© 2003 by European Society of Cardiology
Copyright © 2003, European Society of Cardiology
Effects of sildenafil on myocardial infarct size, microvascular function, and acute ischemic left ventricular dilation
The Heart Institute, Good Samaritan Hospital, University of Southern California, 1225 Wilshire Boulevard, Los Angeles, CA 90017-2395, USA
* Corresponding author. Tel.: +1-213-977-4050; fax: +1-213-977-4107. rkloner{at}goodsam.org
Objective: Adverse cardiac events in patients treated with the phosphodiesterase-5 inhibitor sildenafil for erectile dysfunction raised concerns about its safety in ischemic heart disease. Methods: In anesthetized open-chest rabbits, receiving 1.45 mg/kg sildenafil intravenously or saline 30 min prior to ischemia (n = 12, each), infarct size (IS, triphenyltetrazolium), the area of no-reflow (ANR, thioflavin S) (% of the risk area, RA, blue dye), and regional myocardial blood flow (RMBF, radioactive microspheres) were measured after 30 min of coronary occlusion and 180 min of reperfusion. Left ventricular hemodynamics and dimensions (echocardiography) were determined in a separate series of animals (n = 5, each). Results: Sildenafil significantly lowered arterial blood pressure before occlusion (–17 to –19 mmHg over 30 min), but during ischemia and reperfusion hemodynamics were comparable to controls. IS in treated animals (51±4%) did not significantly differ from control animals (47±4%). No major arrhythmias or lengthening of QT/QTc occurred. While sildenafil slightly increased RMBF and significantly reduced specific vascular resistance in the RA during reperfusion (51±7 versus 73±10 mmHg g min/ml, P<0.05), the ANR (46±3%) was similar to control animals (44±4%). Sildenafil reduced left ventricular dP/dtmax (P<0.05) and dP/dtmin (P<0.01) in non-ischemic conditions, and slightly during ischemia, along with a pronounced decrease in ischemic left ventricular end-diastolic pressure (9±2 versus 15±2 mmHg after saline, P<0.05), but did not attenuate acute ischemic left ventricular dilation. Conclusions: Sildenafil reduced cardiac pre- and afterload, and parameters of left ventricular contractility. Myocardial necrosis and microvascular dysfunction were neither exacerbated nor attenuated.
KEYWORDS Coronary circulation; Hemodynamics; Infarction; Reperfusion; Regional blood flow
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  T. Reffelmann and R. A. Kloner Phosphodiesterase 5 inhibitors: are they cardioprotective? Cardiovasc Res, July 15, 2009; 83(2): 204 - 212. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Kloner Erectile Dysfunction: The New Harbinger for Major Adverse Cardiac Events in the Diabetic Patient J. Am. Coll. Cardiol., May 27, 2008; 51(21): 2051 - 2052. [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. Elrod, J. J. M. Greer, and D. J. Lefer Sildenafil-mediated acute cardioprotection is independent of the NO/cGMP pathway Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H342 - H347. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Fesler, A. Pagnamenta, B. Rondelet, F. Kerbaul, and R. Naeije Effects of sildenafil on hypoxic pulmonary vascular function in dogs J Appl Physiol, October 1, 2006; 101(4): 1085 - 1090. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Fung, R. R. Fiscus, A. P. C. Yim, G. D. Angelini, and A. A. Arifi The Potential Use of Type-5 Phosphodiesterase Inhibitors in Coronary Artery Bypass Graft Surgery Chest, October 1, 2005; 128(4): 3065 - 3073. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. K. Thethi, N. O. Asafu-Adjaye, and V. A. Fonseca Erectile Dysfunction Clin. Diabetes, July 1, 2005; 23(3): 105 - 113. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. J. Gross Sildenafil and Endothelial Dysfunction in Humans Circulation, February 15, 2005; 111(6): 721 - 723. [Full Text] [PDF]
|
|
|
|
|
|
T. Gori, S. Sicuro, S. Dragoni, G. Donati, S. Forconi, and J. D. Parker Sildenafil Prevents Endothelial Dysfunction Induced by Ischemia and Reperfusion via Opening of Adenosine Triphosphate-Sensitive Potassium Channels: A Human In Vivo Study Circulation, February 15, 2005; 111(6): 742 - 746. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Kloner Cardiovascular Effects of the 3 Phosphodiesterase-5 Inhibitors Approved for the Treatment of Erectile Dysfunction Circulation, November 9, 2004; 110(19): 3149 - 3155. [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]
|
|
|
|
|
|
T. Reffelmann and R. A Kloner Cardiovascular effects of sildenafil in experimental ischemia-reperfusion (reply to "Sildenafil-induced cardioprotection in rabbits, by Kukreja, R.C., Ockaili, R., Salloum, F., Xi, L.") Cardiovasc Res, December 1, 2003; 60(3): 702 - 703. [Full Text] [PDF]
|
|