Department of Clinical Medicine, Cardiology (Research), Aarhus University Hospital, Aarhus, Denmark.
J Cardiovasc Pharmacol. 2013 Aug;62(2):167-73. doi: 10.1097/FJC.0b013e318294a1cf.
We investigated if soluble guanylate cyclase stimulation either alone or in combination with phosphodiesterase-5 (PDE5) inhibition could prevent pressure overload-induced right ventricular (RV) hypertrophy and failure.
The soluble guanylate cyclase stimulator BAY 41-2272 (BAY, 10 mg · kg⁻¹ · d⁻¹) either alone or in combination (BAY + SIL) with a PDE5 inhibitor sildenafil (SIL, 100 mg · kg⁻¹ · d⁻¹) was examined for prevention of RV hypertrophy and failure in Wistar rats (n = 73) operated by pulmonary trunk banding.
All treatments failed to inhibit the development of RV hypertrophy and failure. In the BAY and BAY + SIL groups, there was an increased mortality. Mean arterial blood pressure was lowered and cardiac output increased in the BAY + SIL group. Systolic RV pressure was increased in the BAY and BAY + SIL groups possibly because of an inotropic response and/or increased venous return.
Stimulation of soluble guanylate cyclase by BAY 41-2272 alone or in combination with sildenafil failed to prevent the development of RV hypertrophy and failure in rats subjected to pulmonary trunk banding. An increased mortality was observed in animals treated by BAY 41-2272 alone and in combination with sildenafil.
我们研究了单独使用可溶性鸟苷酸环化酶刺激剂或联合使用磷酸二酯酶-5（PDE5）抑制剂是否可以预防压力超负荷引起的右心室（RV）肥厚和衰竭。
我们用可溶性鸟苷酸环化酶刺激剂 BAY 41-2272（BAY，10mg·kg⁻¹·d⁻¹）单独或联合（BAY+SIL）使用 PDE5 抑制剂西地那非（SIL，100mg·kg⁻¹·d⁻¹），对其预防肺动脉结扎术大鼠的 RV 肥厚和衰竭进行了研究（n=73）。
所有治疗方法均未能抑制 RV 肥厚和衰竭的发展。在 BAY 和 BAY+SIL 组中，死亡率增加。BAY+SIL 组的平均动脉血压降低，心输出量增加。BAY 和 BAY+SIL 组的收缩期 RV 压力增加，可能是由于正性肌力作用和/或增加静脉回流。
单独使用 BAY 41-2272 或联合使用西地那非刺激可溶性鸟苷酸环化酶，均不能预防肺动脉结扎大鼠 RV 肥厚和衰竭的发展。单独使用 BAY 41-2272 和联合使用西地那非的动物死亡率增加。
