Effect of naloxone-3-glucuronide and N-methylnaloxone on the motility of the isolated rat colon after morphine

The effect of the opioid antagonists naloxone-3-glucuronide and N-methylnaloxone on rat colon motility after morphine stimulation was measured. The rat model consisted of the isolated, vascularly perfused colon. The antagonists (10(-4) M, intraluminally) and morphine (10(-4) M, intra-arterially) were administered from 20 to 30 and from 10 to 50 min, respectively. Colon motility was determined by the luminal outflow. The antagonist concentrations in the luminal and venous outflow were measured by high-performance liquid chromatography. Naloxone-3-glucuronide and N-methylnaloxone reversed the morphine-induced reduction of the luminal outflow to baseline within 10 and 20 min, respectively. These antagonists were then excreted in the luminal outflow and could not be found in the venous samples. Naloxone, produced by hydrolysis or demethylation, was not detectable. In conclusion, highly polar naloxone derivatives peripherally antagonize the motility-lowering effect of morphine in the perfused isolated rat colon, are stable, and are not able to cross the colon-mucosal blood barrier.

Is alcohol ablation of the septum associated with recurrent tachyarrhythmias?

QUESTIONS UNDER STUDY: Alcohol ablation (AA) of the septum has been introduced as new therapy in hypertrophic cardiomyopathy (HCM). It was feared that iatrogenic myocardial infarction due to AA may induce re-entry tachyarrhythmias and increase sudden cardiac death. METHODS AND RESULTS: Twenty-four patients (mean age 52 years) underwent successful AA. Clinical follow-up (FU) ranged from 0.3 to 0.7 years (mean 2.8). One patient died (suicide) 4 years after AA. Left ventricular (LV) outflow gradient (peak-to-peak) decreased (median) after AA from 43 (IQR 25 to 4) mmHg to 1 (IQR 0 to 12) mmHg (rest) (p <0.001) and from 130 (IQR 75 to 165) mmHg to 13 (IQR 0 to 31) mmHg (postextrasystolic) (p <0.001). Transient AV block occurred in 22% (5/24) necessitating temporary pacing. A permanent pacemaker was implanted in 4% (1/24). NYHA-class was 2.5 (IQR 2.0 to 3.0) before and 1.5 (IQR 1.3 to 2.0) (p <0.001) after AA. During FU, 2 pacemakers were implanted due to bradycardia (no AV block). A right bundle branch block was found in 13% (2/24) before and 46 % (11/24) after AA (p = 0.003). Non-sustained ventricular tachycardia (NSVT) was observed in 13% (2/16) before and 22% (5/23) (p = 0.46) after AA. Two patients required ICD implantation. CONCLUSIONS: Long-term FU is excellent in HCM after AA. The pressure gradient drops below 25 mm Hg in 95% (23/24) of all patients. Transient AV block occurs in 22% (5/24), but permanent pacemaker implantation is rarely needed (13%, 2/24). Severe NSVT occurs in 13% (2/16) before and 22% (5/23) after AA but ICD implantation is only occasionally required.

Stenting of common iliac vein obstructions combined with regional thrombolysis and thrombectomy in acute deep vein thrombosis

OBJECTIVES: To evaluate the efficacy of stent placement after infrainguinal loco-regional thrombolysis and iliac thrombectomy (surgical TT) of acute deep vein thrombosis (DVT) in patients with May-Thurner-Syndrome. MATERIAL AND METHODS: We retrospectively analysed a group of 11 patients (9 women) (mean age 34 years, range 16-64 years) with surgical TT and additional intra-operative stenting due to compression of the common iliac vein. Patients underwent venography to demonstrate outflow patency after surgical TT, and to identify any obstruction at the level of the left-sided common iliac vein ("Beckenvenen-Sporn"). Obstruction at the level of arterial crossing was treated using Wallstents placed via an introducer sheath from the inguinal access site. Stents were fully deployed using balloons adjusted to the size of vein. Patients were treated with oral anticoagulants for 6 months, and followed using duplex ultrasonography. RESULTS: Technical success defined as complete vein patency and normal valve function was documented in all 11 patients. One patient needed early stent extension due to residual stenosis. At 6 months follow-up one patient (9%) had an asymptomatic occlusion of the stented common iliac vein. In all 11/11 (100%) patients the femoral segment was found to be patent, and in 1/11 (9%) there was mild reflux with few clinical symptoms of post-thrombotic syndrome. The calculated cumulative primary patency rate for venous iliac stents was 82%, and assisted patency rate was 91%, which remained unchanged over a mean follow-up of 22 months. CONCLUSION: Combining surgical TT and stenting of common iliac vein obstructions in DVT is safe, effective, and results in a acceptable venous patency.

Chronic pulmonary valve insufficiency after repaired tetralogy of Fallot: diagnostics, reoperations and reconstruction possibilities

Complete correction of Tetralogy of Fallot, the most common cyanotic congenital heart defect, has now become routine. However, late residual lesions, primarily chronic pulmonary valve insufficiency, may have a negative impact on right-ventricular function, leading to the need for reoperation to insert a competent valve at the right-ventricular outflow. The diagnostic modalities pertaining to the failing right ventricle, the timing for eventual reintervention and the various surgical reconstruction possibilities of the right-ventricular outflow tract are still controversial and evolving, and are reviewed with a brief overview on current trends and future outlooks.

[Positive ibopamine provocative test in normal-tension glaucoma suspects]

BACKGROUND: Ibopamine is an alpha-adrenergic agent and causes an elevation of intraocular pressure in eyes with increased outflow resistance. It has been proposed as a test substance for the detection of early ocular hydrodynamic disorders. PATIENTS AND METHODS: A total of 64 normal-tension glaucoma suspect eyes without anti-hypertensive treatment were enrolled. A daily pressure curve was registered with measurements at 7:00 am, 8:00 am, 12:00 am, 17:00 pm using an applanation tonometer and a contour tonometer followed by instillation of ibopamine 2% in both eyes. Tonometry was performed every 15 minutes during the following hour. An IOP increase of > 2.0 mmHg was considered positive. RESULTS: The positive test group showed a significant pressure increase from 18.04 to 22.06 mmHg. Ocular pulse amplitude increased from 2.96 to 3.97 mmHg and was positively correlated with the pressure. Intraocular pressure was unchanged in the negative test group. Central corneal thickness was not significantly different in the two groups (p = 0.32). CONCLUSIONS: Ibopamine 2% eye drops have a positive pressure effect in 50% of suspected normal-tension glaucoma eyes and may differentiate between eyes with normal trabecular outflow capacity and eyes with increased resistance in the trabecular meshwork that are prone to pressure peaks and deterioration to glaucoma.

A feasibility study on model-based evaluation of kidney perfusion measured by means of FAIR prepared true-FISP arterial spin labeling (ASL) on a 3-T MR scanner

RATIONALE AND OBJECTIVES: A feasibility study on measuring kidney perfusion by a contrast-free magnetic resonance (MR) imaging technique is presented. MATERIALS AND METHODS: A flow-sensitive alternating inversion recovery (FAIR) prepared true fast imaging with steady-state precession (TrueFISP) arterial spin labeling sequence was used on a 3.0-T MR-scanner. The basis for quantification is a two-compartment exchange model proposed by Parkes that corrects for diverse assumptions in single-compartment standard models. RESULTS: Eleven healthy volunteers (mean age, 42.3 years; range 24-55) were examined. The calculated mean renal blood flow values for the exchange model (109 +/- 5 [medulla] and 245 +/- 11 [cortex] ml/min - 100 g) are in good agreement with the literature. Most important, the two-compartment exchange model exhibits a stabilizing effect on the evaluation of perfusion values if the finite permeability of the vessel wall and the venous outflow (fast solution) are considered: the values for the one-compartment standard model were 93 +/- 18 (medulla) and 208 +/- 37 (cortex) ml/min - 100 g. CONCLUSION: This improvement will increase the accuracy of contrast-free imaging of kidney perfusion in treatment renovascular disease.

The Ross procedure in infants and young children

BACKGROUND: This study reviews our experience with the Ross procedure in infants and young children. METHODS: From September 1993 to September 2004, 52 children less than 15 years of age underwent a Ross procedure. The patients ranged in age from 4 days to 15 years old (median, 5 years). Fifteen patients (29%) were less than 2 years of age. The predominant indication for the Ross procedure was aortic stenosis. Sixteen patients underwent a Ross-Konno procedure for severe left ventricular outflow tract obstruction. Thirty-four patients had 48 previous interventions. Preoperatively, 6 patients showed severe left ventricular dysfunction, and 2 of the patients required ventilation and inotropic support. Concomitant procedures were performed in 8 patients. Three patients had a mitral valve replacement, 2 patients had a ventricular septal defect closure and an aortic arch reconstruction, 2 patients had aortic arch reconstructions, and 1 patient had resection of a coarctation and a ventricular septal defect closure. RESULTS: Patients were followed up for a median of 43 months (range, 1 to 130). Overall survival was 85% +/- 5% at 1 and 82% +/- 5% at 2, 5, and 10 years. Hospital mortality was 5 of 52 patients (9.6%). All deaths occurred in neonates or infants less than 2 months of age, who needed urgent surgery. Three patients died late of noncardiac causes. At last follow-up, all patients were classified in New York Heart Association functional class I or II. No patient had endocarditis of the autograft or the right ventricular outflow tract replacement. During the follow-up, no event of thrombembolism was observed. No patient required the insertion of a permanent pacemaker. Overall freedom from reoperation is 57% +/- 15% at 10 years. One patient required the replacement of the autograft at 6 months postoperatively. The development of mild aortic insufficiency was observed in 24 patients, and moderate aortic insufficiency in 1 patient during follow-up. Freedom from reoperation for the right ventricular outflow tract replacement is 60% +/- 15% at 10 years. CONCLUSIONS: The Ross procedure represents an attractive approach to aortic valve disease in young children. However, a high early mortality rate has to be considered when performing this procedure in neonates or infants who present in critical preoperative condition.

Valved stents for transapical pulmonary valve replacement

OBJECTIVES: Pulmonary valve insufficiency remains a leading cause for reoperations in congenital cardiac surgery. The current percutaneous approach is limited by the size of the access vessel and variable right ventricular outflow tract morphology. This study assesses the feasibility of transapical pulmonary valve replacement based on a new valved stent construction concept. METHODS: A new valved stent design was implanted off-pump under continuous intracardiac echocardiographic and fluoroscopic guidance into the native right ventricular outflow tract in 8 pigs (48.5 +/- 6.0 kg) through the right ventricular apex, and device function was studied by using invasive and noninvasive measures. RESULTS: Procedural success was 100% at the first attempt. Procedural time was 75 +/- 15 minutes. All devices were delivered at the target site with good acute valve function. No valved stents dislodged. No animal had significant regurgitation or paravalvular leaking on intracardiac echocardiographic analysis. All animals had a competent tricuspid valve and no signs of right ventricular dysfunction. The planimetric valve orifice was 2.85 +/- 0.32 cm(2). No damage to the pulmonary artery or structural defect of the valved stents was found at necropsy. CONCLUSIONS: This study confirms the feasibility of direct access valve replacement through the transapical procedure for replacement of the pulmonary valve, as well as validity of the new valved stent design concept. The transapical procedure is targeting a broader patient pool, including the very young and the adult patient. The device design might not be restricted to failing conduits only and could allow for implantation in a larger patient population, including those with native right ventricular outflow tract configurations.

Nighttime vagal cardiac control and plasma fibrinogen levels in a population of working men and women

BACKGROUND: Elevated plasma fibrinogen levels have prospectively been associated with an increased risk of coronary artery disease in different populations. Plasma fibrinogen is a measure of systemic inflammation crucially involved in atherosclerosis. The vagus nerve curtails inflammation via a cholinergic antiinflammatory pathway. We hypothesized that lower vagal control of the heart relates to higher plasma fibrinogen levels. METHODS: Study participants were 559 employees (age 17-63 years; 89% men) of an airplane manufacturing plant in southern Germany. All subjects underwent medical examination, blood sampling, and 24-hour ambulatory heart rate recording while kept on their work routine. The root mean square of successive differences in RR intervals during the night period (nighttime RMSSD) was computed as the heart rate variability index of vagal function. RESULTS: After controlling for demographic, lifestyle, and medical factors, nighttime RMSSD explained 1.7% (P = 0.001), 0.8% (P = 0.033), and 7.8% (P = 0.007), respectively, of the variance in fibrinogen levels in all subjects, men, and women. Nighttime RMSSD and fibrinogen levels were stronger correlated in women than in men. In all workers, men, and women, respectively, there was a mean +/- SEM increase of 0.41 +/- 0.13 mg/dL, 0.28 +/- 0.13 mg/dL, and 1.16 +/- 0.41 mg/dL fibrinogen for each millisecond decrease in nighttime RMSSD. CONCLUSIONS: Reduced vagal outflow to the heart correlated with elevated plasma fibrinogen levels independent of the established cardiovascular risk factors. This relationship seemed comparably stronger in women than men. Such an autonomic mechanism might contribute to the atherosclerotic process and its thrombotic complications.

Phenotypes and echocardiographic characteristics of a European population of domestic shorthair cats with idiopathic hypertrophic cardiomyopathy

111 Domestic Shorthair cats with idiopathic hypertrophic cardiomyopathy were reviewed retrospectively. Two-dimensional echocardiography was used to classify cases in 6 established phenotypes. Hypertrophy was diffuse in 61 % of cats and involved major portions of the ventricular septum and the left ventricular free wall (phenotype D). In the remaining cats, distribution of hypertrophy was more segmental and was identified on the papillary muscles exclusively (phenotype A, 6 %), on the anterior and basal portion of the ventricular septum (phenotype B, 12 %), on the entire septum (phenotype C, 14 %), or on the left ventricular free wall (phenotype E, 7 %). Echocardiographic characteristics and clinical findings were determined for each phenotype to study the correlation between distribution of hypertrophy and clinical implications. 31 cats demonstrated systolic anterior motion of the mitral valve, 75 % of them belonged to phenotype C of hypertrophy. Left ventricular-outflow turbulences were identified more frequently with patterns of hypertrophy involving the ventricular septum (65.5 %), while prevalence of mitral regurgitation was higher when hypertrophy included the papillary muscles (phenotypes A and E, 85 % and 87 %, respectively). Left atrial dilatation occurred more frequently when hypertrophy was diffuse or confined to the left ventricular free wall (61 % of cats with phenotype D or E) rather than to the ventricular septum (31 % of cats with phenotype B or C).

What next after failed septal ventricular tachycardia ablation?

Ablation of ventricular tachycardia (VT) by conventional radiofrequency ablation can be impossible if the ventricular wall at the targeted ablation site is very thick, as for example the ventricular septum. We present a case of a patient with incessant, non-sustained slow VT originating from the septal part of the lower outflow tracts. Radiofrequency catheter ablation from both ventricles as well as from the anterior cardiac vein were not successful. Both high power radiofrequency ablation and bipolar radiofrequency ablation neither were successfull. Finally, ethanol ablation of the first septal perforator successfully terminated arrhythmia. We discuss the possibilities to overcome failed conventional radiofrequency VT ablation of a septal focus.

Radiofrequency catheter ablation of idiopathic ventricular tachycardia originating in the main stem of the pulmonary artery.

We report the case of a patient in whom successful radiofrequency catheter ablation of an idiopathic ventricular tachycardia (VT) originating in the main stem of the pulmonary artery was performed. After successful ablation of the index arrhythmia, which was an idiopathic right ventricular outflow tract VT, a second VT with a different QRS morphology was reproducibly induced. Mapping of the second VT revealed the presence of myocardium approximately 2 cm above the pulmonary valve. Application of radiofrequency energy at this site resulted in termination and noninducibility of this VT. After 6-month follow-up, the patient remained free from VT recurrences.

Electrocardiographic pattern as a guide for management and radiofrequency ablation of idiopathic ventricular tachycardia.

BACKGROUND Idiopathic ventricular tachycardia (VT) often originates from the right ventricular outflow tract (RVOT), but foci deep to the endocardium, in the epicardium, or in the left ventricle are not uncommon. Although these extra-RVOT foci can be targeted with ablation, risks involved are higher and success rates lower. Simple electrocardiographic (ECG) criteria allowing (1) discrimination of RVOT foci from extra-RVOT foci and (2) assessment of the chance of success of a right heart ablation procedure are desirable. METHODS Twenty-five consecutive patients referred for radiofrequency (RF) ablation of idiopathic VT or severely symptomatic idiopathic ventricular premature contractions were included. Localization of VT origin and success rates of VT ablation in the RVOT were analyzed according to the ECG pattern. RESULTS The analysis of the R wave in V2 was the strongest single predictor of whether the VT had an RVOT or an extra-RVOT origin. An R wave amplitude < or =30% of the QRS amplitude designated the VT focus in the RVOT with positive and negative predictive values of 95 and 100%, respectively. Analysis of R wave duration in V2 had similar predictive values, whereas the R/S transition zone in precordial leads had slightly lower predictive values. Seventeen of 20 arrhythmias (85%) with an R wave amplitude < or =30% of the QRS amplitude in V2 could be successfully abolished by an exclusively right heart procedure. CONCLUSIONS The analysis of ECG pattern makes it possible to guide the management of patients with idiopathic VT in predicting the arrhythmias that can be safely targeted with RF ablation from the RVOT with high success rates.

Solute transport in crystalline rocks at Äspö — II: Blind predictions, inverse modelling and lessons learnt from test STT1

Based on the results from detailed structural and petrological characterisation and on up-scaled laboratory values for sorption and diffusion, blind predictions were made for the STT1 dipole tracer test performed in the Swedish A¨ spo¨ Hard Rock Laboratory. The tracers used were nonsorbing, such as uranine and tritiated water, weakly sorbing 22Na+, 85Sr2 +, 47Ca2 +and more strongly sorbing 86Rb+, 133Ba2 +, 137Cs+. Our model consists of two parts: (1) a flow part based on a 2D-streamtube formalism accounting for the natural background flow field and with an underlying homogeneous and isotropic transmissivity field and (2) a transport part in terms of the dual porosity medium approach which is linked to the flow part by the flow porosity. The calibration of the model was done using the data from one single uranine breakthrough (PDT3). The study clearly showed that matrix diffusion into a highly porous material, fault gouge, had to be included in our model evidenced by the characteristic shape of the breakthrough curve and in line with geological observations. After the disclosure of the measurements, it turned out that, in spite of the simplicity of our model, the prediction for the nonsorbing and weakly sorbing tracers was fairly good. The blind prediction for the more strongly sorbing tracers was in general less accurate. The reason for the good predictions is deemed to be the result of the choice of a model structure strongly based on geological observation. The breakthrough curves were inversely modelled to determine in situ values for the transport parameters and to draw consequences on the model structure applied. For good fits, only one additional fracture family in contact with cataclasite had to be taken into account, but no new transport mechanisms had to be invoked. The in situ values for the effective diffusion coefficient for fault gouge are a factor of 2–15 larger than the laboratory data. For cataclasite, both data sets have values comparable to laboratory data. The extracted Kd values for the weakly sorbing tracers are larger than Swedish laboratory data by a factor of 25–60, but agree within a factor of 3–5 for the more strongly sorbing nuclides. The reason for the inconsistency concerning Kds is the use of fresh granite in the laboratory studies, whereas tracers in the field experiments interact only with fracture fault gouge and to a lesser extent with cataclasite both being mineralogically very different (e.g. clay-bearing) from the intact wall rock.

Analysis of Band 4.1B in Integrin-Mediated Cell Adhesion and Signaling

Band 4.1B is a cytoskeletal adaptor protein that regulates various cellular behavior; however, the mechanisms by which Band 4.1B contributes to intracellular signaling are unclear. This project addresses in vivo and in vitro functions for Band 4.1B in integrin-mediated cell adhesion and signaling. Band 4.1B has been shown to bind to β8 integrin, although cooperative functions of these two proteins have not been determined. Here, functional links between β8 integrin and Band 4.1B were investigated using gene knockout strategies. Ablation of β8 integrin and Band 4.1B genes resulted in impaired cardiac morphogenesis, leading to embryonic lethality by E11.5. These embryos displayed malformation of the outflow tract that was likely linked to abnormal regulation of cardiac neural crest migration. These data indicate the importance of cooperative signaling between β8 integrin and Band 4.1B in cardiac development. The involvement of Band 4.1B in integrin-mediated cell adhesion and signaling was further demonstrated by studying its functional roles in vitro. Band 4.1B is highly expressed in the brain, but its signaling in astrocytes is not understood. Here, Band 4.1B was shown to promote cell spreading likely by interacting with β1 integrin via its band 4.1, ezrin, radixin, and moesin (FERM) domain in cell adhesions. In astrocytes, both Band 4.1B and β1 integrin were expressed in cell-ECM contact sites during early cell spreading. Exogenous expression of Band 4.1B, especially its FERM domain, enhanced cell spreading on fibronectin, an ECM ligand for β1 integrin. However, the increased cell spreading was prohibited by blocking β1 integrin. These findings suggest that Band 4.1B is crucial for early adhesion assembly and/or signaling that are mediated by β1 integrin. Collectively, this study was the first to establish Band 4.1B as a modulator of integrin-mediated adhesion and signaling.