Outcomes of hypothalamic oxytocin neuron-driven cardioprotection after acute myocardial infarction.

Altered autonomic balance is a hallmark of numerous cardiovascular diseases, including myocardial infarction (MI). Although device-based vagal stimulation is cardioprotective during chronic disease, a non-invasive approach to selectively stimulate the cardiac parasympathetic system immediately after an infarction does not exist and is desperately needed. Cardiac vagal neurons (CVNs) in the brainstem receive powerful excitation from a population of neurons in the paraventricular nucleus (PVN) of the hypothalamus that co-release oxytocin (OXT) and glutamate to excite CVNs. We tested if chemogenetic activation of PVN-OXT neurons following MI would be cardioprotective. The PVN of neonatal rats was transfected with vectors to selectively express DREADDs within OXT neurons. At 6 weeks of age, an MI was induced and DREADDs were activated with clozapine-N-oxide. Seven days following MI, patch-clamp electrophysiology confirmed the augmented excitatory neurotransmission from PVN-OXT neurons to downstream nuclei critical for parasympathetic activity with treatment (43.7 ± 10 vs 86.9 ± 9 pA; MI vs. treatment), resulting in stark improvements in survival (85% vs. 95%; MI vs. treatment), inflammation, fibrosis assessed by trichrome blue staining, mitochondrial function assessed by Seahorse assays, and reduced incidence of arrhythmias (50% vs. 10% cumulative incidence of ventricular fibrillation; MI vs. treatment). Myocardial transcriptomic analysis provided molecular insight into potential cardioprotective mechanisms, which revealed the preservation of beneficial signaling pathways, including muscarinic receptor activation, in treated animals. These comprehensive results demonstrate that the PVN-OXT network could be a promising therapeutic target to quickly activate beneficial parasympathetic-mediated cellular pathways within the heart during the early stages of infarction.

Open thoracic surgical implantation of cardiac pacemakers in rats.

Genetic engineering and implantable bioelectronics have transformed investigations of cardiovascular physiology and disease. However, the two approaches have been difficult to combine in the same species: genetic engineering is applied primarily in rodents, and implantable devices generally require larger animal models. We recently developed several miniature cardiac bioelectronic devices suitable for mice and rats to enable the advantages of molecular tools and implantable devices to be combined. Successful implementation of these device-enabled studies requires microsurgery approaches that reliably interface bioelectronics to the beating heart with minimal disruption to native physiology. Here we describe how to perform an open thoracic surgical technique for epicardial implantation of wireless cardiac pacemakers in adult rats that has lower mortality than transvenous implantation approaches. In addition, we provide the methodology for a full biocompatibility assessment of the physiological response to the implanted device. The surgical implantation procedure takes ~40 min for operators experienced in microsurgery to complete, and six to eight surgeries can be completed in 1 d. Implanted pacemakers provide programmed electrical stimulation for over 1 month. This protocol has broad applications to harness implantable bioelectronics to enable fully conscious in vivo studies of cardiovascular physiology in transgenic rodent disease models.

Fully implantable and bioresorbable cardiac pacemakers without leads or batteries.

Temporary cardiac pacemakers used in periods of need during surgical recovery involve percutaneous leads and externalized hardware that carry risks of infection, constrain patient mobility and may damage the heart during lead removal. Here we report a leadless, battery-free, fully implantable cardiac pacemaker for postoperative control of cardiac rate and rhythm that undergoes complete dissolution and clearance by natural biological processes after a defined operating timeframe. We show that these devices provide effective pacing of hearts of various sizes in mouse, rat, rabbit, canine and human cardiac models, with tailored geometries and operation timescales, powered by wireless energy transfer. This approach overcomes key disadvantages of traditional temporary pacing devices and may serve as the basis for the next generation of postoperative temporary pacing technology.

Complications and Management of the Thoracic Endovascular Aortic Repair.

Endovascular treatment in thoracic aortic diseases has increased in use exponentially since Dake and colleagues first described the use of a home-made transluminal endovascular graft on 13 patients with descending thoracic aortic aneurysm at Stanford University in the early 1990s. Thoracic endovascular aneurysm repair (TEVAR) was initially developed for therapy in patients deemed unfit for open surgery. Innovations in endograft engineering design and popularization of endovascular techniques have transformed TEVAR to the predominant treatment choice in elective thoracic aortic repair. The number of TEVARs performed in the United States increased by 600% from 1998 to 2007, while the total number of thoracic aortic repairs increased by 60%. As larger multicenter trials and meta-analysis studies in the 2000s demonstrate the significant decrease in perioperative morbidity and mortality of TEVAR over open repair, TEVAR became incorporated into standard guidelines. The 2010 American consensus guidelines recommend TEVAR to be "strongly considered" when feasible for patients with degenerative or traumatic aneurysms of the descending thoracic aorta exceeding 5.5 cm, saccular aneurysms, or postoperative pseudoaneurysms. Nowadays, TEVAR is the predominant treatment for degenerative and traumatic descending thoracic aortic aneurysm repair. Although TEVAR has been shown to have decreased early morbidity and mortality compared with open surgical repair, endovascular manipulation of a diseased aorta with endovascular devices continues to have significant risks. Despite continued advancement in endovascular technique and devices since the first prospective trial examined the complications associated with TEVAR, common complications, two decades later, still include stroke, spinal cord ischemia, device failure, unintentional great vessel coverage, access site complications, and renal injury. In this article, we review common TEVAR complications with some corresponding radiographic imaging and their management.

Use of an inverted On-X mitral valve in the aortic position in a resource limited setting.

Implanting an inverted aortic valve prosthesis in the mitral position has shown to be a viable solution for a small mitral annulus. We describe a case of implanting an inverted in the mitral prosthesis in the aortic position in a patient with an excessively large aortic annulus. A 46-year-old male with severe aortic insufficiency underwent aortic valve replacement during a surgical outreach program in Tegucigalpa, Honduras. Aortic valve annulus measured 30 mm on preoperative echocardiogram. An inverted On-X mechanical mitral heart valve with Conform-X sewing ring 25/33 mm was implanted with an excellent hemodynamic result and no paravalvular leak. To the best of our knowledge, this case demonstrates the first inverted mitral prosthesis implanted in the aortic valve position.

30-Day outcomes and predictors of complications after Puestow procedure.

BACKGROUND: A lateral pancreaticojejunostomy, or a Puestow procedure, is used in chronic pancreatitis with ductal dilation and pain. The current literature on the Puestow is sparse. This study examines outcomes of Puestow procedures nationwide. METHODS: Using ACS-NSQIP database, patients who underwent a Puestow procedure from 2010 to 2016 were identified. Univariate analysis and multivariable regression models were used to identify predictors of mortality and morbidities. Covariates included in the regression models were chosen based on clinical significance. RESULTS: The cohort included 524 patients. The 30-day mortality rate was 1.2%(n = 6). At least one major complication occurred in 19.1% of patients including death (1.2%), major organ dysfunction (8.2%), pulmonary embolism (1.3%), and surgical site infections (13.0%). Diabetes, COPD, and transfusions were the strongest predictors of complications. CONCLUSIONS: The Puestow procedure is an acceptable treatment modality with low rates of morbidity and mortality. Minimizing transfusions and optimizing pulmonary status may improve 30-day outcomes.

Giant Intracardiac Smooth-Muscle Cell Tumor Presenting as Superior Vena Cava Syndrome.

We report the case of a 53-year-old man presenting with a superior vena cava syndrome secondary to a giant intracardiac mass occupying the majority of the right-side cavities of the heart. A mass measuring 10.5 × 9.5 × 4.0 cm originating from the superior vena cava and occupying most of the right atrium extended through the tricuspid valve into the right ventricle. The mass was resected. The patient was discharged on postoperative day 11. The pathology report revealed the mass to be a smooth-muscle cell tumor of unknown malignant potential.

At the Atrioventricular Crossroads: Dual Pathway Electrophysiology in the Atrioventricular Node and its Underlying Heterogeneities.

The atrioventricular node (AVN) is a complex structure that performs a variety of functions in the heart. The AVN is primarily an electrical gatekeeper between the atria and ventricles and introduces a delay between atrial and ventricular excitation, allowing for efficient ventricular filling. The AVN is composed of several compartments that safely transmit electrical excitation from the atria to the ventricles via the fast or slow pathways. There are many electrophysiological differences between these pathways, including conduction time and electrical refractoriness, that increase the predisposition of the atrioventricular junction to arrhythmias such as atrioventricular nodal re-entrant tachycardia. These varied electrophysiological characteristics of the fast and slow pathways stem from their unique structural and molecular composition (tissue and cellular geometry, ion channels and gap junctions). This review summarises the structural and molecular heterogeneities of the human AVN and how they result in electrophysiological variations and arrhythmias.