Department of Cardiology, University of Ioannina, Ioannina, Greece.
J Pharm Pharmacol. 2010 Mar;62(3):346-51. doi: 10.1211/jpp.62.03.0009.
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.
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.
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).
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.
西地那非在心肌缺血/再灌注时可能有益，但这种作用可能是剂量依赖性的，这解释了之前相互矛盾的结果。我们研究了两种急性和一种慢性给药方案对左心室功能的影响。
该研究在 36 只 Wistar 大鼠（290 ± 7 g）上进行。西地那非在缺血前 30 分钟以低剂量（0.7 mg/kg，n=8）或高剂量（1.4 mg/kg，n=8）给药。慢性治疗组（n=8）由每日两次 0.7 mg/kg 西地那非注射组成，持续 3 周。对照组由 12 只大鼠组成。在离体 Langendorff 灌注标本中测量缺血性挛缩、缺血后恢复和高收缩。
高剂量西地那非后缺血性挛缩倾向于降低，而低剂量或慢性西地那非给药后不变。与对照组（基础压的 62.9 ± 2.0%）相比，低剂量后缺血后恢复更高（P=0.0069）（75.1 ± 2.4%），高剂量后不变（P=0.13）（69.1 ± 2.1%），但慢性后较低（P<0.001）（42.9 ± 4.5%）西地那非给药。与对照组（71.8 ± 3.9 mmHg）相比，慢性西地那非给药后高收缩更高（P=0.0052）（89.5 ± 4.1 mmHg），但急性低剂量后相似（65.7 ± 3.3 mmHg，P=0.33）或高剂量后相似（67.1 ± 4.7 mmHg，P=0.43）。
西地那非在缺血/再灌注后的作用具有强烈的剂量依赖性。急性低剂量预处理后对左心室功能有明显的有益作用，但剂量加倍后作用消失。慢性西地那非给药在缺血和再灌注期间恶化左心室功能。
