Alternative Treatment for Erectile Dysfunction: a Growing Arsenal in Men's Health.

PURPOSE OF REVIEW: To highlight and review encouraging preliminary studies behind several alternative products and interventions for erectile dysfunction (ED). RECENT FINDINGS: Alternative treatments for ED are becoming more prevalent with increased consumer interest. "Natural" products are sold online, and numerous clinics offer various off-label and investigational interventions. These alternative treatments have demonstrated varying degrees of efficacy in randomized trials and meta-analyses, but none of these interventions has robust enough evidence to be considered first-line therapy. These treatments may find a role in combination with guideline treatments or may be used in novel penile rehabilitation research protocols. With growing interest in alternative treatment for men's health, an awareness of the literature is imperative for patient counsel. Alternative treatments, like L-arginine, have a growing body of evidence for efficacy in combination with PDE5i, and low-intensity shock wave therapy and stem cell therapy continue to demonstrate encouraging outcomes in ED trials.

Efficacy of the additional effect of hyperbaric oxygen therapy in combination of systemic steroid and prostaglandin E1 for idiopathic sudden sensorineural hearing loss.

PURPOSE: The efficacies of hyperbaric oxygen therapy (HBO), systemic steroid, prostaglandin E1, or the combination of any two modalities have been reported in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). However, little is known about the combined efficacy of HBO, systemic steroid, and prostaglandin E1 for this disorder. We aimed to investigate the efficacy of HBO combined with systemic steroids and prostaglandin E1 as triple therapy in patients with ISSNHL. MATERIALS AND METHODS: We retrospectively evaluated the records of 67 patients with ISSNHL who were treated with systemic steroid and prostaglandin E1, with (n = 38) or without (n = 29) HBO. The inclusion criteria included a diagnosis of ISSNHL within 14 days of symptom onset, age ≥15 years, treatment according to the protocol, and clinical follow-up of at least 1 month. The patients' hearing levels were evaluated 1 month after hearing loss onset. The primary outcome was hearing improvement on pure tone audiometry. We also evaluated the demographic profiles of patients. RESULTS: Patients treated with triple therapy showed significantly greater hearing improvement (p < 0.01) than those treated without HBO, despite some differences between the two treatment groups. Multivariate logistic regression analysis revealed a significant positive correlation between pure tone audiometry improvement and hyperbaric oxygen therapy, after adjustment for confounding factors (odds ratio = 7.42; 95% and confidence interval = 2.37-23.3; p = 0.001). CONCLUSION: HBO with systemic steroid and prostaglandin E1 administration conferred significant therapeutic benefits for ISSNHL. Therefore, routine use of triple therapy is recommended for patients with ISSNHL.

Effectiveness and safety of intracoronary papaverine, alprostadil, and high dosages of nicorandil and adenosine triphosphate for measurement of the index of coronary microcirculatory resistance in a pig model.

BACKGROUND: Papaverine is used to induce maximal hyperemia for index of coronary microcirculatory resistance (IMR) measurement in animal experiments, although it can lead to polymorphic ventricular tachycardia and ventricular fibrillation. OBJECTIVES: This study investigated the effect of an intracoronary (IC) bolus of high adenosine triphosphate (ATP) and nicorandil doses for IMR measurement and explored the possibility of inducing maximal hyperemia with an IC alprostadil bolus. MATERIAL AND METHODS: Index of coronary microcirculatory resistance was measured in a hyperemic state induced by 7 experimental conditions in 21 pigs (IC bolus of papaverine (18 mg), ATP (40 µg, 80 µg, 160 µg, and 240 µg), and nicorandil (2 mg and 4 mg)). The 7 conditions were induced sequentially, and the average IMR was calculated. Because of the long-term hyperemic condition in the pilot experiments, the IMR was measured 1, 3, 5, 8, and 10 min after an IC bolus of alprostadil (10 µg) in another 7 pigs. RESULTS: The IMR induced by 240 µg of ATP or 4 mg of nicorandil was not significantly different from that induced by 18 mg of papaverine (both p > 0.05). A strong linear correlation was observed between IMRs with papaverine (18 mg) and nicorandil (4 mg) (R2 = 0.936, p < 0.001) and with papaverine (18 mg) and ATP (240 µg) (R2 = 0.838, p < 0.05). The IC bolus of nicorandil (4 mg) produced the smallest changes, whereas papaverine caused the most significant changes in mean blood pressure and heart rate (p < 0.05). Tachypnea and transient ST depression were more common with increasing ATP dosages (especially 240 µg). Alprostadil (5 min) yielded a significant hyperemic response but reduced baseline blood pressure by almost 40% for a long time. CONCLUSIONS: Intracoronary bolus administration of 4 mg of nicorandil was better than 18 mg of papaverine or 240 µg of ATP for induction of maximal hyperemia and IMR measurement in a pig model, whereas alprostadil was not suitable for IMR measurement.

Systematic Review of Oral Combination Therapy for Erectile Dysfunction When Phosphodiesterase Type 5 Inhibitor Monotherapy Fails.

INTRODUCTION: On-demand phosphodiesterase type 5 inhibitor (PDE5i) monotherapy is a first-line treatment for erectile dysfunction (ED), but 30%-40% of patients exhibit little or no response. The success rate of alprostadil therapy is high in these patients, but this treatment requires painful intracavernosal injection. AIM: To systematically review the efficacy and safety of second-line oral pharmacologic combination therapies of ED when PDE5i monotherapy fails. METHODS: PubMed and Embase were searched to identify reports providing quantitative data on the treatment of ED in patients failing PDE5i monotherapy. MAIN OUTCOME MEASURES: The measures of erectile function were the International Index of Erectile Function (IIEF) and the Erectile Function Domain (EFD). RESULTS: Chronic treatment with the PDE5i tadalafil alone or in combination with sildenafil on demand showed similar IIEF-5 score improvements. None of the 3 randomized controlled trials (RCTs) in patients who had failed PDE5i monotherapy found a superior effect on IIEF scores from the combination of androgen plus PDE5i compared with PDE5i monotherapy. Combination therapy with androgen supplementation and PDE5i appears safe. In 1 RCT, combination therapy with PDE5i and an α1-adrenoceptor antagonist was not superior to PDE5i monotherapy. Six other studies, each with a different combination of PDE5i and another drug (eg, metformin, folic acid, 5-alpha-reductase inhibitors), were identified, but further research is required to investigate their efficacy in treating ED. CONCLUSION: For ED, chronic treatment with low-dose PDE5i can be attempted when standard on-demand regimens fail. Combination therapy with androgen supplementation and a PDE5i appears to be safe. The combination of an α1-adrenoceptor antagonist and PDE5i shows no advantageous effect on ED compared with PDE5i monotherapy. The efficacy of combining PDE5i with metformin, folic acid, or 5-alpha-reductase inhibitors is uncertain and requires further research. There is an unmet need for oral treatment of ED in nonresponders to PDE5i treatment. Munk NE, Knudsen JS, Comerma-Steffensen S, et al. Systematic Review of Oral Combination Therapy for Erectile Dysfunction When Phosphodiesterase Type 5 Inhibitor Monotherapy Fails. Sex Med Rev 2019;7:430-441.

Clinical efficacy of different doses of lipo-prostaglandin E1 in the treatment of painful diabetic peripheral neuropathy.

OBJECTIVE: To observe the clinical efficacy of different doses of alprostadil (lipo-prostaglandin E1, lipo-PGE1) in the treatment of painful diabetic peripheral neuropathy (DPN). METHODS: Sixty patients with painful DPN were equally and randomly assigned into three groups. Two groups received different doses of lipo-PGE1 by intravenous drip injection (A group: low-dose lipo-PGE1; B group: high-dose lipo-PGE1) following intravenous bolus injection of mecobalamin (MeCbl, 0.5mg once daily (QD)); the third group received MeCbl alone (C group). All patients received optimized treatment to lower blood glucose, blood pressure, and blood lipids to target levels. The efficacy of lipo-PGE1 in the three groups of patients was observed after 3weeks of treatment. RESULTS: The overall response rate was 90% in the B group, significantly higher than that in the A and C groups (80% and 55%, respectively; P<0.05). During the observation period, there was no incidence of serious adverse reactions (e.g., acute heart failure, sudden drop in blood pressure, or malignant arrhythmias) in any of the three groups. CONCLUSIONS: High-dose lipo-PGE1 has better efficacy than low-dose lipo-PGE1 or MeCbl alone in the treatment of painful DPN.

Efficacy of psychosocial interventions in men and women with sexual dysfunctions--a systematic review of controlled clinical trials: part 1-the efficacy of psychosocial interventions for male sexual dysfunction.

INTRODUCTION: As yet, a summary of research evidence concerning the efficacy of psychological treatment in male sexual dysfunction is lacking. AIM: Our systematic review gives an overview of the efficacy of psychosocial interventions in all male sexual dysfunctions. MAIN OUTCOME MEASURES: Main outcome measures included, for example, psychometrically validated scales, interviews, and clinical assessment by an independent rater. The efficacy of psychosocial interventions was measured, for example, by the frequency of and satisfaction with sexual activity and sexual functioning. METHODS: The systematic literature search included electronic database search, handsearch, contact with experts, and an ancestry approach. Studies were included if the man was given a formal diagnosis of a sexual dysfunction (International Statistical Classification of Diseases and Related Health Problems [ICD10/-9]; Diagnostic and Statistical Manual of Mental Disorders [DSM-IV/-III-R]) and when the intervention was psychosocial or psychotherapeutic. The control group included either another treatment or a waiting-list control group. The report of relevant outcomes was necessary for inclusion as well as the design of the study (randomized controlled trials [RCTs] and controlled clinical trials [CCTs]). The assessment of methodological quality comprised aspects of randomization, blinding, incomplete outcome data, selective reporting, and allegiance. RESULTS: We identified 19 RCTs and one CCT that investigated the efficacy in male sexual dysfunction and two further studies that examined male and female sexual dysfunction together. Twelve out of 20 trials in men used either a concept derived from Masters and Johnson or a cognitive-behavioral treatment program. Overall, psychosocial interventions improved sexual functioning. While one study found that psychotherapy is superior to sildenafil, another study found the opposite. In men with premature ejaculation, behavioral techniques proved to be effective. A shortcoming was the rather low methodological quality of included studies. CONCLUSIONS: Most of the compared interventions proved to be similarly effective. Possibly, there are underlying constructs throughout all therapies that have an effect on the outcome.

[Effect of prostaglandin E1 combined with Xuebijing injection on transforming growth factor-ß1 in rats with pulmonary interstitial fibrosis].

OBJECTIVE: To investigate the effect of prostaglandins E1 combined with Xuebijing injection on the expression of transforming growth factor-ß1 (TGF-ß1) and tumor necrosis factor-α (TNF-α) in rats with acute pulmonary interstitial fibrosis. METHODS: A rat model of pulmonary interstitial fibrosis was established by intratracheal injection of bleomycin (1 ml/kg). One hundred and eight Wistar rats were randomly divided into six groups with 18 in each group, which were normal control group, model group, hormone (methylprednisolone) treatment group, Xuebijing treatment group, prostaglandin E1 treatment group and combination treatment group (prostaglandin E1 and Xuebijing injection). Except for those in the normal control group, the rats in each group were sacrificed on the 7th, 14th and 28th day after treatment. The TGF-ß1 expression in lung tissue was measured by immunohistochemical staining. The TNF-α concentration in bronchoalveolar lavage fluid (BALF) of rat model was determined by enzyme-linked immunosorbent assay. RESULTS: The combination treatment group showed significantly more macrophages with TGF-ß1 expression in lung tissue at each time point, as compared with the model group, Xuebijing treatment group, methylprednisolone treatment group and prostaglandin E1 treatment group (P < 0.05). On the 7th day, the TNF-α concentration in BALF in the combination treatment group was significantly lower than those in the model group, methylprednisolone treatment group and prostaglandin E1 treatment group (P < 0.05); on the 14th day, the TNF-α concentration in BALF in the combination treatment group was significantly lower than that in the model group (P < 0.05); on the 28th day, the levels of TNF-α in the prostaglandin E1 treatment group and combination treatment group were significantly lower than that in the model group (P < 0.05). CONCLUSION: Prostaglandin E1 combined with Xuebijing injection may significantly inhibit TGF-ß1 expression in the lung tissue of rats with acute pulmonary interstitial fibrosis, which reduces alveolar inflammatory response.

[Synergic effect of alprostadil injection and ginaton in treating sudden deafness].

OBJECTIVE: To explore synergic effect of Alprostadil injection and ginaton in treating sudden deafness. METHOD: ninety one patients with sudden deafness were divided into group A, group B and group C at random; 33 ears of group A were treated with 70 mg ginaton by vein, 30 ears of group B were treated with 10 microg Alprostadil injection by vein, 31 ears of group C were treated with 10 microg Alprostadil injection and ginaton by vein,once a day, the time of treatment is 14 days. RESULT: the effective rate of group A is 60.61%, the effective rate of group B is 60.00%, the effective rate of group C is 87.09% the treating effect was significantly different in the group A and C (P < 0.05), it was significantly different in the group B and C (P < 0.05)). CONCLUSION: It is effective for Alprostadil injection and ginaton to treat sudden deafness, and it has significantly Synergic effect in treating sudden deafness with Alprostadil injection and ginaton.

Intratympanic dexamethasone as initial therapy for idiopathic sudden sensorineural hearing loss: Clinical evaluation and laboratory investigation.

OBJECTIVE: To evaluate the effect of intratympanic dexamethasone (ITD) as initial therapy for idiopathic sudden sensorineural hearing loss (ISSHL) as well as to determine the concentration-dependent time course distribution of dexamethasone in the inner ear. METHODS: Sixty-six patients with profound ISSHL were included. Twenty-two were treated with ITD and the rest as control. Audiograms were performed before the treatment and one month afterwards. In the animal study, dexamethasone of different concentrations (5, 10 and 20mg/ml) was injected into the tympanums of three groups of SD rats (Groups A, B and C), their inner ears dissected free at various postinjection survival intervals. Immunofluorescence was applied to detect the locations of dexamethasone. RESULTS: The overall rate of good prognosis was 77.27% in ITD group, which was not significantly different from 81.82% in the control group. In the animal study, the higher local concentration and longer lasting period was found in Groups B and C. CONCLUSIONS: ITD at 5mg/ml did not add effect to systemic steroids in improving hearing outcomes in patients with ISSHL. An increase in dexamethasone concentration led to large variations in pharmacokinetics in animal study, showing potential value in optimizing the drug delivery protocols and improving the therapeutic results.

[Efficacy of prostaglandin E1 and systemic antibacterial therapy application in patients with diabetes mellitus and purulent-necrotic lesions of the foot].

The results of prostaglandin E1 et systemic antibacterial therapy use in 1836 patients, suffering purulent-necrotic affection of foot, were summarized. There was established, that cefuroxym constitutes the first line preparation for the ostheoarthropathy focus elimination, when the affection is limited and the patient state is stable, and meronem--for extended affection and unstable patient's state. In the pronounced ischemia of the foot the initial administration of cefepim is the most effective. For purulent-necrotic affection as a consequence of the foot wounding, erysipelas or operative intervention it is expedient to use carbapenem or meropenem. The systemic antibacterial therapy administration had promoted significant reduction of the treatment duration and improvement of its result.

Prostaglandin E1 encapsulated into lipid nanoparticles improves its anti-inflammatory effect with low side-effect.

Prostaglandin E(1) (PGE1) shows various pharmacological activities including anti-inflammation. However, the rapid metabolization and inactivation of the intravenously administered PGE1 during the first passage through the lungs result in significant non-compliance in clinical trials which greatly limits its application. The aim of this work was to prepare the lipid nanoparticles loading PGE1 to improve its anti-inflammatory effect with low side-effect. The experimental results showed that PGE1 loaded lipid nanoparticles (PLNs) could be successfully prepared by high pressure homogenization with particle size 68.1+/-4.7 nm, zeta potential -3.32+/-0.37 mV and entrapment efficiency 92.1+/-1.3%. PLNs exhibited a sustained release with low burst drug release. PLNs could improve the inhibition effects of PGE1 on lipopolysaccharides (LPS)-induced TNF-alpha expression on macrophage RAW264.7 cells, and improve the inhibition of lymphocyte to endothelial cell adhesion and ICAM-1 adhesion molecule expression on HUVEC and MDA-MB-468 cell membrane. No allergenicity, vascular and muscle irritation were induced in animals by PLNs even at double of the highest drug concentration of clinical infusion. As a result, PLNs could be a more potential delivery system for PGE1 in the treatment of inflammation-related diseases.

Prostaglandin E1 in combination with hyperbaric oxygen therapy for idiopathic sudden sensorineural hearing loss.

CONCLUSIONS: Prostaglandin E1 (PGE1) is less effective than stellate ganglion block (SGB) in the treatment of idiopathic sudden sensorineural hearing loss (ISSNHL) patients with severe hearing losses when used together with hyperbaric oxygen (HBO) therapy. In contrast with the systemic action of intravenous PGE1, SGB's localized vasodilating action may explain its advantage over intravenous PGE1. OBJECTIVES: To investigate the effect of PGE1 plus HBO therapy on ISSNHL in comparison with that of SGB plus HBO therapy. PATIENTS AND METHODS: We retrospectively analyzed 205 consecutive patients with ISSNHL (hearing levels > or = 40 dB; time from the onset of hearing loss to the start of treatment < or = 30 days). Ninety-five patients underwent intravenous PGE1 plus HBO therapy (PG group) and 110 underwent SGB plus HBO therapy (SGB group). Hearing recovery was evaluated by grade assessment and by hearing improvement compared to that in the unaffected contralateral ear. RESULTS: The overall hearing outcome was not statistically different between the two groups. For patients with initial hearing levels <80 dB, the groups had roughly equivalent hearing outcomes, whereas in patients with initial hearing levels > or = 80 dB, the hearing improvement rate was significantly higher in the SGB group than in the PG group (53.0 +/- 5.0% vs 35.3 +/- 6.8%; p <0.05).

[Clinical study on interventional therapy with Chinese and Western medicine for avascular necrosis of femoral head].

OBJECTIVE: To study the clinical effect of interventional therapy with Chinese and Western medicine for avascular necrosis of femoral head (ANFH). METHODS: A total of 168 ANFH patients (285 hips) were subjected to interventional therapy with Chinese and Western medicine (prostaglandin E1 injection, uroki-nase and Compound Danshen Injection) and examined by digital substruction arterography (DSA) before and after treatment. The imaging of DSA and clinical effect were observed and compared. RESULTS: After treatment, hip pain and joint dysfunction were alleviated to different degrees, and the blood vessel count shown by DSA significantly increased. The effect was obviously better in patients of Grade III than in those of other grades. CONCLUSION: Interventional therapy with Chinese and Western medicine could improve the blood circulation of the femoral head, and is an effective method for the treatment of ANFH.

Prostaglandin E1 treatment in patent ductus arteriosus dependent congenital heart defects.

Prostaglandin E1 (PGE1) treatment can be life saving in patients suffering from ductus dependent congenital heart defect. We analyzed the indications and side-effects of PGE1 therapy over a five-year period. The purpose of the study was also to examine whether a change in serum electrolyte levels could be detected. Forty-nine patients were treated with PGE1 during this period. PGE1 treatment was indicated by ductus dependent systemic circulation in 16 cases, ductus dependent pulmonary circulation in 17 cases, transposition of the great arteries in 13 cases and pulmonary hypertension (persistent fetal circulation) in three cases. As early side-effects of the treatment, fever occurred in 27/49 cases while apnoea was observed in 15 patients. In a one-week-old neonate with coarctation of the aorta grade III intraventricular hemorrhage developed. A mild decrease of sodium, potassium and chloride levels and a slight shift of pH levels toward metabolic alkalosis could be detected after one day and one week of PGE1 treatment. Because of these side-effects of PGE1 patients should be monitored in an intensive care unit. According to our observations electrolyte levels may exhibit a slight decrease; however, in the case of a short-term therapy extra salt supplementation is not necessary.

CCK-8 and PGE1: central effects on circadian body temperature and activity rhythms in rats.

Cholecystokinin-octapeptide (CCK-8) has been shown to possess an acute thermogenic and hyperthermic action when given intracerebroventricularly in slightly restrained rats. To substantiate the febrile nature of that hyperthermia freely moving animals should be used and together with body core temperature, at least one behavioral parameter, such as general activity, should also be recorded. In the present studies, Wistar rats (N=34) exposed to thermoneutral (26-28 degrees C) or cold (4 degrees C) ambient temperature and to a 12:12-h light/darkness schedule were infused intracerebroventricularly with CCK-8 or prostaglandin E1 (PGE1) for several days using ALZET minipump and changes in body core temperature and general activity were recorded by biotelemetry (Minimitter). In rats exposed to a thermoneutral ambient temperature, low doses of CCK-8 induced slight but significant rises of day minima of circadian body temperature rhythm (CBTR) and with a high dose (1 microg/h) of the peptide--infused either at thermoneutrality or during cold exposure--an increase of acrometron could also be recorded. All of these changes were observed only during the first 2-4 days of 7-day-long infusions. Intracerebroventricular infusion of PGE1 administered at thermoneutrality in a dose of 1 microg/h for 7 days induced a marked rise in body core temperature with a disappearance of CBTR in some rats for 2-3 days or with rises of day minima/acrometron in others. General activity--running parallel with CBTR in periods without infusions--tended to be decreased when core temperature rose during the first couple of days of intracerebroventricular infusion of higher doses of CCK-8 or of PGE1. The decreased general activity--one component of sickness behavior--together with an increased body core temperature found in the present study, supports the view that they are components of a genuine fever induced by the central effect of the two mediators used.

Effects of OP-1206 alpha-CD on walking dysfunction in the rat neuropathic intermittent claudication model: comparison with nifedipine, ticlopidine and cilostazol.

The systemic treatment effects of OP-1206 alpha-CD (17S-20-dimethyl-trans-delta 2-PGE1 alpha-cyclodextrin clathrate), a prostaglandin E1 (PGE1) analogue, on walking dysfunction, spinal cord blood flow (SCBF) and skin blood flow (SKBF) were assessed in the rat neuropathic intermittent claudication (IC) model in comparison with nifedipine (dimethyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylate), ticlopidine (5-[(2-chlorophenyl)methyl]-4,5,6,7-tetrahydrothieno[3,2-C]pyridine hydrochloride) and cilostazol (6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)-butoxy]-3,4-dihydro-2(1H)-quinolinone). Two pieces of silicone rubber strips were placed in the lumbar (L4 and L6) epidural space in rats. After surgery, walking function was measured using a treadmill apparatus. SCBF and SKBF were measured using a laser-Doppler flow meter. Drugs were administered orally twice a day for 11 days from day 3 post-surgery. Treatment with OP-1206 alpha-CD significantly improved walking dysfunction on days 5, 7 and 14, and improved SCBF on day 14 post-surgery. SKBF remained unaffected. Treatment with nifedipine, ticlopidine or cilostazol had no significant effects on any of the parameters measured in this model. These data suggest that the therapeutic effect of OP-1206 alpha-CD is primarily mediated by the improved local SCBF at the territory of spinal stenosis and not due to improvement of peripheral perfusion and/or antiplatelet activity.

Hypertrophic osteoarthropathy caused by PGE1 in a patient with congestive heart failure during cardiac rehabilitation.

Continuous chronic drug infusion with PGE1 via a portable pump and neuromuscular electrical stimulation (NMES) help to improve the quality of life in patients with severe chronic heart failure waiting for a donor heart, as both treatments can be performed at home. We report a 56-year-old woman suffering from severe chronic heart failure, who was referred for a cardiac rehabilitation program because of progressive muscle weakness and weight loss. Due to her underlying heart disease she was unable to perform voluntary exercise. NMES of both knee extensor muscles was started. Under simultaneous chronic drug infusion with PGE1 via a portable pump the patient developed clinical signs of hypertrophic osteoarthropathy, which prevented her from continuing the rehabilitation program. X-ray examinations and bone scans concurred with the diagnosis of secondary hypertrophic osteoarthropathy. After the PGE1 dose had been reduced, the clinical signs of the osteoarthropathy resolved and the patient was able to continue the rehabilitation program with no difficulty. This case report underlines the importance of being aware of the potential side effects of modern cardiac drugs in the complex treatment of patients waiting for a donor heart.

Inhibitory effects of alprostadil (prostaglandin E1) incorporated in lipid microspheres of soybean oil on intimal hyperplasia following balloon injury in rabbits.

The present study was performed to assess the inhibitory effects of alprostadil (CAS 745-65-3, prostaglandin E1, PGE1) incorporated in lipid microspheres (here-in-after referred to as lipo PGE1; Palux inj.) on intimal thickening following balloon injury in the carotid artery of normal rabbits. Lipo PGE1 was given intravenously to animals twice a day at doses of 20 or 40 micrograms/kg/day from ballooning (day 1) until day 3, and at half these doses from day 4 to day 20. The carotid artery was removed for histopathological staining on the next day (day 21) after the last administration. Lipo PGE1 significantly reduced both the intimal/medial are (I/M) ratio and stenosis ratio by about half in the 40 micrograms/kg/day on day 21 after ballooning, compared with the vehicle group. Infiltration of macrophage, expression of proliferating cell nuclear antigen (PCNA)-positive cells was inhibited by the administration of lipo PGE1 on day 3 after ballooning. Adhesion of platelets to injured arterial walls was also inhibited on day 3. Lipo PGE1 at 40 micrograms/kg/day exerted more potent inhibitory effects on I/M and stenosis ratios and histopathological changes such as infiltration of macrophage and expression of PCNA-positive cells than at 20 micrograms/kg/day. These findings suggest that lipo PGE1 inhibits the intimal hyperplasia after balloon injury in rabbit carotid artery, possibly by inhibiting platelet functions.