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.
This article has been cited by other articles:
|
|
|
|
 
J. W. M. Cheng and S. R. Berhane
Managing Erectile Dysfunction in Patients With Cardiovascular Diseases: The Efficacy and Safety of Phosphodiesterase-5 Inhibitors
American Journal of Lifestyle Medicine,
May 1, 2009;
3(3):
201 - 211.
[Abstract]
[PDF]
|
|
|
|
|
|
|
C. S.P. Lam, V. L. Roger, R. J. Rodeheffer, B. A. Borlaug, F. T. Enders, and M. M. Redfield
Pulmonary hypertension in heart failure with preserved ejection fraction a community-based study.
J. Am. Coll. Cardiol.,
March 31, 2009;
53(13):
1119 - 1126.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Guazzi
Clinical Use of Phosphodiesterase-5 Inhibitors in Chronic Heart Failure
Circ Heart Fail,
November 1, 2008;
1(4):
272 - 280.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. A. Yassin and F. Saad
Testosterone and Erectile Dysfunction
J Androl,
November 1, 2008;
29(6):
593 - 604.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. R. Wilkins, J. Wharton, F. Grimminger, and H. A. Ghofrani
Phosphodiesterase inhibitors for the treatment of pulmonary hypertension
Eur. Respir. J.,
July 1, 2008;
32(1):
198 - 209.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Guazzi, M. Samaja, R. Arena, M. Vicenzi, and M. D. Guazzi
Long-Term Use of Sildenafil in the Therapeutic Management of Heart Failure
J. Am. Coll. Cardiol.,
November 27, 2007;
50(22):
2136 - 2144.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. Kass, H. C. Champion, and J. A. Beavo
Phosphodiesterase Type 5: Expanding Roles in Cardiovascular Regulation
Circ. Res.,
November 26, 2007;
101(11):
1084 - 1095.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. D. Lewis, J. Lachmann, J. Camuso, J. J. Lepore, J. Shin, M. E. Martinovic, D. M. Systrom, K. D. Bloch, and M. J. Semigran
Sildenafil Improves Exercise Hemodynamics and Oxygen Uptake in Patients With Systolic Heart Failure
Circulation,
January 2, 2007;
115(1):
59 - 66.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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.
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. R. Schwarz, S. Rastogi, V. Kapur, N. Sulemanjee, and J. J. Rodriguez
Erectile Dysfunction in Heart Failure Patients
J. Am. Coll. Cardiol.,
September 19, 2006;
48(6):
1111 - 1119.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Zheng, M. Patel, K. Hryniewicz, and S. D. Katz
Association of extended work shifts, vascular function, and inflammatory markers in internal medicine residents: a randomized crossover trial.
JAMA,
September 6, 2006;
296(9):
1049 - 1050.
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Kiowski, H. Brunner, and C. Schalcher
Sex, the heart, and heart failure.
Seminars in Cardiothoracic and Vascular Anesthesia,
September 1, 2006;
10(3):
256 - 258.
[Abstract]
[PDF]
|
|
|
|
|
|
|
M. Clozel, P. Hess, M. Rey, M. Iglarz, C. Binkert, and C. Qiu
Bosentan, Sildenafil, and Their Combination in the Monocrotaline Model of Pulmonary Hypertension in Rats
Exp Biol Med,
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
Heart,
February 1, 2006;
92(2):
170 - 176.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Fries, K. Shariat, H. von Wilmowsky, and M. Bohm
Sildenafil in the Treatment of Raynaud's Phenomenon Resistant to Vasodilatory Therapy
Circulation,
November 8, 2005;
112(19):
2980 - 2985.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. A. Borlaug, V. Melenovsky, T. Marhin, P. Fitzgerald, and D. A. Kass
Sildenafil Inhibits {beta}-Adrenergic-Stimulated Cardiac Contractility in Humans
Circulation,
October 25, 2005;
112(17):
2642 - 2649.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Das, L. Xi, and R. C. Kukreja
Phosphodiesterase-5 Inhibitor Sildenafil Preconditions Adult Cardiac Myocytes against Necrosis and Apoptosis: ESSENTIAL ROLE OF NITRIC OXIDE SIGNALING
J. Biol. Chem.,
April 1, 2005;
280(13):
12944 - 12955.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. J. Gross
Sildenafil and Endothelial Dysfunction in Humans
Circulation,
February 15, 2005;
111(6):
721 - 723.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. L. Bots, J. Westerink, T. J. Rabelink, and E. J.P. de Koning
Assessment of flow-mediated vasodilatation (FMD) of the brachial artery: effects of technical aspects of the FMD measurement on the FMD response
Eur. Heart J.,
February 2, 2005;
26(4):
363 - 368.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. D. Katz, K. Hryniewicz, I. Hriljac, K. Balidemaj, C. Dimayuga, A. Hudaihed, and A. Yasskiy
Vascular Endothelial Dysfunction and Mortality Risk in Patients With Chronic Heart Failure
Circulation,
January 25, 2005;
111(3):
310 - 314.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Guazzi, G. Tumminello, F. Di Marco, C. Fiorentini, and M. D. Guazzi
The effects of phosphodiesterase-5 inhibition with sildenafil on pulmonary hemodynamics and diffusion capacity, exercise ventilatory efficiency, and oxygen uptake kinetics in chronic heart failure
J. Am. Coll. Cardiol.,
December 21, 2004;
44(12):
2339 - 2348.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. G. Raja and S. H. Nayak
Sildenafil: Emerging Cardiovascular Indications
Ann. Thorac. Surg.,
October 1, 2004;
78(4):
1496 - 1506.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. C Kukreja, R. Ockaili, F. Salloum, and L. Xi
Sildenafil-induced cardioprotection in rabbits
Cardiovasc Res,
December 1, 2003;
60(3):
700 - 701.
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Vlachopoulos, K. Hirata, and M. F O'Rourke
Effect of sildenafil on arterial stiffness and wave reflection
Vascular Medicine,
November 1, 2003;
8(4):
243 - 248.
[Abstract]
[PDF]
|
|
|
|
|
|
|
T. Reffelmann and R. A. Kloner
Therapeutic Potential of Phosphodiesterase 5 Inhibition for Cardiovascular Disease
Circulation,
July 15, 2003;
108(2):
239 - 244.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Kimura, Y. Higashi, K. Hara, K. Noma, S. Sasaki, K. Nakagawa, C. Goto, T. Oshima, M. Yoshizumi, and K. Chayama
PDE5 Inhibitor Sildenafil Citrate Augments Endothelium-Dependent Vasodilation in Smokers
Hypertension,
May 1, 2003;
41(5):
1106 - 1110.
[Abstract]
[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.,
October 2, 2002;
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
Circulation,
August 27, 2002;
106(9):
1097 - 1103.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Desouza, A. Parulkar, D. Lumpkin, D. Akers, and V. A. Fonseca
Acute and Prolonged Effects of Sildenafil on Brachial Artery Flow-Mediated Dilatation in Type 2 Diabetes
Diabetes Care,
August 1, 2002;
25(8):
1336 - 1339.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Zheng, C. Dimayuga, A. Hudaihed, and S. D. Katz
Effect of Dexrazoxane on Homocysteine-Induced Endothelial Dysfunction in Normal Subjects
Arterioscler Thromb Vasc Biol,
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]
|
|
|
|
