Dose-dependent effects of sildenafil on post-ischaemic left ventricular function in the rat isolated heart
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Ημερομηνία
Τίτλος Εφημερίδας
Περιοδικό ISSN
Τίτλος τόμου
Εκδότης
Περίληψη
Τύπος
Είδος δημοσίευσης σε συνέδριο
Είδος περιοδικού
peer-reviewed
Είδος εκπαιδευτικού υλικού
Όνομα συνεδρίου
Όνομα περιοδικού
J Pharm Pharmacol
Όνομα βιβλίου
Σειρά βιβλίου
Έκδοση βιβλίου
Συμπληρωματικός/δευτερεύων τίτλος
Περιγραφή
OBJECTIVES: 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.
Περιγραφή
Λέξεις-κλειδιά
Animals, Cardiotonic Agents/*administration & dosage/adverse effects/*pharmacology, Dose-Response Relationship, Drug, Heart/drug effects/physiopathology, Ischemic Contracture/prevention & control, Male, Myocardial Ischemia/*physiopathology, Myocardial Reperfusion Injury/physiopathology/*prevention & control, Phosphodiesterase Inhibitors/administration & dosage/adverse effects/pharmacology, Piperazines/*administration & dosage/adverse effects/*pharmacology, Purines/administration & dosage/adverse effects/pharmacology, Random Allocation, Rats, Rats, Wistar, Sulfones/*administration & dosage/adverse effects/*pharmacology, Vasodilator Agents/administration & dosage/adverse effects/pharmacology, Ventricular Dysfunction, Left/etiology/physiopathology/prevention & control, Ventricular Function, Left/*drug effects, Ventricular Pressure/drug effects
Θεματική κατηγορία
Παραπομπή
Σύνδεσμος
http://www.ncbi.nlm.nih.gov/pubmed/20487218
http://onlinelibrary.wiley.com/store/10.1211/jpp.62.03.0009/asset/jpp.62.03.0009.pdf?v=1&t=h0oxy28o&s=2c50232837c3f51f8d38e6254501434eca45f032
http://onlinelibrary.wiley.com/store/10.1211/jpp.62.03.0009/asset/jpp.62.03.0009.pdf?v=1&t=h0oxy28o&s=2c50232837c3f51f8d38e6254501434eca45f032
Γλώσσα
en
Εκδίδον τμήμα/τομέας
Όνομα επιβλέποντος
Εξεταστική επιτροπή
Γενική Περιγραφή / Σχόλια
Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος
Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής