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This note analyses a peculiar feature of the ESM, namely the lack of an acceptable set of standards for the fundamental democratic principle of transparency. Moving from the particular nature of this mechanism, we will highlight the most critical concerns connected to secrecy, confidentiality and inviolability of documents, looking not only at the ESM Treaty but also at relevant documents approved by its bodies (in particular the Code of Conduct and the By-Laws).

The theoretical possibilities and the practical limitations of the Xenon-133 (133Xe) method for the study of regional myocardial perfusion in man are discussed.The techniques for data acquisition and processing developed over the past 5 years are described in detail. Illustrative examples of experimental findings are reported. The practical interpretation of the data, at the light of the influence of injection site, initial tracer distribution, constancy of counting geometry, spatial resolution, and Xenon retention in fat, is presented. [ABSTRACT FROM PUBLISHER]

Hypercontractile phenotype (HP) of the left ventricle (LV) is an actionable therapeutic target in patients with chronic coronary syndromes (CCS) or heart failure (HF), but its clinical recognition remains difficult. To assess the clinical variables associated with the HP. In a prospective, observational, multicenter study, we recruited 5122 patients (age 65 ± 11 years, 2974 males, 58%) with CCS and/or HF with preserved ejection fraction (EF). Systolic blood pressure (SBP) was measured. We assessed wall motion score index (WMSI), LV end-diastolic volume (EDV), end-systolic volume (ESV), EF, force (SBP/ESV), stroke volume (SV), arterial elastance (SBP/SV), and ventricular-arterial coupling (VAC, as SV/ESV). Univariable and multivariable logistic regression analysis assessed independent factors associated with the highest force sextile. For all the studied patients, force was 4.51 ± 2.11 mmHg/ml, with the highest sextile (Group 6) > 6.36 mmHg/ml. By multivariable logistic regression model, the highest sextile of force was associated with age > 65 years (OR 1.62, 95% CI 1.36-1.93, p < 0.001), hypertension (OR 1.76, 95% CI 1.40-2.21, p < 0.001), female sex (OR 4.52, 95% CI 3.77-5.42, p < 0.001), absence of beta-blocker therapy (OR 1.41, 95% CI 1.16-1.68), rest SBP ≥ 160 mmHg (OR 2.81, 95% CI 2.21-3.56, p < 0.001), high heart rate (OR 2.08, 95% CI 1.61-2.67, p < 0.001), and absence of prior myocardial infarction (OR 1.34, 95% CI 1.07-1.68, p = 0.012). Patients in the highest sextile of force showed lower values of WMSI, SV, EDV, and ESV, and higher values of arterial elastance and VAC. HP of the LV with high force was clinically associated with advanced age, female sex, high resting SBP, and the absence of β-blocker therapy. By transthoracic echocardiography, HP was associated with a small heart with reduced EDV, reduced SV despite high EF, and higher arterial elastance., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Stroke volume response during stress is a major determinant of functional status in heart failure and can be measured by two-dimensional (2-D) volumetric stress echocardiography (SE). The present study hypothesis is that SE may identify mechanisms underlying the change in stroke volume by measuring preload reserve through end-diastolic volume (EDV) and left ventricular contractile reserve (LVCR) with systolic blood pressure and end-systolic volume (ESV)., Methods: We enrolled 4735 patients (age 63.6±11.3 years, 2800 male) referred to SE for known or suspected coronary artery disease (CAD) and/or heart failure (HF) in 21 SE laboratories in 8 countries. In addition to regional wall motion abnormalities (RWMA), force was measured at rest and peak stress as the ratio of systolic blood pressure by cuff sphygmomanometer/ESV by 2D with Simpson's or linear method. Abnormal values of LVCR (peak/rest) based on force were ≤1.10 for dipyridamole (N.=1992 patients) and adenosine (N.=18); ≤2.0 for exercise (N.=2087) or dobutamine (N.=638)., Results: Force-based LVCR was obtained in all 4735 patients. Lack of stroke volume increase during stress was due to either abnormal LVCR and/or blunted preload reserve, and 57% of patients with abnormal LVCR nevertheless showed increase in stroke volume., Conclusions: Volumetric SE is highly feasible with all stresses, and more frequently impaired in presence of ischemic RWMA, absence of viability and reduced coronary flow velocity reserve. It identifies an altered stroke volume response due to reduced preload and/or contractile reserve.

An enlarged left atrial volume index (LAVI) at rest mirrors increased LA pressure and/or impairment of LA function. A cardiovascular stress may acutely modify left atrial volume (LAV) within minutes. Aim of this study was to assess the feasibility and functional correlates of LAV-stress echocardiography (SE) Out of 514 subjects referred to 10 quality-controlled labs, LAV-SE was completed in 490 (359 male, age 67 ± 12 years) with suspected or known chronic coronary syndromes (n = 462) or asymptomatic controls (n = 28). The utilized stress was exercise in 177, vasodilator in 167, dobutamine in 146. LAV was measured with the biplane disk summation method. SE was performed with the ABCDE protocol. The intra-observer and inter-observer LAV variability were 5% and 8%, respectively. ∆-LAVI changes (stress-rest) were negatively correlated with resting LAVI (r = - 0.271, p < 0.001) and heart rate reserve (r = -.239, p < 0.001). LAV-dilators were defined as those with stress-rest increase ≥ 6.8 ml/m 2 , a cutoff derived from a calculated reference change value above the biological, analytical and observer variability of LAVI. LAV dilation occurred in 56 patients (11%), more frequently with exercise (16%) and dipyridamole (13%) compared to dobutamine (4%, p < 0.01). At multivariable logistic regression analysis, B-lines ≥ 2 (OR: 2.586, 95% CI = 1.1293-5.169, p = 0.007) and abnormal contractile reserve (OR: 2.207, 95% CI = 1.111-4.386, p = 0.024) were associated with LAV dilation. In conclusion, LAV-SE is feasible with high success rate and low variability in patients with chronic coronary syndromes. LAV dilation is more likely with reduced left ventricular contractile reserve and pulmonary congestion.

Objectives: The purpose of this study was to assess the functional and prognostic correlates of B-lines during stress echocardiography (SE)., Background: B-profile detected by lung ultrasound (LUS) is a sign of pulmonary congestion during SE., Methods: The authors prospectively performed transthoracic echocardiography (TTE) and LUS in 2,145 patients referred for exercise (n = 1,012), vasodilator (n = 1,054), or dobutamine (n = 79) SE in 11 certified centers. B-lines were evaluated in a 4-site simplified scan (each site scored from 0: A-lines to 10: white lung for coalescing B-lines). During stress the following were also analyzed: stress-induced new regional wall motion abnormalities in 2 contiguous segments; reduced left ventricular contractile reserve (peak/rest based on force, ≤2.0 for exercise and dobutamine, ≤1.1 for vasodilators); and abnormal coronary flow velocity reserve ≤2.0, assessed by pulsed-wave Doppler sampling in left anterior descending coronary artery and abnormal heart rate reserve (peak/rest heart rate) ≤1.80 for exercise and dobutamine (≤1.22 for vasodilators). All patients completed follow-up., Results: According to B-lines at peak stress patients were divided into 4 different groups: group I, absence of stress B-lines (score: 0 to 1; n = 1,389; 64.7%); group II, mild B-lines (score: 2 to 4; n = 428; 20%); group III, moderate B-lines (score: 5 to 9; n = 209; 9.7%) and group IV, severe B-lines (score: ≥10; n = 119; 5.4%). During median follow-up of 15.2 months (interquartile range: 12 to 20 months) there were 38 deaths and 28 nonfatal myocardial infarctions in 64 patients. At multivariable analysis, severe stress B-lines (hazard ratio [HR]: 3.544; 95% confidence interval [CI]: 1.466 to 8.687; p = 0.006), abnormal heart rate reserve (HR: 2.276; 95% CI: 1.215 to 4.262; p = 0.010), abnormal coronary flow velocity reserve (HR: 2.178; 95% CI: 1.059 to 4.479; p = 0.034), and age (HR: 1.031; 95% CI: 1.002 to 1.062; p = 0.037) were independent predictors of death and nonfatal myocardial infarction., Conclusions: Severe stress B-lines predict death and nonfatal myocardial infarction. (Stress Echo 2020-The International Stress Echo Study [SE2020]; NCT03049995)., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The assessment of coronary flow velocity reserve (CFVR) in left anterior descending coronary artery (LAD) expands the risk stratification potential of stress echocardiography (SE) based on stress-induced regional wall motion abnormalities (RWMA)., Objectives: The purpose of this study was to assess the feasibility and functional correlates of CFVR., Methods: This prospective, observational, multicenter study initially screened 3,410 patients (2,061 [60%] male; age 63 ± 11 years; ejection fraction 61 ± 9%) with known or suspected coronary artery disease and/or heart failure. All patients underwent SE (exercise, n = 1,288; vasodilator, n = 1,860; dobutamine, n = 262) based on new or worsening RWMA in 20 accredited laboratories of 8 countries. CFVR was calculated as the stress/rest ratio of diastolic peak flow velocity pulsed-Doppler assessment of LAD flow. A subset of 1,867 patients was followed up., Results: The success rate for CFVR on LAD was 3,002 of 3,410 (feasibility = 88%). Reduced (≤2.0) CFVR was found in 896 of 3,002 (30%) patients. At multivariable logistic regression analysis, inducible RWMA (odds ratio [OR]: 6.5; 95% confidence interval [CI]: 4.9 to 8.5; p < 0.01), abnormal left ventricular contractile reserve (OR: 3.4; 95% CI: 2.7 to 4.2; p < 0.01), and B-lines (OR: 1.5; 95% CI: 1.1 to 1.9; p = 0.01) were associated with reduced CFVR. During a median follow-up time of 16 months, 218 events occurred. RWMA (hazard ratio: 3.8; 95% CI: 2.3 to 6.3; p < 0.001) and reduced CFVR (hazard ratio: 1.5; 95% CI: 1.1 to 2.2; p = 0.009) were independently associated with adverse outcome., Conclusions: CFVR is feasible with all SE protocols. Reduced CFVR is often accompanied by RWMA, abnormal LVCR, and pulmonary congestion during stress, and shows independent value over RWMA in predicting an adverse outcome., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The peak stress/rest ratio of left ventricular (LV) elastance, or LV force, is a load-independent index of left ventricular contractile reserve (LVCR) with stress echo (SE). To assess the accuracy of LVCR calculated during SE with approaches of different complexity. Two-hundred-forty patients were referred to SE for known or suspected coronary artery disease or heart failure and, of those, 200 patients, age 61 ± 15, 99 females, with interpretable volumetric SE were enrolled. All readers had passed the upstream quality control reading for regional wall motion abnormality (RWMA) and end-systolic volume (ESV) measurement. The employed stress was dipyridamole (0.84 mg, 6 min) in 86 (43%) and dobutamine (up to 40 mcg/kg/min) in 114 (57%) patients. All underwent SE with evaluation of RWMA and simultaneous LVCR assessment with stress/rest ratio of LV force (systolic blood pressure by cuff sphygmomanometer/ESV). ESV was calculated in each patient by two of three methods: biplane Simpson rule (S, in 100 patients), single plane area-length (AL, apical four-chamber area and length, in 100 patients), and Teichholz rule (T, from parasternal long axis and/or short axis view, in 200 patients). RMWA were observed in 54 patients. Success rate for ESV measurement was 76% (100/131) for S, 92% (100/109) for AL, and 100% (240/240) for T. There were 100 paired measurements (rest and stress) with S versus T, and 100 with AL versus T. The analysis time was the shortest for T (33 ± 8 s at rest, 34 ± 7 s at stress), intermediate for AL (70 ± 22 s at rest 67 ± 21 s at stress), and the longest for S (136 ± 24 at rest 129 ± 27 s at stress, p < 0.05 vs. T and AL). ESV absolute values were moderately correlated: T versus S (r rest = 0.746, p < 0.01, n = 100; r stress = 0.794, p < 0.01, n = 100); T vs. AL (r = 0.603 p < 0.01, n = 100, at rest and r = 0.820 p < 0.01 n = 100 at peak stress). LVCR values were tightly correlated independently of the method employed: T versus S (r = 0.899, p < 0.01, n = 100), and T versus AL (r = 0.845, p < 0.01, n = 100). LVCR can be accurately determined with all three methods used to extract the raw values of ESV necessary to generate the calculation of Force. Although S is known to be more precise in determining absolute ESV values, the relative (rest-stress) changes can be assessed, with comparable accuracy, with simpler and more feasible T and AL methods, characterized by higher success rate, shorter imaging and analysis time.

Background: The trial "Stress Echo (SE) 2020" evaluates novel applications of SE beyond coronary artery disease. The aim of the study was control quality and harmonize reading criteria., Methods: One reader from 78 centers of the SE 2020 network asked for credentials to read a set of 20 SE video-clips selected by the core lab. All aspiring centers met the pre-requisite of high-volume and the years of experience in SE ranged from 5 to 31years (mean value 18years). The diagnostic gold standard was a reading by the core lab. The a priori determined pass threshold was 18/20 (≥90%)., Results: Of the initial 78 who started, 57 completed the first attempt: individual readers' score on first attempt ranged from 07/20 to 20/20 (accuracy from 35% to 100%, mean 78.7±13%) and 44 readers passed it. There was a very poor correlation between years of experience and the reader's score on first attempt (r=-0.161, p=0.231). Of the 13 readers who failed the first attempt, 12 took it again after the web-based session and their accuracy improved (74% vs. 96%, p<0.001). The kappa inter-observer agreement before and after web-based training was 0.59 on first attempt and rose to 0.91 on the last attempt., Conclusions: In SE reading, the volume of activity or years of experience is not synonymous with diagnostic quality. Qualitative analysis and operator-dependence can become a limiting weakness in clinical practice, in the absence of strict pathways of learning, credentialing and audit., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: The added value of routine echocardiography, in respect to clinical examination and ECG, has received little attention. We sought to evaluate the contribution of two-dimensional echocardiography, in respect to clinical examination and ECG, in detecting left ventricular (LV) dilatation and systolic dysfunction., Method: A group of 100 patients, scheduled for cardiac magnetic resonance imaging (MRI), was prospectively studied., Results: Clinical examination identified moderate-to-severe LV dysfunction, defined as a LV ejection fraction (EF) < 45% at MRI, with a sensitivity of 62% and a specificity of 68%. After ECG, sensitivity and specificity slightly improved (71 and 70%, respectively). After the echocardiographic report, sensitivity reached 84% and specificity 90%. LV EF by echocardiography (routine studies) was closely related with that by MRI (r = 0.84). LV function was scored as undefined in 17% of patients after clinical examination, in 5% of patients after ECG and in no patient after echocardiography (P < 0.0001). Clinical examination identified patients with LV dilatation (LV end-diastolic volume > or = 110 ml/m2) with a poor sensitivity (33%) but a good specificity (88%). After ECG, sensitivity was 39% and specificity 87%; after echocardiography, sensitivity reached 53% and specificity 92%., Conclusion: Echocardiography provides information on LV function and dimensions that vastly exceeds that obtained by clinical examination and ECG. This study supports the use of echocardiography to improve patient diagnosis and management after history and physical examination.

Background: The diagnostic process has become increasingly dependent on instrumental and laboratory investigation., Aim: To evaluate the accuracy of symptoms and signs in identifying left ventricular (LV) dilatation and/or systolic dysfunction., Methods: A group of 100 patients in stable clinical condition and scheduled for cardiac magnetic resonance imaging was prospectively examined by two cardiologists, who were unaware of the individual patient's condition. Patients were interviewed and underwent physical examination., Results: Several symptoms and signs were associated with LV dilatation and systolic dysfunction at univariate analysis. Using multiple logistic regression, a mitral systolic murmur, a laterally displaced LV impulse, orthopnoea and hepatomegaly were all independent predictors of LV dilatation (end-diastolic volume >or=110 ml/m(2)) (p<0.0001) and LV dysfunction (ejection fraction <45%) (p<0.0001). The combination of the above variables correctly identified 79% of patients with LV dilatation (sensitivity 51%, specificity 92%), and 82% of patients with LV dysfunction (sensitivity 68%, specificity 90%). Considering LV dilatation and dysfunction, 77% of patients were correctly identified after history alone (kappa=0.13), 84% after LV impulse examination (kappa=0.55) and 86% after cardiac auscultation (kappa=0.58)., Conclusion: Symptoms and signs predict LV dilatation and/or dysfunction with fair sensitivity and excellent specificity.

Objective: We evaluated the feasibility, safety, and diagnostic accuracy of noninvasive pacemaker stress echocardiography (PASE) test as a potential alternative to exercise or pharmacologic stress in patients with suspected or known coronary artery disease (CAD)., Background: Transesophageal atrial pacing echocardiography is an accurate test for detection of CAD, but its practical impact has been blunted by semi-invasiveness. In the expanding population of patients with permanent pacemakers (PMs), a pacing stress test can be administered noninvasively by external programming of the PM., Methods: In a prospective, multicenter, international study design, transthoracic stress-pacing echocardiography was performed in 46 consecutive patients with a permanent PM (33 men, 13 women; age 66.6 +/- 11.1 years) with suspected or known CAD. All patients underwent noninvasive PM-stress test by external programming (10 beats/min increments up to ischemia or target heart rate). Coronary angiography was performed in all patients independently of test results. Significant CAD was defined as >/=50% visually assessed diameter reduction in at least one major epicardial coronary artery. All coronary angiograms were scored by Duke prognostic weight values., Results: Fifteen patients were stimulated in atrial, and the remaining 31 in ventricular mode during stress. No significant side effects were observed. Echocardiographic images were interpretable in all patients. The average duration of stress was 8.9 +/- 3.5 min. Significant CAD was found in 27 patients. Sensitivity of PASE for identifying patients with significant CAD was 70%, specificity was 90%, and accuracy was 78%. When any abnormal wall motion at rest that remained unchanged at peak stress was regarded as a positive result of PASE, then the sensitivity, specificity, and accuracy levels for identifying patients with significant CAD were 85%, 84%, and 85%, respectively. Four of the eight patients with a false negative did not reach the target heart rate. The Duke values had significant correlation with values of wall motion score index at peak stress (r = 0.67) and with peak heart rate (r = -0.3)., Conclusions: Noninvasive PASE is a simple, rapid, safe, and diagnostically efficient option for patients with permanent PM and suspected or known CAD.

Background: Several studies have demonstrated a consistently high sensitivity of dobutamine echocardiography whereas test specificity in these series has been variable. The aim of this study was to evaluate whether coronary vasospasm--elicited by alpha1 adrenoreceptor stimulation--may be a significant source of false positive responses during dobutamine stress., Methods: From the data bank of four institutions we selected 113 patients (75 males, 38 females, mean age 55 +/- 12 years) with dobutamine echocardiography performed (up to 40 micrograms/kg/min and atropine 1 mg if needed) before a coronary angiography showing normal or near normal (visually assessed stenosis severity < 50%) coronary arteries. The following variables--which were previously reported influencing dobutamine echo specificity--entered the multivariate statistical analysis: age, sex, heart rate at baseline and at peak stress, baseline echo, hypertension, site of asynergy, and spasm at coronary angiography., Results: Twenty-five patients had a positive dobutamine test. The positivity occurred in the left coronary territory in 15 and in the right coronary territory in 10 cases. All the 6 patients with spontaneous spasm during angiography had a false positive stress test result. By multivariate analysis only coronary artery spasm during angiography (p = 0.0015) and history of hypertension (p = 0.0031) were significant predictors of false positive results of dobutamine stress echocardiography., Conclusions: Coronary artery spasm may be an important source of false positive results during dobutamine stress echocardiography.

Background: Even late restoration of anterograde coronary flow may have beneficial effects on left ventricular function, electrophysiology, and survival in postinfarction patients., Hypothesis: The patency or occlusion of an infarct-related coronary artery in the chronic phase may also be associated with myocardial ischemia provoked by pharmacologic and physiologic stress tests., Methods: High-dose dipyridamole echocardiography test (DET) (up to 0.84 mg/kg over 10 min), exercise electrocardiography (EET), and coronary angiographic data in a group of 127 in-hospital patients who had survived an acute myocardial infarction were analyzed. Patients who had only angiographic evidence of infarct-related single artery disease (> or = 50% luminal diameter reduction) and no previous revascularization were enrolled in the study. DET and EET were performed (DET in all, EET in 118 patients) within 5 days before coronary angiography. Fifty-seven patients had total occluded infarct arteries (Group 1) with various degrees of collateral circulation (2.6 +/- 1.1 collateral score, by a 3 grading system), whereas the other 70 patients had patent infarct arteries (Group 2) with significant residual stenoses (82 +/- 13% diameter reduction)., Results: The prevalence of rest angina or effort angina and topography of the infarct-related coronary artery did not differ between the two groups (all p = NS). There were more patients with Q wave in Group 1 than in Group 2 (72 vs. 57%, p = 0.08) compared with non-Q wave infarction (Group 1 = 28 vs. Group 2 = 43%, p = 0.08). Ischemia in the infarct-related artery territory detected by DET (defined as new wall motion dyssynergy or marked worsening of resting hypokinesia) was 61% in Group 1 and 41% in Group 2 (p = 0.025). EET was positive in 26 of 54 (48%) Group 1 and in 21 of 64 (33%) Group 2 patients (p = 0.09)., Conclusions: Patients with occluded infarct-related arteries have a higher prevalence of ischemia during DET and EET regardless of the presence of collateral flow. These results suggest that the presence of partial anterograde flow in the prolonged period could have a favorable influence on prevalence of residual ischemia in these patients.

Regional coronary flow reserve and regional myocardial contractility were evaluated in 29 patients after maximal pharmacologic coronary vasodilation (intravenous dipyridamole, 0.56 mg/kg body weight, administered over 4 minutes). Nineteen patients had a severe (80 to 99%) proximal and isolated stenosis of the left anterior descending coronary artery and 10 patients had normal coronary arteries; all had normal ventricular function under rest conditions. Myocardial contractility was assessed by means of continuous two-dimensional echocardiographic monitoring; coronary reserve was evaluated by coronary sinus thermodilution. After dipyridamole infusion, 9 of the 19 patients with left anterior descending artery stenosis had transient myocardial asynergy involving the septum or apex, or both (Group IA), whereas 10 patients showed no asynergy (Group IB). No impairment of contractility was observed in the 10 patients with normal coronary arteries (Group II). Coronary blood flow was measured under basal conditions and up to 10 minutes after the end of dipyridamole infusion. In patients in Group II, dipyridamole induced an increase in great cardiac vein flow of 167 +/- 68% (mean +/- SD). The 10 patients in Group IB showed a response comparable with that of the control group (Group II) (136 +/- 45% increase in great cardiac vein flow; NS versus Group II), whereas the 9 patients in Group IA had an increase of 46 +/- 30% (p less than 0.01 versus both Group IB and Group II). No significant difference was found in the angiographic severity of the stenosis expressed in terms of minimal cross-sectional area (Group IA = 0.30 +/- 0.13 mm2, Group IB = 0.34 +/- 0.18 mm2; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

The cardiovascular effects of dilazep, a new antianginal drug, were investigated in 18 patients, who underwent cardiac catheterization and coronary angiography for the evaluation of chest pain. Dilazep, 0.2 mg/kg, was injected intravenously over 1 to 2 minutes. The changes induced by dilazep in coronary tone were assessed by quantitative angiography in four patients, changes in systemic and coronary hemodynamics and blood gases in eight patients, and changes in systemic and pulmonary hemodynamics and blood gases in six. In 6 of the 18 patients the effects on hemoglobin-O2 oxygen binding were also investigated. Following dilazep administration, we observed a marked reduction of coronary resistance (six patients) (0.5 vs 1.0 mm Hg X min X ml-1, p less than 0.01) and of aortic-coronary sinus oxygen difference (seven patients) (4.6 vs 12.3 vol%, p less than 0.01), and a 23% increase in coronary diameter (four patients) (p less than 0.001). Total systemic resistance was also reduced by dilazep (six patients). Conversely, only minimal or insignificant changes were observed in heart rate (14 patients), aortic pressure (14 patients), total pulmonary resistance (six patients), myocardial oxygen consumption (six patients), double product (14 patients), blood gases (seven patients), and hemoglobin-oxygen affinity (six patients). We conclude that dilazep exerts a powerful dilating action on coronary vasculature without appreciable increase of myocardial oxygen consumption and cardiac work simultaneously with a reduction of peripheral resistance.

The possible role of prostaglandins in mediating large coronary artery vasodilation by nitrates was investigated by quantitative magnification coronary angiography. The effects of aspirin (1 g systemically and 100 mg intracoronary) in preventing large coronary artery vasodilation induced by intracoronary isosorbide dinitrate was investigated in 16 patients. Of these, 5 received 0.3 mg (Group 1A) and 11 received 3 mg (Group 1B) intracoronary isosorbide dinitrate, before and 15 minutes after aspirin. Relative to control, 0.3 mg isosorbide dinitrate induced a 19 +/- 9% (mean +/- SD) (p less than 0.01) and 19.5 +/- 11% (p less than 0.01) increase in coronary diameter before and after aspirin, respectively (p = NS). Changes after 3 mg isosorbide were 23 +/- 12% (p less than 0.01) and 26.5 +/- 14% (p less than 0.01), respectively, before and after aspirin (p = NS). In 10 additional patients (Group 2), the effect of the same dose of aspirin on rest coronary artery tone was assessed: changes relative to control were 0.9 +/- 5.5% (p = NS) minutes after aspirin. The intracoronary administration of 3 mg isosorbide dinitrate produced a 24.7 +/- 11% increase in coronary diameter (p = NS versus pre- and postaspirin isosorbide in Group 1B). Urinary 6-ketoprostaglandin-F1 alpha values in urine samples collected in the 8 hours before and the 8 hours after the study in five patients in Group 1B and five patients of Group 2, revealed a 36 +/- 14% (mean +/- SD) reduction in excretion of prostacyclin (p less than 0.01). These data rule out a role for prostaglandins both in mediating dilation of large coronary arteries by nitrates and in affecting their vascular tone at rest.

The possible role of prostaglandins in mediating coronary vasodilation by nitrates was investigated in 13 patients. In nine patients (Group 1), the effects of ISDN on coronary-artery diameter and (in four of the nine) coronary sinus flow before and after administration of ASA were compared. In four additional patients (Group 2) the first ISDN administration was omitted in order to investigate the effect of ASA on resting coronary artery tone. Dosages used were 3 mg intracoronary ISDN and 1.0 g intravenous and 100 mg intracoronary ASA. Coronary artery diameter was analyzed by means of quantitative magnification coronary angiography. Coronary sinus flow was investigated by means of coronary sinus thermodilution. ASA was not able to induce significant changes in coronary artery diameter when injected before administration of ISDN or to prevent ISDN-induced vasodilation. At the coronary resistance level, ASA was not able to prevent the relative vasodilation induced by ISDN. It is concluded that coronary vasodilation by nitrates is not mediated by the prostaglandin system.