Dose-dependent effects of sildenafil on post-ischaemic left ventricular function in the rat isolated heart
Φόρτωση...
Ημερομηνία
Συγγραφείς
Kolettis, T. M.
Kontaras, K.
Spartinos, I.
Maniotis, C.
Varnavas, V.
Koutouzis, M.
Mourouzis, I.
Papalois, A.
Pantos, C.
Kyriakides, Z. S.
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