CLINICAL STUDY
Acute type 5 phosphodiesterase inhibition with sildenafil enhances flow-mediated vasodilation in patients with chronic heart failure
Stuart D. Katz, MDa,
Kujtim Balidemaj, MDa,
Shunichi Homma, MDb,
Henry Wu, MDb,
Jie Wang, MD, PhDa and
Simon Maybaum, MDa
a Division of Circulatory Physiology, Columbia Presbyterian Medical Center, New York, New YorkUSA
b Division of Cardiology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA
Manuscript received August 13, 1999;
revised manuscript received March 7, 2000,
accepted April 14, 2000.
Reprint requests and correspondence: Dr. Stuart D. Katz, Columbia Presbyterian Medical Center, Division of Circulatory Physiology, Room MHB5-435, 177 Fort Washington Avenue, New York, New York 10032
sdk8{at}columbia.edu
OBJECTIVES
To determine the acute effects of type 5 phosphodiesterase inhibition with sildenafil on flow-mediated vasodilation in the brachial artery of patients with chronic heart failure.
BACKGROUND
Impaired endothelium-dependent, flow-mediated vasodilation in patients with heart failure is partly attributable to hyporesponsiveness of cyclic guanosine monophosphate (cGMP) mediated vasorelaxation effector mechanisms in vascular smooth muscle. The effect of inhibition of cGMP degradation with sildenafil, a specific type 5 cGMP phosphodiesterase inhibitor, on flow-mediated dilation in heart failure is unknown.
METHODS
Flow-mediated vasodilation after release of 1, 3 and 5 min of transient arterial occlusion was measured in the brachial artery with high resolution two-dimensional ultrasound imaging in 48 patients with chronic heart failure before and 1 h after randomized, double-blind assignment to a single oral dose of sildenafil 12.5, 25 or 50 mg or matching placebo.
RESULTS
In response to oral administration of a single dose of study drug, the change in flow-mediated vasodilation after release of 1, 3 and 5 min of arterial occlusion was significantly greater in patients receiving sildenafil 25 mg (3.3 ± 1.9, 3.8 ± 1.8 and 4.0 ± 1.8%, respectively, p < 0.05) and patients receiving sildenafil 50 mg (3.7 ± 1.3, 4.1 ± 1.1, 3.9 ± 1.3%, respectively, p < 0.05) than that of patients receiving placebo (0.7 ± 1.1, 0.2 ± 1.2, 0.6 ± 0.8%, respectively).
CONCLUSIONS
Acute type 5 phosphodiesterase inhibition with sildenafil 25 and 50 mg increases endothelium-dependent, flow-mediated vasodilation in patients with chronic heart failure when compared with placebo.
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|
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|
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|
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|
|
|
|
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Phosphodiesterase inhibitors for the treatment of pulmonary hypertension
Eur. Respir. J.,
July 1, 2008;
32(1):
198 - 209.
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|
|
|
|
|
|
|
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J. Am. Coll. Cardiol.,
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50(22):
2136 - 2144.
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[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. Kass, H. C. Champion, and J. A. Beavo
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November 26, 2007;
101(11):
1084 - 1095.
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[Full Text]
[PDF]
|
|
|
|
|
|
|
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115(1):
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|
|
|
|
|
|
|
I. H. Zucker, H. D. Schultz, W. Wang, M. Guazzi, A. C. Scott, C. E. Negrao, M. U. P. B. Rondon, E. S. Prakash, A. L. Clark, A. Crisafulli, et al.
Increased mechanoreceptor/metaboreceptor stimulation explains the exaggerated exercise pressor reflex seen in heart failure
J Appl Physiol,
January 1, 2007;
102(1):
498 - 501.
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[PDF]
|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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296(9):
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|
|
|
|
|
|
|
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[Abstract]
[PDF]
|
|
|
|
|
|
|
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June 1, 2006;
231(6):
967 - 973.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S D Robinson, C A Ludlam, N A Boon, and D E Newby
Phosphodiesterase type 5 inhibition does not reverse endothelial dysfunction in patients with coronary heart disease
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February 1, 2006;
92(2):
170 - 176.
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|
|
|
|
|
|
|
R. Fries, K. Shariat, H. von Wilmowsky, and M. Bohm
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November 8, 2005;
112(19):
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|
|
|
|
|
|
|
B. A. Borlaug, V. Melenovsky, T. Marhin, P. Fitzgerald, and D. A. Kass
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|
|
|
|
|
|
|
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April 1, 2005;
280(13):
12944 - 12955.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. J. Gross
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111(6):
721 - 723.
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|
|
|
|
|
|
|
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February 2, 2005;
26(4):
363 - 368.
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|
|
|
|
|
|
|
S. D. Katz, K. Hryniewicz, I. Hriljac, K. Balidemaj, C. Dimayuga, A. Hudaihed, and A. Yasskiy
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111(3):
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
R. C Kukreja, R. Ockaili, F. Salloum, and L. Xi
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60(3):
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|
|
|
|
|
|
|
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8(4):
243 - 248.
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|
|
|
|
|
|
|
T. Reffelmann and R. A. Kloner
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108(2):
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|
|
|
|
|
|
|
M. Kimura, Y. Higashi, K. Hara, K. Noma, S. Sasaki, K. Nakagawa, C. Goto, T. Oshima, M. Yoshizumi, and K. Chayama
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May 1, 2003;
41(5):
1106 - 1110.
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[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Jackson
Phosphodiesterase type 5 inhibition in cardiovascular disease: experimental models and potential clinical applications
Eur. Heart J. Suppl.,
December 1, 2002;
4(suppl_H):
H19 - H23.
[Abstract]
[PDF]
|
|
|
|
|
|
|
J. P. J. Halcox, K. R. A. Nour, G. Zalos, R. Mincemoyer, M. A. Waclawiw, C. E. Rivera, G. Willie, S. Ellahham, and A. A. Quyyumi
The effect of sildenafil on human vascular function, platelet activation, and myocardial ischemia
J. Am. Coll. Cardiol.,
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40(7):
1232 - 1240.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. A. Bocchi, G. Guimaraes, A. Mocelin, F. Bacal, G. Bellotti, and J. F. Ramires
Sildenafil Effects on Exercise, Neurohormonal Activation, and Erectile Dysfunction in Congestive Heart Failure: A Double-Blind, Placebo-Controlled, Randomized Study Followed by a Prospective Treatment for Erectile Dysfunction
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August 27, 2002;
106(9):
1097 - 1103.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Desouza, A. Parulkar, D. Lumpkin, D. Akers, and V. A. Fonseca
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August 1, 2002;
25(8):
1336 - 1339.
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[Full Text]
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|
|
|
|
|
|
|
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July 1, 2002;
22(7):
e15 - 18.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Arruda-Olson, D. W. Mahoney, A. Nehra, M. Leckel, and P. A. Pellikka
Cardiovascular Effects of Sildenafil During Exercise in Men With Known or Probable Coronary Artery Disease: A Randomized Crossover Trial
JAMA,
February 13, 2002;
287(6):
719 - 725.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. D. Katz, D. V. Parums, B. G. Phillips, M. Kato, C. A. Pesek, V. K. Somers, M. Winnicki, D. Davison, and K. Narkiewicz
Sympathetic Activation by Sildenafil Response
Circulation,
November 27, 2001;
104
(22):
e119 - e120.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R D Rakhit and M S Marber
Nitric oxide: an emerging role in cardioprotection?
Heart,
October 1, 2001;
86(4):
368 - 372.
[Full Text]
[PDF]
|
|
|
|
