医学
伐地那非
心肌保护
cGMP特异性磷酸二酯酶5型
西地那非
缺血
心室
心脏病学
内科学
再灌注损伤
缺血预处理
麻醉
磷酸二酯酶抑制剂
刺激
药理学
他达拉非
作者
Asger Andersen,Jonas Agerlund Povlsen,Jacob Johnsen,Nichlas Riise Jespersen,Hans Erik Bøtker,Jens Erik Nielsen‐Kudsk
标识
DOI:10.1016/j.ijcard.2016.08.264
摘要
Background To investigate whether modulation of the sGC–cGMP–PKG pathway protects against ischemia and reperfusion injury in the healthy and the failing right ventricle (RV). Methods Hearts from male Wistar rats with a healthy RV (n = 39) or a hypertrophic and failing RV induced by pulmonary trunk banding (n = 57) were isolated and perfused in a pressure-controlled modified Langendorff setup. The isolated hearts were randomized to control, ischemic preconditioning (IPC, 2 × 5 min of global ischemia), a phosphodiesterase-5 (PDE5) inhibitor vardenafil (66 nM) alone and in combination with a cGMP-dependent protein kinase (PKG) blocker KT 5823 (1 μM). Failing hearts were exposed to the same protocols and to soluble guanylate cyclase stimulation/activation, and phosphodiesterase 9 inhibition. All interventions were followed by 40 min of global ischemia and 120 min of reperfusion. The effects on the RV were evaluated by measurement of the infarct size/area-at-risk ratio (IS/AAR). Results In healthy hearts, IPC and pharmacological preconditioning with vardenafil reduced RV infarct size. PKG blockade by KT-5823 did not alter infarct size per se but abolished the cardioprotective effect of vardenafil. In the hypertrophic and failing hearts, none of the conditioning strategies altered RV infarct size. Conclusion PDE-5 inhibition by vardenafil protects the healthy right ventricle against ischemia and reperfusion injury by a PKG dependent mechanism. Neither ischemic preconditioning nor pharmacologic stimulation of the sGC–cGMP–PKG pathway induces cardioprotection in the hypertrophic and failing RV.
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