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An efficient capacity management of the Operation Room (OR) is crucial for the optimization of resources and consequent cost minimization. However, the duration of each surgery is hard to predict and often prone to variability and unforeseen events that may delay or accelerate each procedure. Automatic surgical phase identification strategies can lead to a more accurate and automated estimation of the surgery duration, improving OR schedule optimization. One possible contribution for these methods is the introduction of speech recognition systems. The described work aims at the implementation of a speech recognition (SR) engine for surgical phase identification, specifically optimized for Laparoscopic Radical Prostatectomy (LRP). For this application the performance of 3 engines was tested under different background noise and distance circumstances: Microsoft Speech SDK; Google Speech Recognition API; and an optimization of the first, with the introduction of specific vocabulary. Action/target binomials were used to identify the Laparoscopic Prostatectomy surgical phases. 15 participants were selected to perform the tests and Word Error Rate (WER) was calculated as the main comparison metric. The values for the total WER indicate that AzureGrammar (specific vocabulary inserted) has superior performance, reaching a lower error rate of 29.25%, when compared to Azure and Google with 67.91% and 67.48%, respectively. Phase Accuracy Ratio (PAR), considering only the AzureGrammar SR engine, are 84% and 83%, for 1 m and 2 m, without background noise; 61% and 51%, for 1 m and 2 m, with background noise. This study demonstrates that using a conventional SR engine, with specific vocabulary incorporated, has the potential to achieve an acceptable performance with minimal setup. Clinical Relevance- Speech based, surgical phase identification, can be achieved with minimal setup to existing SR engines, showing potential to be implemented in Operating Room, with further optimization.

No documento o autor Jorge Correia Pinto aparece, por lapso, como Jeorge Correia Pinto, The aim of this study was to analyse natural orifice transluminal endoscopic surgery (NOTES)-related publications over the last 5 years. A systematic literature search was done to retrieve publications related to NOTES from 2006 to 2011. The following variables were recorded: year of publication; article type; study design; setting; Journal Citation Reports® journal category; authors area of surgical speciality; geographic area of origin; surgical procedure; NOTES technique; NOTES access route; number of clinical cases. A time-trend analysis was performed by comparing early (2006-2008) and late (2009-2011) study periods. Overall, 644 publications were included in the analysis and most papers were found in general surgery journals (50.9%). Studies were most frequently clinical series (43.9%) and animal experimental (48%), with the articles focusing primarily on cholecystectomy, access creation and closure, and peritoneoscopy. Pure NOTES techniques were performed in most of the published reports (85%) with the remaining cases being hybrid NOTES (7.4%) and NOTES-assisted procedures (6.1%). The access routes included transgastric (52.5%), transcolonic (12.3%), transvesical (12.5%), transvaginal (10.5%), and combined (12.3%). From the early to the late period, there was a significant increase in the number of randomised controlled trials (5.6% vs 7.2%) or non-randomised but comparative studies (5.6% vs 22.9%) (P < 0.001) and there was also a significant increase in the number of colorectal procedures and nephrectomies (P = 0.002). Pure NOTES remained the most studied approach over the years but with increased investigation in the field of NOTES-assisted techniques (P = 0.001). There was also a significant increase in the adoption of transvesical access (7% vs 15.6%) (P = 0.007). NOTES is in a developmental stage and much work is still needed to refine techniques, verify safety and document efficacy. Since the first description of the concept of NOTES, >2000 clinical cases, irrespective of specialty, have been reported. NOTES remains a field of intense clinical and experimental research in various surgical specialities.

OBJECTIVE: To assess the feasibility of a pure endoscopic closure method for vesical perforations using fully absorbable material. MATERIALS AND METHODS: A pilot experimental study was performed in eight anaesthetized female pigs. Four 10-mm and four 20-mm endoscopic full thickness cystotomies were created. An endoscopic suturing machine (RD-180(®) ; LSI Solutions, Victor, NY, USA) was deployed through the working channel of a cystoscope and used to close the incisions with absorbable sutures. Immediate assessment of the quality of the closure was obtained by distending the bladder with saline solution stained with methylene blue under laparoscopic control. After 3 weeks of follow-up, a necropsy examination was performed to check for signs of peritonitis and wound dehiscence and to assess the quality of healing. RESULTS: The experiment was completed in all eight pigs without complications. The median procedure time was 10 ± 4.3 min. The immediate bladder distention test did not show any methylene blue leakage. The postoperative period was uneventful. The post mortem examination after 3 weeks revealed complete healing of the bladder wall incisions with no signs of infection, wound dehiscence or adhesions in the peritoneal cavity of any of the pigs. CONCLUSION: This study describes a successful novel method for endoscopic closure of bladder perforations. The technique was easy, reproducible and safe. Nevertheless, further experimental investigation should be carried out before clinical application of this method.

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Duodenal atresia is the most common cause of congenital bowel obstruction. Often it is associated with other congenital anomalies, such as annular pancreas. The laparoscopic approach, although technically demanding, brings about clear benefits to the newborn. The authors report the case of a newborn with prenatal diagnosis of duodenal atresia, proposed for a laparoscopy, during which an annular pancreas was identified and a laparoscopic diamond-shaped duodenal anastomosis was performed.

Retinoic acid (RA) and ghrelin levels are altered in human hypoplastic lungs when compared to healthy lungs. Although considerable data have been obtained about RA, ghrelin and bombesin in the congenital diaphragmatic hernia (CDH) rat model, neuroendocrine factors have never been associated with the RA signalling pathway in this animal model. In this study, the interaction between neuroendocrine factors and RA was explored in the CDH rat model. The authors found that normal fetal lung explants treated with RA, bombesin and ghrelin showed an increase in lung growth. Hypoplastic lungs presented higher expression levels of the RA receptors α and γ. Moreover bombesin and ghrelin supplementation, in vitro, to normal lungs increased RA receptor α/γ expression whereas administration of bombesin and ghrelin antagonists to normal and hypoplastic lungs decreased it. These data reveal for the first time that there is a link between neuroendocrine factors and RA, and that neuroendocrine factors sensitise the lung to the RA action through RA receptor modulation.

AIM: The aim of this study was to evaluate how simple it is to build a homemade low-cost simulator using a simple 5-step scheme. METHODS: A scheme explaining how to build an endoscopic surgery simulator in 5 easy steps was presented to 26 surgeons. The simulator required a pair of scissors and easy-to-find materials. Its total cost was less than €35. The participants assessed the simulator using common endoscopic training toys or ex vivo tissue and completed an anonymous query comparing it with other commercial simulators that they had experienced before. RESULTS: In all, 84.6% found the simulator really easy to build. Every participant felt that he or she could do the same simulator themselves. Comparing with other commercial available box simulators, the majority of participants found the homemade simulator easier to (a) mount and dismount, (b) transport, (c) clean, and (d) use when practicing alone. CONCLUSIONS: Anyone can build its own simulator for a small amount of money.

BACKGROUND: Left atrial appendage (LAA) exclusion is a well-known procedure for the prevention of stroke in high-risk patients with atrial fibrillation and contraindication to long-term oral anticoagulant therapy. OBJECTIVE: To evaluate a natural orifice transluminal endoscopic surgery (NOTES) approach for LAA ligation. DESIGN: In 4 acute and 6 survival pigs, we performed LAA by using a forward-viewing, single-channel gastroscope and an operative thoracoscope with a 3-mm working channel (introduced through an 8-mm single transthoracic port). SETTING: Animal laboratory. INTERVENTIONS: The gastroscope was introduced in the thoracic cavity through an esophageal submucosal tunnel. An end loop introduced through the gastroscope was used to legate the LAA. In the survival experiments, the esophageal mucosa was closed using hemoclips. MAIN OUTCOME MEASUREMENTS: The time, safety, and feasibility of the procedure were recorded. In the survival experiments, endoscopy and postmortem examination were performed on postoperative day 14. RESULTS: Creation of a submucosal tunnel and esophagotomy were safely performed in all animals without incidents. The mean time for esophagotomy was 17.0 ± 6.3 minutes. Pericardial dissection and LAA ligation were performed in all animals but 1. The mean time for LAA ligation was 34.4 ± 19.1 minutes. No adverse events occurred during the survival period. Endoscopy showed complete esophageal closure. Postmortem examination revealed pleural adhesions on the site of pericardial dissection, and the LAA was fibrotic with the endoloop in place. LIMITATIONS: Animal study. CONCLUSIONS: LAA ligation with single transthoracic trocar assistance is feasible and may be an alternative to anticoagulant therapy or to permanent intracardiac implants in patients with atrial fibrillation.

TRANSESOPHAGEAL RIGHT UPPER PULMONARY LOBECTOMY - IN VIVO PORCINE EXPERIMENTAL STUDY João Moreira-Pinto, MD1,2,3; Aníbal Ferreira, MD1,2,4; Alice Miranda, DVM1,2; Carla Rolanda, MD, PhD1,2,4; Jorge Correia-Pinto, MD, PhD1,2,5 1Surgical Sciences Research Domain, Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal; 2ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães, Portugal; 3Pediatric Surgery division, Centro Hospitalar do Porto, Porto, Portugal; 4Department of Gastroenterology, Hospital de Braga, Braga, Portugal; 5Pediatric Surgery division, Hospital de Braga, Braga, Portugal. Background and Study Aims Video-assisted thoracoscopic surgery (VATS) has been widespread as the better approach to carry out pulmonary lobectomy. Natural Orifice Transluminal Endoscopic Surgery (NOTES) is being assessed as an alternative to the transthoracic endoscopic surgery. We designed this study to test the feasibility of peroral transesophageal right upper pulmonary lobectomy with the assistance of a single transthoracic trocar. Material and Methods In ten anesthetized pigs (35-45 Kg), we performed right upper pulmonary lobectomy using a forward viewing single-channel gastroscope (introduced perorally) and an operative thoracoscope with a 5 mm working channel (introduced through a single-transthoracic 10 mm port) (Karl Storz). After introducing the gastroscope throughout an oroesophageal overtube into the esophagus, a 1 cm transverse esophagotomy was carried out in the upper third using an ESD-knife under thoracoscope control. Anatomic dissection of the right upper hilum was performed using flexible (gastroscope) and rigid (thoracoscope) instruments. After individual dissection, right upper pulmonary arteries, veins and correspondent bronchus were independently stapled using a 45-mm long, linear endostapler (EndoPath®, Ethicon Endo-Surgery) introduced through the oroesophageal overtube. After completing the lobe resection using an endoscopic snare with cautery, the specimen was extracted retrogradely through the mouth. The esophagotomy was stitched and tied using Endo Stitch™ (Covidien) and a long knot-pusher, which were handled through the oroesophageal overtube. Results Esophagotomy was performed safely in all animals. Dissection of the right upper lobe hilum elements (arteries, veins and bronchus) was also carried out in all animals without significant problems. Oroesophageal handling of the endostapplers for independent ligation of the hilum elements under transthoracic imaging was surprisingly feasible, reasonably easy to perform and reliable in 7 cases. In two cases ligation of the vessels was en bloc. In one case, severe hemorrhage occurred from incomplete vein ligation, although we could control it using electrocoagulation. Esophagotomy closure was feasible but its reliability was not tested in survival studies. All but one animal were kept alive until the end of the acute experiment when they were sacrificed. Conclusions Transesophageal right upper pulmonary lobectomy using single transthoracic trocar assistance is feasible and it may represent a step towards scarless pulmonary lobectomy. Additional survival studies are necessary to test the reliability of this procedure. Apresentador: João Moreira-Pinto, Médico Interno de Cirurgia Pediátrica, CHP.

PURPOSE: To test different sets of prebent instruments and a new reusable access device for laparoendoscopic single-site (LESS) surgery. MATERIALS AND METHODS: Three surgeons with previous experience in LESS performed 12 nephrectomies in six pigs. In all procedures, a multichannel access device (X-CONE) and a 5-mm extra-long telescope were used. Four sets of prebent instruments with different profiles (S-portal) were tested: Standard (one straight scissors and one curved grasper), Cuschieri, Carus, and Leroy set (each of them consisting of two curved instruments with different configurations). Assessment was performed based on both objective (procedure time; time to manage the pedicle; time to free kidney) and subjective parameters (entry/exit of instruments; triangulation; dissection up/down; dissection lateral; retraction; interdependence). The subjective assessment tool used was a Likert type scale (1 = easy to 5 = prohibitive). The access device was assessed by using objective (time to complete insertion of device after skin incision) and subjective (significant air leakage, movement constraint) parameters. RESULTS: Time to insertion of the X-CONE was

BACKGROUND: Gastrotomy closure remains the major limiting factor for human translation of transgastric surgery; the over-the-scope clip (OTSC) system was proposed as a possibility for this purpose. Transgastric access is good for a pelvic approach, making varicocelectomy a possible indication for natural orifice transluminal endoscopic surgery (NOTES). OBJECTIVE: To evaluate the reliability of the OTSC system in vivo after transgastric testicular vessel ligation (varicocelectomy model). DESIGN: There were 3 experimental groups (5 animals in each): groups 1 and 3, gastrotomy dilation up to 18 mm, surgery was performed with a double-channel endoscope; group 2, gastrotomy dilation up to 13 mm, surgery was performed with a single-channel endoscope. SETTING: Surgical Sciences Research Domain, Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal. INTERVENTIONS: Bilateral testicular vessel ligation by transgastric access. Gastrotomy closed with the largest version of OTSC system (12 mm): a single clip in groups 1 and 2, and 2 clips in group 3. Animals were monitored for 2 weeks, killed, and submitted for necropsy. MAIN OUTCOME MEASUREMENTS: Adequacy of closure and healing after the use of the OTSC system. Statistical analysis. RESULTS: Vessel ligation was easily achieved in all groups. Although differences in the complication rate did not reach statistical significance (P = .099), there was a clear tendency for a better prognosis in groups 2 and 3 than group 1. In fact, only 2 animals from group 1 had complications related to incomplete gastrotomy closure. LIMITATIONS: Small number of animals per group; nonrandomized study. CONCLUSIONS: The OTSC system was shown to be easy and efficient for gastrotomy closure in a survival experimental model of varicocelectomy, when correctly matching the gastrotomy size with the clip size and/or number.

JOAQUIM L. REIS, M.D., PH.D.,1,2 JORGE CORREIA-PINTO, M.D., PH.D.,3,4 MARIANA P. MONTEIRO, M.D., PH.D.,1 MADALENA COSTA, B.SC.,1 AND GROVER M. HUTCHINS, M.D.5 1Department of Anatomy, Abel Salazar Institute for the Biomedical Sciences and Unit for Multidisciplinary Biomedical Research, University of Porto; 2Department of Neurosurgery, Santo António General Hospital; 4Department of Pediatric Surgery, São João Hospital, Porto; 3Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal; and 5Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland Object. Myelomeningocele (MMC) is a primary neurulation defect that is associated with devastating neurological disabilities in affected newborns. To better characterize the in utero neurodegenerative process of MMC, the authors investigated the changes in vascular organization, apoptosis, and the presence of inflammatory cells during gestation by using a mutant mouse model of MMC. Methods. The curly tail/loop tail (ct/lp) mutant mouse model of MMC was chosen to obtain fetuses at different stages of gestation. Mouse fetuses harboring MMC were harvested by caesarean section at embryonic Days 14.5, 16.5, and 18.5 (complete mouse gestation at 19 days, 6 mice/group); littermate fetuses with the same gestational age but without an MMC were used as controls. Samples of the MMC placode or normal spinal cord were stained for immunocytochemical labeling with caveolin antibody (endothelium marker) and activated caspase-3 antibody (apoptosis marker). Samples were morphometrically analyzed with a computer-assisted image analyzer. Results. The MMC mice presented with an increase in vascular density from embryonic Days 16.5–18.5 and an enhanced number of apoptotic cells at embryonic Day 18.5, compared with controls. There were scarce signals of an inflammatory reaction in the MMC placode, as a few infiltrating neutrophils were seen only at embryonic Day 18.5. Conclusions. Fetal placodes in MMC mice showed evidence of increased vascular density since embryonic Day 16.5 and increased apoptosis at embryonic Day 18.5. These new data support the view that in utero changes of the MMC placode, occurring during the last stages of gestation, contribute to the neuropathological manifestations in fullterm newborns with MMC. (DOI: 10.3171/PED/2008/2/8/150)

Chylothorax is a possible complication after thoracotomy. Treatment is initially conservative and includes drainage and correction of nutritional losses. Surgical treatment is reserved for cases not responsive to medical measures. The authors report on the clinical case of a premature neonate with a traumatic chylothorax secondary to esophageal atresia surgical correction. The use of octreotide allowed the resolution of the effusion without adverse effects and avoided the surgical treatment.

INTRODUCTION: TNF-alpha blockade in ischemic heart failure is still the subject of debate since clinical trials show conflicting results. However, its benefit in heart failure secondary to pulmonary hypertension has yet to be determined. It has been reported that transgenic rats overexpressing TNF-alpha develop pulmonary hypertension. The aim of this study was to assess the morphologic and hemodynamic effects of administration of an anti-TNF-alpha monoclonal antibody (etanercept) in rats with monocrotaline (MCT)-induced pulmonary hypertension. METHODS: Adult Wistar rats were injected with MCT (60 mg/Kg sc), or vehicle only (day 0). Beginning one day later, the animals were randomly treated with etanercept (ETC, 0.03 mg/Kg sc, three times a week) or with a similar volume of vehicle. The study thus had four groups: Ctrl (n = 6), Ctrl + ETC (n = 6), MCT (n = 6) and MCT + ETC (n = 6). On days 22-23, the rats were instrumented to record right ventricular systolic and end-diastolic pressures, dP/dtmax and tau. At the end of each experiment the heart and lungs were weighed. RESULTS AND CONCLUSIONS: Chronic administration of etanercept induced only a slight increase in relaxation velocity, with no effect on other hemodynamic parameters, including pulmonary hypertension, and no reduction in right ventricular hypertrophy. These results suggest that etanercept does not lead to a significant improvement in heart failure secondary to pulmonary hypertension.

Urol. 2007 Dec;178(6):2648-54. Epub 2007 Oct 22. Third-generation nephrectomy by natural orifice transluminal endoscopic surgery. Lima E, Rolanda C, Pêgo JM, Henriques-Coelho T, Silva D, Osório L, Moreira I, Carvalho JL, Correia-Pinto J. Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal. Abstract PURPOSE: Recently there has been increasing enthusiasm for performing simple abdominal procedures by transgastric surgery. We previously reported the usefulness of a combined transgastric and transvesical approach to cholecystectomy. In this study we assessed the feasibility of combined transgastric and transvesical approach for performing a more complex surgical procedure, such as nephrectomy, in a porcine model. MATERIALS AND METHODS: In a nonsurvival study combined transgastric and transvesical approaches were established in 6 female pigs. Under ureteroscope guidance we installed a transvesical 5 mm over tube into the peritoneal cavity and a flexible gastroscope was passed orally into the peritoneal cavity by a gastrotomy. We performed right or left nephrectomy with instruments introduced by the 2 devices that worked in the renal hilum, alternating device intervention for dissection and retraction procedures. RESULTS: Four right and 2 left nephrectomies were performed. There were no complications during the creation of transvesical and transgastric access. In all animals we visualized the 2 kidneys. The renal vessels and ureter were reasonably individualized and ligated separately with ultrasonic scissors, which were introduced through the transvesical port. In 2 early cases mild hemorrhage occurred after ultrasonic ligation. To overcome this complication we applied clips successfully before ultrasonic ligation in the remaining animals. Thus, complete renal release and mobilization to the stomach were achieved in all animals. CONCLUSIONS: Nephrectomy by natural orifices using the combined transgastric and transvesical approach is technically feasible, although to our knowledge there is no reliable method for removing the specimen with current instruments. PMID: 17945287 [PubMed - indexed for MEDLINE]

BACKGROUND: An isolated transgastric port has some limitations in performing transluminal endoscopic cholecystectomy. However, transvesical access to the peritoneal cavity has recently been reported to be feasible and safe. OBJECTIVE: To assess the feasibility and the technical benefits of transgastric and transvesical combined approach to overcome the limitations of isolated transgastric ports. DESIGN: We created a transgastric and transvesical combined approach to perform cholecystectomy in 7 consecutive anesthetized female pigs. The transgastric access was achieved after perforation and dilation of the gastric wall with a needle knife and with a balloon, respectively. Under cystoscopic control, an ureteral catheter, a guidewire, and a dilator of the ureteral sheath were used to place a transvesical 5-mm overtube into the peritoneal cavity. By using a gastroscope positioned transgastrically and a ureteroscope positioned transvesically, we carried out cholecystectomy in all animals. RESULTS: Establishment of transvesical and transgastric accesses took place without complications. Under a carbon dioxide pneumoperitoneum controlled by the transvesical port, gallbladder identification, cystic duct, and artery exposure were easily achieved in all cases. Transvesical gallbladder grasping and manipulation proved to be particularly valuable to enhance gastroscope-guided dissection. With the exclusion of 2 cases where mild liver-surface hemorrhage and bile leak secondary to the sliding of cystic clips occurred, all remaining cholecystectomies were carried out without incidents. LIMITATIONS: Once closure of the gastric hole proved to be unreliable when using endoclips, the animals were euthanized; necropsy was performed immediately after the surgical procedure. CONCLUSIONS: A transgastric and transvesical combined approach is feasible, and it was particularly useful to perform a cholecystectomy through exclusive natural orifices.

In utero gene transfer to the developing lung may have clinical or research applications. In this study, we developed a new method for specifically targeting the fetal rat lung with adeno and lentiviral vectors encoding the enhanced green fluorescence protein (EGFP) marker gene at E15.5 using ultrasound biomicroscopy (UBM). Survival rate, morphometric parameters, viral biodistribution, and lung transduction efficiency were analyzed and compared to the intra-amniotic route of administration. Expression of EGFP started as early as 24 and 72 h after the injection of adenoviral and lentiviral vectors, respectively. Both vectors transduced lung parenchyma with gene expression limited to interstitial cells of the injected region, in contrast to intra-amniotic injection, which targeted the pulmonary epithelium. Expression of EGFP was most intense at E18.5 and E21.5 for adenoviral and lentiviral vectors, respectively. In contrast to lentivirus, adenoviral expression significantly declined until final analysis at 1 week of age. This study demonstrates the feasibility of targeting the fetal rat lung interstitium with viral vectors under UBM guidance during the pseudoglandular stage. This model system may facilitate in vivo studies of dynamic lung morphogenesis and could provide insight into the efficacy of prenatal gene transfer strategies for treatment of specific lung disorders.

J Urol. 2006 Aug;176(2):802-5. Transvesical endoscopic peritoneoscopy: a novel 5 mm port for intra-abdominal scarless surgery. Lima E, Rolanda C, Pêgo JM, Henriques-Coelho T, Silva D, Carvalho JL, Correia-Pinto J. Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Portugal. Abstract PURPOSE: Recently various groups reported successful attempts to perform intra-abdominal surgery through a transgastric pathway. We assessed the feasibility and safety of a novel transvesical endoscopic approach to the peritoneal cavity through a 5 mm port in a porcine model. MATERIALS AND METHODS: Transvesical endoscopic peritoneoscopy was performed in 8 anesthetized female pigs, including 3 nonsurvival and 5 survival animals. Under cystoscopic guidance a vesical hole was created on the ventral bladder wall with an open-ended ureteral catheter. An over tube with a luminal diameter of 5.5 mm was placed in the peritoneal cavity, guided by a 0.035-inch guidewire. In all animals we performed peritoneoscopy of the entire abdomen as well as liver biopsy and falciform ligament section. A vesical catheter was placed for 4 days in all survival animals, which were sacrificed by day 15 postoperatively. RESULTS: After a learning curve in the first 3 nonsurvival animals the creation of a vesical hole and placement of the over tube were performed without complication in all survival animals. In these animals we easily introduced an EndoEYEtrade mark into the peritoneal cavity, which provided a view of all intra-abdominal viscera, as well as a 9.8Fr ureteroscope, which allowed simple surgical procedures without complications. In survival experiments all pigs recovered. Necropsy examination revealed complete healing of the vesical hole and no signs of infection or adhesions into the peritoneal cavity. CONCLUSIONS: Transvesical endoscopic peritoneoscopy was technically feasible and it could be safely performed in a porcine model. This study provides encouragement for additional preclinical studies of transvesical surgery with or without combinations with other natural orifices approaches to design new intra-abdominal scarless procedures in what seems to be third generation surgery. PMID: 16813951 [PubMed - indexed for MEDLINE]

In monocrotaline (MCT)-induced pulmonary hypertension (PH), only the right ventricle (RV) endures overload, but both ventricles are exposed to enhanced neuroendocrine stimulation. To assess whether in long-standing PH the left ventricular (LV) myocardium molecular/contractile phenotype can be disturbed, we evaluated myocardial function, histology, and gene expression of autocrine/paracrine systems in rats with severe PH 6 wk after subcutaneous injection of 60 mg/kg MCT. The overloaded RV underwent myocardial hypertrophy (P < 0.001) and fibrosis (P = 0.014) as well as increased expression of angiotensin-converting enzyme (ACE) (8-fold; P < 0.001), endothelin-1 (ET-1) (6-fold; P < 0.001), and type B natriuretic peptide (BNP) (15-fold; P < 0.001). Despite the similar upregulation of ET-1 (8-fold; P < 0.001) and overexpression of ACE (4-fold; P < 0.001) without BNP elevation, the nonoverloaded LV myocardium was neither hypertrophic nor fibrotic. LV indexes of contractility (P < 0.001) and relaxation (P = 0.03) were abnormal, however, and LV muscle strips from MCT-treated compared with sham rats presented negative (P = 0.003) force-frequency relationships (FFR). Despite higher ET-1 production, BQ-123 (ET(A) antagonist) did not alter LV MCT-treated muscle strip contractility distinctly (P = 0.005) from the negative inotropic effect exerted on shams. Chronic daily therapy with 250 mg/kg bosentan (dual endothelin receptor antagonist) after MCT injection not only attenuated RV hypertrophy and local neuroendocrine activation but also completely reverted FFR of LV muscle strips to positive values. In conclusion, the LV myocardium is altered in advanced MCT-induced PH, undergoing neuroendocrine activation and contractile dysfunction in the absence of hypertrophy or fibrosis. Neuroendocrine mediators, particularly ET-1, may participate in this functional deterioration.

Ghrelin is an endogenous peptide that has a dual effect by activating specific receptors and by stimulating release of growth hormone. There is increasing evidence that ghrelin has a potent vasodilator effect. Recently, we demonstrated that exogenous administration of ghrelin modulates its endogenous levels and attenuates the majority of alterations induced by monocrotaline (MCT). In the present study, we evaluate the effects of chronic administration of ghrelin on hemodynamic and morphometric parameters of the right ventricle, as well as on myocardial levels of SERCA2a and endothelin-1. Adult Wistar rats were injected with MCT (60 mg/kg, sc) or just the vehicle (day 0). One week later, the animals treated with MCT were randomly divided into two groups and treated with ghrelin (100 microg/kg, bid, sc) or with a similar volume of vehicle. Between days 21-25 the animals were instrumented to record right ventricular (RV) pressures and samples were collected for morphological and molecular analysis. Ghrelin treatment attenuated the effects of MCT, namely: RV myocyte fiber diameter, pulmonary vascular remodeling (evaluated by % medial wall thickness of peripheral arteries), RV peak systolic pressure, RV end-diastolic pressure, time constant tau, and SERCA2a and endothelin-1 mRNA levels. Chronic ghrelin administration attenuates MCT-induced pulmonary hypertension, vascular remodeling and RV hypertrophy. These results suggest a potential therapeutic role for the ghrelin-growth hormone axis in pulmonary hypertension.

Pattern of right ventricular pressure (RVP) fall and its afterload dependence were examined by analyzing ventricular pressure curves and corresponding pressure dP/dt phase planes obtained in both ventricles in the rat heart in situ. Time and value of dP/dt(min), and the time constant tau were measured at baseline and during variable RV afterload elevations, induced by beat-to-beat pulmonary trunk constrictions. RVP and left ventricular pressure (LVP) decays were divided into initial accelerative and subsequent decelerative phases separated by corresponding dP/dt(min). At baseline, LVP fall was decelerative during 4/5 of its course, whereas only 1/3 of RVP decay occurred in a decelerative fashion. During RV afterload elevations, the absolute value of RV-dP/dt(min) and RV-tau increased, whilst time to RV dP/dt(min) decreased. Concomitantly, the proportion of RVP decay following a decelerative course increased, so that in highly RV afterloaded heartbeats RVP fall became more similar to LVP fall. In conclusion, RVP and LVP decline have distinct patterns, their major portion being decelerative in the LV and accelerative in the RV. In the RV, dP/dt(min), tau and the proportional contribution of accelerative and decelerative phases for ventricular pressure fall are afterload-dependent. Consequently, tau evaluates a relatively much shorter segment of RVP than LVP fall.