The Journal of Heart and Lung Transplantation
Volume 28, Issue 7 , Pages 676-682, July 2009

Acute Hemodynamic Effects of Intravenous Sildenafil Citrate in Congestive Heart Failure: Comparison of Phosphodiesterase Type-3 and -5 Inhibition

  • Phil Botha, MRCS

      Affiliations

    • Department of Cardiopulmonary Transplantation, Freeman Hospital, Newcastle upon Tyne, United Kingdom
    • Corresponding Author InformationReprint requests: Phil Botha, Department of Cardiopulmonary Transplantation, Freeman Hospital, High Heaton, Newcastle upon Tyne, NE7 7DN, UK. Telephone: 0044-191-213-7140. Fax: 0044-191-223-1152
  • ,
  • Gareth Parry, FRCP

      Affiliations

    • Department of Cardiopulmonary Transplantation, Freeman Hospital, Newcastle upon Tyne, United Kingdom
  • ,
  • John H. Dark, FRCS

      Affiliations

    • Department of Cardiopulmonary Transplantation, Freeman Hospital, Newcastle upon Tyne, United Kingdom
  • ,
  • Guy A. MacGowan, MD, FRCPI

      Affiliations

    • Department of Cardiology, Freeman Hospital, Newcastle upon Tyne, United Kingdom

Received 28 December 2008; received in revised form 11 March 2009; accepted 7 April 2009. published online 15 May 2009.

Background

The reversibility of elevated pulmonary vascular resistance in heart failure bears an important relation to outcome after cardiac transplantation. The phosphodiesterase 3 (PDE3) and PDE5 inhibitors both increase levels of cyclic nucleotides in the vascular smooth muscle, causing vasodilatation. PDE3 inhibitors also have direct inotropic effects. We contrasted the acute hemodynamic responses to intravenous PDE3 and PDE5 inhibitors in patients with congestive cardiac failure to assess their relative suitability for reversibility testing in this setting.

Methods

Thirty patients undergoing assessment for cardiac transplantation underwent right heart catheterization. Patients were randomized to receive an intravenous bolus of milrinone (0.05 mg/kg) or sildenafil citrate at a high (0.43 mg/kg) or low dose (0.05 mg/kg).

Results

Differences between low- and high-dose sildenafil were not significant. Both agents caused similar reductions in systemic and pulmonary vascular resistance. Milrinone caused significantly greater reductions in pulmonary artery wedge and mean pulmonary artery pressure, and increases in heart rate. In all study groups, greater increases in cardiac index (>25%) were seen in patients with a higher pulmonary artery wedge pressure at baseline (29 ± 1 vs 20 ± 2 mm Hg; p < 0.001).

Conclusions

In end-stage congestive cardiac failure, intravenous milrinone and sildenafil both cause similar reductions in systemic and pulmonary vascular resistance; however, milrinone has more cardiac selective effects on left ventricular filling and heart rate. Both agents appear to have a suitable hemodynamic profile for testing of reversibility of secondary pulmonary hypertension in congestive cardiac failure. Larger studies are needed to confirm these results.

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 This study was funded by a grant from the Newcastle Hospitals NHS Trust Special Trustees.

PII: S1053-2498(09)00235-6

doi:10.1016/j.healun.2009.04.013

The Journal of Heart and Lung Transplantation
Volume 28, Issue 7 , Pages 676-682, July 2009