Document Detail


Acute hemodynamic effects of intravenous sildenafil citrate in congestive heart failure: comparison of phosphodiesterase type-3 and -5 inhibition.
MedLine Citation:
PMID:  19560695     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Phil Botha; Gareth Parry; John H Dark; Guy A Macgowan
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2009-05-13
Journal Detail:
Title:  The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation     Volume:  28     ISSN:  1557-3117     ISO Abbreviation:  J. Heart Lung Transplant.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-06-29     Completed Date:  2009-10-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9102703     Medline TA:  J Heart Lung Transplant     Country:  United States    
Other Details:
Languages:  eng     Pagination:  676-82     Citation Subset:  IM    
Affiliation:
Department of Cardiopulmonary Transplantation, Freeman Hospital, Newcastle upon Tyne, United Kingdom. P.Botha@ncl.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Adult
Blood Pressure / drug effects,  physiology
Cyclic Nucleotide Phosphodiesterases, Type 3 / antagonists & inhibitors*,  metabolism
Cyclic Nucleotide Phosphodiesterases, Type 5 / antagonists & inhibitors*,  metabolism
Female
Heart Failure / complications,  drug therapy*,  physiopathology*
Heart Rate / drug effects,  physiology
Heart Transplantation / physiology
Humans
Hypertension, Pulmonary / complications,  drug therapy,  physiopathology
Injections, Intravenous
Male
Middle Aged
Milrinone / administration & dosage,  pharmacology,  therapeutic use
Phosphodiesterase Inhibitors / administration & dosage,  pharmacology,  therapeutic use*
Piperazines / administration & dosage,  pharmacology,  therapeutic use*
Pulmonary Wedge Pressure / drug effects,  physiology
Purines / administration & dosage,  pharmacology,  therapeutic use
Sulfones / administration & dosage,  pharmacology,  therapeutic use*
Vascular Resistance / drug effects,  physiology
Chemical
Reg. No./Substance:
0/Phosphodiesterase Inhibitors; 0/Piperazines; 0/Purines; 0/Sulfones; 139755-83-2/sildenafil; 78415-72-2/Milrinone; EC 3.1.4.17/Cyclic Nucleotide Phosphodiesterases, Type 3; EC 3.1.4.35/Cyclic Nucleotide Phosphodiesterases, Type 5

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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