Double-crowned valved stents for off-pump mitral valve replacement.

OBJECTIVE: An animal model has been designed to assess the feasibility of off-pump mitral valve replacement using valved stents. METHODS: Glutaraldehyde-preserved homograft was sutured inside a prosthetic tube (Dacron). Then, two self-expandable nitinol Z-stents were sutured on the external surface of the prosthesis in such a way to create two self-expanding crowns for fixation. In adult pigs and under general anesthesia, the left atrium was exposed through a left thoracotomy and atrio-ventricular roadmapping was performed with intravascular ultrasound (IVUS) and fluoroscopy. The double-crowned valved stents were loaded into a delivery sheath. The sheath was then introduced into the left atrium and the valved stents was deployed in mitral position in such a way that the part in between the two stents was at the level of the mitral annulus. Intracardiac Unltrasound (ICUS) was used to assess the valve function. Hemodynamic parameters were gathered as well. Animal survived for no more than 3h after the valve deployment and gross anatomy examination of the left heart was carried out. RESULTS: The mean height of the valved stents was 29.4+/-0.2 mm, with an internal diameter of 20.4+/-1.0mm, and an external diameter of 25.5+/-0.8 mm. The procedure was successfully carried out in eight animals. In vivo evaluation showed a native mitral annulus diameter of 24.9+/-0.6 mm, and a mean mitral valve area of 421.4+/-17.5 mm2. ICUS showed a mild mitral regurgitation in three out of eight animals. Mean pressure gradient across the valved stents was 2.6+/-3.1 mmHg. Mean pressure gradient across the left ventricular outflow tract (LVOT) was 6.6+/-5.2 mmHg. The mean survival time was 97.5+/-56.3 min (survival time range was 40-180 min). One animal died due to the occlusion of the LVOT because of valved stents displacement. Postmortem evaluation confirmed correct positioning of the valved stent in the mitral position in seven out of eight animals. No atrial or ventricular lesions due to the valved stents were found. CONCLUSIONS: Off-pump implantation of a self-expandable valved stent in the mitral position is technically feasible. Further studies will assess if this procedure is also feasible in humans.     

Severity of coronary artery stenosis at preoperative angiography and midterm mammary graft status

BACKGROUND: The purpose of this study was to evaluate the correlation between the midterm angiographic results of mammary artery grafts and the preoperative stenosis of the target vessel. METHODS: We analyzed preoperative and postoperative angiograms of 93 patients who underwent postoperative midterm (> or = 3 years) angiograms of an internal mammary artery (IMA) to left anterior descending artery graft for clinical or study purposes. Patients were divided into three groups on the basis of the percentage of the coronary artery stenosis at preoperative angiography: < 70%, 70% to 90%, and > 90% stenosis. RESULTS: Preoperative characteristics were similar in the three groups. The overall incidence of IMA occlusion was 19% in the entire population, without significant differences between groups (19% versus 29% versus 14%). The mean mammary artery diameter significantly increased in direct proportion to the severity of the coronary stenosis (2.0 +/- 0.2 mm in the < 70% versus 2.5 +/- 0.3 mm in the 70% to 90% and 2.7 +/- 0.4 mm in the > 90% series; p < 0.05). CONCLUSIONS: Chronic native competitive flow does not significantly affect midterm graft status but does influence mammary graft diameter.     

Laparotomic versus laparoscopic Duhamel pull-through for Hirschsprung disease in infants and children

PURPOSE: The aim of this study was to analyze the results from laparotomic and laparoscopic Duhamel pull-through in the treatment of Hirschsprung disease. MATERIALS AND METHODS: In our department, the Duhamel pull-through technique was adopted in most patients and the laparoscopic technique used since 1999 follows the original Duhamel procedure. Patients were identified retrospectively and followed up in our outpatient clinic. Preoperative, operative, and postoperative data were collected and analyzed. RESULTS: Between January 1992 and March 1999, 21 children with Hirschsprung disease underwent primary surgical correction using the classic open Duhamel pull-through. The mean age at operation was 14 months, the median operating time was 297 minutes, and the average postoperative stay was 10 days. From April 1999 to December 2003, 22 children underwent laparoscopic Duhamel pull-through. The mean age at operation was 14.6 months, the mean operative time was 253 minutes, and the mean postoperative stay was 6.8 days. The rates of early (4.7% vs. 4.7%) and late (19% vs. 23.8%) complications were similar in the two groups, but in the laparoscopic group the mean operative time and postoperative hospital stay were lower. CONCLUSION: With these encouraging results, laparoscopic Duhamel pull-through has become our procedure of choice in the surgical management of Hirschsprung's disease.     

Management of pulmonary embolism during acrylic vertebroplasty

A 55-year-old man diagnosed with osteogenesis imperfecta had multiple pulmonary embolism from acrylic cement during vertebroplasty. The patient immediately developed respiratory distress, renal failure, and right cardiac failure. A computed tomographic scan showed the presence of cement in the right and left pulmonary arteries, and in both lungs. Cardiac and respiratory functions did not improve with medical treatment, therefore the patient underwent pulmonary artery embolectomy. Cement was easily removed from both pulmonary arteries. The patient quickly recovered from respiratory and cardiac failure. We believe pulmonary embolectomy is a reliable and effective procedure to treat this rare and dreadful complication of acrylic vertebroplasty.     

CREB Activation and Ischaemic Preconditioning

PURPOSE: Previous studies from our laboratory showed that activation of p38 MAPK is one of the triggers of ischaemic preconditioning. The signalling events downstream of p38 MAPK and their links to the putative final effectors of preconditioning are not clear. The cAMP responsive element-binding protein (CREB) is also phosphorylated by exposure to short episodes of ischaemia/reperfusion, suggesting a triggering action. The aim of this study was to systematically investigate (1) the signalling pathways leading to CREB phosphorylation during an ischaemic or beta-adrenergic preconditioning protocol (2) changes in CREB phosphorylation during sustained ischaemia and their significance in ischaemia/reperfusion injury. METHODS: The isolated perfused working rat heart was preconditioned by 1 x 5 min global ischaemia or 3 x 5 min global ischaemia and freeze-clamped. Drugs to manipulate CREB activation were added 5 min before onset of ischaemia. Non-preconditioned and preconditioned hearts were subjected to 25 min global or 35 min regional ischaemia, followed by 30 min reperfusion. Infarct sizes were determined using tetrazolium staining. Phosphorylation of CREB was determined by Western blots. RESULTS: Exposure of hearts to 5 min global ischaemia followed by reperfusion, significantly increased CREB phosphorylation This is mediated by, amongst others, release of endogenous catecholamines and adenosine, as indicated by the use of receptor blockers. Events downstream of receptor stimulation were evaluated using inhibitors for PKA (H89), MSK-1 (H89, Ro318220), PKC (bisindolylmaleimide), p38 MAPK (SB203580) and ERK (PD98059). Activation of PKA, PKC, ERK and p38 MAPK is involved in preconditioning-induced CREB phosphorylation. Ischaemia-induced activation of iPLA(2) and cPLA(2) also contribute to CREB phosphorylation as indicated by the use of the inhibitors 4-bromo-enol-lactone (BEL) and AACOF(3,) respectively. Inhibition of CREB phosphorylation by either BEL or AACOF(3) during a preconditioning protocol partially attenuated cardioprotection. CREB phosphorylation was attenuated during sustained global ischaemia of both non-preconditioned and preconditioned hearts. CONCLUSIONS: These data suggest that CREB phosphorylation during an ischaemic preconditioning protocol may contribute to triggering preconditioning, while reduced phosphorylation during sustained ischaemia does not appear to be associated with cardioprotection.     

Coronary collateral flow: effect of drugs and perfusion pressure

Summary In 35 mongrel dogs acute myocardial infarction was produced by ligating the anterior descending branch of the left coronary artery and subsequent embolization of the peripheral area of the descending branch with microspheres. Retrograde flow and coronary retrograde pressure were measured before and after embolization as well as after embolization before and during the action of coronary dilating drugs. After embolization, the mean retrograde flow represented the whole coronary collateral flow, and the retrograde pressure equalled the true coronary collateral perfusion pressure. Following embolization, the mean retrograde pressure significantly increased from 20±2 to 69±3 mm Hg, i.e. to 73% of the mean aortic pressure. There was a simultaneous rise in retrograde flow from 3.99±0.78 to 6.19±1.16 ml/(min · 100 g), i.e. 12% of the antegrade perfusion. A significant correlation between coronary collateral flow and collateral perfusion pressure could be demonstrated. The average increase in collateral flow was 1.14 ml/(min · 100 g), i.e. 21 %, when the perfusion pressure rose from 70 to 80 mm Hg.After drug infusions, a slight increase in coronary collateral flow was observed, provided that the perfusion pressure remained unchanged. This increase was significant after nitroglycerine (+ 13±3 %) and after papaverine (+ 11±5%). When the perfusion pressure decreased, there was a decrease in collateral flow. When, however, under isoproterenol the decreased perfusion pressure was brought back to control level my means of a blood infusion, the collateral flow also increased and was then slightly, but significantly, above control (+ 4%).It can be concluded that, provided the perfusion pressure remains constant, the application of coronary dilating drugs can slightly improve the coronary collateral flow. This small effect might be of vital importance for the treatment of myocardial infarction. Myocardial steal only appeared when the perfusion pressure decreased.

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Über den Einfluß von Pharmaka und des Perfusionsdruckes auf die Kollateraldurchblutung des Herzens

Zusammenfassung Bei 35 narkotisierten Hunden wurde der Ramus descendens der linken Koronararterie akut unterbunden und das zugehörige Stromgebiet mit Latexpartikeln embolisiert. Der retrograde Fluß und der retrograde Druck wurden vor und nach Embolisation sowie nach der Embolisation vor und während des Einflusses von Koronardilatatoren gemessen. Der retrograde Fluß nach Mikroembolisation entspricht dem wahren Kollateralfluß und der retrograde Druck dem wahren Perfusionsdruck der Kollateralgefäße. Nach Mikroembolisation stieg der retrograde Druck signifikant von 20±2 auf 69±3 mm Hg, das entspricht 73% des mittleren Aortendruckes. Gleichzeitig stieg der retrograde Fluß von 3,99±0,78 auf 6,19±1,16 ml/(min · 100 g), das sind 12% der antegraden Durchblutung. Der durchschnittliche Anstieg der Kollateraldurchblutung betrug 1,14 ml/(min. · 100 g), das sind + 21%, bei einer Zunahme des Perfusionsdruckes von 70 auf 80 mm Hg.Unter der Applikation von Koronardilatatoren konnte ein geringer Anstieg der Kollateraldurchblutung beobachtet werden, vorausgesetzt, daß der Perfusionsdruck unverändert blieb. Dieser Anstieg war unter Nitroglycerin, (+ 13 ±3%) und unter Papaverin (+11±5%) signifikant. Die Kollateraldurchblutung nahm ab, wenn der Perfusionsdruck unter dem Einfluß des Pharmakons abfiel. Wurde der unter Isoproterenol gesunkene Perfusionsdruck mittels Bluttransfusion wieder auf den Ausgangswert angehoben, so stieg die Kollateraldurchblutung wieder an und lag dann mit +4% gering, aber signifikant über dem Ausgangswert.Aufgrund dieser Befunde kann geschlossen werden, daß Koronardilatatoren die Kollateraldurchblutung geringgradig verbessern können unter der Voraussetzung, daß der Perfusionsdruck nicht absinkt. Dieser geringe pharmakologische Effekt könnte jedoch von entscheidender Bedeutung bei der Behandlung des Myokardinfarktes sein. Ein myocardial steal tritt nur bei einem Abfall des Perfusionsdruckes ein.

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With 2 figures and 3 tables

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Supported by a grant of the Deutsche Forschungsgemeinschaft, Sonderforschungsbereich 30, Kardiologie, Düsseldorf.     

Dopamine transporter binding in social anxiety disorder: the effect of treatment with escitalopram

Social anxiety disorder (SAD) is characterised by fear of social or performance situations where the individual is exposed to unfamiliar people or to possible scrutiny by others. The literature on dopamine ligands and dopamine genotypes in SAD is however inconsistent. In this study we measured the effects of SSRI pharmacotherapy on dopamine transporter (DAT) binding in patients with SAD, also addressing variability in DAT genotype. Adult subjects meeting DSM-IV criteria for generalised SAD were studied before and after 12 weeks of pharmacotherapy with the selective serotonin reuptake inhibitor (SSRI) escitalopram. DAT single photon emission computed tomography (SPECT) using ¹²³I-FP-CIT was performed at baseline, and repeated at 12 weeks. Striatal DAT binding was analysed for changes following therapy, and for correlations with clinical efficacy, in the whole group as well as for a subgroup with the A10/A10 DAT genotype. The study included 14 subjects (9 male, 5 female) with a mean (SD) age of 41 (±13) years. The subjects’ Liebowitz Social Anxiety Scale (LSAS) score was significantly decreased following pharmacotherapy. In the combined group the left caudate and left putamen showed clusters of increased DAT binding after therapy. The left caudate changes were also observed in the subgroup of 9 A10/A10 homozygotes. However no correlation was found between improved symptoms and DAT binding. The changes found in DAT binding in the caudate and putamen may be due to serotonergic activation of dopamine function by SSRI therapy. This is consistent with previous work indicating decreased DAT binding in SAD, and increased DAT binding after SSRI administration.