Dose-dependent effects of sildenafil on post-ischaemic left ventricular function in the rat isolated heart

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dc.contributor.authorKolettis, T. M.en
dc.contributor.authorKontaras, K.en
dc.contributor.authorSpartinos, I.en
dc.contributor.authorManiotis, C.en
dc.contributor.authorVarnavas, V.en
dc.contributor.authorKoutouzis, M.en
dc.contributor.authorMourouzis, I.en
dc.contributor.authorPapalois, A.en
dc.contributor.authorPantos, C.en
dc.contributor.authorKyriakides, Z. S.en
dc.date.accessioned2015-11-24T19:23:39Z
dc.date.available2015-11-24T19:23:39Z
dc.identifier.issn2042-7158-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/22350
dc.rightsDefault Licence-
dc.subjectAnimalsen
dc.subjectCardiotonic Agents/*administration & dosage/adverse effects/*pharmacologyen
dc.subjectDose-Response Relationship, Drugen
dc.subjectHeart/drug effects/physiopathologyen
dc.subjectIschemic Contracture/prevention & controlen
dc.subjectMaleen
dc.subjectMyocardial Ischemia/*physiopathologyen
dc.subjectMyocardial Reperfusion Injury/physiopathology/*prevention & controlen
dc.subjectPhosphodiesterase Inhibitors/administration & dosage/adverse effects/pharmacologyen
dc.subjectPiperazines/*administration & dosage/adverse effects/*pharmacologyen
dc.subjectPurines/administration & dosage/adverse effects/pharmacologyen
dc.subjectRandom Allocationen
dc.subjectRatsen
dc.subjectRats, Wistaren
dc.subjectSulfones/*administration & dosage/adverse effects/*pharmacologyen
dc.subjectVasodilator Agents/administration & dosage/adverse effects/pharmacologyen
dc.subjectVentricular Dysfunction, Left/etiology/physiopathology/prevention & controlen
dc.subjectVentricular Function, Left/*drug effectsen
dc.subjectVentricular Pressure/drug effectsen
dc.titleDose-dependent effects of sildenafil on post-ischaemic left ventricular function in the rat isolated hearten
heal.abstractOBJECTIVES: Sildenafil may be beneficial during myocardial ischaemia/reperfusion, but this effect may be dose-dependent, accounting for previous conflicting results. We have explored the effects of two acute and one chronic administration regimen on left ventricular function. METHODS: The study was conducted on 36 Wistar rats (290 +/- 7 g). Sildenafil was administered 30 min before ischaemia at a low (0.7 mg/kg, n= 8) or high (1.4 mg/kg, n= 8)dosage. The chronic treatment arm (n= 8) consisted of two daily injections of sildenafil (0.7 mg/kg) for three weeks. The control group was formed by 12 rats. Ischaemic contracture, post-ischaemic recovery and hypercontracture were measured in isolated, Langendorff-perfused preparations. KEY FINDINGS: Ischaemic contracture tended to be lower after high-dose sildenafil, while remaining unchanged after low-dose or chronic sildenafil administration. Compared with controls (62.9 +/- 2.0% of baseline developed pressure), post-ischaemic recovery was higher (P= 0.0069) after low dose (75.1 +/- 2.4%), unchanged (P= 0.13) after high dose (69.1 +/- 2.1%), but lower (P < 0.001) after chronic (42.9 +/- 4.5%) sildenafil administration. Compared with controls (71.8 +/- 3.9 mmHg), hypercontracture was higher (P= 0.0052) after chronic sildenafil administration (89.5 +/- 4.1 mmHg), but similar after acute low dose (65.7 +/- 3.3 mmHg, P= 0.33) or high dose (67.1 +/- 4.7 mmHg, P= 0.43). CONCLUSIONS: The effects of sildenafil after ischaemia/reperfusion were strongly dose-dependent. Beneficial actions on left ventricular function were evident after acute pretreatment with a low dosage, but were lost after doubling the dose. Chronic sildenafil administration deteriorated left ventricular function during ischaemia and reperfusion.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.primary10.1211/jpp.62.03.0009-
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/20487218-
heal.identifier.secondaryhttp://onlinelibrary.wiley.com/store/10.1211/jpp.62.03.0009/asset/jpp.62.03.0009.pdf?v=1&t=h0oxy28o&s=2c50232837c3f51f8d38e6254501434eca45f032-
heal.journalNameJ Pharm Pharmacolen
heal.journalTypepeer-reviewed-
heal.languageen-
heal.publicationDate2010-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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