Martínez-Salamanca Juan I, La Fuente José M, Fernández Argentina, Martínez-Salamanca Eduardo, Pepe-Cardoso Augusto J, Carballido Joaquín, Angulo Javier
Servicio de Urología, Hospital Universitario Puerta de Hierro, Madrid, Spain.
J Sex Med. 2015 Mar;12(3):590-9. doi: 10.1111/jsm.12801. Epub 2014 Dec 21.
Radical prostatectomy (RP) frequently results in erectile dysfunction (ED). It has been hypothesized that alterations of cavernosal tissue subsequent to RP contribute to ED but functional evaluation of the impact of RP on human erectile structures is lacking.
This study aims to evaluate endothelial function of human corpus cavernosum (HCC) and human penile resistance arteries (HPRA) and neurogenic responses of HCC from patients with ED secondary to RP (ED-RP).
HCC strips and HPRA were obtained from organ donors without history of ED (No-ED) and patients with ED who were segregated depending on ED etiology: ED-RP or vasculogenic (ED-VASC). Functional evaluation of HCC and HPRA was performed in organ chambers and wire myographs, respectively. Histological evaluation of cavernosal tissue consisted of trichrome staining for fibrosis quantification and TUNEL assay for determination of apoptosis.
Endothelium-dependent and endothelium-independent relaxation, electrical field stimulation (EFS)-induced neurogenic contraction and relaxation, and cavernosal fibrosis and apoptosis.
Endothelium-dependent relaxations were significantly impaired in HCC and HPRA from ED-VASC patients while these responses in ED-PR patients were not different to No-ED. Similarly, sildenafil-induced relaxations were reduced in HCC and HPRA from ED-VASC but were preserved in ED-RP. Adrenergic contractions induced by EFS in HCC were potentiated in both ED-RP and ED-VASC. EFS-induced nitrergic relaxation was significantly reduced in HCC from ED-VASC but was almost abolished in ED-RP. Fibrous tissue content and cavernosal apoptosis in HCC from ED-RP were not significantly different from No-ED.
Endothelial function and cavernosal sensitivity to phosphodiesterase type 5 inhibitors are preserved in erectile tissue from ED-RP while a marked imbalance in neurogenic modulation of cavernosal tone favoring adrenergic contractile responses over nitrergic relaxation is manifested. Fibrotic and apoptotic processes in cavernosal tissue are not specifically associated to ED-RP. These evidences could help to retarget therapeutic strategies in the management of ED after RP.
根治性前列腺切除术(RP)常导致勃起功能障碍(ED)。据推测,RP后海绵体组织的改变会导致ED,但目前缺乏对RP对人体勃起结构影响的功能评估。
本研究旨在评估RP继发ED(ED-RP)患者的人海绵体(HCC)和人阴茎阻力动脉(HPRA)的内皮功能以及HCC的神经源性反应。
从无ED病史的器官供体(No-ED)以及根据ED病因分类的ED患者中获取HCC条带和HPRA:ED-RP或血管源性(ED-VASC)。分别在器官腔和线肌动描记器中对HCC和HPRA进行功能评估。海绵体组织的组织学评估包括用于纤维化定量的三色染色和用于测定细胞凋亡的TUNEL分析。
内皮依赖性和非内皮依赖性舒张、电场刺激(EFS)诱导的神经源性收缩和舒张,以及海绵体纤维化和细胞凋亡。
ED-VASC患者的HCC和HPRA中的内皮依赖性舒张明显受损,而ED-PR患者的这些反应与No-ED患者无差异。同样,西地那非诱导的舒张在ED-VASC患者的HCC和HPRA中降低,但在ED-RP患者中保留。EFS在HCC中诱导的肾上腺素能收缩在ED-RP和ED-VASC患者中均增强。EFS诱导的一氧化氮能舒张在ED-VASC患者的HCC中明显降低,但在ED-RP患者中几乎消失。ED-RP患者的HCC中的纤维组织含量和海绵体细胞凋亡与No-ED患者无显著差异。
ED-RP患者的勃起组织中内皮功能和海绵体对5型磷酸二酯酶抑制剂的敏感性得以保留,而海绵体张力的神经源性调节存在明显失衡,有利于肾上腺素能收缩反应而非一氧化氮能舒张。海绵体组织中的纤维化和凋亡过程与ED-RP无特异性关联。这些证据有助于重新调整RP后ED管理中的治疗策略。