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PubMed1997

Effect of prostaglandin E1 infusion in severe chronic heart failure.

Prostaglandin E1 (PGE1, alprostadil) is a potent vasodilating agent that is frequently used to resolve cardiogenic pulmonary hypertension. To investigate the effect of PGE1 in refractory chronic heart failure in a double-blind trial, twenty patients (17 men, 3 women, 58 +/- 2 years, cardiac index < or = 2.5 l/min/m2, pulmonary capillary wedge pressure > or = 20 mmHg), who were in NYHA functional class IV on optimized treatment with ACE inhibitors and furosemide were infused with 30 ng/kg/min PGE1 or placebo through 48 hours. All patients received a concomitant therapy with standardized catecholamine infusions which were given 24 hours in advance and were continued throughout the study. There was no difference in baseline values between the randomized groups before PGE1 or placebo was added. PGE1 resulted in decrements in pulmonary artery pressure (from 37 +/- 4 to 30 +/- 4 mmHg; p < 0.01), pulmonary capillary wedge pressure (from 26 +/- 4 to 19 +/- 3 mmHg p < 0.001) systemic vascular resistance index (from 2048 +/- 213 to 1506 +/- 13 dyn.sec/cm5.m2, p < 0.05) and in increments in cardiac index and stroke volume index (from 2.2 +/- 0.1 to 2.8 +/- 0.2 l/min.m2; p < 0.05 and from 23 +/- 2 to 28 +/- 2 l/m2; p < 0.05, respectively). Moreover, creatinine clearance increased (p < 0.05). Placebo infusions did not result in any hemodynamic or renal effect. Between groups percentage hemodynamic changes differed with respect to pulmonary artery pressure (p < 0.01), cardiac index (p < 0.05), stroke volume index (p < 0.05) and pulmonary vascular resistance index (p < 0.05). It is concluded that intravenous infusions with PGE1 may add further substantial benefit to the hemodynamic state in refractory heart failure patients who are already stabilized on i.v. inotropic support with catecholamines.

Aged↗
PubMed2003

Effect of single-drug treatment on idiopathic sudden sensorineural hearing loss.

OBJECTIVES: In order to evaluate the effect of a medical administration for the sudden deafness patients, single-drug treatment for idiopathic sudden sensorineural hearing loss (ISSHL) was assessed at multi-centers participating in the Acute Severe Hearing Loss Study Group sponsored by the Ministry of Health, Labor and Welfare of Japan. METHODS: The subjects consisted of ISSHL patients who were (1) 20 years of age or older, (2) diagnosed within 2 weeks after the onset of hearing loss, (3) showing a mean hearing level of 40-90 dB at five frequencies from 250 to 4000 Hz, (4) previously untreated, and (5) with normal for age in hearing of the opposite ear. The drugs used in this study were ATP, alprostadil, hydrocortisone and amidotrizoate, which were administered intravenously, and beraprost sodium and betamethasone, which were given orally. Two drugs were assigned to each center, one of which was selected according to the code hidden in envelopes and administered for 1 week. The treatment after the single-drug administration was conducted at the discretion of each center. The hearing gain and recovery rate at 1 week after the initiation of single-drug treatment and at 1 month or over when the hearing level was fixed, were evaluated based on the criteria for hearing recovery prepared by the Acute Severe Hearing Loss Study Group. RESULTS: There was no statistically significant difference in the recovery rate among drugs either at 1 week after the initiation of single-drug treatment or at the time of fixed hearing level. At the time when the hearing level was fixed, a statistically significant difference in the complete recovery rate was detected only between amidotrizoate and beraprost sodium. CONCLUSION: From these results, we could not find any specific drugs recommended for ISSNHL. In evaluating the effect of the drugs, however, several problems in the clinical trial for ISSHL should be considered.

Adenosine Triphosphate↗
PubMed2002

A chromatographic method for the quantification of prostaglandin E(1) and prostaglandin A(1) encapsulated in an intravenous lipid formulation.

Peripheral vascular disease is a common ailment of the aged and diabetic communities. As the numbers of these individuals increase, the need for therapeutic interventions will continue to grow. One of the possible therapies is the use of prostaglandins (PGE(1), prostacyclin and Iloprost) to decrease the vascular tone and increase vascular blood flow. Due to the hydrophobicity of the prostaglandins and prostaglandin analogues, various vehicles have been utilized to maintain the active pharmaceutical ingredient in a stable solution, e.g. alpha-cyclodextrin (Alprostadil, Edex) or emulsified lipid vehicles. In our laboratory, we designed a method for separating and assaying lipid-encapsulated PGE(1). Utilizing organic extraction, automated solid-phase extraction and precipitation techniques, we validated the measurement of the PGE(1) and PGA(1) content of the clinical drug formulation in the microgram per milliliter concentration range with an high performance liquid chromatography (HPLC) assay.

Alprostadil↗
PubMed1993

Experimental assessment of thrombogenicity in vascular prostheses before and during prostaglandin E1 treatment.

The effect of prostaglandin E1 (PGE1; Prostavasin), a powerful platelet blocking agent, was assessed on various new synthetic or biological prostheses in a 6-min in vivo extra corporal arterio-venous (AV) shunt. In eight anaesthetised and heparinised minipigs (weight 25.1 +/- 1.9 kg) the following materials were tested before and during PGE1 infusion (alprostadil-alpha-CD; 40 micrograms/50 ml NaCl/50 min or 0.8 microgram/min): PTFE, (Gore-tex, TW, 4 mm ID); Xenograft, Biologic (Solcograft, 5 mm ID), (non-porous) and Dacron (Atrium, 4 mm ID); polyurethane 1 (Braun-Melsungen, 4 mm ID); polyurethane 2 (S. Gogolewski, 4 mm ID), (porous). Technetium-labelled platelet deposition and blood flow were measured; morphology was assessed by scanning electron microscopy (SEM) and histology. Compared to control levels, PGE1 infusion had a significant systemic effect on mean arterial pressure required by the protocol (MAP 82.6 vs. 66.6 mm Hg; p < 0.001) and flow (173.6 vs. 134.8 mm/min; p < 0.001). Standardised platelet counts per area showed a marked overall decrease from 197 to 130 counts/min/mm2; NS). The morphological assessment by SEM showed a slight increase of surface cellular deposition (score: 6.7 vs. 8.3), the histology score being unchanged (3.9 vs. 3.7). Looking at deposition of platelets for each prosthesis, the porous materials showed a net improvement after PGE1 treatment as compared to non-porous materials. We conclude that PGE1 may be of benefit by reducing platelet deposition in synthetic porous vascular prostheses in the early phase.

Alprostadil↗
PubMedDate not supplied

A standardized procedure for using human corpus cavernosum strips to evaluate drug activity.

The main problem of using human corpus cavernosum (HCC) tissue to perform bioassay is linked to its limited availability further complicated by the heterogeneous source of the tissues used. Here, we show that gender reassignment is a reliable source of human tissue without major ethical problems. Indeed, the entire corpus cavernosum is obtained from the surgery procedure, which allows creating a standardized procedure to prepare HCC strip. In addition, human tissue, if kept in the fridge in the condition described, does not loose its ability to contract to phenylephrine (PE; alpha agonist), angiotensin II (AG II) and KCl up to 4 days. Furthermore, once contracted with PE, HCC relaxes to acetylcholine (endothelium-dependent mechanism); sodium nitroprusside (endothelium-independent mechanism); cromakalim (CRK), a K(ATP) channel opener; or alprostadil, a synthetic PGE2 (ALPR). In conclusion, we have standardized a procedure that allows the use of HCC strips to evaluate drug activity and/or to study pathophysiological mechanisms with an intact functional human tissue up to 4 days from the surgery procedure.

Acetylcholine↗
PubMed1993

Long-term exposure to beta 2-receptor agonist specifically desensitizes beta-receptor-mediated venodilation.

Desensitization of human vascular smooth muscle has not been shown after long-term exposure to agonist. Using the dorsal hand vein compliance technique, we measured the vascular sensitivity to isoproterenol, alprostadil, and nitroglycerin. Nine volunteers were studied after receiving no treatment or after 7 days of the beta 2-agonist terbutaline (5 mg three times daily). Terbutaline pretreatment desensitized the vascular response to isoproterenol, resulting in a fourfold increase in the dose of isoproterenol required to produce 10% vasodilation (geometric mean after terbutaline, 100.8 ng/min; without terbutaline, 26.7 ng/min; p < 0.001). The desensitization was specific for beta 2-receptor-mediated effects. We have therefore shown that dynamic regulation of vascular responsiveness by long-term exposure to beta 2-receptor agonist occurs in humans. This selective desensitization of vascular beta-adrenergic responsiveness will result in mixed alpha- and beta-adrenergic agonists, such as epinephrine, becoming relatively more vasoconstrictive, and it also has important implications in blood pressure response to stress.

Adrenergic beta-Agonists↗
PubMed1998

Quantitative analysis of penile ultrasonographic shape during the erectile cycle: a new diagnostic tool for erectile dysfunction? Repeatability of the method and preliminary results.

Penile modifications during erection interest not only penile length and circumference, but also its size and shape. In this investigation, the size and shape repeatability of a single standardized ultrasonographic image of penis during flaccidity and erection was quantified in a group of 19 patients complaining of erectile dysfunction. The penis of each patient was placed in the dorsal position and scanned by a 10 MHz linear ultrasonographic probe at the site of maximal corporeal size: (1) during flaccidity; (2) after an intracorporeal injection of 10 micrograms alprostadil; and (3) after a genital stimulation. Each scan was repeated three times for each patient and printed. On each print the outline of the tunica albuginea was drawn, digitized, and mathematically reconstructed by Fourier series that allow a separate quantification of the size and shape differences. Reliability of the tunica albuginea outline and repeatability of probe positioning were separately assessed within patient and functional phase, and found to be good. The actual examinations of two impotence patients performed using the described method are also given. The shape of the corpora cavernosa may be potentially indicative of the homogeneous function of the tunica albuginea, and it may be of use in patients' follow up.

Adult↗
PubMed2002

Acceptance, efficacy and preference of Sildenafil in patients on long term auto-intracavernosal therapy: a study with follow-up at one year.

PURPOSE: To assess the acceptance, long term efficacy and preference of Sildenafil in impotent patients previously on auto-intracavernosal therapy. MATERIALS AND METHODS: The patients were the 107 men (mean age 58.4 y) on auto-intracavernosal therapy (auto-IC) for more than 6 months (mean duration 32.7 months >12 months in 100) who were consecutively seen within 6 months of the launch of Sildenafil in France. If there was no contra-indications to Sildenafil they were proposed a trial of Sildenafil at home. Following this trial they were given the possibility to change their therapy and were followed for 1 y at 3 months intervals. RESULTS: Three patients had contra-indications to Sildenafil. Of the remaining 104, 45 (43%) refused the trial, mainly because they were afraid of possible cardiac risks (n=21, including 51% of the psychogenic and mixed patients compared to 8% of the predominantly organic ones). Among the 59 who tried it, Sildenafil gave good results in 46 (78%), including 100% of the predominantly psychogenic and 61.5% of the predominantly organic ones) with minimum effective doses of 25 mg in 7, 50 mg in 18 and 100 mg in 21. It failed in 9 (15%) and gave average results in 4 (penetration with a non fully satisfying erection). There was a clear relationship between the sensitivity to Sildenafil and that to Alprostadil, the vasoactive agent predominantly used for the auto-ICIs. Every 46 patients with good result of Sildenafil elected to continue with this drug, including 3 who used both Sildenafil and auto-ICIs in alternance. Every 4 patients with average results elected to continue with auto-ICI including 1 who also used Sildenafil in alternance. Five of the 50 patients with good or average results were lost to follow-up within 6 months. At the 1 y follow-up visit, 43 of the 45 others were still using Sildenafil, in alternance with auto-ICI in 1. No one reported a decrease in efficacy with time. The 2 patients with average results still in the study were on auto-ICIs. CONCLUSION: Sildenafil is highly effective in the impotent men previously treated with auto-ICI and its efficacy is maintained at least for 1 y. When tried and effective it is preferred by most men but almost half of our patients refused trying it.

Adult↗
PubMedDate not supplied

Surgical treatment of Peyronie's disease based on penile length and degree of curvature.

The aim of the study was to present the selection criteria for surgical techniques for the treatment of patients with Peyronie's disease. A total of 55 men with Peyronie's disease were surgically treated. We created specific criteria for selection of the appropriate surgical technique. All patients had a stable disease for 6 months and impossible vaginal intromission. All patients had subjective (as reported by the patient) and/or objective normal penile rigidity (as observed after intracavernous administration of alprostadil). Also, they all underwent drug therapy, which was unsuccessful. Among them, 40 patients with penile curvature of <60 degrees and erect penile length of >13 cm underwent Nesbit's operation, whereas plaque excision and grafting with polytetrafluoroethylene patch was performed in 15 patients with penile curvature of > or =60 degrees and/or erect penile length of < or =13 cm. At a mean (+/-s.d.) follow-up of 81.1+/-33.8 and 78.7+/-32.8 months, respectively, straightening of the penis was achieved in 35 out of 40 (87.5%) and 12 out of 15 (80%) patients, respectively, whereas erectile dysfunction developed in two out of 40 (5%) and one out of 15 (6%), respectively. Shortening of the penis occurred in all 40 patients undergoing Nesbit's operation, and in none of the patients undergoing plaque excision. Six out of 40 (15%) patients undergoing Nesbit's operation reported subjective perception of penis shortening, whereas none of the patients undergoing plaque excision complained of this discomfort. In conclusion, we recommend the selection of surgical technique based on penile length and degree of curvature. Nesbit's operation is an appropriate surgical technique for the treatment of patients with erect penile length of >13 and deviation of <60 degrees , whereas the plaque excision and grafting with polytetraflouroethylene patch is a technique of choice in the treatment of patients with erect penile length of < or =13 and/or deviation of > or =60 degrees.

Adult↗
PubMedDate not supplied

Peak systolic velocity in patients with arterial erectile dysfunction and peripheral arterial disease.

The aim of this study is to evaluate whether penile peak systolic velocity (PSV) varies in patients with erectile dysfunction (ED) due to artery insufficiency associated with abnormalities in other arterial districts or not. To accomplish this, cavernous artery PSV was determined 10, 20 and 30 min after intracavernously administering alprostadil by means of echo-color Doppler to a total of 65 consecutive patients (age range 52-78 years). In all, 18 patients had ED alone (group A) and served as controls, 15 had ED plus atheroma plaques and/or marked intima-media thickness of the common carotid artery (group B); 17 had ED plus lower limb artery abnormalities; 17 had ED plus carotid and lower limb artery abnormalities (group D). Group B and C patients had a similar PSV, which turned out to be significantly lower than that in group A. Group D patients had the lowest PSV, which proved to be significantly lower than that in groups A, B and C. This study shows that a more generalized peripheral atherosclerotic process is associated with a severer penile artery insufficiency. Therefore, ED patients with a severe arterial insufficiency should undergo an extensive echo-duplex examination.

Aged↗
PubMed2006

Early combination therapy: intracavernosal injections and sildenafil following radical prostatectomy increases sexual activity and the return of natural erections.

Early pharmacological prophylaxis has been reported to increase the return of spontaneous erections following radical prostatectomy (RP). In this study, we evaluated the role of intracavernosal alprostadil (PGE1) combined with sildenafil in stimulating early recovery of spontaneous erections following RP. In this prospective study, we included 22 patients who underwent bilateral nerve-sparing RP after October 2004. Sildenafil dose of 50 mg/day was started at the time of hospital discharge. Of 22 patients, 18 started on PGE1-4 microg (1-8) and four started on low-dose Trimix (20 U) 2-3 times/week. These patients are followed up at regular intervals (3, 6, 9 and 12 months) with abridged version of the International Index for Erectile Function-5 questionnaire. Patient compliance, return of sexual activity and return of natural erection, adverse effects and reasons for discontinuation were recorded. Penile doppler studies were performed during followup visits to assess the vascular status. After a mean followup of 6 months (3-8 months), 11/22 (50%) patients had return of spontaneous partial erections. Of the 18 PGE1 users, six continued 4 microg PGE1, four increased the dose to 8 microg, six decreased the dose to 2 microg and two patients further reduced the dose to 1 microg. Of four low-dose Trimix users, three increased the dose to 30 U and one reduced the dose to 15 U. Of 22 patients, 21 were sexually active: 12/21 (57%) with the injections alone and 9/21 (42.9%) with combination therapy (injections (PGE1) and sildenafil). Penile doppler studies revealed arterial insufficiency in 77% (17/22) patients and venous insufficiency in one patient. Early intracavernosal injections following RP facilitated early sexual intercourse, patient satisfaction and potentially earlier return of natural erections. Early combination therapy with sildenafil allowed a lower dose of intracavernous injections, minimizing the penile discomfort.

Alprostadil↗
PubMed2001

Sevoflurane and nitrous oxide anaesthesia suppresses heart rate variabilities during deliberate hypotension.

BACKGROUND AND OBJECTIVE: Despite the fact that both general anaesthetics and hypotensive drugs influence autonomic nervous activity, no study has yet examined the heart rate variability during deliberate hypotension and general anaesthesia. The aim of this was to clarify the heart rate variability changes during deliberate hypotension under sevoflurane-nitrous oxide anaesthesia. METHODS: Autonomic nervous system activity in patients (n=45) subjected to deliberate hypotension during sevoflurane in nitrous oxide and oxygen anaesthesia was investigated by a heart rate variability measurement. Three different types of hypotensive drugs, a calcium channel antagonist (nicardipine), a nitric oxide donor (nitroglycerin) and a vasodilatory prostaglandin (alprostadil), were used to induce hypotension. RESULTS: In all groups, low frequency power (sympathetic and parasympathetic indicator) and the ratio of low frequency to high frequency power (the LF/HF ratio, sympathetic indicator) were suppressed by induction of anaesthesia. In the control group, preanaesthesia low frequency power was 195 +/- 139 ms(2), the LF/HF ratio 10.3 +/- 5.7, during anaesthesia 5 +/- 9 ms(2), 0.6 +/- 0.8, respectively, P=0.0093, 0.0034, whereas high frequency power (parasympathetic indicator) was not significantly changed. In those patients receiving nicardipine or nitroglycerin during anaesthesia, these variables did not differ significantly from those in the control group. During prostaglandin E1 infusion, high frequency power was higher compared with the values in the other groups (17 +/- 12 ms(2) in the prostaglandin group, 7 +/- 6 ms(2) in the nicardipine group, 6 +/- 5 ms(2) in the nitroglycerin group and 6 +/- 4 ms(2) in the control group, respectively, P=0.0326, 0.0251, 0.0197). CONCLUSIONS: Sevoflurane in nitrous oxide and oxygen anaesthesia reduces sympathetic autonomic activity considerably, and the expected increases caused by hypotensive agents that occur in awake volunteers were not seen.

Alprostadil↗
PubMed2002

Penile pharmacotesting in diagnosing male erectile dysfunction: evidence for lack of accuracy and specificity.

Penile pharmacotesting (PPT) with alprostadil (PGE1) represents the most common diagnostic approach to male erectile dysfunction (ED). A positive response - i.e. normal erectile rigidity of sustained duration - is presumed to exclude venous or arterial pathology with enough accuracy. To test this assumption we compared PPT vs. flowmetric results obtained by colour-duplex Doppler ultrasound (CDDU) in patients (pts) undergoing diagnostic evaluation for ED under conditions of maximal cavernous relaxation. A total of 195 non-consecutive impotent pts were diagnosed after dynamic CDDU as non-vasculogenic (NOR), or having arteriogenic (AR), veno-occlusive (VO) or mixed (MX) ED. Maximal erection obtained after PPT was scored as: type-1 (full tumescence - no sustained rigidity, angle on the abdominal plane >90 degrees), type-2 (sustained partial erection, valid for intromission, angle=90 degrees) and type-3 (sustained full erection, angle <90 degrees). Comparing PPT with flowmetric results, we found that a type-3 response had 20% false negative diagnosis of NOR (17% of AR- and 3% of VO- and MX-ED, respectively), while a type-2 response had 63% false negative diagnosis (20% of AR, 37% of VO- and 6% MX-ED, respectively). Type-1 response was associated with the presence of VO dysfunction in 99% of cases. These data suggest that a positive response to PPT (type-2 and type-3) assessed by the visual rating of erection is associated with both arterial (up to 20%) and/or VO (up to 43%) ED, as detected by CDDU. We conclude that PPT alone is a misleading diagnostic test to exclude vascular ED and that dynamic CDDU should be offered to pts investigated for male ED.

Adult↗
PubMed2003

Pharmacological management of erectile dysfunction.

Erectile dysfunction (ED) is a common medical condition that affects the sexual life of millions of men worldwide. Many drugs are now available for treating ED; oral pharmacotherapy represents the first-line option for most patients with ED. Sildenafil, an inhibitor of the enzyme phosphodiesterase type 5, is currently the most widely prescribed oral agent and has a very satisfactory efficacy-safety profile in all patient categories. Apomorphine SL is a dopamine D1- and D2-receptor agonist which has recently been approved for marketing in Europe. It is best selected for treating patients with mild to moderate ED. Vardenafil and tadalafil are new phosphodiesterase type 5 inhibitors which are expected to be approved this year. Both of them have significant positive efficacy-safety profiles. Patients who do not respond to oral pharmacotherapy or who cannot use it are good candidates for intracavernosal and intraurethral therapy. Alprostadil is the most widely used drug, both for injection therapy and for the intraurethral route. The efficacy of second-line treatment is high but the attrition rate remains significant.

Administration, Oral↗
PubMed2003

[Current diagnosis and therapy of non-occlusive mesenteric ischemia].

PURPOSE: Non-occlusive mesenteric ischemia (NOMI) is a life threatening disease. Therapy and prognosis depend upon the length of time elapsed between primary clinical manifestation and the time of definitive diagnosis and treatment. MATERIALS AND METHODS: NOMI was diagnosed by intraarterial selective angiography in four patients. After a bolus administration of 20 g Alprostadil (Prostavasin) into the superior mesenteric artery, intraarterial perfusion was continued with 60 microg Alprostadil/day via the catheter for three days. RESULTS: The mesenteric ischemia resolved in all patients. One patient recovered completely. Three patients recovered from mesenteric ischemia, but died subsequently due to complications of their primary diseases. CONCLUSION: When NOMI without perforation or necrosis of the bowel wall is suspected clinically, immediate intraarterial angiography is the diagnostic method of choice. If NOMI is confirmed, the appropriate treatment is the intraarterial application of potent vasodilators for several days. The diagnostic work-up in suspected NOMI and the impact of different radiological examinations are explained. The literature is reviewed.

Aged↗
PubMed1999

[Prostaglandin E1 for prevention of contrast medium-induced kidney dysfunction].

PURPOSE: Acute renal failure is a known complication of contrast media (CM) application in risk patients. Therefore an efficient prevention is highly desirable. The purpose of this pilot study was a) to demonstrate the efficacy and safety of prostaglandin E1 (PGE1 = alprostadil) in the prophylaxis against CM associated renal dysfunction in patients with renal disease, and b) to identify the adequate dose. METHODS: A total of 130 patients with renal dysfunction who were scheduled for intravascular CM administration were enrolled. They received PGE1 (10, 20, or 40 ng/kg/min) or placebo intravenously over a period of six hours (beginning one hour prior to exposure). Efficacy was determined by measuring serum creatinine and creatinine clearance. Safety was assessed by recording adverse experiences throughout the study and close monitoring of vital parameters especially during study drug administration. RESULTS: PGE1 proved to be superior to placebo in all doses. The dose of 20 ng/kg/min was most promising due to the lowest increase of serum creatinine 48 hours after CM administration. With respect to creatinine clearance, no relevant differences between study and control groups were observed. CONCLUSION: Our results suggest that intravenously administered PGE1 may be efficient in preventing CM-induced renal dysfunction in patients with renal impairment.

Acute Kidney Injury↗
PubMed1985

[Vital capillary microscopic examination and transcutaneous pO2-measurements by intravenous prostaglandin E1 infusion].

The ability of a single i. v. application of 40 micrograms alprostadil (PGE1, mean therapeutic dose 0.62 microgram/kg body weight) to cause changes in capillary microscopy parameters and tcpO2 was investigated in an open study in 15 patients with peripheral arterial occlusive disease, Fontaine stage II-IV (8 women and 7 men, average age 70.1 and 70.0 years, respectively). Capillary microscopy investigations and oxygen tension measurements were carried out before and immediately after i. v. infusion of PGE1 or a 5% solution of laevulose using an intra-individual comparison. PGE1 led to an increase in the number of erythrocyte-filled capillaries per mm2, an improvement in the initial condition of the capillaries evaluated according to Fagrell and to a significant increase in the tcpO2, whereas no haemodynamic changes occurred at all after laevulose. These findings substantiate the view that PGE1 is also effective when applied intravenously distal from the arterial occlusion.

Aged↗
PubMed2001

Intravenous prostaglandin E1 reduces soluble vascular cell adhesion molecule-1 in peripheral arterial obstructive disease.

OBJECTIVES: Elevated levels of soluble (s) vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1, pointing to activation of cells involved in vascular inflammation, have been previously reported in peripheral arterial obstructive disease (PAOD). We tested the hypothesis that intravenous prostaglandin E(1) (PGE(1)) treatment, which produces clinical benefits in this condition, might decrease such levels. METHODS: Ten subjects (age range 58 +/- 10 years, 6 male, 4 female) with characterized Fontaine stage IIa to IV PAOD (ankle/arm pressure index <0.96) were entered into a treatment protocol with twice daily intravenous infusions of PGE(1) (alprostadil) at 120 microg per day, repeated for 10 consecutive days. Preinfusion and postinfusion plasma samples were stored for blind enzyme immunoassays of soluble adhesion molecules and the fibrinolytic marker tissue plasminogen activator, type-1 plasminogen-activator inhibitor, and D -dimer. RESULTS: Estimates of severity of pain at rest, consumption of analgesics, magnitude of trophic lesions, remission to lower Fontaine stages, and favorable changes in the venoarteriolar reflex documented significant beneficial effects of the treatment. Significant (P <.01) pretreatment and posttreatment reductions of in all soluble markers explored were found. Particularly, sVCAM-1 exhibited a significant decrease after each infusion, which was sustained at the last day of treatment (from 854 +/- 214 ng/mL to 775 +/- 215 ng/mL across the first infusion, from 773 +/- 146 ng/mL to 680 +/- 110 ng/mL across the last infusion). CONCLUSION: Thus a global decrease of vascular cell activation appears to occur as a result of PGE(1) administration and may contribute to the observed clinical benefits in PAOD.

Aged↗