Surgical reinterventions following the Fontan procedure.

OBJECTIVE: The Fontan procedure is utilized as a final reconstructive procedure for patients with functional single ventricle. Short- and long-term outcomes have improved significantly, however, some patients require additional cardiac procedures following the Fontan operation. The outcomes for these reinterventions are not known. METHODS: Cardiac Surgery and Cardiac Intensive Care Unit databases at The Children's Hospital of Philadelphia were reviewed to identify all patients who underwent cardiac surgery after a previous Fontan operation between January 1, 1995 and December 31, 2001. RESULTS: During the study period, 123 procedures were performed in 71 patients. The median time from Fontan to reoperation was 3.6 years (range 0.1-20 years). Indications for reintervention included arrhythmia, cyanosis, 'failing' Fontan circulation or exercise intolerance, protein losing enteropathy, atrioventricular valve (AVV) regurgitation, and other indications. Procedures included pacemaker insertion or revision (n = 59, 48%), reinclusion of previously excluded hepatic veins (n = 16, 13%), revision to either a lateral tunnel or extra-cardiac conduit Fontan (n = 13, 11%), cardiac transplantation (n = 9, 7%), enlargement or creation of a baffle fenestration (n = 6, 5%), isolated AVV repair or replacement (n = 2, 2%), and other procedures (n = 18, 14%). There were five early and five late deaths. Hospital mortality was greatest for patients undergoing cardiac transplantation (4/9, 44%), accounting for 80% of the early deaths. CONCLUSIONS: Surgical reinterventions following the Fontan procedure may be necessary for multiple indications which result in impairment of the Fontan circulation. Most reinterventions can be performed with minimal morbidity and mortality. Survival for patients requiring cardiac transplantation following the Fontan procedure remains poor.     

Differential effect of taurine and serotonin on the outgrowth from explants or isolated cells of the retina

The sulfur amino acid taurine and the indoleamine serotonin increases and decreases, respectively, the outgrowth from goldfish retinal explants. Taurine seems to be acting, at least partially, through an increase in calcium fluxes, and the serotonin-inhibiting effect appears to be mediated by serotonin_1A receptors and cAMP. Isolated cells of postcrush goldfish retina and of retina from 5-day-old rats were cultured in the presence of taurine or serotonin. In the goldfish, the classical morphology of postcrush ganglion cells was observed. An antibody against the glycoprotein Thy-1 labelled three types of cells in the cultures of goldfish retina. The number of cells outgrowing and the length of the main neurite was measured at 5 days in culture in both species. The number of cells presenting neurites was increased in the goldfish retina by the addition of taurine, and decreased by serotonin. However, the length of the neurites was unaffected by the addition of the modulators. In the rat, only a slight decrease in the number of cells outgrowing was observed in the presence of serotonin. The incorporation of [³H]thymidinewas not modified after 5 days in culture in the presence of taurine or serotonin, either in the goldfish or in the rat retina. The antibody Thy 1.1 can label retinal cells of the goldfish invitro, one of them being ganglion cells. The trophic effect exerted by taurine in the postcrush goldfish retina needs the integrity of the tissue favoring the interaction of cells and factors, because outgrowth increases in retinal explants, but not in isolated cells.     

An efficient SNP system for mouse genome scanning and elucidating strain relationships

A set of 1638 informative SNP markers easily assayed by the Amplifluor genotyping system were tested in 102 mouse strains, including the majority of the common and wild-derived inbred strains available from The Jackson Laboratory. Selected from publicly available databases, the markers are on average ~1.5 Mb apart and, whenever possible, represent the rare allele in at least two strains. Amplifluor assays were developed for each marker and performed on two independent DNA samples from each strain. The mean number of polymorphisms between strains was 608±136 SD. Several tests indicate that the markers provide an effective system for performing genome scans and quantitative trait loci analyses in all but the most closely related strains. Additionally, the markers revealed several subtle differences between closely related mouse strains, including the groups of several 129, BALB, C3H, C57, and DBA strains, and a group of wild-derived inbred strains representing several Mus musculus subspecies. Applying a neighbor-joining method to the data, we constructed a mouse strain family tree, which in most cases confirmed existing genealogies.     

Tissue engineering of arteries by directed remodeling of intact arterial segments

Traditional approaches to generating tissue-engineered arteries in vitro rely on expansion of cells in culture to seed appropriate scaffolds. In most envisioned applications, small autologous blood vessels would be harvested and used as a source for these cells. We propose that small autologous arteries, not the cells derived from them, may be an attractive starting point for engineered arteries. This approach capitalizes on the ability of intact arteries to grow and remodel in response to chronic changes in their mechanical environment. Carotid arteries from juvenile (approximately 30-kg) pigs were stretched longitudinally in an ex vivo perfusion system over 9 days. This resulted in a 40% increase in artery length at physiological longitudinal stress and a 20 +/- 3% increase when unstressed. Control arteries were perfused for 9 days ex vivo at their physiological loaded length. Control and elongated arteries displayed native appearance (macroscopic and histological), excellent viability (cellularity and mitochondrial activity), normal vasoactivity, and similar mechanical properties (ultimate stress and ultimate strain) as compared with freshly harvested arteries. Growth, as opposed to just redistribution of existing mass, contributed to elongation as evidenced by an increase in artery weight. Results on elongation of arteries from neonatal and adolescent pigs are also presented and discussed.     

Hemodynamic Conditions Alter Axial and Circumferential Remodeling of Arteries Engineered <Emphasis Type="Italic">Ex Vivo</Emphasis>

We previously demonstrated that growth and remodeling was stimulated in arteries elongated ex vivo using step increases in axial strain. Viability and vasoactivity were similar to fresh arteries, however there was a substantial decrease in the ultimate circumferential stress. To test the hypothesis that the subphysiological perfusion conditions (i.e., low pressure and flow) previously used caused the reduction, arteries were subjected to the identical elongation protocol (50% increase over 9 days) while being perfused with physiological levels of flow, viscosity and pulsatile pressure. A significant increase in unloaded length was achieved by elongation under both perfusion conditions, although the increase was less under physiological (7 ± 1%) than under subphysiological conditions (19 ± 2%, p < 0.005). When length at physiological stress was estimated using mechanical testing data the values were similar. The ultimate circumferential stress of arteries elongated under physiological conditions was increased (33%), whereas the ultimate axial stress was decreased (50%) as compared with arteries elongated under subphysiological conditions. Elongated arteries under both perfusion conditions showed significant increases in proliferation and collagen mass, and similar viability and appearance to fresh arteries. These data suggest that there is substantial cross-talk between perfusion conditions and axial strain that modulates arterial remodeling and length.     

Microtubule-associated protein 2 and tubulin are differently distributed in the dendrites of developing neurons

We have followed the appearance of two microtubule proteins, tubulin and microtubule-associated protein 2, in rat hippocampal neurons differentiating in cell culture. Double-label immunofluorescence staining showed that from day 1 in vitro onward tubulin appeared as filaments but that microtubule-associated protein 2 remained distributed throughout the cytoplasm. This difference persisted throughout development and was also detectable in cells that had reached morphological maturity. When cells were treated with the microtubule-depolymerizing agent nocodazole, the depolymerized tubulin became spread throughout the cytoplasm so that its distribution was then identical to microtubule associated protein 2. At the same time, multiple side branches began to emerge along the dendrites. When cells which had been exposed to nocodazole were allowed to recover before staining, the tubulin was again present as filaments but the microtubule-associated protein 2 remained distributed throughout the dendritic cytoplasm. Under these conditions the previously extended proximal side branches were resorbed into the main process. These results suggest that cellular microtubule-associated protein 2 is not necessarily exclusively associated with microtubules. Neuronal dendrites in particular appear to contain this protein at levels in excess of the capacity of microtubular microtubule-associated protein 2 binding sites. In view of the known effectiveness of microtubule-associated protein 2 as a promoter of tubulin polymerization, its abundance in dendrites suggests that it acts to ensure total polymerization of dendritic microtubules. In this way it would contribute both to the support of the growing process and the suppression of adventitious sidebranching.     

Modulation of cardiac contractility by serine/threonine protein phosphatase type 5

Background

Protein phosphatase 5 (PP5) a serine/threonine phosphatase is ubiquitously expressed in mammalian tissues including the heart, but its physiological role in the heart is still unknown. Therefore, we used a transgenic mouse model to get a first insight into the cardiac role of PP5.

Methods and results

We generated transgenic mice with cardiac myocyte specific overexpression of PP5. Successful overexpression of PP5 was demonstrated by Western blotting, immunohistochemistry and enhanced arachidonic acid-stimulated protein phosphatase activity in transgenic hearts. Cardiac function was examined on the level of isolated cardiac myocytes, isolated organs and in intact animals. Whereas Ca²⁺ transients and cell shortening remained unchanged, L-type Ca²⁺ currents were decreased in isolated cardiac myocytes from transgenic mice. Ventricular contractility was reduced in isolated perfused hearts under basal conditions and after β-adrenergic stimulation. In intact animals, echocardiography revealed increased left ventricular diameters and decreased contractility and invasively measured hemodynamic performance by left ventricular catheterization demonstrated a reduced response to β-adrenergic stimulation in transgenic mice compared to wild type.

Conclusions

Overexpression of PP5 affected contractility and β-adrenergic signaling in the hearts of transgenic mice. Taken together, these findings are indicative of a regulatory role of PP5 in cardiac function.     

Decline of Systolic and Diastolic 2D Strain Rate During Follow-Up of HLHS Patients After Fontan Palliation

Accurate assessment of ventricular function is particularly important in children with hypoplastic left heart syndrome (HLHS) after completion of the total cavopulmonary connection (TCPC). For this purpose, two-dimensional speckle tracking (2DST) is a promising technique as it does not depend on the angle of insonation or the geometry of the ventricle. The objective of this study was to assess changes in systolic and diastolic right ventricular (RV) function within a 5-year follow-up period of HLHS patients after TCPC using conventional and 2DST echocardiography. RV fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE), E/A, E/e′ and 2DST parameters [global longitudinal peak systolic strain (GS) and strain rate (GSRs), global strain rate in early (GSRe) and late (GSRa) diastole] of 40 HLHS patients were compared at 1.6 and at 5.1 years after TCPC. RVFAC, E/A, E/e′ and GS did not change, whereas TAPSE (13.7 ± 3.2 vs. 10.5 ± 2.4 mm/m², p < 0.001), GSRs (?1.56 ± 0.28 vs. ?1.35 ± 0.31 1/s, p < 0.001), GSRe (2.22 ± 0.49 vs. 1.96 ± 0.44 1/s, p = 0.004) and GSRa (1.19 ± 0.39 vs. 0.92 ± 0.39 1/s, p < 0.001) decreased significantly. Systolic and diastolic RV function parameters of HLHS patients decreased from 1.6 to 5.1 years after TCPC in our patients. Changes in global strain rate parameters may be signaling early RV dysfunction that is not detectable by traditional echocardiography. Further study is needed to verify this and to determine whether these changes are clinically relevant.     

Post-liver transplant biliary complications: Current knowledge and therapeutic advances

Liver transplantation is the current standard of care for end-stage liver disease and an accepted therapeutic option for acute liver failure and primary liver tumors.Despite the remarkable advances in the surgical techniques and immunosuppressive therapy,the postoperative morbidity and mortality still remain high and the leading causes are biliary complications,which affect up to one quarter of recipients.The most common biliary complications are anastomotic and non-anastomotic biliary strictures,leaks,bile duct stones,sludge and casts.Despite the absence of a recommended treatment algorithm many options are available,such as surgery,percutaneous techniques and interventional endoscopy.In the last few years,endoscopic techniques have widely replaced the more aggressive percutaneous and surgical approaches.Endoscopic retrograde cholangiography is the preferred technique when duct-to-duct anastomosis has been performed.Recently,new devices and techniques have been developed and this has led to a remarkable increase in the success rate of minimally invasive procedures.Understanding the mechanisms of biliary complications helps in their early recognition which is the prerequisite for successful treatment.Aggressive endoscopic therapy is essential for the reduction of morbidity and mortality in these cases.This article focuses on the common post-transplant biliary complications and the available interventional treatment modalities.