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Background: The aim of the study is to compare the impact of intravenous glucose versus lipid versus saline on exercise-induced myocardial ischemia in patients with stable angina., Methods: Twelve men with coronary artery disease and positive exercise tests performed a symptom-limited, modified Bruce electrocardiogram (ECG) exercise test at 3 sessions, 3 weeks apart. They randomly received, in double-blind design, at each session equal intravenous volumes of 10% glucose/insulin or Intralipid plus heparin or saline. We assessed the effects on (1) ischemic threshold (heart rate x systolic pressure at 1-mm ST-segment depression [STD]) and (2) maximum ST-depression (Max STD) corresponding to the highest heart rate x systolic pressure common to the 3 tests., Results: During glucose infusion, glycemia increased from 5.7 +/- 0.4 to 9.4 +/- 3.0 mmol/L but did not change during lipid or saline infusion. During lipid infusion, free fatty acids increased from 0.32 +/- 0.19 to 1.44 +/- 0.46 mmol/L but decreased during glucose infusion from 0.39 +/- 0.21 to 0.04 +/- 0.03 mmol/L and did not change during saline. Exercise times were 10.0 +/- 3.4, 9.8 +/- 3.4, and 10.3 +/- 3.5 minutes, during glucose, lipid, and saline infusions, respectively. Ischemic thresholds (x 10(-3)) were 16.5 +/- 2.8, 16.8 +/- 2.7, and 16.6 +/- 2.6, respectively. MaxSTD was 2.5 +/- 1.4, 2.5 +/- 1.0, and 2.5 +/- 1.0 mm, respectively., Conclusion: Neither glucose-insulin nor lipid infusion modified exercise ischemic parameters compared with saline control, suggesting that marked and acute changes in exogenous energy substrate are unlikely to affect exercise-induced myocardial ischemia.

Atrial natriuretic factor release during transient myocardial ischemia was investigated in 29 patients with coronary artery disease and symptoms of angina (Canadian Cardiovascular Association classes II-III). Eleven patients (group I) underwent single-vessel percutaneous transluminal coronary angioplasty. Repeat determinations of mean pulmonary artery wedge pressure and blood sampling from pulmonary artery for atrial natriuretic factor measurements were performed at baseline, and at 2, 5, and 15 minutes after percutaneous transluminal coronary angioplasty was begun. Baseline atrial natriuretic factor levels (34.6 +/- 4.5 pg/ml) rose to 56.3 +/- 7.3 pg/ml (p = 0.02) and decreased at 5 minutes (43.7 +/- 5.7 pg/ml, not significant) and 15 minutes (35.3 +/- 4.4 pg/ml, not significant). Changes in atrial natriuretic factor concentrations were significantly correlated with those in mean pulmonary artery wedge pressure (2 minutes: r = 0.69, p = 0.02; 5 minutes: r = 0.90, p less than 0.001). In group II (n = 10) the increase in atrial natriuretic factor after dye load occurred later (baseline: 25.8 +/- 2.1; 60 minutes: 40.6 +/- 2.6 pg/ml; p = 0.005) than that observed in group I after percutaneous transluminal coronary angioplasty. In group III, atrial natriuretic factor during angina rose as early (baseline 11.3 +/- 1.3; 5 minutes: 20 +/- 2.3 pg/ml; p = 0.006) as after percutaneous transluminal coronary angioplasty. Results indicate that transient myocardial ischemia stimulates atrial natriuretic factor release, probably through changes in cardiac function.

In order to investigate whether coronary vasodilating prostaglandins (PGI2 and PGE2) have a role in the pathophysiology of myocardial ischemia, 26 patients with angina pectoris and 23 control subjects (nonischemic patients) were studied by assessing coronary hemodynamics and prostaglandin formation in relation to sympathetic stimulation. Following a cold pressor test (CPT), coronary prostaglandin output markedly increased (p less than 0.001) and coronary vascular resistance (CVR) decreased (p less than 0.001) in all control subjects. In contrast, in anginal patients prostaglandins in the coronary sinus were undetectable and after CPT prostaglandin output did not increase, whereas CVR paradoxically increased (p less than 0.001). In control subjects the inhibition of coronary prostaglandin formation (by ketoprofen [1 mg/kg intravenously] or by aspirin [15 mg/kg intravenously]) caused a paradoxical increase of CVR following CPT (p less than 0.001). In anginal patients the inhibition of prostaglandins further exaggerated the increase of CVR after CPT (p less than 0.001). These results indicate that coronary vasodilating prostaglandin PGI2 and PGE2 play a role in modulating coronary vascular response to sympathetic stimulation induced by CPT. Their defective production in anginal patients may be responsible for the paradoxical increase in CVR following sympathetic stimulation.

Thirteen patients with angina pectoris underwent measurements of great cardiac vein blood flow at rest, with the onset of angina pectoris induced by atrial pacing, and again during angina pectoris induced by exercise in order to compare the regional coronary blood flow response to differing myocardial stresses. All patients had significant obstructions of the left anterior descending artery. Exercise-induced angina, compared to pacing-induced angina, was associated with a higher systolic pressure, higher left ventricular end-diastolic pressure, and a lower heart rate. Indices of myocardial oxygen demand, that is, the systolic pressure-heart rate product and the tension-time index, increased to a similar degree during both types of myocardial stress and great cardiac vein blood flow paralleled these changes. We conclude that in a given patient the level of regional coronary blood flow is similar at the onset of either pacing- or exercise-induced angina, despite significant differences in the hemodynamic response to these myocardial stresses.

The aim of this study was to assess whether myocardial oxygen consumption can be responsible for aminophylline resistance in dipyridamole-induced ischemia. We analyzed 163 consecutive patients who had a positive low-dose (0.56 mg/kg over 4 minutes) dipyridamole-echocardiography test, requiring intravenous aminophylline as an antidote. All patients also performed an exercise stress test. In 141 of these patients, the signs of ischemia were reversed by administration of intravenous aminophylline (group I), while the remaining 22 patients were resistant to aminophylline (240 mg/kg over 3 minutes) and received additional treatment with nitrates to relieve ischemia (group II). The increase in rate-pressure product (RPP = mm Hg x beats/min x 100) measured during the exercise stress test in the patients in group I was significantly greater than that determined during dipyridamole-induced ischemia (204 +/- 41 versus 145 +/- 33, p less than 0.01). However, the increases in RPP under both conditions were similar for the patients in group II (147 +/- 24 versus 150 +/- 20, p = ns). In patients with dipyridamole-induced ischemia who were resistant to aminophylline, the rise in myocardial oxygen consumption--probably linked to reflex sympathetic activation--might maintain ischemia independently from flow maldistribution, which should be reversed by aminophylline.

To determine whether the association of nicardipine with propranolol had additive effects on myocardial metabolism, 16 patients with angina pectoris were studied invasively before and after 1 month of therapy with a combination of nicardipine and propranolol and compared to a group of 42 patients treated with nicardipine (n = 17) or propranolol (n = 25) alone. When data were compared at a fixed heart rate (atrial pacing), mean blood pressure was reduced with combined treatment from 96 +/- 19 to 76 +/- 13 mm Hg (p less than 0.003). Myocardial oxygen uptake and coronary sinus flow decreased significantly from 20 +/- 9 to 14 +/- 6 ml/min (p less than 0.015) and from 152 to 111 ml/min (p less than 0.05), respectively. The arterio-coronary sinus difference in oxygen content also decreased (13.3 to 12.5 ml/dl; p less than 0.0025), suggesting an improved balance between oxygen supply and demand. Such changes in coronary blood flow and myocardial oxygen uptake were not observed in the group of patients assigned to monotherapy. Lactate uptake rose and the abnormal glutamine production, which worsened with propranolol monotherapy, improved with nicardipine and propranolol (-2.0 to -1.4 mumol/min; p less than 0.05 vs propranolol). The superiority of nicardipine and propranolol over propranolol monotherapy was maintained during a pacing stress test. Thus the combination of nicardipine with a beta blocker had greater oxygen-sparing effects and restored aerobic metabolism better than either drug alone, allowing optimal use of the coronary reserve.

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.

The effects of oral dipyridamole administration (150 mg) on coronary hemodynamics, myocardial metabolism, and pacing threshold were studied in 10 patients with significant coronary artery disease (CAD). Following dipyridamole through 120 minutes, there was no significant change in resting heart rate, arterial pressure, coronary venous flow, coronary resistance, myocardial lactate extraction, or myocardial oxygen consumption. Rapid atrial pacing performed before and at 60, 90, and 120 minutes after dipyridamole failed to demonstrate any significant reduction in pacing threshold or evidence of increased ischemia after dipyridamole. Blood dipyridamole levels showed variable and slow absorption which probably explains the difference between intravenous and oral dipyridamole on coronary dynamics and myocardial response to pacing.

Anginal threshold and cardiac metabolism during infusion of glucose, 350 mg/min, were compared with control values before, during, and after pacing in nine patients with coronary artery disease (CAD) and nine patients without coronary artery disease (non-CAD). Pacing induced no ischemia in non-CAD patients; in CAD patients, intolerable angina developed in less than 5 minutes. However, glucose infusion in the latter group increased the time to onset of angina (110 +/- 24 seconds before infusion versus 140 +/- 24 seconds following infusion) and decreased the extent of ST segment depression (1.8 +/- 0.3 mm before infusion versus 0.9 +/- 0.2 mm following infusion, p less than 0.01) following pacing. In all subjects, arterial levels and cardiac uptake of glucose rose by 100% (p less than 0.001) and those of free fatty acids fell by 50% (p less than 0.01). Arterial lactate and uptake of lactate by nonischemic myocardium increased by 30% (p less than 0.05). During pacing in CAD patients, this elevated uptake was outweighed by similar increases of lactate release from ischemic areas, leaving mean negative global exchanges unaltered. In CAD patients solely, rebuilding of cardiac glycogen after pacing was suggested from augmented citrate efflux in the control period but not during glucose infusion, suggesting a glycogen-sparing effect. Arterial concentrations and net cardiac fluxes of oxygen, glutamate, and alanine remained unaltered. In conclusion, beneficial effects of glucose during ischemia are associated with increased aerobic and anaerobic glycolysis, saving of glycogen, and decreased lipolysis.

Seventeen subjects ranging from 36 to 58 years of age presented with chest pain suggestive of myocardial ischemia. Each patient had a positive double Master's two-step test with ST segment depression of 0.5 mm. or more in the postexercise ECG. In each case coronary angiography and left ventriculography were normal. Hemodynamic and metabolic investigations were carried out during sinus rhythm and atrial pacing. Thirteen patients experienced pain during pacing but only one showed an abnormal hemodynamic response. Two patients showed abnormal myocardial lactate metabolism during the control period and four during pacing-induced tachycardia. The increase in ejection fractions in this group suggests hyperdynamic ventricular contraction which could result in increased oxygen requirements and thus induce ischemic pain in the absence of arteriographically demonstrable coronary artery disease.