Comparison of dipyrone/propofol versus fentanyl/propofol anaesthesia during surgery in rabbits.

In this study, the investigation of the intraoperative effects of dipyrone (metamizol) on heart rate (HR), mean arterial pressure (MAP) and analgesic efficacy in rabbits is described for the first time. This was carried out to evaluate the cardiovascular stability achieved using dipyrone compared with fentanyl. In this prospective study, 17 female New Zealand White rabbits were randomly allocated to either one of two groups: dipyrone/propofol (DP) or fentanyl/propofol (FP). Anaesthesia was induced in both groups using propofol to effect (4.0-8.0 mg/kg intravenously) until the swallowing reflex was lost for intubation. After induction, anaesthesia was maintained with continuous infusion of propofol 1.5-1.7 mg/kg/min intravenously. Analgesics were then injected in defined boluses of either dipyrone 65 mg/kg or fentanyl 0.0053 mg/kg. After surgical tolerance, defined as loss of the ear pinch reflex and loss of the anterior and posterior pedal withdrawal reflex, was achieved, two surgical procedures were performed. The surgical procedures (implantation of either a pacemaker or an electrocardiogram transmitter), both require a comparable level of analgesic depth. During and after surgery, clinical variables, such as MAP, HR, peripheral arterial oxygen saturation (SpO2) and end-tidal CO2 (P(E')CO2) were recorded simultaneously every 2 min. Eight time points were chosen for comparison: baseline, surgical tolerance (ST), values at 10, 20 and 30 min after reaching ST, values at the end of propofol infusion (EI) and data at 10 and 20 min after EI. Both FP and DP combinations provided effective anaesthesia and analgesia in rabbits. In both groups a significant decrease of HR and MAP was measured. The results of this study indicate that the non-opioid drug dipyrone produces similar analgesic and even better cardiovascular effects by trend in rabbits. Therefore we conclude that dipyrone in combination with propofol can be used as an alternative to FP for intraoperative analgesia.

Partial antagonization of midazolam-medetomidine-ketamine in cats--atipamezole versus combined atipamezole and flumazenil.

Two different methods, administered both subcutaneously and intravenously, to reverse intramuscular midazolam-medetomidine-ketamine, are evaluated. Eighteen cats were anaesthetized twice each 5 min after premedication with atropine 0.04 mg/kg using midazolam 0.5 mg/kg, medetomidine 0.02 mg/kg and ketamine 2.0 mg/kg intramuscularly in one syringe. Because this study was conducted in co-operation with a dental prophylaxis project, cats had to be immobilized for approximately 1 h. Therefore, anaesthesia was prolonged with propofol to effect, if necessary. After 68+/-11 min on average, immobilization was partially reversed by either atipamezole 0.05 mg/kg subcutaneously (group A/SC, n=7) or intravenously (group A/IV, n=10), or by atipamezole 0.05 mg/kg and flumazenil 0.05 mg/kg subcutaneously (group AF/SC, n=10) or intravenously (group AF/IV, n=9), respectively. These four groups were additionally compared with a non-reversed group. Recovery time and total time of immobilization (until cats regained a standing position) were not significantly shortened using the antagonists. However, unconsciousness and sedation (expressed through parameters like the time taken to head lifting, crawling, sitting and the return of righting reflex) were significantly shortened by the antagonists, especially if administered intravenously. Abnormal behaviour, such as vocalization, licking, hyperaesthesia, restlessness or salivation, was observed in all groups. However, excitation and hyperaesthesia were not observed in group AF/IV, whereas in this group only intensified salivation occurred. The addition of flumazenil showed no significant difference to atipamezole alone, but subcutaneous administration of atipamezole alone was not sufficient in the dosage used to show an advantage compared to non-reversed cats.

A comparative clinical study of three different dosages of intramuscular midazolam-medetomidine-ketamine immobilization in cats.

A low dose of midazolam-medetomidine-ketamine (MMK) combination was evaluated in three increasing dosages. Each of the 18 cats was randomly allocated for several times to one of four groups. Five minutes after premedication with intramuscular (IM) 0.04 mg/kg atropine, group A (n = 43), B (n = 40) and C (n = 28) all were anaesthetized with 0.5 mg/kg midazolam, combined with 10, 20 or 30 microg/kg medetomidine, and 1.0, 2.0 or 3.0 mg/kg ketamine, respectively, IM in one syringe. Group D (n = 11) received the established combination of 50 microg/kg medetomidine and 10.0 mg/kg ketamine for comparison. Because this study was in cooperation with a project on dental prophylaxis, cats had to be immobilized for approximately 1 h. Therefore, anaesthesia was prolonged with propofol to effect, if necessary. Duration of MMK anaesthesia was between 30 +/- 15, 45 +/- 19 and 68 +/- 28 min in groups A, B and C respectively. A significant decrease of respiratory rate was observed with increasing dosage, but venous carbon dioxide (pCO(2)) and pH values in combination with arterial oxygen saturation (SpO(2)) values were not alarming. The diastolic blood pressure particularly showed an increase. MMK combination A showed the best cardiovascular results, but it cannot be recommended due to disadvantages like a long induction time sometimes accompanied by excitations and the short duration of surgical immobilization. Dosage C in contrast had fewer side effects but less favourable cardiovascular results and a longer recovery period. However, either dosage B or C was suitable as a repeatable IM immobilization method for non-invasive procedures in healthy cats.

Biomechanical and histomorphometric comparison between zirconia implants with varying surface textures and a titanium implant in the maxilla of miniature pigs.

BACKGROUND: Mechanical properties and biocompatibility make zirconia ceramics suitable implant material. The characteristics of tooth-color like, the ability to be machined and the low plaque affinity make zirconia especially suitable as a dental implant material. The influence of surface modification on the osseointegration of this material has not been extensively investigated. PURPOSE: Long-term investigations with titanium implants have shown superior biomechanical results with the sandblasted acid-etched (SLA) surface, demonstrating a high bone-implant interaction. The objective of this study was to compare two different zirconia surface topographies biomechanically and histologically with the well-documented titanium SLA surface. MATERIAL AND METHODS: Zirconia implants with either a machined (ZrO2m) or a sandblasted (rough, ZrO2r) surface were manufactured with the exact same cylindrical shape with a standard ITI thread configuration as the SLA titanium implants. The incisors 2 and 3 were removed from both sides of the maxillae of 13 adult miniature pigs and the tissues left to heal for 6 months. After this time period the animals received a total of 78 implants using a randomized scheme, with the titanium SLA implant used as an only individual reference. After healing periods of 4, 8, and 12 weeks 20, 24, and 25 implants, respectively, were subjected to removal torque tests (RTQ) as the main biomechanical analysis of the of the study. A fewer number was resected on bloc, embedded in methylmethacrylat and analyzed for their direct bone apposition under a light microscope. RESULTS: Surface analysis revealed the highest surface roughness for the SLA-implant, followed by ZrO2r and ZrO2m. The turned ZrO2m implants showed statistically significant lower RTQ values than the other two implants types after 8 and 12 weeks, while the SLA implant showed significantly higher RTQs values than ZrO2r surface after 8 weeks. Differences in the bone apposition were observed in the histomorphometric analysis using light microscopy for all surfaces at any time point. CONCLUSION: The findings suggest that ZrO2r implants can achieve a higher stability in bone than ZrO2m implants. Roughening the turned zirconia implants enhances bone apposition and has a beneficial effect on the interfacial shear strength.

[Nerve repair strategies for restoration of erectile function after radical pelvic surgery]. / Nerveninterponate zur Wiederherstellung der erektilen Funktion bei radikalen Beckenoperationen.

Iatrogenic cavernous nerve lesions occurring during radical pelvic surgery often lead to irreversible erectile dysfunction. The nerve defects after excision of the neurovascular bundles must be reconstructed by interposition grafting to supply a permissive scaffold for oriented axonal regrowth. The use of autologous nerve grafts for the repair of human cavernous nerves during radical prostatectomy has been controversial regarding the limited success achieved with bilateral nerve grafting. Artificial nerve guides consisting of natural or synthetic materials have been successfully used for bridging peripheral nerve defects. The combination with Schwann cells, neurotrophic factors and extracellular matrix components has been shown to promote cavernous nerve regeneration.

Nerve replacement strategies for cavernous nerves.

OBJECTIVE: This article reviews novel restorative therapies for cavernous nerves that may be used to replace resected cavernous nerves at the time of pelvic surgery. METHODS: A literature-based presentation (Medline search) on current nerve replacement strategies was conducted with emphasis on neurobiological factors contributing to the restoration of erectile function after cavernous nerve injuries. RESULTS: A promising alternative to autologous nerve grafts for extending the length of successful nerve regeneration are artificial nerve guides. The addition of neurotrophic factors, extracellular matrix components and Schwann cells has been shown to promote cavernous nerve regeneration. Neurotrophic factors can be incorporated in the scaffold or can be supplied by cells seeded into the stroma. The regenerative capacity of these cells can be further enhanced by genetic modification with neurotrophic factor encoding genes. CONCLUSIONS: Artificial nerve guides, especially biodegradable ones containing growth-promoting factors or cells, are a promising option for the repair of cavernous nerve lesions.

[Magnetic Drug Targeting--a new approach in locoregional tumor therapy with chemotherapeutic agents. Experimental animal studies]. / Magnetisches Drug Targeting--ein neuer Ansatz in der lokoregionären Tumortherapie mit Chemotherapeutika. Tierexperimentelle Untersuchungen.

BACKGROUND: Advanced squamous cell carcinomas of the head and neck region were often treated with combined radio-chemotherapy. Radiotherapy allows a focused treatment of the tumor, and healthy tissue can be protected from radiation. Chemotherapy, however, is mostly given systemically and the unwanted negative side effects also develop in many other organs. AIM OF THE STUDY: Locoregional application of chemotherapeutic agents with Magnetic Drug Targeting on an animal experimental study. METHODS AND RESULTS: Magnetic Drug Targeting is a new approach to the locoregional treatment of tumors. Ferrofluids (colloidal dispersion of magnetic nanoparticles) were reversibly bound to chemotherapeutic agents and injected intra-arterially, while focused with an external magnetic field to a certain body compartment (i.e. the tumor). With only 20% or 50% percent of the regular systemic chemotherapeutic dose, we achieved an up to 26 times higher concentration in the tumor region with this application compared to the usual systemic administration. CONCLUSION: Magnetic Drug Targeting offers an unique opportunity to treat tumors locoregionally with chemotherapeutic agents.

Investigation on the precaecal and faecal digestibility of lactulose and inulin and their influence on nutrient digestibility and microbial characteristics.

This study was conducted to determine the pre-caecal and faecal digestibility of lactulose and inulin and the influence of these substances on nutrient digestibility and microbial characteristics. In metabolic trials three of six male growing pigs (German Landrace x Pietrain) were fitted with an ileo-rectal anastomosis (IRA) in end-to-end technique with preserved ileo-caeco-colic valve. The metabolic trials were conducted from day 21-63 after surgery. The remaining pigs were used as intact partners (IN) for the IRA pigs. The experimental diets, based on corn, wheat, barley and soybean meal, were supplemented with either 1.5% lactulose or 2% inulin in replacement of diatomaceous earth (control). Pre-caecal digestibility of lactulose and inulin was assessed to be 79 and 98%, respectively. faecal digestibility was determined as 100%. The supplementation of lactulose and inulin had only minor effects on the pre-caecal and faecal digestibility of nutrients. Significant differences in nutrient digestibility were obvious between IRA and IN pigs, whereas the IRA pigs showed lower digestibility values with the exception of ether extracts (EE). Bacterial population in the digesta of IRA and IN pigs were not affected by the experimental diets except the concentration of gram-negative anaerobes, which inclined when the IRA pigs received the lactulose diet. The pH of chyme was significantly lower than the pH of faeces, however the pH was unaffected by the different supplemented diets. The concentration of volatile fatty acids (VFA) in pre-caecal chyme decreased significantly when IRA pigs received the lactulose supplemented diet whereas VFA in faeces were unaffected by the supplementation. IRA pigs administered with lactulose excreted more N via the urine, but the nitrogen balance remained unaffected. From the present investigation it can be concluded that lactulose and inulin did only partly or scarcely fulfill the expectation of acting as prebiotics in pigs.

[Tissue engineering of erectile nerves]. / Tissue Engineering erektiler Nerven.

Dissection of the cavernous nerves eliminates spontaneous erections and may lead to irreversible erectile dysfunction due to degeneration of cavernous tissue. Novel procedures to reconstruct penile innervation include cavernous nerve interposition grafting and neurotrophic treatments to revitalize penile neural input, evaluated thus far in various preclinical models of cavernous nerve injury. Schwann cells crucially contribute to successful axonal regeneration by mechanical and paracrine mechanisms in the injured nerve, and Schwann cells seeded into guidance channels have been successfully employed to support regeneration in animal models of cavernous nerve injury. Gene therapy, tissue engineering, and reconstructive techniques have been combined to deliver neurotrophic factors and recover erectile function.

Anaesthesia with midazolam/medetomidine/fentanyl in chinchillas (Chinchilla lanigera) compared to anaesthesia with xylazine/ketamine and medetomidine/ketamine.

We studied four different drug regimes for anaesthetic management in chinchillas and evaluated and compared their cardiovascular and respiratory effects. In this randomized, cross-over experimental study, seven adult chinchillas, five females, two males [515 +/- 70 (SD) g] were randomly assigned to one of the following groups: group 1 [midazolam, medetomidine and fentanyl (MMF), flumazenil, atipamezole and naloxone (FAN); MMF-FAN] received 1.0 mg/kg midazolam, 0.05 mg/kg medetomidine and 0.02 mg/kg fentanyl i.m., and for reversal 0.1 mg/kg flumazenil, 0.5 mg/kg atipamezole and 0.05 mg/kg naloxone s.c. after 45 min; group 2 (MMF) 1.0 mg/kg midazolam, 0.05 mg/kg medetomidine and 0.02 mg/kg fentanyl i.m.; group 3 [xylazine/ketamine (X/K)] 2.0 mg/kg xylazine and 40.0 mg/kg ketamine i.m.; and group 4 [medetomidine/ketamine (M/K)] 0.06 mg/kg medetomidine and 5.0 mg/kg ketamine i.m. Reflexes were judged to determine anaesthetic stages and planes. Anaesthesia with X/K and M/K was associated with a prolonged surgical tolerance and recovery period. By reversing MMF, recovery period was significantly shortened (5 +/- 1.3 min versus 40 +/- 10.3 min in MMF without FAN, 73 +/- 15.0 min in X/K, and 31 +/- 8.5 min in M/K). Without reversal, MMF produced anaesthesia lasting 109 +/- 16.3 min. All combinations decreased respiratory and heart rate but compared with X/K and M/K, respiratory and cardiovascular complications were less in the MMF groups. Focussing on the clinical relevance of the tested combinations, completely reversible anaesthesia showed two major advantages: anaesthesia can be antagonized in case of emergency and routinely shortens recovery. In small animals particularly these advantages lead to less complications and discomfort and thus often can be lifesaving. As all analgesic components (medetomidine and fentanyl) are reversed, postoperative analgesia should be provided before reversal of anaesthesia.

Schwann cell seeded guidance tubes restore erectile function after ablation of cavernous nerves in rats.

PURPOSE: Dissection of the cavernous nerves eliminates spontaneous erections. We evaluated the ability of Schwann cell seeded nerve guidance tubes to restore erections after bilateral cavernous nerve resection in rats. MATERIALS AND METHODS: Sections (5 mm) of the cavernous nerve were excised bilaterally, followed by immediate bilateral microsurgical reconstruction. In 10 animals per group (20 study nerves) reconstruction was performed by genitofemoral nerve interposition, interposition of silicone tubes or interposition of silicone tubes seeded with homologous Schwann cells. As the control 10 animals (20 study nerves) underwent sham operation (positive control) and bilateral nerve ablation (without reconstruction) was performed in a further 10 (negative control). Erectile function was evaluated 3 months postoperatively by relaparotomy, electrical nerve stimulation and intracavernous pressure recording. RESULTS: After 3 months neurostimulation resulted in an intact erectile response in 90% (18 of 20) of Schwann cell grafts, while treatment with autologous nerves (30% or 6 of 20) or tubes only (50% or 10 of 20) was less successful (p <0.01). Whereas untreated ablated rats showed no inducible erections (0% or 0 of 20), all sham operated animals had an intact erectile response (100% or 20 of 20). Maximum intracavernous pressure upon electrostimulation was significantly elevated using Schwann cell grafts compared to results in the other treatment groups (p <0.001). Morphological evaluation revealed advanced regeneration within Schwann cell grafts. CONCLUSIONS: Schwann cell seeded guidance tubes restore erectile function after the ablation of cavernous nerves in rats and they are superior to autologous nerve grafts.

Periarterial application of papaverine during laparoscopic donor nephrectomy improves early graft function after kidney transplantation in pigs.

BACKGROUND: Laparoscopic donor nephrectomy (LDN) increases incentives to donation by subjects who might refuse an open operation. However, the incidence of delayed graft function is higher after LDN than after open operation. This may be caused by the reduction of renal perfusion as a result of the raised intraabdominal pressure and mechanically induced renal angiospasm during the operation. We conducted experiments to find out whether the application of papaverine around the renal artery during LDN could improve early graft function after transplantation. METHODS: Renal function was studied in 10 male pigs (weight approximately 25 kg). The left kidney was harvested laparoscopically (intraabdominal pressure 8 mmHg). Five animals were randomly selected to have perivascular application of 50 mg papaverine (treatment group) before preparation of the vessels. In controls no papaverine was used. After LDN and open right nephrectomy the left kidney was autotransplanted. The main outcome measures were volume of urine produced and creatinine clearance during the first 20 h after the transplant. RESULTS: The groups were comparable in respect of body weight, hemodynamic values, amount of infusions, warm and cold ischemia time, and duration of anastomosis. Urine output and creatinine clearance were significantly higher in pigs treated with papaverine than in controls. CONCLUSIONS: Papaverine substantially improved early graft function in pigs when applied around the renal artery during LDN. Whether this is applicable to procurement of human kidneys remains to be evaluated.

The influence of periarterial papaverine application on intraoperative renal function and blood flow during laparoscopic donor nephrectomy in a pig model.

BACKGROUND: The transplantation of live donor kidneys harvested laparoscopically is associated with a higher incidence of delayed graft function than the transplantation of grafts harvested via the open technique. The delay is believed to be due to a decrease in renal blood flow during laparoscopic donor nephrectomy (LDN). The aim of this study was to evaluate whether renal function and blood perfusion can be enhanced by the periarterial application of papaverine during LDN. METHODS: Renal function and blood flow were studied in a porcine model that included a total of 24 pigs (20-30 kg). In 12 of the pigs, urine output and creatinine clearance were determined as measures of renal function. In the other 12 pigs, renal blood flow was determined using fluorescent-labeled microspheres. In each group, the pigs were randomized into two subgroups, one with and one without a perivascular injection of 50 mg papaverine. RESULTS: As compared to the controls, the animals receiving papaverine had a significantly higher urine output (3.1 +/- 1.6 vs 0.9 +/- 0.45 ml/h/kg; p = 0.02), superior creatinine clearance (2.22 +/- 0.5 vs 0.95 +/- 0.1 ml/min/kg; p = 0.038), and enhanced renal blood flow (4.9 +/- 2.2 vs 2.1 +/- 0.8 ml/min/g; p = 0.008). CONCLUSIONS: When applied to the tissue surrounding the renal artery, papaverine substantially improves renal function and blood flow during laparoscopic live kidney donation. Whether graft optimization during kidney procurement also translates into improved posttransplantation function remains to be established.

Plasma epinephrine levels after epinephrine administration using different tracheal administration techniques in an adult CPR porcine model.

The aim of the study was to compare arterial plasma epinephrine levels after tracheal epinephrine application using three different tracheal instillation techniques at different tracheal levels in a porcine adult cardiopulmonary resuscitation model. In the prospective, randomized study, electrically-induced cardiopulmonary arrest was applied to 32 anaesthetized and paralyzed domestic pigs. After 3 min of cardiopulmonary arrest and 2 min of external chest compressions using a pneumatic compression device and mechanical ventilation, epinephrine was administered intravenously (20 microg/kg) or tracheally (50 microg/kg): using either direct injection into the upper end of the tracheal tube, via a catheter placed into the bronchial system and using a special tracheal application tube. In each group, there were eight pigs. Arterial blood samples were taken before and up to 10 min after epinephrine administration. Regression analysis was performed of the correlated data. The values of mean arterial blood pressure and end-tidal CO(2) during the time of observation did not differ between groups. Total plasma epinephrine concentrations showed a significant increase in all groups, but with no difference between the tracheal groups. However, peak epinephrine levels in the intravenous group were significantly higher than in tracheal groups. We conclude that administration using three different tracheal instillation levels result in similar onset and peak plasma epinephrine levels in this setting and therefore the preferred method of tracheal epinephrine application for cardiopulmonary resuscitation may be selected by other criteria.

Locoregional cancer treatment with magnetic drug targeting.

The specific delivery of chemotherapeutic agents to their desired targets with a minimum of systemic side effects is an important, ongoing challenge of chemotherapy. One approach, developed in the past to address this problem, is the i.v. injection of magnetic particles [ferrofluids (FFs)] bound to anticancer agents that are then concentrated in the desired area (e.g., the tumor) by an external magnetic field. In the present study, we treated squamous cell carcinoma in rabbits with FFs bound to mitoxantrone (FF-MTX) that was concentrated with a magnetic field. Experimental VX-2 squamous cell carcinoma was implanted in the median portion of the hind limb of New Zealand White rabbits (n = 26). When the tumor had reached a volume of approximately 3500 mm3, FF-MTX was injected intraarterially (i.a.; femoral artery) or i.v. (ear vein), whereas an external magnetic field was focused on the tumor. FF-MTX i.a. application with the external magnetic field resulted in a significant (P < 0.05), complete, and permanent remission of the squamous cell carcinoma compared with the control group (no treatment) and the i.v. FF-MTX group, with no signs of toxicity. The intratumoral accumulation of FFs was visualized both histologically and by magnetic resonance imaging. Thus, our data show that i.a. application of FF-MTX is successful in treating experimental squamous cell carcinoma. This "magnetic drug targeting" offers a unique opportunity to treat malignant tumors locoregionally without systemic toxicity. Furthermore, it may be possible to use these magnetic particles as a "carrier system" for a variety of anticancer agents, e.g., radionuclides, cancer-specific antibodies, and genes.

Endohyperthermia--experimental evaluation of a new therapeutic approach for treatment of biliary carcinoma.

BACKGROUND AND STUDY AIMS: To improve the prognosis of patients with unresectable, locally advanced bile duct carcinoma, new treatment strategies need to be evaluated. Hyperthermia has been successfully applied as part of multimodal therapy in esophageal and rectal carcinoma. We performed in-vitro and in-vivo experiments with a new intraluminal hyperthermia system in the biliary tract. METHODS: A radiofrequency system (13.56 MHz, Endoradiotherm XERT-200A; Olympus Optical Co., Tokyo, Japan) was used with a special intraluminal microelectrode (diameter 4.5 mm, length 40 mm) covered by a silicone balloon with cooling water and a large counter electrode for focusing the electromagnetic field around the electrode. The heating capacity of the endohyperthermia unit was examined in vitro in a muscle-equivalent phantom (agar 4 %), in isolated livers of pigs and cows, as well as in vivo in anesthetized sheep. Continuous thermometry was done with thermosensors at the applicator surface, and with multichannel thermocouple probes in the environment of the applicator. RESULTS: Endohyperthermia induced a homogeneous heating of the phantom and the isolated liver bile duct preparation to a temperature > or = 40 degrees C in an area at least 10 mm in depth. After placement of the applicator into the common bile duct of anesthetized sheep, endohyperthermia led to a consistent and repeatable heating of the surrounding tissue to 40.5 +/- 0.5 degrees C at 1 cm distance, and 39.9 +/- 0.7 degrees C at 2 cm distance. Blood pressure, heart rate, and systemic temperature did not change in vivo. Histological examination of the bile duct showed superficial mucosal necrosis (depth 100-200 microm), microvascular damage with petechiae, congestion and edema of the bile duct wall and adventitia after hyperthermia treatment in vivo. CONCLUSIONS: The intraluminal endohyperthermia system produces consistent and repeatable heating of the surrounding tissue. Since effective thermal power can reach a depth of up to 2 cm, tumors may also be heated adequately.

Inhibition of neointima formation after experimental coronary artery stenting: a new biodegradable stent coating releasing hirudin and the prostacyclin analogue iloprost.

BACKGROUND: To minimize acute stent thrombosis and development of restenosis, stents coated with biodegradable and nonbiodegradable polymers have been proposed to serve as sustained-release drug carriers. METHODS AND RESULTS: In both a sheep and a pig model, we examined the vascular response to standard and high-pressure implantation of coronary Palmaz-Schatz stents coated with a 10-microm layer of polylactic acid (MW 30 kDa) releasing recombinant polyethylene glycol (r-PEG)-hirudin and the prostacyclin analogue iloprost, both drugs with antithrombotic and potentially antiproliferative effects. Study observation time was 28 days. Between the corresponding stent groups, no differences were observed with regard to preplacement and postplacement implantation parameters. The morphometric analysis demonstrated that the coating was associated with a greater lumen diameter through a reduction in the mean restenosis area by 22.9% (P<0.02) in the standard-pressure model (sheep) and by 24.8% (P<0.02) in the overstretch pig model compared with uncoated control stents without inducing a local inflammatory response. CONCLUSIONS: The results from this study demonstrate beneficial effects of a polymeric stent coating with polylactic acid releasing r-PEG-hirudin and iloprost on the development of restenosis after coronary stent placement at 4 weeks, independent of the extent of vascular injury. Future studies are proposed to investigate the integration of other substances to further enhance the potential of the stent coating on reducing neointimal formation.