Circulation, Vol 90, 2761-2771, Copyright © 1994 by American Heart Association
SP Friedrich, BH Lorell, MF Rousseau, W Hayashida, OM Hess, PS Douglas, S Gordon, CS Keighley, C Benedict and HP Krayenbuehl
BACKGROUND: Cardiac hypertrophy is associated with elevated intracardiac
angiotensin-converting enzyme activity, which may contribute to diastolic
dysfunction. METHODS AND RESULTS: We infused enalaprilat (0.05 mg/min) for
15 minutes into the left coronary arteries of 20 adult patients with left
ventricular (LV) hypertrophy due to aortic stenosis (mean aortic valve
area, 0.7 +/- 0.2 cm2) and 10 patients with dilated cardiomyopathy (mean
ejection fraction, 35 +/- 4%) and assessed (1) simultaneous changes in LV
micromanometer pressure and dimensions, (2) LV regional wall motion
analyzed by the area method, and (3) Doppler flow-velocity profiles.
Systemic neurohormonal activation did not occur with the selective left
coronary artery infusion; there were no changes in plasma renin activity,
angiotensin- converting enzyme activity, or atrial natriuretic peptide. In
patients with aortic stenosis, LV end-diastolic pressure declined from 25
+/- 2 to 20 +/- 2 mm Hg (P < .05). LV pressure-volume and LV pressure-
dimension relations showed downward shifts by ventriculography and
echocardiography, respectively, indicating improved diastolic
distensibility. Regional area change during isovolumic relaxation increased
in the anterior segments perfused with enalaprilat but decreased in the
inferior segments, indicating acceleration of isovolumic relaxation in the
anterior segments and reciprocal shortening in the inferior segments.
Regional peak filling rate increased in the anterior segments but not in
the inferior segments, and the regional area stiffness constant decreased
in the anterior segments but not in the inferior segments. There were no
changes in heart rate, cardiac output, or right atrial pressure, excluding
alterations in right ventricular/pericardial constraint. In contrast, in
the patients with dilated cardiomyopathy the decrease in LV end- diastolic
pressure from 22 +/- 2 to 18 +/- 2 mm Hg (P < .05) was accompanied by a
significant fall in right atrial pressure (9 +/- 1 to 6 +/- 1 mm Hg),
implicating alterations in pericardial constraint. The patients with
dilated cardiomyopathy showed no improvement in regional diastolic
relaxation, filling, or distensibility. CONCLUSIONS: Intracoronary
enalaprilat at a dosage that did not cause systemic neurohormonal
activation improved LV diastolic chamber distensibility and regional
relaxation and filling in patients with LV hypertrophy due to aortic
stenosis. In contrast, these effects of intracoronary enalaprilat on
diastolic function were not observed in patients with dilated
cardiomyopathy who did not have concentric hypertrophy. These observations
support the hypothesis that the cardiac renin-angiotensin system is
activated in patients with concentric pressure-overload hypertrophy and
that this activation may contribute to impaired diastolic function.
ARTICLES
Intracardiac angiotensin-converting enzyme inhibition improves diastolic function in patients with left ventricular hypertrophy due to aortic stenosis
Charles A. Dana Research Institute, Boston, Mass.
This article has been cited by other articles:
 |
|
 |
|
  J Jimenez-Candil, J Bermejo, R Yotti, C Cortina, M Moreno, J L Cantalapiedra, and M A Garcia-Fernandez Effects of angiotensin converting enzyme inhibitors in hypertensive patients with aortic valve stenosis: a drug withdrawal study Heart, October 1, 2005; 91(10): 1311 - 1318. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Kass, J. G.F. Bronzwaer, and W. J. Paulus What Mechanisms Underlie Diastolic Dysfunction in Heart Failure? Circ. Res., June 25, 2004; 94(12): 1533 - 1542. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Zeitz, D. J. Campbell, and J. D. Horowitz Myocardial Uptake and Biochemical and Hemodynamic Effects of ACE Inhibitors in Humans Hypertension, March 1, 2003; 41(3): 482 - 487. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. G. Angeja and W. Grossman Evaluation and Management of Diastolic Heart Failure Circulation, February 11, 2003; 107(5): 659 - 663. [Full Text] [PDF]
|
|
|
|
|
|
M. Fujii, A. Wada, T. Tsutamoto, M. Ohnishi, T. Isono, and M. Kinoshita Bradykinin Improves Left Ventricular Diastolic Function Under Long-Term Angiotensin-Converting Enzyme Inhibition in Heart Failure Hypertension, May 1, 2002; 39(5): 952 - 957. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. S. Wittstein, D. A. Kass, P. H. Pak, W. L. Maughan, B. Fetics, and J. M. Hare Cardiac nitric oxide production due to angiotensin-converting enzyme inhibition decreases beta-adrenergic myocardial contractility in patients with dilated cardiomyopathy J. Am. Coll. Cardiol., August 1, 2001; 38(2): 429 - 435. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Fielitz, S. Hein, V. Mitrovic, R. Pregla, H. R. Zurbrugg, C. Warnecke, J. Schaper, E. Fleck, and V. Regitz-Zagrosek Activation of the cardiac renin-angiotensin system and increased myocardial collagen expression in human aortic valve disease J. Am. Coll. Cardiol., April 1, 2001; 37(5): 1443 - 1449. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.Y.H Lip, D.C Felmeden, F.L Li-Saw-Hee, and D.G Beevers Hypertensive heart disease. A complex syndrome or a hypertensive 'cardiomyopathy'? Eur. Heart J., October 2, 2000; 21(20): 1653 - 1665. [PDF]
|
|
|
|
|
|
B. H. Lorell and B. A. Carabello Left Ventricular Hypertrophy : Pathogenesis, Detection, and Prognosis Circulation, July 25, 2000; 102(4): 470 - 479. [Full Text] [PDF]
|
|
|
|
|
|
W. Grossman Defining Diastolic Dysfunction Circulation, May 2, 2000; 101(17): 2020 - 2021. [Full Text] [PDF]
|
|
|
|
|
|
A Cohen-Solal, M Desnos, F Delahaye, J.P Emeriau, and G Hanania A national survey of heart failure in French hospitals Eur. Heart J., May 1, 2000; 21(9): 763 - 769. [Abstract] [PDF]
|
|
|
|
|
|
L. J. Dell’Italia and S. Oparil Bradykinin in the Heart : Friend Or Foe? Circulation, December 7, 1999; 100(23): 2305 - 2307. [Full Text] [PDF]
|
|
|
|
 |
|
 B. K. Slinker, Y. Wu, A. J. Brennan, K. B. Campbell, and J. W. Harding Angiotensin IV has mixed effects on left ventricle systolic function and speeds relaxation Cardiovasc Res, June 1, 1999; 42(3): 660 - 669. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Matter, L. Mandinov, P. A. Kaufmann, G. Vassalli, Z. Jiang, and O. M. Hess Effect of NO Donors on LV Diastolic Function in Patients With Severe Pressure-Overload Hypertrophy Circulation, May 11, 1999; 99(18): 2396 - 2401. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Warner Jr., D. C. Metzger, D. W. Kitzman, D. J. Wesley, and W. C. Little Losartan improves exercise tolerance in patients with diastolic dysfunction and a hypertensive response to exercise J. Am. Coll. Cardiol., May 1, 1999; 33(6): 1567 - 1572. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Koide, B. A. Carabello, C. C. Conrad, J. M. Buckley, G. DeFreyte, M. Barnes, R. J. Tomanek, C.-C. Wei, L. J. Dell'Italia, G. Cooper IV, et al. Hypertrophic response to hemodynamic overload: role of load vs. renin-angiotensin system activation Am J Physiol Heart Circ Physiol, February 1, 1999; 276(2): H350 - H358. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Bartunek, S. Dempsey, E. O. Weinberg, N. Ito, M. Tajima, S. Rohrbach, and B. H. Lorell Chronic L-arginine treatment increases cardiac cyclic guanosine 5'-monophosphate in rats with aortic stenosis: effects on left ventricular mass and beta-adrenergic contractile reserve J. Am. Coll. Cardiol., August 1, 1998; 32(2): 528 - 535. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kyriakidis, F. Triposkiadis, J. Dernellis, A. E. Androulakis, P. Mellas, G. A. Kelepeshis, and J. E. Gialafos Effects of Cardiac Versus Circulatory Angiotensin-Converting Enzyme Inhibition on Left Ventricular Diastolic Function and Coronary Blood Flow in Hypertrophic Obstructive Cardiomyopathy Circulation, April 14, 1998; 97(14): 1342 - 1347. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Hayashida, J. Donckier, H. Van Mechelen, A. A. Charlier, and H. Pouleur Load-sensitive diastolic relaxation in hypertrophied left ventricles Am J Physiol Heart Circ Physiol, February 1, 1998; 274(2): H609 - H615. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. T. Weber Extracellular Matrix Remodeling in Heart Failure : A Role for De Novo Angiotensin II Generation Circulation, December 2, 1997; 96(11): 4065 - 4082. [Full Text]
|
|
|
|
|
|
E. O. Weinberg, M. A. Lee, M. Weigner, K. Lindpaintner, S. P. Bishop, C. R. Benedict, K. K. L. Ho, P. S. Douglas, E. Chafizadeh, and B. H. Lorell Angiotensin AT1 Receptor Inhibition : Effects on Hypertrophic Remodeling and ACE Expression in Rats With Pressure-Overload Hypertrophy due to Ascending Aortic Stenosis Circulation, March 18, 1997; 95(6): 1592 - 1600. [Abstract] [Full Text]
|
|
|
|
|
|
W. Hayashida, J. Donckier, H. Van Mechelen, A. A. Charlier, and H. Pouleur Diastolic properties in canine hypertensive left ventricular hypertrophy: Effects of angiotensin converting enzyme inhibition and angiotensin II type-1 receptor blockade Cardiovasc Res, January 1, 1997; 33(1): 54 - 62. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. B. Anning, R. M. Grocott-Mason, M. J. Lewis, and A. M. Shah Enhancement of Left Ventricular Relaxation in the Isolated Heart by an Angiotensin-Converting Enzyme Inhibitor Circulation, November 1, 1995; 92(9): 2660 - 2665. [Abstract] [Full Text]
|
|
|
|
|
|
A.J. Marian and R. Roberts Recent Advances in the Molecular Genetics of Hypertrophic Cardiomyopathy Circulation, September 1, 1995; 92(5): 1336 - 1347. [Full Text]
|
|
|
|
|
|
S. E. Litwin, S. E. Katz, E. O. Weinberg, B. H. Lorell, G. P. Aurigemma, and P. S. Douglas Serial Echocardiographic-Doppler Assessment of Left Ventricular Geometry and Function in Rats With Pressure-Overload Hypertrophy : Chronic Angiotensin-Converting Enzyme Inhibition Attenuates the Transition to Heart Failure Circulation, May 15, 1995; 91(10): 2642 - 2654. [Abstract] [Full Text]
|
|