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Oral sildenafil is an effective and specific pulmonary vasodilator in patients with pulmonary arterial hypertension: Comparison with inhaled nitric oxide
The prognosis of patients with severe pulmonary hypertension (PHT) is poor. To determine prognosis and guide therapy, an acute hemodynamic trial of selective pulmonary vasodilators, usually inhaled nitric oxide (iNO), was performed. We hypothesized that oral sildenafil, a phosphodiesterase-5 inhibit...
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| Published in: | Circulation (New York, N.Y.) N.Y.), 2002-05, Vol.105 (20), p.2398-2403 |
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| container_title | Circulation (New York, N.Y.) |
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| creator | MICHELAKIS, Evangelos TYMCHAK, Wayne LIEN, Dale WEBSTER, Linda HASHIMOTO, Kyoko ARCHER, Stephen |
| description | The prognosis of patients with severe pulmonary hypertension (PHT) is poor. To determine prognosis and guide therapy, an acute hemodynamic trial of selective pulmonary vasodilators, usually inhaled nitric oxide (iNO), was performed. We hypothesized that oral sildenafil, a phosphodiesterase-5 inhibitor, is a safe and effective alternative to iNO.
We studied 13 consecutive patients (mean+/-SEM, 44+/-2 years of age; 9 women) referred for consideration of heart-lung transplantation or as a guide to medical therapy. All but one were functional class III or IV. Patients had primary PHT (n=9), pulmonary arterial hypertension (n=2), or secondary PHT (n=2). Hemodynamics and serum cyclic guanosine-monophosphate levels (cGMP) were measured at baseline and at peak effects of iNO (80 ppm), sildenafil (75 mg), and their combination. The decrease in pulmonary vascular resistance was similar with iNO (-19+/-5%) and sildenafil (-27+/-3%), whereas sildenafil+iNO was more effective than iNO alone (-32+/-5%, P |
| doi_str_mv | 10.1161/01.CIR.0000016641.12984.DC |
| format | article |
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We studied 13 consecutive patients (mean+/-SEM, 44+/-2 years of age; 9 women) referred for consideration of heart-lung transplantation or as a guide to medical therapy. All but one were functional class III or IV. Patients had primary PHT (n=9), pulmonary arterial hypertension (n=2), or secondary PHT (n=2). Hemodynamics and serum cyclic guanosine-monophosphate levels (cGMP) were measured at baseline and at peak effects of iNO (80 ppm), sildenafil (75 mg), and their combination. The decrease in pulmonary vascular resistance was similar with iNO (-19+/-5%) and sildenafil (-27+/-3%), whereas sildenafil+iNO was more effective than iNO alone (-32+/-5%, P<0.003). Sildenafil and sildenafil+iNO increased cardiac index (17+/-5% and 17+/-4%, respectively), whereas iNO did not (-0.2+/-2.0%, P<0.003). iNO increased, whereas sildenafil tended to decrease, pulmonary capillary wedge pressure (+15+/-6 versus -9+/-7%, P<0.0007). Systemic arterial pressure was similar among groups and did not decrease with treatment. cGMP levels increased similarly with iNO and sildenafil, and their combination synergistically elevated cGMP (P<0.0001).
A single oral dose of sildenafil is as effective and selective a pulmonary vasodilator as iNO. Sildenafil may be superior to iNO in that it increases cardiac output and does not increase wedge pressure. Future studies are indicated to establish whether sildenafil could be effective over a longer duration.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/01.CIR.0000016641.12984.DC</identifier><identifier>PMID: 12021227</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Administration, Oral ; Adult ; Biological and medical sciences ; Cyclic GMP - blood ; Diuretics - therapeutic use ; Drug Therapy, Combination ; Female ; Headache - etiology ; Hemodynamics - drug effects ; Humans ; Hypertension, Pulmonary - drug therapy ; Hypertension, Pulmonary - physiopathology ; Male ; Medical sciences ; Middle Aged ; Nitric Oxide - administration & dosage ; Pharmacology. Drug treatments ; Phosphodiesterase Inhibitors - administration & dosage ; Phosphodiesterase Inhibitors - adverse effects ; Piperazines - administration & dosage ; Piperazines - adverse effects ; Predictive Value of Tests ; Pulmonary Artery - drug effects ; Pulmonary Artery - physiopathology ; Pulmonary Circulation - drug effects ; Pulmonary Wedge Pressure - drug effects ; Purines ; Respiratory system ; Sildenafil Citrate ; Sulfones ; Treatment Outcome ; Vascular Resistance - drug effects ; Vasodilator Agents - administration & dosage ; Vasodilator Agents - adverse effects ; Warfarin - therapeutic use</subject><ispartof>Circulation (New York, N.Y.), 2002-05, Vol.105 (20), p.2398-2403</ispartof><rights>2002 INIST-CNRS</rights><rights>Copyright American Heart Association, Inc. May 21, 2002</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c415t-c0a5376d148dbfec650a229f037f18a42b1e74cbaeb527a9ae53b3afed4309b93</citedby><cites>FETCH-LOGICAL-c415t-c0a5376d148dbfec650a229f037f18a42b1e74cbaeb527a9ae53b3afed4309b93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13692518$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12021227$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>MICHELAKIS, Evangelos</creatorcontrib><creatorcontrib>TYMCHAK, Wayne</creatorcontrib><creatorcontrib>LIEN, Dale</creatorcontrib><creatorcontrib>WEBSTER, Linda</creatorcontrib><creatorcontrib>HASHIMOTO, Kyoko</creatorcontrib><creatorcontrib>ARCHER, Stephen</creatorcontrib><title>Oral sildenafil is an effective and specific pulmonary vasodilator in patients with pulmonary arterial hypertension: Comparison with inhaled nitric oxide</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>The prognosis of patients with severe pulmonary hypertension (PHT) is poor. To determine prognosis and guide therapy, an acute hemodynamic trial of selective pulmonary vasodilators, usually inhaled nitric oxide (iNO), was performed. We hypothesized that oral sildenafil, a phosphodiesterase-5 inhibitor, is a safe and effective alternative to iNO.
We studied 13 consecutive patients (mean+/-SEM, 44+/-2 years of age; 9 women) referred for consideration of heart-lung transplantation or as a guide to medical therapy. All but one were functional class III or IV. Patients had primary PHT (n=9), pulmonary arterial hypertension (n=2), or secondary PHT (n=2). Hemodynamics and serum cyclic guanosine-monophosphate levels (cGMP) were measured at baseline and at peak effects of iNO (80 ppm), sildenafil (75 mg), and their combination. The decrease in pulmonary vascular resistance was similar with iNO (-19+/-5%) and sildenafil (-27+/-3%), whereas sildenafil+iNO was more effective than iNO alone (-32+/-5%, P<0.003). Sildenafil and sildenafil+iNO increased cardiac index (17+/-5% and 17+/-4%, respectively), whereas iNO did not (-0.2+/-2.0%, P<0.003). iNO increased, whereas sildenafil tended to decrease, pulmonary capillary wedge pressure (+15+/-6 versus -9+/-7%, P<0.0007). Systemic arterial pressure was similar among groups and did not decrease with treatment. cGMP levels increased similarly with iNO and sildenafil, and their combination synergistically elevated cGMP (P<0.0001).
A single oral dose of sildenafil is as effective and selective a pulmonary vasodilator as iNO. Sildenafil may be superior to iNO in that it increases cardiac output and does not increase wedge pressure. Future studies are indicated to establish whether sildenafil could be effective over a longer duration.</description><subject>Administration, Oral</subject><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Cyclic GMP - blood</subject><subject>Diuretics - therapeutic use</subject><subject>Drug Therapy, Combination</subject><subject>Female</subject><subject>Headache - etiology</subject><subject>Hemodynamics - drug effects</subject><subject>Humans</subject><subject>Hypertension, Pulmonary - drug therapy</subject><subject>Hypertension, Pulmonary - physiopathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Nitric Oxide - administration & dosage</subject><subject>Pharmacology. Drug treatments</subject><subject>Phosphodiesterase Inhibitors - administration & dosage</subject><subject>Phosphodiesterase Inhibitors - adverse effects</subject><subject>Piperazines - administration & dosage</subject><subject>Piperazines - adverse effects</subject><subject>Predictive Value of Tests</subject><subject>Pulmonary Artery - drug effects</subject><subject>Pulmonary Artery - physiopathology</subject><subject>Pulmonary Circulation - drug effects</subject><subject>Pulmonary Wedge Pressure - drug effects</subject><subject>Purines</subject><subject>Respiratory system</subject><subject>Sildenafil Citrate</subject><subject>Sulfones</subject><subject>Treatment Outcome</subject><subject>Vascular Resistance - drug effects</subject><subject>Vasodilator Agents - administration & dosage</subject><subject>Vasodilator Agents - adverse effects</subject><subject>Warfarin - therapeutic use</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><recordid>eNpNkV1rFDEUhoModq3-BQkFL2fM53z0TqatFgoF0etwJh9symwyJtnW_hT_ram7sOYmOZznzZuTF6ELSlpKO_qZ0Ha6_d6Sl0W7TtCWsnEQ7dX0Cm2oZKIRko-v0ab2x6bnjJ2hdzk_1LLjvXyLzigjjDLWb9Cf-wQLzn4xNoDzC_YZQ8DWOauLf7S1MDivVnvnNV73yy4GSM_4EXI0foESE_YBr1C8DSXjJ1-2_2GQik2-OmyfV1vPIfsYLvEUdyskn2M4CHzYwmINDr6kahN_e2PfozcOlmw_HPdz9PPm-sf0rbm7_3o7fblrtKCyNJqA5H1nqBjMXB_dSQKMjY7w3tEBBJup7YWewc6S9TCClXzm4KwRnIzzyM_RxeHeNcVfe5uLeoj7FKqlqn_UDUyOfYUuD5BOMedknVqT39UJFSXqJRRFqKqhqFMo6l8o6mqq4o9Hh_28s-YkPaZQgU9HALKGxSUI2ucTx7uRSTrwvxiEmdw</recordid><startdate>20020521</startdate><enddate>20020521</enddate><creator>MICHELAKIS, Evangelos</creator><creator>TYMCHAK, Wayne</creator><creator>LIEN, Dale</creator><creator>WEBSTER, Linda</creator><creator>HASHIMOTO, Kyoko</creator><creator>ARCHER, Stephen</creator><general>Lippincott Williams & Wilkins</general><general>American Heart Association, Inc</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>U9A</scope></search><sort><creationdate>20020521</creationdate><title>Oral sildenafil is an effective and specific pulmonary vasodilator in patients with pulmonary arterial hypertension: Comparison with inhaled nitric oxide</title><author>MICHELAKIS, Evangelos ; TYMCHAK, Wayne ; LIEN, Dale ; WEBSTER, Linda ; HASHIMOTO, Kyoko ; ARCHER, Stephen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c415t-c0a5376d148dbfec650a229f037f18a42b1e74cbaeb527a9ae53b3afed4309b93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Administration, Oral</topic><topic>Adult</topic><topic>Biological and medical sciences</topic><topic>Cyclic GMP - blood</topic><topic>Diuretics - therapeutic use</topic><topic>Drug Therapy, Combination</topic><topic>Female</topic><topic>Headache - etiology</topic><topic>Hemodynamics - drug effects</topic><topic>Humans</topic><topic>Hypertension, Pulmonary - drug therapy</topic><topic>Hypertension, Pulmonary - physiopathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Nitric Oxide - administration & dosage</topic><topic>Pharmacology. Drug treatments</topic><topic>Phosphodiesterase Inhibitors - administration & dosage</topic><topic>Phosphodiesterase Inhibitors - adverse effects</topic><topic>Piperazines - administration & dosage</topic><topic>Piperazines - adverse effects</topic><topic>Predictive Value of Tests</topic><topic>Pulmonary Artery - drug effects</topic><topic>Pulmonary Artery - physiopathology</topic><topic>Pulmonary Circulation - drug effects</topic><topic>Pulmonary Wedge Pressure - drug effects</topic><topic>Purines</topic><topic>Respiratory system</topic><topic>Sildenafil Citrate</topic><topic>Sulfones</topic><topic>Treatment Outcome</topic><topic>Vascular Resistance - drug effects</topic><topic>Vasodilator Agents - administration & dosage</topic><topic>Vasodilator Agents - adverse effects</topic><topic>Warfarin - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>MICHELAKIS, Evangelos</creatorcontrib><creatorcontrib>TYMCHAK, Wayne</creatorcontrib><creatorcontrib>LIEN, Dale</creatorcontrib><creatorcontrib>WEBSTER, Linda</creatorcontrib><creatorcontrib>HASHIMOTO, Kyoko</creatorcontrib><creatorcontrib>ARCHER, Stephen</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><jtitle>Circulation (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>MICHELAKIS, Evangelos</au><au>TYMCHAK, Wayne</au><au>LIEN, Dale</au><au>WEBSTER, Linda</au><au>HASHIMOTO, Kyoko</au><au>ARCHER, Stephen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Oral sildenafil is an effective and specific pulmonary vasodilator in patients with pulmonary arterial hypertension: Comparison with inhaled nitric oxide</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>2002-05-21</date><risdate>2002</risdate><volume>105</volume><issue>20</issue><spage>2398</spage><epage>2403</epage><pages>2398-2403</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>The prognosis of patients with severe pulmonary hypertension (PHT) is poor. To determine prognosis and guide therapy, an acute hemodynamic trial of selective pulmonary vasodilators, usually inhaled nitric oxide (iNO), was performed. We hypothesized that oral sildenafil, a phosphodiesterase-5 inhibitor, is a safe and effective alternative to iNO.
We studied 13 consecutive patients (mean+/-SEM, 44+/-2 years of age; 9 women) referred for consideration of heart-lung transplantation or as a guide to medical therapy. All but one were functional class III or IV. Patients had primary PHT (n=9), pulmonary arterial hypertension (n=2), or secondary PHT (n=2). Hemodynamics and serum cyclic guanosine-monophosphate levels (cGMP) were measured at baseline and at peak effects of iNO (80 ppm), sildenafil (75 mg), and their combination. The decrease in pulmonary vascular resistance was similar with iNO (-19+/-5%) and sildenafil (-27+/-3%), whereas sildenafil+iNO was more effective than iNO alone (-32+/-5%, P<0.003). Sildenafil and sildenafil+iNO increased cardiac index (17+/-5% and 17+/-4%, respectively), whereas iNO did not (-0.2+/-2.0%, P<0.003). iNO increased, whereas sildenafil tended to decrease, pulmonary capillary wedge pressure (+15+/-6 versus -9+/-7%, P<0.0007). Systemic arterial pressure was similar among groups and did not decrease with treatment. cGMP levels increased similarly with iNO and sildenafil, and their combination synergistically elevated cGMP (P<0.0001).
A single oral dose of sildenafil is as effective and selective a pulmonary vasodilator as iNO. Sildenafil may be superior to iNO in that it increases cardiac output and does not increase wedge pressure. Future studies are indicated to establish whether sildenafil could be effective over a longer duration.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>12021227</pmid><doi>10.1161/01.CIR.0000016641.12984.DC</doi><tpages>6</tpages></addata></record> |
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| subjects | Administration, Oral Adult Biological and medical sciences Cyclic GMP - blood Diuretics - therapeutic use Drug Therapy, Combination Female Headache - etiology Hemodynamics - drug effects Humans Hypertension, Pulmonary - drug therapy Hypertension, Pulmonary - physiopathology Male Medical sciences Middle Aged Nitric Oxide - administration & dosage Pharmacology. Drug treatments Phosphodiesterase Inhibitors - administration & dosage Phosphodiesterase Inhibitors - adverse effects Piperazines - administration & dosage Piperazines - adverse effects Predictive Value of Tests Pulmonary Artery - drug effects Pulmonary Artery - physiopathology Pulmonary Circulation - drug effects Pulmonary Wedge Pressure - drug effects Purines Respiratory system Sildenafil Citrate Sulfones Treatment Outcome Vascular Resistance - drug effects Vasodilator Agents - administration & dosage Vasodilator Agents - adverse effects Warfarin - therapeutic use |
| title | Oral sildenafil is an effective and specific pulmonary vasodilator in patients with pulmonary arterial hypertension: Comparison with inhaled nitric oxide |
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