The neural basis of reversal learning: An updated perspective.

Reversal learning paradigms are among the most widely used tests of cognitive flexibility and have been used as assays, across species, for altered cognitive processes in a host of neuropsychiatric conditions. Based on recent studies in humans, non-human primates, and rodents, the notion that reversal learning tasks primarily measure response inhibition, has been revised. In this review, we describe how cognitive flexibility is measured by reversal learning and discuss new definitions of the construct validity of the task that are serving as a heuristic to guide future research in this field. We also provide an update on the available evidence implicating certain cortical and subcortical brain regions in the mediation of reversal learning, and an overview of the principal neurotransmitter systems involved.

Ruptured poly-implant protheses breast implant after aesthetic breast augmentation: diagnosis, case management, and histologic evaluation.

Since the scandal of the poly-implant protheses (PIP) breast implants, all patients with PIP are advised to have their implants removed. With approximately 400,000 PIP implants sold worldwide breast, surgeons will be confronted with these patients. Histologic examination in the reported case showed silicone infiltration into fatty tissue and breast tissue without signs of malignancy. A general histologic analysis for the rare event of an anaplastic large T cell lymphoma is not advised. The malignant potential of PIP implants currently is uncertain, and further investigation is required. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Prescription of the Morning-After Pill in a Berlin Emergency Department Over a Four-Year Period - User Profiles and Reasons for Use.

Questions: There are no current health care studies from Germany regarding the "morning-after pill". This paper will use routine data to analyse details regarding the users' profiles, reasons for using it and the utilisation of hospital outpatient facilities. Patient Collective and Methods: Retrospective analysis of all triage sheets in the emergency department of the Virchow Hospital Campus/Charité University Hospital, Berlin, over a four-year period from 2007 to 2010 that were coded with the ICD diagnosis Z30 (= contraception advice) and statistical processing of the associated administrative data. Results: 860 triage sheets were included in the analysis. The emergency department is used most frequently for the prescription of the "morning-after pill" at the weekend. The average age of the users was 25.1 years. The most common reason cited for needing emergency contraception was unprotected sexual intercourse, with the second-most common being "condom failure". Around half of the women attended the department within 12 hours of having unprotected sex. Less than 2 % (n = 14) of all women decided against a prescription of emergency contraceptive after counselling. Conclusions: The user profile and reasons for using emergency oral contraception correlate largely with the information contained in international literature. Although the "morning-after pill" is probably prescribed mainly in general practices in Germany, and despite the availability of new drugs with a permitted post-exposure interval of up to 120 hours after unprotected sex, there appears to still be a high demand for counselling and prescriptions of the "morning-after pill" in the context of the emergency department.

[The Göttingen manual for OR managers]. / Göttinger Leitfaden für OP-Manager.

Economic pressures are forcing German hospitals to take measures to secure the cost effectiveness of medical care. Surgical facilities are particularly affected as a high-cost segment. As a consequence hospital operators and administrators have begun to hire surgical facility (OR) managers whose task it is to implement efficiency-oriented steps and reorganization measures aimed at increasing productivity and profitability of the surgical services. The OR manager is confronted with high expectations in a complex environment full of potential conflicts. With this in mind, the following article defines and comments on the most important aspects of OR managerial duties and responsibilities. The authors are experienced in OR management and are able to give the reader not only the theoretical fundamentals but also recommendations and guidelines which are particularly valuable to those contemplating a career as OR manager.

[Another case of "Lazarus phenomenon" during surgery? Spontaneous return of circulation in a patient with a pacemaker]. / Intraoperatives "Lazarus-Phänomen"? Spontane Kreislaufstabilisierung bei einem Patienten mit Herzschrittmacher.

A case is presented of spontaneous return of circulation after cardiac arrest in a patient with a pacemaker without intraoperative resuscitation. In the literature this kind of situation is called the Lazarus phenomenon. Cardiac arrest of the patient occurred during surgery and because of the poor prognosis no cardiopulmonary resuscitation was initiated. After 6 min of apnoea and cessation of circulation, the circulation restarted spontaneously and surgery was continued. Afterwards the patient was transferred to the intensive care unit but died 2 days later without regaining consciousness. The pathophysiological mechanisms for the Lazarus phenomenon are poorly understood but several mechanisms and multifactorial events are discussed in the literature.

[Teaching and simulation. Methods, demands, evaluation and visions]. / Lehre und Simulation. Methoden, Anforderungen, Evaluation und Visionen.

Since 1st October 2003 the new German "Approbationsordnung für Arzte" (Medical Licensing Regulations) requires an increasing amount of small group teaching sessions and encourages a multidisciplinary and more practical approach to the related topics. In 2004 the German Society of Anaesthesiology and Intensive Care Medicine has provided almost all anaesthesia faculties of German Universities with equipment for full-scale simulation. This article describes methods for a simulation-based medical education training program. Basic requirements for a successful training program using full scale simulators are the provision of an adequate logistical and material infrastructure, teacher attendance of train-the-trainer courses, implementation in the medical curriculum and an instructor-student ratio of 1:3, equivalent to that for bedside teaching. If these requirements were fulfilled, medical students scored the simulation scenarios "induction of anaesthesia", "acute pulmonary embolism", "acute management of a multiple trauma patient" and "postoperative hypotension" as 1.5, 1.6, 1.5 and 1.5, respectively, on a scale of 1-6. These scores were better than those given for other segments of the curriculum.

Hemodynamic effects of spontaneous breathing in the post-operative period.

BACKGROUND: During mechanical ventilatory support, spontaneous breathing has been linked to improved hemodynamics. These findings may be explained by a decrease in intrathoracic pressure which may improve venous return to the heart. Such a mechanism should result in a dose-response relation between the amount of spontaneous breathing and an increase in the global end-diastolic volume (GEDV) and cardiac output (Q(t)). METHODS: To test this hypothesis, 15 patients were studied after major elective surgery during weaning from mechanical ventilation using bilevel positive airway pressure (BIPAP). BIPAP allows unrestricted spontaneous breathing during every phase of the respiratory cycle. Thus, ventilatory support was modified by changing the mechanical respiratory rate only, whereas inspiratory airway pressure and PEEP were kept constant. GEDV and Q(t) were measured by transpulmonary thermodilution. RESULTS: GEDV (P = 0.055), stroke volume (P = 0.027) and subsequently also Q(t) (P < 0.001) increased when spontaneous breathing increased. In contrast, no difference was observed for central venous pressure (P = 0.19). CONCLUSION: The beneficial hemodynamic effects of spontaneous breathing during mechanical ventilatory support can partially be explained by improved venous return to the heart which increases stroke volume and Q(t).

[New pathways in undergraduate medical education - first experiences with the cross section speciality emergency and intensive care medicine]. / Neue Wege der studentischen Lehre - Erste Erfahrungen im Querschnittsbereich Notfall- und Intensivmedizin.

OBJECTIVE: On October 1 (st) 2003 Emergency Medicine was recognised for the first time as an independent cross section speciality in the new German "Approbationsordnung fuer Aerzte" (Medical Licensing Regulations). These amendments were made not only to increase the amount of small group teaching sessions but also to encourage a multidisciplinary and rather practical approach to the related topics. This article portrays the realisation of these objectives in form of a multidisciplinary module, as it has been established at University of Göttingen Medical School since the summer semester of 2004. We present the new curriculum, calculate the associated personnel resources and demonstrate the results of the structured evaluation given by the participating students. METHODS: We linked the fields of emergency and intensive care medicine by splitting them up into submodules which the students had to run through according to a set rota. 162 students were allocated to 27 small groups. Every student received a total of 38.5 hours of teaching, with the workshops coming to 46.8 %. The workshops comprised of nine sessions, three in Emergency Medicine, four in Intensive Care Medicine and two at human patient simulators. In addition we scheduled a seminar and an accompanying lecture. The final examination was performed as an Objective Structured Clinical Evaluation (OSCE). RESULTS: The realisation of the new module required a total of 1290 working hours for medical staff and 130 for our student aids. Compared to all other modules of Goettingen University Medical School the module here presented obtained the highest overall evaluation score by the medical students. Lessons with a high amount of practical involvement (i. e. Emergency Medicine and simulator-based workshops) were significantly better evaluated than rather formal teaching techniques, such as the lectures and the seminar. According to the students' self-assessment the simulator-based workshops were seen particularly valuable for the facilitation of knowledge transfer into clinical practice. CONCLUSION: The determined realisation of the new German Medical Licensing Regulations requires considerable time resources. However, its evaluation by the medical students is strikingly positive.

Mechanisms involved in the relaxing effect of midazolam on coronary arteries.

BACKGROUND AND OBJECTIVE: Hypotension, especially in elderly and hypovolaemic patients, is frequently associated with intravenous midazolam administration. The mechanisms are not completely understood. This study was designed to investigate the mechanisms involved in the relaxing effect of midazolam on coronary arteries. METHODS: The substance was studied in isolated porcine coronary artery rings precontracted by either potassium chloride or prostaglandin F2alpha. RESULTS: Midazolam caused vasodilatation in a concentration-dependent manner. Relaxation was more pronounced in prostaglandin F2alpha precontracted segments than in those treated with potassium chloride (P < 0.001). Vasodilatation was unaffected by Nomega-nitro-L-arginine, indomethacin and glibenclamide. Tetraethylammonium chloride, an inhibitor of the BK(Ca) K+ channel (a high conductance Ca(2+)-sensitive K+ channel), dose dependently attenuated the vasodilating effect of midazolam (P < 0.01). CONCLUSIONS: Hyperpolarization of the smooth muscle cell in the vessel wall, elicited by the activation the BK(Ca) K+ channel, may contribute to the vasorelaxing effect of midazolam.

Ketamine enantiomers differentially relax isolated coronary artery rings.

BACKGROUND AND OBJECTIVE: It has been shown that racemic ketamine increases coronary blood flow and that this effect is at least in part due to a direct vasorelaxing effect of this substance. This study was designed to determine whether ketamine might stereoselectively relax isolated porcine coronary arteries. METHODS: Using the model of isolated vessels we studied the effects of S(+) ketamine, R(-) ketamine, and racemic ketamine (5-500 microg mL(-1)) on artery strips pre-contracted by either potassium chloride (KCl) or prostaglandin F2alpha (PGF2alpha). To elucidate possible mechanisms of action these experiments were repeated in the presence of one of the following compounds: N(omega)-nitro-L-arginine (L-NNA), indomethacin, glibenclamide, and tetraethylammonium (TEA) chloride, an inhibitor of the BK(Ca) K+ channel. RESULTS: Both isoforms and racemic ketamine relaxed isolated coronary arteries in a concentration-dependent manner in concentrations beyond those used in clinical practice. S(+) ketamine exerted the strongest vasorelaxing effect, followed by racemic ketamine and R(-) ketamine. Pretreatment with L-NNA, indomethacin, or glibenclamide did not alter the vasodilating properties of ketamine, whereas TEA chloride significantly attenuated the vasorelaxing effects of all the three forms of ketamine. CONCLUSIONS: Ketamine dilates coronary arteries in vitro when administered in high concentrations. There is a stereoselective difference with a stronger vasorelaxing effect of S(+) ketamine compared to racemic and R(-) ketamine. The impact of TEA chloride suggests that the activation of the BK(Ca) channel may contribute to the vasodilating effect of ketamine.

Rutkow PerFix-plug repair for primary and recurrent inguinal hernias--a prospective study.

Surgery of the groin hernia has become more a question of the applied tension-free, mesh technique. Whereas studies on laparascopic versus open tension-free hernia repair or open-mesh versus open-nonmesh repair have been performed sufficiently, data regarding the open tension-free plug-and-patch technique are rather poor. During the period from January 2001 to October 2003, we followed and filed 766 hernia repairs in the plug-and-patch technique of Rutkow. Follow up was during the hospital stay, 4 weeks, and minimally 12 months after operation. The main follow-up variables were complications, recurrence rate, and pain. The mean operating time was 37.8 +/- 15.85 (12-135) minutes. In 141 (19.3%) patients (n=730), the ilioinguinal nerve was resected. The 1 intraoperative complication that occurred was a severed small intestine. Length of hospital stay was 2.09 +/- 1.35 (0-17) days, work leave lasted for 15.3 +/- 12.42 (0-60) days, and return to normal daily activities was possible within 6.54 +/- 6.86 (0-35) days. Twenty-two (2.9%) patients (n=766) developed a postoperative hematoma as the most common complication, and a reoperation was required 17 (2.2%) times during the hospital stay. Early complications included hematoma (3.7%), seroma (3.5%), infection (0.2%), necrosis of 1 testicle (0.2%), persisting scrotal swelling (1.5%), persisting pain (0.9%), and hypoesthesia (2.4%). Within 4 weeks, 4 (0.9%) patients were reoperated for 1 seroma, hematoma, infection, and testicle necrosis. After 605.4 +/- 154.5 (365-1018) days, the following 19 (5.7%) patient complaints were noted: persisting pain (2.1%), hypoesthesia (1.8%), foreign-body feeling (0.6%), scrotal swelling (0.6%), and 1 (0.3%) mesh dislocation. Six (1.8%) reoperations have been performed. The overall recurrence rate was 1.8% (n=6), for primary 1.5% (n=4), and 3.3% (n=2) for recurrent hernias; 96.3% of the patients would agree to undergo the same operation a second time. Tension-free repair of the inguinal hernia by the plug-and-patch technique is a quick and secure method that simplifies hernia surgery without compromising the high-quality standards such as a low recurrence rate and low pain load of the patient. Patients had a fast recovery with a subsequent short work leave. The method is a simple, effective, and economical operation, suitable as a standard performed in local anesthesia on an out-patient basis.

[Tracheotomy for the long-term ventilator-dependent patient?]. / Tracheotomie - Luftweg der Wahl für den langzeitbeatmeten Patienten?

OBJECTIVE: Tracheotomy is commonly performed in long-term ventilated patients. The aim of this review is to discuss the advantages and disadvantages of tracheotomy. METHODS: Review of the literature. RESULTS: Disadvantages of tracheotomy include the risk of bleeding, infection, injury of the truncus brachiocephalicus, and of long-term tracheal injury. These risks must be compared with the risk of vocal cord trauma, laryngeal trauma, and subglottic stenosis following translaryngeal intubation. Despite a number of disadvantages and potentially even life-threatening complications, however, tracheotomy is a well-established technique for long-term airway management in critically ill patients. Potential advantages of tracheotomy include enhanced patient comfort, reduced airway resistance and dead space, a lower incidence of ventilator-associated pneumonia and a shorter duration of mechanical ventilation and hospital stay. Patient comfort before and after tracheotomy has not yet been seriously evaluated, using modern ventilators airway resistance does not longer play a major role. No data from randomized controlled trials actually support the thesis that tracheotomy reduces the incidence of ventilator-associated pneumonia. There is weak evidence for the concept that the duration of mechanical ventilation can be reduced in patients while using tracheotomy. Patients undergoing percutaneous dilational tracheotomy seem to have a reduced risk of bleeding and site infection and a shorter duration of the procedure when compared to those with conventional surgical tracheotomy. CONCLUSIONS: Many clinicians perform tracheotomies on the basis of expert opinion and clinical experience. So far, the benefits, however, have not been proven in large-scale randomized trials. Many of these studies suffer from design flaws, insufficient randomization and the absence of blinding. On the other hand, the lack of positive results do not rule out that tracheotomy may be beneficial for the ventilator-dependent patient. Percutaneous tracheotomy procedures may be superior to conventional surgical tracheotomies. Long-term results, however, will have to prove this preliminary observation.

[Malposition of a central venous catheter in a patient with severe chest trauma]. / Fehllage eines zentralen Venenkatheters bei einem Patienten mit schwerem Thoraxtrauma.

The placement of a central venous catheter is associated with specific risks including malposition of the catheter. We report the case of a 32 year old man who suffered from a severe thoracic trauma including haematopneumothorax on his left side. In the emergency room a large-bore central venous catheter was placed in the left subclavian vein, after blood had been aspirated successfully. Later, the haemodynamic state of the patient deteriorated, so that cardiopulmonary resuscitation had to be started. While great amounts of blood transfusions were applied via the catheter using a rapid transfusion device, the blood loss over the left sided chest tube increased rapidly. Emergency thoracotomy was performed, revealing that the catheter was not in intravenous position, but in intrapleural malposition. Haematothorax was caused by a laceration of the upper lobe of the left lung with severe bleeding from great vessels. This case shows that successful aspiration of blood does not exclude malposition of a central venous catheter. Correct position of the catheter must be verified using appropriate methods including chest X-ray, intracardiac ECG tracing or display of the central venous pressure curve on a monitor.

Activation of the K+ channel BK(Ca) is involved in the relaxing effect of propofol on coronary arteries.

BACKGROUND AND OBJECTIVE: Propofol may cause undesirable hypotension due to vasodilation. The underlying mechanisms are not completely understood. We investigated the mechanisms by which propofol relaxes vascular segments. METHODS: We studied the effect of propofol on isolated porcine coronary artery rings precontracted with potassium chloride or prostaglandin F2alpha. RESULTS: Propofol, in a concentration-dependent manner, relaxed all segments at concentrations of 5 microg mL(-1) and above. This relaxation was unaltered in the presence of N(omega)-nitro-L-arginine, indomethacin, diltiazem and glibenclamide. Tetraethylammonium chloride, an inhibitor of the BK(Ca) K+ channel (a high conductance Ca2+-sensitive K+ channel), dose-dependently attenuated the vasodilating effect of propofol (P < 0.001). CONCLUSIONS: Our results suggests that the activation of the BK(Ca) channel may contribute to the vasodilating effect of propofol, hereby causing hyperpolarization of the smooth muscle membrane and reduction of smooth muscle tone.

[Blunt chest trauma with total rupture of the right main stem bronchus--a case report]. / Hauptbronchusruptur nach stumpfem Thoraxtrauma--Eine Kasuistik.

Tracheo-bronchial lesions in blunt chest trauma are rare--the incidence is about 1%--but potentially life-threatening events. Indirect signs such as pneumothorax, pneumomediastinum, subcutaneous emphysema or an insufficient expansion of the lungs after drainage of a pneumothorax are ominous. The fastest and most reliable method to assess the definite diagnosis of tracheo-bronchial lesion is fibre-optic tracheobronchoscopy. Early surgical treatment is mandatory to prevent major pulmonary resection. This case shows that computer tomography might fail to provide the right diagnosis. Independent lung ventilation is an option to protect the bronchial anastomosis during the early postoperative period. Reported here is the case of a young man who sustained a total traumatic rupture of the right main stem bronchus after being thrown from the passenger seat through the windshield of a motor vehicle. When the emergency doctor arrived on the scene, he found the patient with dyspnoea and massive thoracic subcutaneous emphysema. Reduced breath sounds on the left and no breath sounds on the right side led to an immediate placement of two chest tubes and controlled mechanical ventilation. After primary care in a district hospital, the patient was transferred to our university hospital for further treatment of his head injury. On admission, the patient was making breath sounds on both sides and a CT scan showed no clear sign of a tracheo-bronchial lesion. After neurosurgical intervention, the diagnosis of a rupture of the right main stem bronchus was made with delay by fibre-optic bronchoscopy. The patient was intubated with a left-sided double lumen endotracheal tube followed by surgical end-to-end anastomosis of the lesion. The initial postoperative ventilator support consisted of BIPAP-mode ventilation of the left lung, while the right lung was kept open with positive airway pressure. Forty-eight hours later, synchronised independent lung ventilation with two ventilators was established to protect the surgical result. The ventilation was switched to conventional mode a further 48 hours later. Extubation and the remaining ICU stay were uneventful.

[Ketamine attenuates the contractile response to vasoconstrictors in isolated coronary artery rings]. / Ketamin hemmt die Wirkung von Vasokonstriktoren an isolierten Koronararterien.

OBJECTIVE: Ketamine was shown to increase coronary blood flow. It was the aim of this study to answer the question whether ketamine directly dilates coronary arteries. METHODS: Using the model of isolated vessel rings we studied the effects of ketamine (2.5, 25, and 250 microg ml(-1)) on the contractile response to three vasoconstrictors, acetylcholine, histamine, and serotonin in porcine coronary artery segments. Other rings were contracted with KCl or PGF (2a) and then treated with ketamine (5 up to 500 microg ml(-1) added cumulatively). RESULTS: Ketamine dose-dependently dilated coronary arteries in concentrations beyond those used in clinical practice. In intact rings ketamine racemate (250 microg ml(-1)) attenuated contractions mediated by acetylcholine by 38.8 +/- 2.8%, histamine by 33.0 +/- 4.4% and serotonin by 42.1 +/- 3.7% (p < 0.05). There were no differences between intact and denuded rings (acetylcholine 38.5 +/- 2.8%, histamine 26.6 +/- 4.7%, serotonin 30.0 +/- 3.2%). With low concentrations of ketamine (2.5 microg ml(-1)) a slight tendency towards a contraction was recorded (n. s.). In rings precontracted with either KCl or PGF (2a) ketamine caused a small enhancement of contraction (KCl: 101.4 +/- 0.4%, PGF (2a): 101.3 +/- 1.4%) when administered in low concentration (5 microg ml(-1)), but almost complete relaxation (KCl: 0.4 +/- 1.3%, PGF (2a): 0.0 +/- 5.4%) in high concentration (500 microg ml(-1)). CONCLUSIONS: It is concluded that ketamine dose-dependently dilates porcine coronary arteries in concentrations beyond those used in clinical practice and that this effect is independent of endothelial function.

High-dose midazolam and the attenuation of the contractile response to vasoconstrictors in coronary artery segments.

BACKGROUND AND OBJECTIVE: Benzodiazepines may cause hypotension and are reported to interfere with smooth vascular muscle activity. The aim was to elucidate the influence of three different benzodiazepines on the vascular reactivity of coronary arteries. METHODS: Using the model of isolated vessels, we studied the impact of midazolam (0.15, 1.5, 15 microg mL(-1)), diazepam (0.1, 1.0, 10 microg mL(-1)) and flunitrazepam (0.01, 0.1, 1.0 microg mL(-1)) on the contractile responses to histamine (2 x 10(-5) mol L(-1)) and serotonin (3 x 10(-5) mol L(-1)) in isolated intact and denuded coronary arteries. RESULTS: Midazolam significantly attenuated the contractile response when administered in high concentrations (15 microg mL(-1)). This effect was more pronounced in intact than in denuded preparations (histamine: -22.7 versus -7.3%, P = 0.0079; serotonin: -47.1 versus -15.9%, P < 0.0001). Diazepam and flunitrazepam exerted no significant effects on the vascular tone of coronary arteries. CONCLUSIONS: Midazolam, but not diazepam or flunitrazepam, attenuates the contractile responses to vasoconstrictors in concentrations beyond those used in clinical practice. This effect is in part mediated by endothelial factors.

[Opioid intoxication following transdermal administration of fentanyl]. / Opioidintoxikation durch transdermales Fentanyl.

The case of a 77-year-old woman is described, who was found unconscious, with decreased respiration and miotic pupils, having previously experienced dizziness, nausea and drowsiness before. In the emergency room a fentanyl patch was detected, which had obviously been mistakenly applied by the patient the day before. Opioid intoxication was assumed and successfully treated with naloxon. The patient was supervised in an ICU for 24 h and sent home the next day without serious sequelae. The consequences following inappropriate use of transdermal fentanyl are discussed.

[F. W. Sertürner and the discovery of morphine. 200 years of pain therapy with opioids]. / F. W. Sertürner und die Entdeckung des Morphins - 200 Jahre Schmerztherapie mit Opioiden -

Since many centuries mankind has been aware of the poppy (papaver somniferum) and has known its product opium as an analgesic drug. Until the beginning of the 19 (th) century its compounds were not known, making it almost impossible to apply the substance in exact doses. 1803/04, Friedrich Wilhelm Sertürner (1783 - 1841) succeeded in isolating a crystalline substance from opium in the test tube, which he called morphium. In animals and in man he was able to prove that this new compound he had discovered was the principium somniferum of opium. He isolated morphine, the first pure opioid available for calculated pain therapy with one defined compound. Moreover, he laid the foundations of a new class of pharmaceutical drugs, the alcaloids.

Influence of opioids on the vascular tone of isolated porcine coronary artery segments.

BACKGROUND: It was the aim of this study to elucidate the influence of opioids on coronary vascular tone using the model of isolated porcine coronary artery segments. METHODS: We studied the effects of fentanyl (0.01, 0.1, 1.0 microg ml(-1)), alfentanil (0.1, 1.0, 10 microg ml(-1)), and sufentanil (0.01, 0.1, 1.0 microg ml(-1)) on the contractile response to three vasoconstrictors, acetylcholine, histamine and serotonin. RESULTS: Fentanyl (0.1, 1.0 microg x ml(-1)) dose-dependently attenuated the contractile response to acetylcholine, but not to histamine and serotonin. There were no differences in fentanyl's vasorelaxing potency between rings with intact and denuded endothelium. Alfentanil and sufentanil did not exert any significant influence on any of the vasoconstrictors tested. CONCLUSION: It is concluded that, in isolated porcine coronary artery rings, fentanyl at high concentrations has an attenuating effect on acetylcholine-induced contractions, which is independent of endothelial function, whereas alfentanil and sufentanil do not influence coronary vascular tone.