transparent gif


Ej inloggad.

Göteborgs universitets publikationer

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

Författare och institution:
Theofilos M Kolettis (-); Konstantinos Kontaras (-); Ioannis Spartinos (-); Christos Maniotis (-); Varnavas Varnavas (-); Michael Koutouzis (Institutionen för medicin, avdelningen för molekylär och klinisk medicin); Iordanis Mourouzis (-); Apostolos Papalois (-); Constantinos Pantos (-); Zenon S Kyriakides (-)
Publicerad i:
The Journal of pharmacy and pharmacology, 62 ( 3 ) s. 346-51
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
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.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Klinisk medicin ->
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
Postens nummer:
Posten skapad:
2010-12-09 15:54
Posten ändrad:
2011-01-20 09:59

Visa i Endnote-format

Göteborgs universitet • Tel. 031-786 0000
© Göteborgs universitet 2007