increments over six weeks or 2.5 mg isradipine three times a day rising to 7.5 mg three times a day in three dosage increments over six weeks, and then received the alternate preparation. There were no significant differences between the drugs in terms of the frequency and severity of angina attacks or the consumption of glyceryl trinitrate. The increases in systolic blood pressure and the double product during exercise were significantly less with isradipine than with nifedipine. There was a similar trend in heart rates. There was no difference between the treatments in respect of exercise induced ST-segment depression or diastolic blood pressure. We conclude that isradipine and nifedipine have similar anti-anginal effects and that isradipine may be a useful new anti-anginal agent.     

Coronary hemodynamic and metabolic effects of nifedipine in patients with coronary artery disease treated with beta-blocking drugs

In humans, reflex sympathetic nerve activation modulates the direct cardiac action of nifedipine after systemic administration and results in a positive chronotropic and inotropic response. The coronary hemodynamic and metabolic effects of nifedipine were evaluated after propranolol-induced acute beta-receptor blockade in 12 patients with angiographically documented coronary artery disease. The intravenous injection of propranolol led to a decrease in heart rate, coronary blood flow and myocardial oxygen consumption and an increase in coronary vascular resistance and the coronary arteriovenous oxygen difference. Mean aortic pressure did not change. The subsequent intravenous administration of nifedipine resulted in a transient increase in coronary blood flow and a reduction in coronary vascular resistance and the coronary arteriovenous oxygen difference and a sustained decrease in mean aortic pressure and myocardial oxygen consumption without significant changes in heart rate. Thus, in the presence of beta-receptor blockade, the positive chronotropic response to nifedipine is attenuated and nifedipine reduces myocardial oxygen consumption significantly. The vasodilatory effect of nifedipine is maintained and a potential propranolol-related inappropriate vasoconstriction may be reversed. The combination of nifedipine and beta-receptor blocking agents may be useful in the treatment of patients with both effort-induced angina and angina related to changes in coronary vasomotor tone.     

Effects of intravenous glucose during pacing-induced angina pectoris in patients with coronary artery disease

The effects of hypertonic glucose infusion on the anginal threshold determined by atrial pacing was studied in 14 patients with significant coronary artery disease. After glucose, angina occurred at a significantly lower heart rate and double product (systolic arterial pressure × heart rate), suggesting a decreased tolerance to ischemic stress. No stoichiometric relationship was noted between glucose uptake and lactate production, and there was no evidence that hypertonic glucose infusion resulted in enhanced anaerobic glycolysis in the ischemic myocardium. Acute elevation of plasma glucose levels may not be beneficial to patients with coronary artery disease.     

Therapy of coronary vasoconstriction in patients with coronary artery disease

Patients with obstructive coronary artery disease and stable, exertional angina respond to the alpha adrenergic stimulus of the cold pressor test with an inappropriate increase in coronary vascular resistance. The clinical significance of this abnormal response and its possible role in the pathogenesis of ischemic heart disease are discussed. Comparison of the anti-anginal agents currently in use of undergoing investigation suggests that the calcium antagonists may be the most effective therapy for coronary vasoconstriction. Nifedipine, 10 mg buccally, successfully prevented the increase in coronary vascular resistance during the cold pressor test in 10 of 10 patients, whereas the response in placebo-treated patients was unaltered. This dose of nifedipine was without effect on systemic hemodynamics or myocardial oxygen consumption, suggesting a selective antivasoconstrictor effect on the coronary vasculature.     

Evidence for transient limitations in coronary blood flow during unstable angina pectoris: hemodynamic changes with spontaneous pain at rest versus exercise-induced ischemia following stabilization of angina

The pathophysiologic basis for the deterioration of patients with stable angina pectoris to unstable angina is unclear. Central to this issue is the question of whether myocardial ischemia occurs at the same or at a lower myocardial oxygen demand during unstable periods as during stable periods. Consequently, we compared myocardial oxygen demand in 12 patients at the onset of spontaneous pain during unstable angina to myocardial oxygen demand during exercise-induced ischemia after resumption of stable angina, 6–12 weeks later. Myocardial oxygen demand was estimated from values for heart rate (HR), systolic blood pressure (BP), and the rate-pressure product (RPP). Rate-pressure product is the heart rate × systolic blood pressure × 10^-2 (mmHg/min/10²). There was definite evidence for coronary artery spasm for only one patient. There was no difference in heart rate, blood pressure, or rate-pressure product during pain-free intervals in the hospital and just before the start of exercise testing. Mean H R (71.2± 11.1 beats/min; mean ± standard deviation) and RPP (95.8±20.0 mmHg/min/10²) just before spontaneous angina during the unstable period were significantly lower (p<0.001) than at the termination of bicycle ergometry in both the supine (HR, 96.9±10.5 beats/min; RPP, 141.8±25.0 mmHg/min/10²) and upright (HR, 98.1±13.6 beats/min; RPP, 143.0±32.2 mmHg/min/10²) positions. Blood pressure (134.5 ± 17.6 mmHg) just before spontaneous angina was significantly lower than at the conclusion of both supine (145.6±13.3 mmHg) and upright (145.1 ±18.6 mmHg) ergometry. The observation that myocardial oxygen demand was lower at the threshold of ischemia with spontaneous angina than with exercise-induced ischemia is consistent with the hypothesis that there were transient, reversible limitations in coronary blood flow during the period of unstable angina. There was also a moderate but significant rise in estimated myocardial oxygen demand just before spontaneous angina in these patients, but the nature of the data do not allow us to distinguish whether or not this rise was part of the cause or an effect of ischemia. While the results of this study did not identify the cause for the transient limitations in coronary flow, coronary artery spasm without ST-segment elevation, intracoronary platelet aggregates, and hemorrhage into atherosclerotic plaques are possibilities that are consistent with these hemodynamic observations.