The phosphodiesterase-5 inhibitors (PDE5Is) are the first-line treatment option for men with erectile dysfunction (ED), with alprostadil considered a second-line choice. Consideration has to be given to patients who fail these treatments and what their options are. This review evaluates the data on the combination of a PDE5I with alprostadil in patients who have previously failed therapy with either drug. A PubMed search was conducted and identified nine publications relating to combination treatment with alprostadil as intracavernosal, intraurethral or topical application. The results indicate that with all three formulations the combination therapy resulted in an improved outcome compared with either of the drugs as monotherapy. This was demonstrated by the increased total International Index of Erectile Function (IIEF) scores as well as IIEF erectile function domain scores. This finding was also valid for patients with post-prostatectomy ED. The associated side effects of the combined treatment did not result in treatment discontinuation. These findings suggest that combination therapy with a PDE5I and alprostadil might be considered a treatment option in patients who have previously had a poor response to either drug.

Objective: To explore effect of alprostadil on wound healing of scalded rats and the mechanism. Methods: According to random number table method, forty-eight Sprague Dawley rats were divided into sham scald group, simple scald group, lithium chloride group, and alprostadil group, with 12 rats in each group. Rats in sham injury group were sham injured on the back, and rats in the other three groups were inflicted with 30% total body surface area deep partial thickness scald on the back.Immediately after scald, rats in sham scald group and simple scald group were injected with 1 mL saline through caudal vein, and rats in lithium chloride group and alprostadil group were injected respectively with 1 mL lithium chloride and alprostadil through caudal vein. Saline, lithium chloride, and alprostadil were injected once in a day and lasted for 14 days. General wound appearance and wound healing rate on post scald day (PSD) 7, 10, 14 were observed and calculated. Expressions of protein and mRNA of Wnt1 and β-catenin on PSD 14 were detected. Data were processed with analysis of variance of factorial design, one-way analysis of variance, Student Newman Keuls q test, t test, and Bonferroni correction. Results: (1) On PSD 7, wounds of scalded rats in each group formed dry eschar and had little exudation. On PSD 10, wounds of rats in simple scald group were covered with eschar, with little exudation, and wounds of rats in lithium chloride group were covered with eschar, and partial wounds healed under the eschar. On PSD 10, partial eschar of rats in alprostadil group desquamated; partial wounds healed; newly burned skin was ruddy. On PSD 14, partial wounds of rats in simple scald group were healed under eschar with little exudation. On PSD 14, most of the eschar of rats in lithium chloride group were desquamated with patial wounds healed and little exudation. On PSD 14, wounds of rats in alprostadil group were basically healed with vigorously growing hair on the back. (2) On PSD 7, the wound healing rates of rats in simple scald group, lithium chloride group, and alprostadil group were close (F=0.41, P>0.05). On PSD 10 and 14, wound healing rate of rats in lithium chloride group and alprostadil group were significantly higher than that in simple scald group (q=5.73, 17.45, 26.30, 11.28, P<0.05), and wound healing rate of rats in alprostadil group was significantly higher than that in lithium chloride group (q=32.03, 28.73, P<0.05). (3) On PSD 14, the mRNA expressions of Wnt1 and β-catenin of rats in lithium chloride group and alprostadil group were significantly higher than those in simple scald group (q=65.40, 19.16, 66.79, 18.41, P<0.05), and the mRNA expressions of Wnt1 and β-catenin of rats in simple scald group was significantly higher than those in sham scald group (t=14.86, 4.46, P<0.05). (4) On PSD 14, the protein expressions of Wnt1 and β-catenin of rats in lithium chloride group and alprostadil group were 0.98±0.05, 0.98±0.06, 0.97±0.06, and 1.00±0.06, which were significantly higher than 0.49±0.04 and 0.66±0.04 of rats in simple scald group (q=34.62, 22.38, 33.61, 23.47, P<0.05). On PSD 14, the protein expressions of Wnt1 and β-catenin of rats in simple scald group was significantly higher than 0.29±0.03 and 0.31±0.03 of rats in sham scald group (q=14.73, 23.88, P<0.05). Conclusions: Alprostadil can accelerate wound healing through activating Wnt/β-catenin signal pathway and upregulating the expressions of Wnt1 and β-catenin.

To evaluate the clinical efficacy of Panax notoginseng extract combined with alprostadil in the treatment of arteriosclerosis occlusion and investigate its effects on the degree of atherosclerosis. CNKI, Wanfang, VIP journal database, Chinese biomedical literature database(CBM), PubMed, the Cochrane Library and Science Citation Index(SCI) database were searched between inception to December 2017 for relevant studies. Two researchers independently screened and extracted the literature in strict accordance with the inclusion criteria and exclusion criteria. The bias risk assessment method recommended by Cochrane was used to evaluate the bias risk and extract data, and then Review Manager 5.3 was used for Meta analysis. 10 RCTs involving a total of 1 032 cases were included in the study. Analysis results showed that the P. notoginseng extract combined with alprostadil had higher clinical efficacy than alprostadil alone in the treatment of arteriosclerosis occlusion disorder, with statistically significant difference(OR=6.39, 95%CI[3.97, 10.30], P<0.000 01); the atherosclerosis was obviously improved, including ankle brachial index(ABI) (MD=0.08, 95%CI[0.04, 0.13], P=0.000 3), toe brachial index(TBI) (MD=0.09, 95%CI[0.05, 0.12], P<0.000 01), and maximum walking distance(WD) (MD=471.62, 95%CI[383.54, 559.70], P<0.000 01). Studies have shown that P. notoginseng extract combined with the conventional treatment had significantly improved clinical efficacy in the treatment of arteriosclerosis occlusion, and could improve the atherosclerosis degree of lower extremities. However, the quality of the included literature was not high, in addition, due to the small number of included literature as well as bias and low-quality bias in some of the literature, more high quality RCTs are still needed to further verify the clinical effect of P. notoginseng extract in the treatment of arteriosclerosis occlusion.