Does enzalutamide related PSMA upregulation affect outcomes of lutetium-177 PSMA radioligand therapy?

BACKGROUND: Enzalutamide is an antiandrogen drug used prior to lutetium-177 prostate specific membrane antigen (Lu-PSMA) radioligand therapy and has shown promising results for upregulating the PSMA expression on prostate cancer cells. In this study, we aim to compare prostate specific antigen (PSA) level changes in prostate cancer patients who received enzalutamide to those who did not. METHODS: Prostate cancer patients who underwent Lu-PSMA between 2021 and 2023 were retrospectively included. Patients were grouped based on prior enzalutamide therapy: those who received enzalutamide (EZ+) for at least 14 days and those who did not (EZ-). PSA changes and F-18 DCFPyL SUV (Standardized Uptake Values) were compared. RESULTS: Thirty-seven patients were included, 18 EZ+ and 19 EZ-. The median age, Gleason score, and prior chemo/hormonal therapies were similar for EZ+ and EZ-, except for radium-223. Eleven patients (61%) in EZ+ and 13 patients (68%) in EZ- showed a decrease in PSA after the first cycle (p = 0.64). Four patients (22%) in EZ+ and seven patients (37%) in EZ- had more than 50% decrease in PSA after the first cycle (p = 0.33). The average percent decline at the end of the treatment was 23.3% in EZ+ and 50.4% in EZ- (p = 0.4). There was no difference in terms of lesion with highest SUVmax, mean SUV, total tumor volume or activity on pre-therapy PSMA imaging. CONCLUSION: Enzalutamide treatment prior to Lu-PSMA does not improve patient outcomes when applied remotely. Larger studies evaluating the combination therapies and the timing of enzalutamide are needed to assess its correlation with Lu-PSMA outcomes.

Enhanced Recovery Pathway Benefits Patients Undergoing Nonelective Colorectal Surgery.

OBJECTIVE: The aim of our study was to determine if an enhanced recovery pathway (ERP) can successfully be applied in nonelective colorectal surgery. BACKGROUND: ERPs have been shown to reduce hospital length of stay (LOS), complications, and costs after elective colorectal surgery. Yet, little data exist regarding the benefits of ERPs in patients undergoing nonelective colorectal surgery. We hypothesized that ERP implementation in a nonelective colorectal surgery population is associated with decreased postoperative LOS. METHODS: A prospectively-maintained database was used to identify consecutive patients undergoing colorectal surgery after emergency room (ER) or hospital transfer admissions over a period from 2 years before until 1 year after implementation of a comprehensive ERP. The primary endpoint was LOS. Secondary endpoints included total LOS [TLOS = postoperative LOS + LOS of readmission(s)], readmission rates, complication rates, 30-day mortality, and hospital costs. Univariate and multivariate analyses were performed to assess the relationship between ERP implementation and LOS. RESULTS: We identified 269 pre-ERP and 135 ERP patients fulfilling the inclusion criteria. Admit source (ER 43.4% vs transfers 56.7%), Charlson comorbidity index, American Society of Anesthesiologists (ASA) status, diagnosis (inflammatory bowel disease 45.8%, malignancy 19.6%, benign intestinal obstructions 10.4%, diverticulitis 9.4%, others 10.4%), and blood loss were comparable (P > 0.05) between the cohorts. Pre-ERP patients had a higher number of previous abdominal surgeries, whereas post-ERP patients had more laparoscopy and more compliance with ERP elements. ERP patients had a shorter postoperative LOS [6 (4, 10) vs 7 (5, 12) days; P = 0.0007]. Hospital costs were 13.4% lower (P = 0.004). Postoperative 30-day morbidity, mortality, and readmissions were comparable, although reoperation rate was higher in the ERP group. On multivariate analysis, ERP implementation and laparoscopy were the only modifiable variables independently associated with shorter LOS, whereas longer operative times and higher ASA classification were associated with longer LOS. CONCLUSIONS: Patients undergoing nonelective colorectal surgery after ER or hospital transfer admission benefit from the use of an ERP, demonstrating decreased LOS and costs without an increase in complications.

Partial Portal Vein Arterialization to Treat Toxic Acute Liver Failure in Elderly Rats.

INTRODUCTION: Toxic acute liver failure can be fatal even after liver transplantation. Since there are data only in young rats, the aim of our study was to verify the effectiveness of the increase of oxygen to the liver by partial portal vein arterialization (PPVA) in elderly rats with acute liver failure induced by carbon tetrachloride (CCl4) intoxication. METHODS: Twenty elderly (30 months) Sprague-Dawley rats underwent a CCl4 intoxication (5 mL/kg). Animals were divided after 24 hours (n = 10 per group) to either undergo PPVA (G1, treated group) or be untreated (G2, control group). PPVA consisted of a shunt between the left renal artery and splenic vein after nephrectomy and spelnectomy. The G2 group animals underwent nephrectomy and splenectomy only. The 10-day survival was evaluated. Before euthanasia, blood samples from the portal vein were detected for blood gas analysis. Liver injury was evaluated by the serum alanine aminotransferase (ALT) and prothrombin time levels. Histology was done to evaluate the liver necrosis. Hepatocyte regeneration was assessed by the mitotic index at immunohistochemistry. RESULTS: The PPVA has resulted in a significant increase in the oxygen partial pressure and saturation in portal blood. A survival improvement at 10 days was registered in the PPVA-treated rats (90% vs 30%; P = .0065). After 24 hours from intoxication, ALT was high in both groups. A rapid decrease of ALT was observed in G1 as compared to G2. At the same time, livers showed a severe centrolobular necrosis. In the suviving G2 rats, a moderate necrosis was present, while only a mild necrosis was observed in the G1 rats. An higher mitotic index was detected in rats treated with PPVA. CONCLUSIONS: In our experimental study, the presence of oxygenated blood in the portal venous system following the PPVA procedure had positive effects on liver regeneration and rats' survival. The PPVA treatment had beneficial effects in elderly rats.

Do Patients With Inflammatory Bowel Disease Benefit from an Enhanced Recovery Pathway?

BACKGROUND: Enhanced recovery pathways (ERPs) have been shown to reduce length of stay (LOS), complications, and costs after colorectal surgery; yet, little data exists regarding patients with inflammatory bowel disease (IBD). We hypothesized that implementation of ERP for IBD patients is associated with shorter LOS and improved economic outcomes. METHODS: An IRB-approved prospective clinical database was used to identify consecutive patients from 2015 to 2017. Patients were grouped as "pre-ERP" and "post-ERP" based on the date of implementation of a comprehensive ERP. Ileostomy closures, redo pouch operations, and outpatient operations were excluded. The relationship between ERP, LOS, and secondary outcomes was assessed using univariate and multivariate analysis. RESULTS: Overall, a total of 671 patients were included: 345 (51.4%) with Crohn's disease (CD) and 326 (48.6%) with ulcerative colitis (UC). Of these, 425 were pre-ERP (63.4%), and 246 were post-ERP (36.6%). The groups did not differ in terms of age, gender, American Society of Anesthesiologist (ASA) scores, comorbidities, estimated blood loss, or ostomy construction. The post-ERP group had a significantly higher mean body mass index (BMI), more patients with CD, longer operative time, and more minimally invasive surgery (MIS; all P < 0.05). The post-ERP group had a significantly shorter LOS (6 vs 4.5 days, median), whereas mean hospital costs decreased by 15.7%. There was no difference in readmissions or complications. On multivariate analysis, MIS and ERP use were both associated with a shorter LOS. CONCLUSION: Inflammatory bowel disease patients benefit from the use of ERP, demonstrating decreased LOS and costs without an increase in complications and readmissions. Enhanced recovery pathways should be routinely implemented in this often challenging patient population.

Post-operative outcomes and predictors of mortality after colorectal cancer surgery in the very elderly patients.

BACKGROUND: The frailty of the very elderly patients who undergo surgery for colorectal cancer negatively influences postoperative mortality. This study aimed to identify risk factors for postoperative mortality in octogenarian and nonagenarian patients who underwent surgical treatment for colorectal cancer. METHODS: This is a single institution retrospective study. The primary outcomes were risk factors for postoperative mortality. The variables of the octogenarians and nonagenarians were compared by using t-test, chi-square test, and Fisher exact test. A multivariate logistic regression analysis was carried out on the combined cohorts. RESULTS: we identified 319 octogenarians and 43 nonagenarians (N = 362) who underwent surgery for colorectal cancer at the Sant'Orsola-Malpighi university hospital in Bologna between 2011 and 2015. The 30-day post-operative mortality was 6% (N = 18) among octogenarians and 21% (N = 9) for the nonagenarians.The groups significantly differed in the type of surgery (elective vs. urgent surgery, p < 0.0001), ASA score (p = 0.0003) and rates of 30-day postoperative mortality (6% vs. 21%, p = 0.0003).In the multivariate analysis ASA > III (OR 2.37, 95% CI [1.43-3.93], p < 0,001), and urgent surgery (OR 2.17, 95% CI [1.17-4.04], p = 0.014) were associated to post-operative mortality. On the contrary, pre-operative albumin≥3.4 g/dL (OR 0.14, 95% CI [0.05-0.52], p = 0.001) was associated with a protective effect on postoperative mortality. CONCLUSIONS: In the very elderly affected by colorectal cancer, preoperative nutritional status and pre-existing comorbidities, rather than age itself, should be considered as selection criteria for surgery. Preoperative improvement of nutritional status and ASA risk assessment may be beneficial for stratification of patients and ultimately for optimizing outcomes.

Surgical outcomes of patients treated with ustekinumab vs. vedolizumab in inflammatory bowel disease: a matched case analysis.

AIM: The association between preoperative use of monoclonal antibodies in inflammatory bowel disease (IBD) patients and postoperative complications is controversial, especially for the latest approved biologics, ustekinumab and vedolizumab, where data is limited. We hypothesized that ustekinumab-treated patients would have a similar overall postoperative complication rate as vedolizumab-treated patients. The aim of this study was to compare postoperative complications in patients receiving preoperative ustekinumab vs. vedolizumab. METHODS: We queried our IRB-approved prospective database to identify Crohn's patients who underwent colorectal surgery and pretreatment with ustekinumab or vedolizumab within 12 weeks of surgery. Ustekinumab-treated patients were matched to vedolizumab-treated patients based on sex, age ± 5 years, date of operation ± 3 years, and type of surgery. Paired univariate analysis and conditional logistic regression of the matched pairs were performed. Our primary outcome was the short-term postoperative complication rate. Secondary outcomes included infectious complications, readmission, reoperation, and length of stay. RESULTS: A total of 103 patients with Crohn's disease (CD) met the inclusion criteria (mean age 38.7 ± 13.4 years; male 51.2%). Overall, 30 patients received preoperative ustekinumab and 73 vedolizumab. In the univariate analysis, vedolizumab-treated patients had a higher postoperative complication rate (p = 0.009) and ileus rate (p = 0.015). After matching, 26 matched pairs were compared and logistic regression models demonstrated no significant difference in the primary outcome. CONCLUSIONS: For our limited experience, the choice of preoperative biologic treatment between ustekinumab and vedolizumab should not be influenced by fear of surgical complications.

Single incision for oncologic breast conserving surgery and sentinel node biopsy in early stage breast cancer: A minimally invasive approach.

INTRODUCTION: Breast conserving surgery (BCS) has a postoperative morbidity up to 30%. We report the feasibility of a single-incision approach for tumor excision and axillary sentinel node biopsy (SNB) sampling intended to minimize patient morbidity and complications. MATERIALS AND METHODS: A tertiary surgical oncology single surgeon database was retrospectively reviewed for all patients undergoing BCS and SNB between January 2013 and December 2015. The single-incision approach used a single breast incision to resect the tumor and the Lymphazurin-tagged SNB. The multi-incision group used a breast incision and a separate axillary incision. RESULTS: The single-incision approach was associated with shorter operative time (56 vs 64 minutes, P = 0.026). Sentinel node retrieval was achieved in 100% in both groups. The single-incision technique was used primarily in the upper outer quadrant (N = 41, 85.4%), but was also selectively applied in other quadrants (N = 5). There was no significant difference in complication rates between the two procedures (P = 0.425), and there were no instances of conversion from single-incision to standard BCS-SNB. CONCLUSIONS: Minimally invasive breast conserving surgery is feasible for patients with early breast cancer located in the upper outer quadrants. This technique may reduce postoperative morbidity and improved cosmetic result.

"To stent or not to stent?": immediate emergency surgery with laparoscopic radical colectomy with CME and primary anastomosis is feasible for obstructing left colon carcinoma.

Great debate exists in the initial acute management of large bowel obstruction from obstructing left colon carcinoma. While endoscopic stenting is well established as the first approach in the setting of palliative care of patients with advanced metastatic disease as well as a bridge to elective surgery in elderly patients who have an increased risk of postoperative mortality (age >70 years and/or ASA status ≥3), controversies exist regarding oncological safety and long-term outcomes of endoscopic colonic stenting in younger patients and ESGE Guidelines do not recommend SEMS placement in patients <70 and fit for curative surgery. Particularly, the Consensus Panelists currently state that SEMS placement as a bridge to surgery is not recommended as the standard treatment because (1) it does not reduce the postoperative mortality in the general population, (2) SEMS may be associated with an increased risk of tumor recurrence, and (3) acute resection is feasible in young and fit patients, with an acceptable postoperative mortality rate. A 32-year-old lady was admitted with complete LBO from obstructing sigmoid carcinoma. Initial i.v. CE-CT scan detected a large bowel partial obstruction with fecal impaction in the entire colon until sigmoid with some mildly dilated SB loops. The presence of a thickened area in the colonic wall could not be assessed because the patient was young and thin and in such patients the CT appearance of bowel wall cannot be clearly appreciated. She was initially managed with laxatives and gastrografin. The patient's obstruction did not improve and abdominal distension worsened with nausea and colicky pain. Urgent endoscopy detected a friable mass, consistent with completely obstructing carcinoma of the mid sigmoid. Biopsies were taken and distal ink marking was made. Whole-body urgent CT scan with i.v. contrast was performed in order to obtain full preoperative staging and to rule out distant metastases. CT scan and the previously given oral gastrografin confirmed complete large bowel obstruction with a tight stricture in the sigmoid. Cecum was markedly distended.

How Safe is Performing Cholecystectomy in the Oldest Old? A 15-year Retrospective Study from a Single Institution.

BACKGROUND: Globally, the number of people aged 80 years or over, the "oldest old," is the fastest growing population group. Because of the strong association between age and gallstone disease, both prevalence and incidence of this disease are increasing. The feasibility of the cholecystectomy in octogenarians has been evaluated in several studies that confirmed the safety of the operation. However, the safety of this procedure in nonagenarians is still controversial. The aim of this study was to evaluate the safety of cholecystectomies in nonagenarians and identify related predictors for postoperative hospital length of stay (LOS) and in-hospital mortality up to 30 days postoperatively. METHODS: More than 500 cholecystectomies, both open and laparoscopic, were performed between January 2000 and September 2015 at our institution in patients 80 years and older. These statistics include both elective and emergent admissions. A retrospective review of charts over the last 15 years was conducted to compare mortality and length of postoperative stay among two patient groups: 319 octogenarians and 36 nonagenarians. Parameters evaluated include demographics, surgical presentation, American Society of Anesthesiologists (ASA) score, main diagnosis, comorbidities, type of surgery performed, LOS and in-hospital mortality. All data were analyzed with STATA (v.13) software, using a multivariate logistic regression after determining the statistically significant variables through a stepwise regression. CONCLUSIONS: We found out that being nonagenarian, compared to octogenarian, is not a significant risk factor in terms of LOS and in-hospital mortality within 30 days postoperatively. Despite that, the mortality rate among nonagenarians is still remarkably high as almost every patient was admitted in an emergent setting. The most remarkable predictor for mortality among the two groups was an "afternoon/night emergency" surgical presentation (OR 25.5, CI 1.53-42.35, p = 0.02). Thus, the surgical emergency management for gallbladder disease at our institution should be critically reevaluated. Performing the procedure in laparoscopy predicted a significant reduction (-5 days, CI -8.5 to -1.4, p = 0.006) of LOS, while presenting with "gallbladder and bile duct stones" (+6.3 days, CI 1.5-11.1, p = 0.01) or "acalculous cholecystitis" (+4.7 days, CI 0.4-9.2, p = 0.03) had the opposite effect. Despite the remarkable mortality rate of our series, being nonagenarian should not be considered as a reason to avoid gallbladder surgery in case of need. Our study suggests that nonagenarians are more suitable surgical candidates than may have previously expected.

2017 update of the WSES guidelines for emergency repair of complicated abdominal wall hernias.

Emergency repair of complicated abdominal wall hernias may be associated with worsen outcome and a significant rate of postoperative complications. There is no consensus on management of complicated abdominal hernias. The main matter of debate is about the use of mesh in case of intestinal resection and the type of mesh to be used. Wound infection is the most common complication encountered and represents an immense burden especially in the presence of a mesh. The recurrence rate is an important topic that influences the final outcome. A World Society of Emergency Surgery (WSES) Consensus Conference was held in Bergamo in July 2013 with the aim to define recommendations for emergency repair of abdominal wall hernias in adults. This document represents the executive summary of the consensus conference approved by a WSES expert panel. In 2016, the guidelines have been revised and updated according to the most recent available literature.

Liver resection for metastases from colorectal cancer in very elderly patients: New surgical horizons.

INTRODUCTION AND AIM: Patients with colorectal cancer (CRC) may develop liver metastases. Surgical resection remains the best treatment of choice for colorectal liver metastases (CRLM) according to resectability criteria, with a long-term survival of 25% up to 41% after 5 years. Advanced age is associated with a higher incidence and co-morbidity, particularly cardiovascular disease, as well as deteriorating physiological reserves. The aim of this study was to analyse the overall and disease-free survival for patients with CRLM according to their chronological age. METHODS: Patients with CRLM were enrolled in the study. Data on gender, age, co-morbidity, metastasis characteristics (number, size and total metastatic volume (TMV)), use of perioperative chemotherapy and operative and post-operative complications were collected. Then, according to recent World Health Organization (WHO) guidelines, the patients were grouped by age. Statistical analysis was performed using the software R (ver. 2.14.1). RESULTS: Hepatic resection was performed in 149 patients (21 patients in the very elderly group, 79 in the elderly group and 49 in the younger group). The three groups were comparable in terms of operative duration, transfusion rate, length of high-dependency unit (HDU) stay and post-operative hospital stay. The very elderly group showed a non-significant increase in post-operative morbidity. The 30-day and 60-day/inpatient mortality rates increased with age without any significant statistically difference between the three groups (very elderly group 4.8% and 4.8%; elderly group: 2.5% and 3.8%; and younger group 0% and 2%). At 5 years, the overall survival was 28.6% for very elderly patients (≥75 years), 33.3% for elderly patients (≥65 to <75 years) and 43.5% for younger patients (≤65 years). The 1-, 3- and 5-year disease-free survival was similar across the groups. CONCLUSIONS: Liver resection for CRLM in carefully selected patients above the age of 75 can be performed with acceptable morbidity and mortality rates, similar to those in younger patients. Moreover, the severity of CRLM in elderly patients is proven to be lesser than in younger patients. Thus, we can conclude that advanced chronological age cannot be considered a contraindication to hepatic resection for CRLM.

Resection of hepatocellular carcinoma in elderly patients and the role of energy balance.

INTRODUCTION: Progressive functional impairment with age has a significant impact on perioperative risk management. Chronic liver diseases induce a strong oxidative stress; in the elderly, in particular, impaired elimination of free radicals leads to insufficient DNA repair. The events associated with a weak response to growth factors after hepatectomy leads to a decline in liver regeneration. Hypercholesterolemia is highly prevalent in the elderly, which may alter the coenzyme Q10 (CoQ) levels and in turn the cellular energy balance. This condition is commonly treated with statins. The aim of this study is to investigate the role of preoperative cellular energy balance in predicting hepatocellular carcinoma (HCC) postresection outcomes. MATERIALS AND METHODS: In a 5-year period (2009-2013), elderly patients with hypercholesterolemia, cardiovascular disease, and diabetes mellitus, undergoing HCC resection, were recruited and grouped by age (<75 and ≥ 75 years old). All patients were previously treated with statins. The risk factors associated with hospital morbidity/mortality and prolonged length of stay (LOS) were evaluated. RESULTS: Forty-five elderly patients were recruited and grouped according to their treatment: Group 1 (n = 23) was treated with statins alone (control group), whereas Group 2 (n = 22) was treated with statins and a CoQ analogue, 3 weeks from the surgery and at least a month later (experimental group). The majority of our patients were treated with atorvastatin [n = 28 (53.84%)] and the minority with simvastatin [n = 17 (32.69%)], 20 mg/day, for at least 3 years before the surgery. Perioperative mortality was observed in one patient of Group 1 (4.3%). Morbidities were noted in 13 patients of Group 1 (56.5%) and four patients of Group 2 (18.2%). The control group showed delayed functional recovery, muscle weakness, increased infection rate, and pleural effusion due to prolonged bed rest (hospital stay 13 days (7-19) vs. 8.5 days (5-12)), compared with the experimental group. The overall survival at 5 years was similar for both groups (n = 10 patients (43%) in Group 1 vs. n = 10 patients (45%) in Group 2). CONCLUSION: In the elderly population, survival is closely linked to postoperative morbidity and mortality. In our study, prolonged LOS was found to be related to delayed bioenergetic recovery. When limited, risk factors such as infections, neutropenia, and red blood cell transfusions could lower LOS and mortality of elderly patients with HCC. Higher age was associated with greater postoperative morbidity and successful hospital stay.

Optimizing Patient Surgical Management Using WhatsApp Application in the Italian Healthcare System.

INTRODUCTION: Smartphones changed the method by which doctors communicate with each other, offer modern functionalities sensitive to the context of use, and can represent a valuable ally in the healthcare system. Studies have shown that WhatsApp™ application can facilitate communication within the healthcare team and provide the attending physician a constant oversight of activities performed by junior team members. The aim of the study was to use WhatsApp between two distant surgical teams involved in a program of elective surgery to verify if it facilitates communication, enhances learning, and improves patient care preserving their privacy. METHODS: We conducted a focused group of surgeons over a 28-month period (from March 2013 to July 2015), and from September 2014 to July 2015, a group of selected specialists communicated healthcare matters through the newly founded "WhatsApp Surgery Group." Each patient enrolled in the study signed a consent form to let the team communicate his/her clinical data using WhatsApp. Communication between team members, response times, and types of messages were evaluated. RESULTS: Forty six (n = 46) patients were enrolled in the study. A total of 1,053 images were used with an average of 78 images for each patient (range 41-143). 125 h of communication were recorded, generating 354 communication events. The expert surgeon had received the highest number of questions (P, 0.001), while the residents asked clinical questions (P, 0.001) and were the fastest responders to communications (P, 0.001). CONCLUSION: Our study investigated how two distant clinical teams may exploit such a communication system and quantifies both the direction and type of communication between surgeons. WhatsApp is a low cost, secure, and fast technology and it offers the opportunity to facilitate clinical and nonclinical communications, enhance learning, and improve patient care preserving their privacy.

Therapeutic ultrasound in physical medicine and rehabilitation: characterization and assessment of its physical effects on joint-mimicking phantoms.

The aim of the study described here was to quantitatively assess thermal and mechanical effects of therapeutic ultrasound (US) by sonicating a joint-mimicking phantom, made of muscle-equivalent material, using clinical US equipment. The phantom contains two bone disks simulating a deep joint (treated at 1 MHz) and a superficial joint (3 MHz). Thermal probes were inserted in fixed positions. To test the mechanical (cavitational) effects, we used a latex balloon filled with oxygen-loaded nanobubbles; the dimensions of the oxygen-loaded nanobubbles were determined before and after sonication. Significant increases in temperature (up to 17°C) with fixed field using continuous waves were detected both in front of and behind the bones, depending on the US mode (continuous wave vs. pulsed wave) and on the treatment modality (fixed vs. massage). We found no significant differences in mechanical effects. Although limited by the in vitro design (no blood perfusion, no metabolic compensation), the results can be used to guide operators in their choice of the best US treatment modality for a specific joint.

The chromogranin A- derived N-terminal peptide vasostatin-I: In vivo effects on cardiovascular variables in the rabbit.

This study is the first to report on vascular effect of the chromogranin A derived Vasostatin-I (CgA(1-76)) in vivo. Cardiovascular parameters were recorded in 29 rabbits with sympathetically decentralized right carotid vascular bed. The recombinant human STA CgA(1-78) (VS-1) was infused at 480 µg/kg over 25 min. Group I was kept awake while groups II-V were anesthetized with Ketamine-xylazine. VS-1 was given alone in groups I-II while in presence of either phentolamine, phentolamine plus propranolol or hexamethonium in groups III-V. Serum VS-1 peaked at 2 µg/ml (200 nM) before onset of vascular effects and declined rapidly to ~200 ng/ml within 30 min. In all groups but III and IV VS-1 induced a brief vasoconstriction, being larger in intact than in sympathetically decentralized beds. The VS-1 induced vasoconstriction was not altered by hexamethonium but was abolished by phentolamine. In presence of the α-adrenergic blocker a long lasting vasodilatation, unaffected by propranolol, was apparent on both innervated and decentralized sides. In conclusion, VS-1 induced an α-adrenoceptor-mediated vasoconstriction presumably brought about by noradrenaline release from sympathetic nerves when infused at a dose giving an initial serum concentration of ~200 nM. This initial vasoconstriction masked a persistent adrenoceptor-independent vasodilatation, consistent with previous reports from in vitro models.