Characteristics of left ventricular filling in coronary artery disease and myocardial ischaemia after dipyridamole provocation.

Doppler echocardiographic measurement of transmitral filling velocities seems to be a sensitive marker for resting left ventricular diastolic abnormalities in patients with coronary artery disease. The behaviour of these filling velocities during induced myocardial ischaemia, however, has not been fully studied. Left ventricular filling was assessed by pulsed Doppler ultrasound in 21 patients with angina pectoris and coronary artery disease and in five controls (patients with chest pain but without myocardial ischaemia). High dose dipyridamole infusion (0.9 mg/kg over 10 minutes) was used to provoke myocardial ischaemia, which was assessed by symptoms and electrocardiographic ST segment change. Doppler indices of diastolic filling were measured and the results expressed as percentage change from baseline values. Dipyridamole increased the heart rate and reduced systolic blood pressure equally in both groups. In the controls dipyridamole increased the peak filling velocities of both the early and atrial filling waves. In the 12 patients with coronary artery disease who did not develop evidence of myocardial ischaemia, the effect on left ventricular filling velocity resembled that in the controls though the time to peak change was delayed. Six of the nine patients with dipyridamole induced myocardial ischaemia had a significantly reduced maximum changes in early (+30% v +18%) and atrial (-0.2% v +33%) filling velocities compared with the controls. The remaining three patients had a decrease in early filling velocity (-20%) with an associated increase in atrial peak filling velocity (+21%). Dipyridamole increased diastolic filling velocities in the controls. In patients with coronary artery disease there was a variable change in diastolic filling indices which may be attributed either to the degree of myocardial ischaemia or to the different haemodynamic changes occurring during myocardial ischaemia.     

Lack of platelet-activating factor release during reversible myocardial ischaemia.

Platelet-activating factor (PAF) is involved in experimental models of myocardial ischaemia, and PAF infusion can cause thromboxane release. Thromboxane is produced during brief episodes of reversible myocardial ischaemia in patients with coronary heart disease. To learn whether PAF synthesis is associated with thromboxane production in mild myocardial ischaemia, we performed rapid atrial pacing in four patients with angina pectoris which caused chest pain, ST segment depression (delta ST = -1.8 +/- 0.2 mm) and lactate excretion in the coronary sinus (percent lactate extraction decreased from 20 +/- 6% to -15 +/- 9%). Thromboxane B2 was produced causing a positive transmyocardial gradient (from 88 +/- 154 pg.ml-1 baseline to 1770 +/- 1407 pg.ml-1 at the peak) but there was no PAF release into coronary sinus blood. In four other patients we determined whether more pronounced ischaemia could be associated with PAF synthesis. Coronary sinus blood was sampled before and during balloon occlusion of a major coronary artery: PAF was not detected in coronary sinus, whereas percent lactate extraction decreased from 24 +/- 6% to -63 +/- 22% (n = 4). We conclude that PAF plays a minor role in short episodes of reversible ischaemia and does not participate in thromboxane production.     

Tolerance and prognostic value of Thallium 201 myocardial tomoscintigraphy with dipyridamole in the aged subject

The authors present a retrospective study of 46 consecutive patients aged from 70 to 79 years (mean 73.3 +/- 2.5 years) with suspected coronary artery disease who, being unfit for exercise tests, were explored by myocardial scintigraphy with thallium 201 after coronary dilatation with intravenous dipyridamole. The examination was well tolerated by 30 patients. Such classical side-effects as chest pain, malaise, dizziness, headache, flushing, vomiting and transient arrhythmia or repolarization disorders were recorded, but they were not more frequent than in younger subjects. However, the occurrence of severe hypotensive malaise relieved by theophylline in two cases and of angina in about one third of patients with myocardial ischaemia means that the procedure must be performed under close supervision. A fall in blood pressure (-11 mmHg on average) and a rise in heart rate (+8 beats/min on average) were usual. Post-scintigraphy follow-up of patients over a mean period of 11.1 +/- 6.2 months showed that a reversible defect of thallium 201 uptake, due to redistribution, is a highly selective indicator of patients who are particularly exposed to a cardiac accident in the short--or mid-term. Only one out of 26 patients without reversible ischaemia (4 p. 100) subsequently presented with a major coronary event (unstable angina). In contrast, in the group of 20 patients with reversible ischaemia three required early myocardial revascularization; furthermore, five serious accidents (29 p. 100) occurred among the 17 patients who were left under medical treatment, including two sudden deaths, two cases of unstable angina and one case of myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Symptomatic bradycardia complicating the use of intravenous dipyridamole for thallium-201 myocardial perfusion imaging

Intravenous dipyridamole was given for routine thallium-201 myocardial perfusion imaging. The patient developed chest discomfort followed by cardiovascular collapse with sinus arrest and a nodal escape rhythm at 28 beats per minute. He was rapidly resuscitated without adverse sequelae. A reversible posteroinferior perfusion defect and proximal right coronary artery occlusion were found. Symptomatic bradycardia after dipyridamole may be mediated by ischaemia.     

Reversibility by dipyridamole of thallium-201 myocardial scan defects in patients with sarcoidosis

PURPOSE: In order to clarify the significance of anginal pain and myocardial thallium-201 scan defects in cardiac sarcoidosis, the pharmacologic effect of dipyridamole on myocardial perfusion was assessed by planar thallium-201 myocardial scintigraphy in patients with sarcoidosis. PATIENTS and METHODS: Thallium-201 myocardial scintigraphy was performed at rest and after 0.56 mg/kg intravenous dipyridamole during four minutes in 16 patients with sarcoidosis. The myocardial scan (45-degree and 70-degree left anterior oblique, and anterior views) was divided into 15 segments. Results were evaluated by the number of segmental defects and with a global perfusion score (from 0 to 60) by a semi-quantitative index depending on the size and severity of myocardial thallium-201 defects. RESULTS: Thirteen of the 16 patients showed partial or total reversion of their thallium-201 defects on redistribution scanning either at rest or after dipyridamole. The mean (+/- SD) number of myocardial perfusion defects that were present in all the patients decreased from 5.31 +/- 1.78 at rest to 3.25 +/- 2.52 after redistribution (p less than 0.001) and to 2.19 +/- 2.10 after dipyridamole (p less than 0.001). The mean global perfusion score increased from 53.2 +/- 3.0 at rest to 56.2 +/- 2.9 after redistribution (p less than 0.001) and to 57.2 +/- 2.7 after dipyridamole (p less than 0.001). A significant correlation (r = 0.82, p less than 0.001) was found between the increase of global perfusion score on redistribution and after dipyridamole. CONCLUSION: The reversibility of myocardial scan defects is a common finding in sarcoidosis. It makes unlikely the role of scar fibrosis or extensive confluent granulomas as a mechanism for such defects. The effect of dipyridamole suggests the presence of reversible disorders lying at the coronary microvascular level.     

High dose intravenous streptokinase for acute myocardial infarction: preliminary results of a multicenter trial

To assess the efficacy of intravenous streptokinase in patients with acute myocardial infarction, 40 patients (30 men and 10 women, mean age 54 years) with acute myocardial infarction were given 1.5 million U of streptokinase intravenously in 1 hour, and coronary arteriography was performed repeatedly to assess reperfusion. Streptokinase treatment was begun 270 +/- 86 (mean +/- SD) minutes after the onset of chest pain. Of the 40 patients, 34 had total or near total coronary occlusion before streptokinase administration. In 14 (41%) of these 34 patients, some reperfusion occurred during the 90 minutes after the administration of streptokinase, but in only 11 of the 14 was reperfusion present at 90 minutes. After streptokinase administration, all patients received heparin for 8 to 10 days; they were subsequently administered aspirin and dipyridamole. Clinical evidence of reocclusion during the first 24 hours of heparin therapy occurred in one patient. Thus, when given to patients with acute myocardial infarction and total coronary occlusion an average of 4 1/2 hours after the onset of chest pain, high dose intravenous streptokinase achieves reperfusion in only about 40% and results in sustained reperfusion in only about 30%.     

Dipyridamole-induced myocardial ischaemia increases ANF release in man.

Atrial natriuretic factor (ANF) release is modulated by several haemodynamic factors, including ventricular and atrial wall stretch. Dipyridamole infusion, which is commonly used as a pharmacological stressor in patients with coronary artery disease, can acutely increase ventricular and atrial pressure via myocardial ischaemia. The aim of this study was to assess whether dipyridamole infusion (up to 0.84 mg kg-1 over 10') can affect ANF release in man. Nineteen patients (13 men, 6 women) with a history of chest pain were studied. Their drug regimen was interrupted and instead they were administered a dipyridamole infusion, combined with two-dimensional echocardiography and 12-lead ECG monitoring. Plasma ANF was measured by RIA while the patients rested, and after dipyridamole infusion. Eight patients had no evidence of myocardial ischaemia, as measured by electrocardiographic and/or echocardiographic criteria, during dipyridamole infusion: among them, ANF values were similar while they were at rest and at peak dipyridamole administration (23.9 +/- 9.5 vs 23.4 +/- 6.9 pg ml-1, P = ns). Eleven patients had dipyridamole-induced transient ischaemia (regional ventricular dyssynergy and/or ST segment depression): among them, ANF values rose significantly at peak dipyridamole administration (31.8 +/- 13.8 vs 65.5 +/- 36.4, P less than 0.01). We conclude that dipyridamole infusion does not increase ANF release in man in the absence of ischaemia. The induction of myocardial ischaemia acutely increases ANF release, probably through a rise in ventricular and atrial wall stress.     

Pharmacodynamic effect of dipyridamole on thallium-201 myocardial perfusion in progressive systemic sclerosis with diffuse scleroderma.

We evaluated the effect of dipyridamole on thallium-201 myocardial perfusion in 23 patients with progressive systemic sclerosis (PSS) with diffuse scleroderma. Thallium-201 single photon emission computed tomography (SPECT) was performed at rest and after coronary artery vasodilatation with intravenous dipyridamole (0.14 mg/kg/min for four minutes). The left myocardium was divided into nine segments; each segment was graded as 2.0, 1.5, 1.0, 0.5, 0 (zero represents no activity). Dipyridamole significantly improved resting thallium-201 myocardial perfusion: the mean (SD) number of segments with thallium defects decreased from 6.0 (2.1) at rest to 4.1 (2.5) after dipyridamole (p less than 0.0001); the mean (SD) score in segments with resting defects increased from 0.92 (0.24) at rest to 1.13 (0.38) after dipyridamole (p less than 0.0001); the mean (SD) global score per patient increased from 10.2 (1.8) at rest to 11.4 (2.1) after dipyridamole (p less than 0.02); the global score increased by at least 2.0 in 12 patients and worsened by at least 2.0 in three patients only (p = 0.05). The results of this acute study suggest that some drugs with potent vasodilator activity on small coronary arteries may be beneficial in the treatment of PSS patients with thallium-201 myocardial perfusion abnormalities.     

Negative stress echocardiographic responses in normotensive and hypertensive patients with angina pectoris, positive exercise stress testing, and normal coronary arteriograms

OBJECTIVES: To systematically compare the results of dobutamine stress echocardiography in matched groups of hypertensive and normotensive patients with anginal chest pain and normal coronary arteriograms (CPNA). SETTING: University hospital. SUBJECTS: 33 patients with exertional anginal chest pain, a positive exercise stress ECG, and a completely normal coronary arteriogram; 17 had a history of systemic hypertension (14 women; mean (SD) age 57 (6) years), and 16 had no hypertensive history (12 women; age 54 (9) years). METHODS: Ambulatory ECG monitoring, dobutamine stress echocardiography, and thallium-201 single photon emission computed tomography (SPECT) were performed in all subjects. RESULTS: All patients had normal left ventricular systolic function at rest and none fulfilled the criteria for ventricular hypertrophy. Eight normotensive patients and 10 hypertensive patients had perfusion abnormalities on thallium SPECT (p = 0.61). Dobutamine infusion reproduced anginal pain in seven normotensive and seven hypertensive patients (p = 0.88). ST segment depression was also recorded in eight normotensive patients and seven hypertensive patients (p = 0. 61). No patient in either group developed regional wall motion abnormalities during dobutamine stress echocardiography. CONCLUSIONS: Neither hypertensive nor normotensive CPNA patients developed regional wall motion abnormalities during dobutamine stress echocardiography, despite the high prevalence of scintigraphic perfusion defects in both groups and the presence of chest pain and ST segment depression. Thus myocardial ischaemia was not present in either group, or else dobutamine stress echocardiography is insensitive to ischaemia caused by microvascular dysfunction.     

Dipyridamole is superior to dobutamine for thallium stress imaging: a randomised crossover study.

OBJECTIVE--To assess the value of dobutamine over dipyridamole as a pharmacological stressing agent in myocardial perfusion imaging with thallium-201. DESIGN--Stress and redistribution tomographic images were taken in a group of patients in a randomised crossover study of both agents. The scans were scored to give a value for the stress and redistribution images and a reversibility score (redistribution--stress). All patients had coronary angiography that was also scored. Differences between the two agents were compared by a paired t test. PATIENTS--30 patients aged 51-70 years with chest pain thought to be caused by myocardial ischaemia. 11 had had previously myocardial infarction. RESULTS--Dipyridamole caused adverse symptoms in six patients whereas dobutamine caused symptoms in 21 patients (chi 2 = 15.15, p < 0.0001). Dobutamine stress took considerably longer than dipyridamole (31 v 6 minutes) and cost more (17 pounds v 1.50 pounds). There were no significant differences between the agents in terms of total stress or redistribution scores, but regional analysis showed that dipyridamole showed significantly more defects during stress at the apex and lateral wall (p < 0.05), with no significant difference at redistribution. Dipyridamole stress also caused significantly more reversible defects at the apex (p < 0.05) and gave a better correlation than dobutamine with coronary score (dipyridamole r = 0.80, p < 0.001 v dobutamine r = 0.64, p < 0.001). In six patients who had continued to take beta blockers the results of dobutamine stress did not correlate with coronary score, r = 0.34 (NS), whereas dipyridamole studies were not affected. CONCLUSION--Compared with dobutamine, dipyridamole was as effective in producing overall perfusion defects and more effective in provoking defects at the apex and lateral segment. The dipyridamole study correlated better with coronary score and was not affected by concurrent beta blocker treatment. It was also better tolerated by the patients, was less time consuming, and was much cheaper.     

Cardiac syndrome X in women: the role of oestrogen deficiency

Cardiac syndrome X (CSX), defined as typical exertional chest pain, a positive response to stress testing, and normal coronary arteriograms, encompasses different pathogenic subgroups. Both cardiac and non-cardiac mechanisms have been suggested to play a pathogenic role, and it has been shown that the syndrome is associated with myocardial ischaemia in at least a proportion of patients. Radionuclide myocardial perfusion defects, coronary sinus oxygen saturation abnormalities and pH changes, myocardial lactate production and stress-induced alterations of cardiac high energy phosphate have been reported in CSX patients, suggesting an ischaemic origin for their symptoms. Microvascular abnormalities often caused by endothelial dysfunction appear to be responsible for myocardial ischaemia in these patients. CSX is more prevalent in women than in men, and the majority of women with CSX are peri- or post-menopausal. Thus oestrogen deficiency has been suggested to have a pathogenic role in CSX. Additional factors such as abnormal pain perception may also contribute to the genesis of chest pain in patients with angina and normal coronary angiograms. The management of this syndrome is difficult because of the heterogeneity of pathogenic mechanisms and uncertainties as to its origin. This article discusses the problem of CSX in women, the potential pathogenic role of oestrogen deficiency, and practical clinical management.     

Symptomatic and silent myocardial ischaemia in hypertensive patients with left ventricular hypertrophy.

OBJECTIVE--To assess the prevalence of symptomatic and silent myocardial ischaemia in patients with hypertensive left ventricular hypertrophy. DESIGN--Cross sectional study. SETTING--University department of medical cardiology. PATIENTS--90 patients (68 men and 22 women; mean age 57 (range 25 to 79)) with left ventricular hypertrophy due to essential hypertension. INTERVENTIONS--48 hour ambulatory ST segment monitoring (all patients), exercise electrocardiography (n = 79), stress thallium scintigraphy (n = 80), coronary arteriography (n = 35). RESULTS--43 patients had at least one episode of ST segment depression on ambulatory electrocardiographic monitoring. The median number of episodes was 16 (range 1 to 84) with a median duration of 8.6 (range 2 to 17) min. Over 90% of these episodes were clinically silent. 26 patients had positive exercise electrocardiography and 48 patients had reversible thallium perfusion defects despite chest pain during exercise in only five patients. 18 of the 35 patients who had coronary arteriography had important coronary artery disease. Seven of these patients gave no history of chest pain. CONCLUSIONS--Symptomatic and silent myocardial ischaemia are common in hypertensive patients with left ventricular hypertrophy, even in the absence of epicardial coronary artery disease.     

Symptomatic and silent myocardial ischaemia in hypertensive patients with left ventricular hypertrophy.

OBJECTIVE--To assess the prevalence of symptomatic and silent myocardial ischaemia in patients with hypertensive left ventricular hypertrophy. DESIGN--Cross sectional study. SETTING--University department of medical cardiology. PATIENTS--90 patients (68 men and 22 women; mean age 57 (range 25 to 79)) with left ventricular hypertrophy due to essential hypertension. INTERVENTIONS--48 hour ambulatory ST segment monitoring (all patients), exercise electrocardiography (n = 79), stress thallium scintigraphy (n = 80), coronary arteriography (n = 35). RESULTS--43 patients had at least one episode of ST segment depression on ambulatory electrocardiographic monitoring. The median number of episodes was 16 (range 1 to 84) with a median duration of 8.6 (range 2 to 17) min. Over 90% of these episodes were clinically silent. 26 patients had positive exercise electrocardiography and 48 patients had reversible thallium perfusion defects despite chest pain during exercise in only five patients. 18 of the 35 patients who had coronary arteriography had important coronary artery disease. Seven of these patients gave no history of chest pain. CONCLUSIONS--Symptomatic and silent myocardial ischaemia are common in hypertensive patients with left ventricular hypertrophy, even in the absence of epicardial coronary artery disease.     

Effects of dipyridamole on coronary collateralization and myocardial perfusion in patients with ischaemic cardiomyopathy.

AIMS: There is evidence that oral dipyridamole, a nucleoside uptake blocker that increases myocardial adenosine levels, lessens myocardial ischaemia by inducing coronary collateral growth in animal models of ischaemic heart disease. However, whether dipyridamole can exert a similar effect in humans with coronary artery disease is controversial. METHODS AND RESULTS: We studied 30 male patients (mean age 55+/-9 years) with coronary artery disease and left ventricular systolic dysfunction (ejection fraction >40%). Patients were randomized into three matched groups. Group A patients (n=10) received dipyridamole alone at a dose of 75 mg t.i.d. orally for 8 weeks. Group B patients (n=10) underwent exercise training at 60% of peak .VO(2)three times a week for 8 weeks, and received dipyridamole. Group C patients (n=10) had neither exercise testing nor dipyridamole. On study entry and after 8 weeks all patients underwent an exercise test with gas exchange analysis, dobutamine stress echocardiography, 201-thallium planar myocardial scintigraphy, and coronary angiography. Peak .VO(2)increased significantly only in trained patients. Thallium uptake of the collateral-dependent myocardium, coronary collateral score and wall thickening score increased significantly only in groups receiving dipyridamole, the greatest improvement being in group B patients. Plasma adenosine levels were also the highest in group B (P<0.001 vs A and C). Correlations were found between changes in adenosine levels and increases of both thallium uptake (r=-0.70;P=0.001) and collateralization (r=0.72;P=0.001). CONCLUSION: Exercise training potentiates the effects of dipyridamole on coronary collateralization and myocardial perfusion in humans with ischaemic cardiomyopathy.     

Continuous coronary sinus and arterial pH monitoring during pacing-induced ischaemia in coronary artery disease.

Catheter tip pH electrodes were used for continuous recording of coronary sinus and arterial pH during atrial pacing in 20 patients undergoing coronary arteriography for chest pain. An ischaemic response to atrial pacing was identified by the onset of angina and/or electrocardiographic abnormalities. Technically satisfactory coronary sinus recordings were obtained in 18 patients. Mean coronary sinus pH at the peak pacing rate fell by 0.021 +/- 0.006 units (n = 9) in the ischaemic group, while there was no significant change in the non-ischaemic group. A larger fall in coronary sinus pH (-0.052 +/- 0.009) was found in the ischaemic group in the 30 seconds after the end of atrial pacing, the maximum change occurring after 16.1 +/- 1.5 seconds. A maximum fall of coronary sinus pH greater then 0.02 units identified patients with an ischaemic response. Changes in arterial pH did not account for these results. The sensitivity of coronary sinus pH recording for the detection of ischaemic heart disease is enhanced by sampling during the "washout" phase after the end of pacing.     

Low-dose dipyridamole infusion acutely increases exercise capacity in angina pectoris: a double-blind, placebo controlled crossover stress echocardiographic study

OBJECTIVES: The aim of this study was to assess whether endogenous accumulation of adenosine, induced by low-dose dipyridamole infusion, protects from exercise-induced ischemia. BACKGROUND: Adenosine is a recognized mediator of ischemic preconditioning in experimental settings. METHODS: Ten patients (all men: mean age 63.4 +/- 7.3 years) with chronic stable angina, angiographically assessed coronary artery disease (n = 7) or previous myocardial infarction (n = 3) and exercise-induced ischemia underwent on different days two exercise-stress echo tests after premedication with placebo or dipyridamole (15 mg in 30 min, stopped 5 min before testing) in a double-blind, placebo controlled, randomized crossover design. RESULTS: In comparison with placebo, dipyridamole less frequently induced chest pain (20% vs. 100%, p = 0.001) and >0.1 mV ST segment depression (50% vs. 100%, p < 0.05). Wall motion abnormalities during exercise-stress test were less frequent (placebo = 100% vs. dipyridamole = 70%, p = ns) and significantly less severe (wall motion score index at peak stress: placebo = 1.55 +/- 0.17 vs. dipyridamole = 1.27 +/- 0.2, p < 0.01) following dipyridamole, which also determined an increase in exercise time up to echocardiographic positivity (placebo = 385.9 +/- 51.4 vs. dipyridamole = 594.4 +/- 156.9 s, p < 0.01). CONCLUSIONS: Low-dose dipyridamole infusion increases exercise tolerance in chronic stable angina, possibly by endogenous adenosine accumulation acting on high affinity A1 myocardial receptors involved in preconditioning or positively modulating coronary flow through collaterals.     

Impaired coronary vasodilatory capacity after dipyridamole administration in hypertrophic cardiomyopathy

To investigate mechanisms for a reduced coronary vasodilatory capacity in patients with hypertrophic cardiomyopathy (HCM), maximum coronary blood flow and minimum coronary vascular resistance were measured by administering dipyridamole (0.56 mg/kg) to 19 patients with non-obstructive HCM and to 7 control subjects. The maximum coronary blood flow was significantly lower (131 +/- 46 vs 192 +/- 41 ml/100 g . min, p less than 0.01, mean +/- SD) and the minimum coronary vascular resistance was significantly higher (0.64 +/- 0.23 vs 0.44 +/- 0.13 mmHg/ml/100 g . min, p less than 0.05) in HCM patients. There were no significant correlations between maximum coronary blood flow or minimum coronary vascular resistance and the baseline left ventricular end-diastolic pressure or the severity of systolic narrowing of the left anterior descending artery of the septal perforator. In contrast, the minimum coronary vascular resistance was correlated significantly with the left ventricular muscle mass (r = 0.55, p less than 0.05), but its correlation to small coronary vessel disease could not be studied. In addition, HCM patients with a reduced exercise tolerance (less than 7 metabolic units) demonstrated a significantly lower maximum coronary blood flow and higher minimum coronary vascular resistance than control subjects. These findings suggest that: (1) there is a group of HCM patients who have a reduced coronary vasodilatory capacity, (2) abnormal coronary vasculature is a possible underlining mechanism of HCM, either due to inadequate growth unassociated with left ventricular hypertrophy or as small coronary vessel disease, and (3) a reduced coronary vasodilatory capacity.     

Intracoronary adenosine causes angina pectoris like pain--an inquiry into the nature of visceral pain

STUDY OBJECTIVE--The aim was to study the tentative role of adenosine as a messenger between myocardial ischaemia and angina pectoris. DESIGN--Adenosine was administered in serial doses of 0.1-20 mg either as an intravenous bolus, or intra-arterially over 10 s into the left coronary artery, the aorta and the iliac artery. Coronary sinus flow was determined by thermodilution. ECG was monitored continuously. The patient was not aware of which site or dose was used. After each injection, the start of, maximum, end, magnitude, and location of pain were noted. PATIENTS--Six patients with angina pectoris referred for coronary angiography entered the study. MEASUREMENTS AND RESULTS--After intracoronary adenosine injection in the absence of ischaemic ECG changes, a dose dependent degree of chest pain was experienced not different in quality or location from the patients' habitual angina pectoris. Adenosine into the aorta provoked pain in lower chest and upper abdomen, whereas injection into the iliac artery provoked pain in the ipsilateral leg. On intravenous injection equipotent doses of adenosine caused chest pain of the same degree and quality as after intracoronary injection. Immediately after intracoronary injection the coronary sinus blood flow started to increase, but the onset of chest pain was delayed. Onset of pain was earlier the higher the dose, the maximum dose resulting in onset after 18(SEM 2) s. Coronary sinus blood flow increased dose dependently after left coronary artery injection but following intravenous injection no further increase was seen beyond that induced by the lowest dose. CONCLUSIONS--We suggest that adenosine is an important messenger for the sensation of angina pectoris and the effect is not due to coronary steal leading to myocardial ischaemia.     

Relationship of exercise or pacing induced ST segment depression and myocardial lactate metabolism in patients with hypertrophic cardiomyopathy

To elucidate a mechanism and clinical implications of chest pain and ST segment depression during exercise in patients with hypertrophic cardiomyopathy (HCM), we investigated myocardial lactate metabolism during atrial pacing in 18 patients with HCM and 7 control subjects with normal coronary arteriograms. At an average peak pacing rate of 146 beats/min, 11 patients with HCM showed the lactate extraction ratio decreasing to less than 5%, and 6 of them produced lactate, suggesting the development of myocardial ischemia. These 11 patients with abnormal lactate metabolism demonstrated ST segment depression (82%) and chest pain (73%) during pacing and also presented abnormal results (55%) on an exercise stress test. These abnormal findings were not observed in the other 7 patients who had ratios of 5% or more at peak pacing. These observations suggest that ST segment depression and chest pain are manifestations of myocardial ischemia even in patients with HCM who have normal coronary arteriograms, and that patients with pacing induced abnormal lactate metabolism are at an increased risk of developing myocardial ischemia during exercise.     

Coronary sinus potassium concentration recorded during coronary angioplasty.

Coronary sinus potassium concentration was measured continuously in two patients undergoing angioplasty of a significant stenosis of the left anterior descending coronary artery. After each coronary occlusion there was a transient rise in coronary sinus plasma potassium concentration caused by washout of potassium which had accumulated in the extracellular fluid during the short period of ischaemia. There were no significant changes in the surface electrocardiogram and the patients experienced no chest pain. Changes in coronary sinus potassium concentration provide a sensitive and early indication of myocardial ischaemia in man.