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      Enalaprilat Improves the Impaired Left Ventricular Pump Function during Exercise in Hypertensives with Coronary Microangiopathy and with Coronary Artery Disease

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          Abstract

          Background: The pump function during exercise can be disturbed not only in hypertensives with coronary artery disease (CAD), but also in those with a normal angiogram. Methods: In 10 hypertensive patients (group 1; aged 52±4 years, 1 men, 9 women) with ST segment depression during exercise and concomitant angina pectoris but normal coronary angiograms (microangiopathy) and without left ventricular hypertrophy (LVMI <110 g/m<sup>2</sup>), the left ventricular function at rest and during exercise was studied by cardiac catheterization and compared with 10 hypertensives with CAD (group 2; aged 57.6±4 years, 7 men, 3 women) and 10 hypertensives without ST segment depression (group 3; aged 51.8±5 years, 10 men) before and after intravenous administration of 1.25 mg enalaprilat. Results: The pulmonary capillary wedge pressure (PCWP) was normal at rest and pathologically increased at 60±13 W only in groups 1 and 2 (27.2±3 and 32.2±8 mm Hg, respectively), but not in group 3 (12.2±4 mm Hg; p<0.001). At the identical load level, the PCWP in patients with microangiopathy (group 1) was significantly (p<0.01) reduced after enalaprilat (–21.7%) and even normalized in 5 of 10 patients. This was accompanied by a significant (p>0.01) decrease in ST segment depression (–73.9%) and in the occurrence of angina pectoris, despite the fact that the rate–pressure product as a measure of myocardial oxygen consumption was significantly (p<0.05) increased. Also in patients with CAD enalaprilat had a significant effect on PCWP (p<0.01), ST segment depression (p<0.01), occurrence of angina pectoris (p<0.001), cardiac index (p<0.05), and stroke index (p<0.05) during exercise. In group 3 there were no significant changes in PCWP, cardiac index, and stroke index after enalaprilat either at rest or during exercise. Conclusion: The functional improvement under the action of enalaprilat suggests that the advantages of the drug may be mediated mainly through an increase in myocardial blood flow and that angiotensin II might be involved in the restricted increase in coronary blood flow during dynamic exercise in hypertensives with coronary microangiopathy.

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          Most cited references 2

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          Evidence of impaired endothelium-dependent coronary vasodilatation in patients with angina pectoris and normal coronary angiograms.

          A group of patients has been described who have chest pain resembling angina and positive exercise tests, but normal coronary angiograms and no coronary-artery spasm. This constellation of features has sometimes been called syndrome X or microvascular angina. We attempted to determine whether endothelium-dependent vasodilatation of the coronary vasculature was impaired in patients with this syndrome. We infused the endothelium-dependent vasodilator acetylcholine and the endothelium-independent vasodilators papaverine and isosorbide dinitrate into the left coronary artery of 9 patients and 10 control subjects. The diameter of the left anterior descending coronary artery was assessed by quantitative angiography, and changes in coronary blood flow were estimated with the use of an intracoronary Doppler catheter. Acetylcholine, given in doses of 1, 3, 10, and 30 micrograms per minute, increased coronary blood flow in a dose-dependent manner in both groups. However, the mean (+/- SD) acetylcholine-induced increases in coronary blood flow were significantly less (P < 0.001) in the patient (8 +/- 14, 37 +/- 37, 59 +/- 67, and 103 +/- 77 percent, respectively) than in the controls (62 +/- 52, 186 +/- 93, 341 +/- 128, and 345 +/- 78 percent, respectively). The changes in coronary blood flow in response to 2 mg of isosorbide dinitrate (236 +/- 66 percent vs. 280 +/- 56 percent) and 10 mg of papaverine (366 +/- 168 percent vs. 411 +/- 92 percent) did not differ significantly between the patients and controls. The administration of papaverine resulted in myocardial lactate production in the patients but not in the controls. The three lower doses of acetylcholine caused a similar degree of dilatation of the left anterior descending coronary artery in the two groups, and the highest dose caused a similar degree of constriction in the two groups. Isosorbide dinitrate and papaverine caused a similar degree of dilatation in both groups. These findings suggest that endothelium-dependent dilatation of the resistance coronary arteries is defective in patients with anginal chest pain and normal coronary arteries, which may contribute to the altered regulation of myocardial perfusion in these patients.
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            Chest pain with normal coronary angiograms.

             R O Cannon (1993)
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              Author and article information

              Journal
              KBR
              Kidney Blood Press Res
              10.1159/issn.1420-4096
              Kidney and Blood Pressure Research
              S. Karger AG
              1420-4096
              1423-0143
              1998
              1998
              06 February 1999
              : 21
              : 6
              : 452-458
              Affiliations
              Klinik Wehrawald der BfA, Todtmoos, Deutschland
              Article
              25899 Kidney Blood Press Res 1998;21:452–458
              10.1159/000025899
              9933831
              © 1998 S. Karger AG, Basel

              Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

              Page count
              Figures: 1, Tables: 3, References: 45, Pages: 7
              Product
              Self URI (application/pdf): https://www.karger.com/Article/Pdf/25899
              Categories
              Original Paper

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