Evaluation of the novel myocardial perfusion positron-emission tomography tracer 18F-BMS-747158-02: comparison to 13N-ammonia and validation with microspheres in a pig model.

BACKGROUND: Positron-emission tomography (PET) tracers for myocardial perfusion are commonly labeled with short-lived isotopes that limit their widespread clinical use. 18F-BMS-747158-02 (18F-BMS) is a novel pyridaben derivative that was evaluated for assessment of myocardial perfusion by comparison with 13N-ammonia (13NH3) and with radioactive microspheres in a pig model. METHODS AND RESULTS: Fourteen pigs injected with 500 MBq of 13NH3 or 100 to 200 MBq of 18F-BMS underwent dynamic PET at rest and during pharmacological stress. In 8 of these pigs, 18F-BMS was injected during stress combined with transient, 2.5-minute constriction of the left anterior descending coronary artery. Radioactive microspheres were coinjected with 18F-BMS. Ratios of myocardial tracer uptake to surrounding tissues were determined, and myocardial blood flow was quantified by compartmental modeling. Both tracers showed high and homogeneous myocardial uptake. Compared with 13NH3, 18F-BMS showed higher activity ratios between myocardium and blood (rest 2.5 versus 4.1; stress 2.1 versus 5.8), liver (rest 1.2 versus 1.8; stress 0.7 versus 2.0), and lungs (rest 2.5 versus 4.2; stress 2.9 versus 6.4). Regional myocardial blood flow assessed with 18F-BMS PET showed good correlation (r=0.88, slope=0.84) and agreement (mean difference -0.10 [25th percentile -0.3, 75th percentile 0.1 mL x min(-1) x g(-1)]) with that measured with radioactive microspheres over a flow range from 0.1 to 3.0 mL x min(-1) x g(-1). The extent of defects induced by left anterior descending coronary artery constriction measured by 18F-BMS and microspheres also correlated closely (r=0.63, slope=1.1). CONCLUSIONS: 18F-BMS-747158-02 is a very attractive new PET perfusion tracer that allows quantitative assessment of regional myocardial perfusion over a wide flow range. The long half-life of 18F renders this tracer useful for clinical PET/CT applications in the workup of patients with suspected or proven coronary artery disease.

NOTES for the cardia: antireflux therapy via transluminal access.

BACKGROUND AND STUDY AIMS: The current standard for surgical antireflux therapy is laparoscopic Nissen fundoplication, but natural orifice transluminal endoscopic surgery (NOTES) enables even less invasive access to the peritoneal cavity. We therefore aimed to evaluate a NOTES approach to antireflux therapy. PATIENTS AND METHODS: An animal study including 24 pigs (16 nonsurvival and eight survival). After the peritoneal cavity had been accessed via the rectosigmoid, the gastroesophageal junction (GEJ) was laid open using conventional endoscopic instruments. Thereafter, a transcutaneously introduced hook was used for tunneling and lifting of the distal esophagus. Finally, an antireflux ring was placed around the cardia. Animals were observed over 10 days in the survival series. Correct application of the prosthesis, adverse events as a result of the procedure, and bacterial contamination were evaluated by autopsy. RESULTS: The esophagogastric junction was strengthened by applying the ring prosthesis in 22 of 24 animals. Four bleeding episodes were observed, three of which were handled endoscopically. Correct placement of the prosthesis was accomplished in 21 of 22 animals. In the survival series, 1 pig died after transhiatal herniation of the stomach, and 1 pig suffered from peritonitis due to intraoperative contamination. In 7 of the 8 survival animals, no bacterial growth was noted by smear culture. The intervention had to be performed as a hybrid NOTES procedure in all cases. CONCLUSION: Exposure of the GEJ and placement of an antireflux prosthesis via a hybrid NOTES procedure is feasible, despite some complications. This approach may be considered as a basis for optimization and further development of pure NOTES antireflux procedures.

A model of ischemic isolated acute liver failure in pigs: standardizing monitoring and treatment.

BACKGROUND: Acute liver failure (ALF) models in pigs have been widely used for evaluating newly developed liver support systems. But hardly any guidelines are available for the surgical methods and the clinical management. METHODS: The study validated several standard operating procedures describing in detail the surgical method and intensive care monitoring and treatment (control of potassium, glucose and bicarbonate levels, cardiovascular and intracranial pressure monitoring, etc.). ALF was induced in animals with a mean of 56 kg. Two surgical methods were compared: ligation of hepatic arteries with either end-to-side portacaval shunt (ESPS) and bile duct ligation or side-to-side portacaval shunt (SSPS) without bile duct ligation. RESULTS: During total portal vein clamping, the animals in the ESPS group developed severe hypotension, splanchnic congestion and metabolic acidosis. One animal died after approximately 1.5 h. This model therefore represents a multiorgan failure model rather than an isolated ALF model. In the SSPS group, none of these side effects were observed, while clinical, laboratory and histopathological signs of ALF were evident. CONCLUSIONS: A reproducible model in pigs representing ALF can be established with the help of the standardized monitoring and treatment procedures presented.

[Treatment of a uterine adenocarcinoma in a miniature pig by ovariohysterectomy]. / Behandlung eines Uterusadenokarzinoms eines Minipigs durch Ovariohysterektomie.

An 11-year-old, 75-kg, miniature pig was presented because of haemorrhagic vulvar discharge attributable to chronic endometritis. Ovariohysterectomy was carried out with the patient in dorsal recumbency and anaesthetised using total intavenous anaesthesia and positive-pressure ventilation. A ventral midline approach was chosen to remove the ovaries and uterus, which contained brown fluid and multifocal masses in the uterine wall. Histological examination of the uterine masses revealed leiomyoma, cystic hyperplasia and adenocarcinoma. After surgery, the miniature pig recovered without complications and remained healthy at follow-up 4 months later.

Nitric oxide inhibition and consecutive Aspisol application show a prolonged survival of orthotopic transplanted livers in a rat model.

BACKGROUND: It is generally accepted that nitric oxide (NO) plays a crucial role in acute rejection caused by inflammatory responses. Therefore, the purpose of this study was to investigate the effect on survival following arterialized orthotopic rat liver transplantations (o-RLTx) of NO inhibition and consequent blockade of platelet aggregation by application of Aspisol. MATERIALS AND METHODS: Inbred LEWIS-(RT(1)) rats underwent arterialized o-RLTx under ether anesthesia with DA-(RT1av1) rats as organ donors. After liver transplantation, serum parameters were determined and hepatic biopsy specimens were sampled on postoperative days 5, 8, 10, 30, and 90. Sixty-one rats were divided into 5 groups: syngenic controls (group I, n = 12); allogenic controls (group II, n = 11); allogenic with FK506 immunosuppression (group III, n = 12); allogenic with AGH-treatment (group IV, n = 13); and allogenic with AGH/low- dose Aspisol treatment for 5 days after liver transplantation (group V, n = 13) (Bayer, Leverkusen, Germany). RESULTS: Rats of group V with AGH/low-dose Aspisol treatment showed significantly longer graft survival (18.2 days +/- 1.8 days) compared with group II rats with untreated grafts (11.3 days +/- 1.7 days) the allogenic group IV with AGH treatment (11.2 days +/- 1.8 days; P < .05). Histological examination revealed moderate graft rejection among the AGH-treated group IV; however, marked platelet aggregation in sinusoids was present, which was not observed in the AGH/low-dose Aspisol-treated animals (group V). CONCLUSION: Our data suggested that simultaneous treatment with AGH/low-dose Aspisol leads to a significant increase in survival and inhibition of platelet aggregation in the graft after orthotopic liver transplantation.

Changes in intra-abdominal pressure, hemodynamics, and peak inspiratory pressure during gastroscopy in a porcine model.

BACKGROUND AND STUDY AIMS: The aim of this experimental study was to assess the effect of gastric insufflation on intra-abdominal pressure (IAP) and associated hemodynamic and respiratory changes during upper gastrointestinal endoscopy. METHODS: Measurements were taken from pigs under general anesthesia with controlled ventilation. Gastroscopy was carried out with continuous insufflation of air by a standard endoscopic light source/insufflator. The cardiac index and global end-diastolic volume index (GEDVI; reflecting preload) were measured by transpulmonary thermodilution. IAP, heart rate, mean arterial pressure (MAP), central venous pressure, systemic vascular resistance index (SVRI; reflecting afterload), peak inspiratory pressure (PIP), and oxygenation (SaO (2)) were also recorded. RESULTS: A total of 266 paired measurements (at the time of transpulmonary thermodilution) were taken from 14 animals. During air insufflation, we observed a significant rise in IAP in all animals up to intermittent values of 22 mm Hg. IAP and PIP correlated well (r = 0.666, P < 0.001), with the latter reaching values as high as 45 mbar in one pig, leading to respiratory compromise. Only marginal changes in heart rate, and a continuous, almost significant rise in MAP (due to a significant increase in SVRI) were recorded. We observed a slight increase in GEDVI, predominantly during the initial phase of air insufflation. The cardiac index showed no substantial changes. There were no episodes of hemodynamic instability, nor a decline in SaO (2). CONCLUSIONS: Air insufflation during gastroscopy resulted in a significant increase in IAP. The main clinically relevant finding was a steady increase in SVRI. Major increments in PIP suggest a role of intra-abdominal hypertension in otherwise unexplained respiratory compromise during upper gastrointestinal endoscopy.

Effect of pneumoperitoneum on hemodynamics and inspiratory pressures during natural orifice transluminal endoscopic surgery (NOTES): an experimental, controlled study in an acute porcine model.

BACKGROUND AND STUDY AIM: Physiologic reactions during natural orifice transluminal endoscopic surgery (NOTES) may differ from those at laparoscopy. This experimental study assessed the effect of pneumoperitoneum induced by endoscope air pump on hemodynamics and inspiratory pressures during transgastric peritoneoscopy. METHODS: Transgastric peritoneoscopy was performed in 11 female pigs (35 - 50 kg) under general anesthesia. Five pigs with controlled insufflation and no endoscopic intervention served as controls. Cardiac index and global end-diastolic volume index (GEDVI; reflecting preload) were measured every 3 minutes by transpulmonary thermodilution. We also recorded: intra-abdominal pressure (IAP), heart rate, mean arterial pressure (MAP), systemic vascular resistance index (SVRI; reflecting afterload), peak inspiratory pressure (PIP), and oxygenation. RESULTS: One study group pig was excluded from analysis because of a major complication related to the gastric incision. In the remaining 15 animals we performed 264 paired measurements. On-demand insufflation in the study group produced wide variation in intra-abdominal pressures; the control group demonstrated minimal fluctuation around a predetermined value. In the study group, IAP and PIP correlated well ( R = 0.667, P = 0.000), with maximum PIP values of 40 mbar contrasting with the control group maximum of 26.5 mbar. Hemodynamically, there was a minor decrease of cardiac index in the study group (in contrast to the control group). Relative changes in cardiac index and IAP during transgastric peritoneoscopy correlated highly significantly ( R = - 0.416, P = 0.000). Neither group showed hemodynamic instability or decline in oxygen saturation. CONCLUSIONS: On-demand insufflation with a standard endoscopic light source/insufflator resulted in a marked median increase and wide variation in IAP throughout transgastric peritoneoscopy. Hemodynamic changes were moderate. However, major increases in PIP suggest a need for stricter control of intra-abdominal hypertension during NOTES.