Percutaneous cardioplegic arrest before repeat sternotomy in patients with retrosternal aortic aneurysm.

OBJECTIVE: Redo sternotomy in patients with arterial cardiac structures adherent to the sternum carries a risk of catastrophic bleeding. In some of those cases, particularly if they have undergone multiple previous operations, deep hypothermic circulatory arrest alone may not provide sufficient time for a controlled dissection. METHODS: We present a series of 6 cases at risk for exsanguination during sternal re-entry successfully reoperated using percutaneous cardioplegic cardiac arrest induced before completed sternal re-entry to avoid or minimize the hypothermic circulatory arrest time. RESULTS: All patients survived their complex operations. CONCLUSIONS: Percutaneous cardioplegic arrest allows safer repeat sternotomy in patients with arterial cardiac structures adherent to the sternum.

Anesthetic Management for Paraesophageal Hernia Repair.

Paraesophageal hernia repairs are complex surgical cases frequently performed on patients of advanced age with multiple comorbidities, both of which create difficulties in the anesthetic management. Preoperative evaluation is challenging because of overlapping cardiopulmonary symptoms. The patient's symptoms and anatomy lead to an increased aspiration risk and the potential need for a rapid sequence induction. Depending on the surgical approach, lung isolation may be required. Communication with the surgeon is vital throughout the case, especially when placing gastric tube and bougies. Multimodal analgesia should include regional and/or neuraxial techniques, in addition to the standard intravenous and oral pain medications.

Prenatal stress-immune programming of sex differences in comorbidity of depression and obesity/metabolic syndrome.

Major depressive disorder (MDD) is the number one cause of disability worldwide and is comorbid with many chronic diseases, including obesity/metabolic syndrome (MetS). Women have twice as much risk for MDD and comorbidity with obesity/MetS as men, although pathways for understanding this association remain unclear. On the basis of clinical and preclinical studies, we argue that prenatal maternal stress (ie, excess glucocorticoid expression and associated immune responses) that occurs during the sexual differentiation of the fetal brain has sex-dependent effects on brain development within highly sexually dimorphic regions that regulate mood, stress, metabolic function, the autonomic nervous system, and the vasculature. Furthermore, these effects have lifelong consequences for shared sex-dependent risk of MDD and obesity/MetS. Thus, we propose that there are shared biologic substrates at the anatomical, molecular, and/or genetic levels that produce the comorbid risk for MDD-MetS through sex-dependent fetal origins.

El trastorno depresivo mayor (TDM) es la causa número uno de incapacidad en el mundo y es comórbido con muchas enfermedades crónicas, incluyendo la obesidad y el síndrome metabólico (SMet). Si bien las mujeres tienen el doble de riesgo que los hombres para el TDM y para la comorbilidad con obesidad y SMet, aun no se han aclarado las bases para comprender esta asociación. En base a estudios clínicos y preclínicos, se argumenta que el estrés materno prenatal (como la expresión excesiva de glucocorticoides y las respuestas inmunes asociadas) que ocurre durante la diferenciación sexual del cerebro fetal tiene efectos dependientes del sexo sobre el desarrollo cerebral en las regiones con alto dimorfismo sexual que regulan el ánimo, el estrés, la función metabólica, el sistema nervioso autónomo y la vascularización. Además, estos efectos tienen consecuencias a lo largo de la vida para el riesgo compartido sexo-dependiente para TDM y obesidad/SMet. Por lo tanto, se propone que hay sustratos biológicos compartidos a niveles anatómicos, moleculares y/o genéticos que producirían el riesgo comórbido para el TDM-SMet a través de orígenes fetales sexo-dependientes.

Le trouble dépressif caractérisé (TDC) est la première cause d'invalidité dans le monde et il existe une comorbidité avec de nombreuses maladies chroniques, dont le syndrome métabolique/obésité (SMet). Le risque de TDC est deux fois plus élevé chez les femmes ayant un SMet que chez les hommes, mais les tenants et les aboutissants de cette association sont encore mal compris. Au vu des études cliniques et précliniques existantes, nous soutenons que le stress maternel prénatal (c'est-à-dire l'excès de libération de glucocorticoïdes et les réponses immunes associées) qui survient pendant la différentiation sexuelle du cerveau du foetus a des effets dépendant du sexe sur le développement cérébral dans des régions très dimorphiques sexuellement, régulant l'humeur, le stress, la fonction métabolique, le système nerveux autonome et la vascularisation. De plus, les conséquences de ces effets pour le risque partagé de TDC et de SMet/obésité en fonction du sexe durent toute la vie. Nous pensons donc qu'il existerait des substrats biologiques partagés aux niveaux anatomique, moléculaire et/ou génétique qui seraient responsables du risque comorbide de TDC-SMet selon le sexe du foetus.

Gene Therapy of the Peripheral Nervous System: Celiac Ganglia.

Gene therapy has played an integral role in advancing our understanding of the central nervous system. However, gene therapy techniques have yet to be widely utilized in the peripheral nervous system. Critical targets for gene therapy within the PNS are the neurons in sympathetic ganglia, which are the final pathway to end organs. Thus they are the most specific targets for organ-specific neuron modification. This presents challenges because neurons are not viscerotopically organized within the ganglia and therefore cannot be targeted by their location. However, organ-specific neurons have been identified in sympathetic ganglia of some species and this offers an opportunity for targeting and transducing neurons by way of their target. In fact, alterations in sympathetic neurons have had pathological effects, and transducing organ-specific sympathetic neurons offer an exciting opportunity to selectively modify sympathetic pathology. In this chapter, we describe a method to virally transduce the celiac ganglion (CG), a prevertebral sympathetic ganglion that innervates abdominal organs, with AAV serotypes 1 and 6; thereby, providing a potential avenue to modulate specific subsets of neurons within the celiac ganglion.

Disruption of mitochondrial DNA replication in Drosophila increases mitochondrial fast axonal transport in vivo.

Mutations in mitochondrial DNA polymerase (pol gamma) cause several progressive human diseases including Parkinson's disease, Alper's syndrome, and progressive external ophthalmoplegia. At the cellular level, disruption of pol gamma leads to depletion of mtDNA, disrupts the mitochondrial respiratory chain, and increases susceptibility to oxidative stress. Although recent studies have intensified focus on the role of mtDNA in neuronal diseases, the changes that take place in mitochondrial biogenesis and mitochondrial axonal transport when mtDNA replication is disrupted are unknown. Using high-speed confocal microscopy, electron microscopy and biochemical approaches, we report that mutations in pol gamma deplete mtDNA levels and lead to an increase in mitochondrial density in Drosophila proximal nerves and muscles, without a noticeable increase in mitochondrial fragmentation. Furthermore, there is a rise in flux of bidirectional mitochondrial axonal transport, albeit with slower kinesin-based anterograde transport. In contrast, flux of synaptic vesicle precursors was modestly decreased in pol gamma-alpha mutants. Our data indicate that disruption of mtDNA replication does not hinder mitochondrial biogenesis, increases mitochondrial axonal transport, and raises the question of whether high levels of circulating mtDNA-deficient mitochondria are beneficial or deleterious in mtDNA diseases.