A Novel Method for Measurement of Cardiovascular Responses to Lower Body Negative Pressure in the Awake Instrumented Rat.

Lower body negative pressure (LBNP) has been used for decades in humans to model arterial baroreceptor unloading and represents a powerful tool for evaluating cardiovascular responses to orthostatic challenge. However, LBNP studies in animals have been limited to conditions of anesthesia or sedation, where cardiovascular reflexes are altered. Given the consequent uncertainties, the usefulness of LBNP studies in these preclinical models has been severely hampered.

Fast skeletal myosin binding protein-C expression exacerbates dysfunction in heart failure.

Unlabelled: During heart failure, gene and protein expression profiles undergo extensive compensatory and pathological remodeling. We previously observed that fast skeletal myosin binding protein-C (fMyBP-C) is upregulated in diseased mouse hearts. While fMyBP-C shares significant homology with its cardiac paralog, cardiac myosin binding protein-C (cMyBP-C), there are key differences that may affect cardiac function.

Unlocking the Role of sMyBP-C: A Key Player in Skeletal Muscle Development and Growth.

Skeletal muscle is the largest organ in the body, responsible for gross movement and metabolic regulation. Recently, variants in the gene have been implicated in a variety of developmental muscle diseases, such as distal arthrogryposis. How variants cause disease is not well understood.

Antenatal consultation and deliberation: adapting to parental preferences.

Objective: To analyze and compare perspectives on antenatal consultation and decision-making from participants with varying degrees of prematurity experience and clinician-experts.

Study Design: Open-ended interviews structured around topics previously identified by recognized clinician-experts were conducted with participants having different levels of prematurity experience. Analysis used mixed methods (thematic and mental models analysis).

HuR inhibition reduces post-ischemic cardiac remodeling by dampening acute inflammatory gene expression and the innate immune response.

Myocardial ischemia/reperfusion (I/R) injury and the resulting cardiac remodeling is a common cause of heart failure. The RNA binding protein Human Antigen R (HuR) has been previously shown to reduce cardiac remodeling following both I/R and cardiac pressure overload, but the full extent of the HuR-dependent mechanisms within cells of the myocardium have yet to be elucidated. In this study, we applied a novel small molecule inhibitor of HuR to define the functional role of HuR in the acute response to I/R injury and gain a better understanding of the HuR-dependent mechanisms during post-ischemic myocardial remodeling.

Pharmacologic Inhibition of Pain Response to Incomplete Vascular Occlusion Blunts Cardiovascular Preconditioning Response.

Complete vascular occlusion to distant tissue prior to an ischemic cardiac event can provide significant cardioprotection via remote ischemic preconditioning (RIPC). Despite understanding its mechanistic basis, its translation to clinical practice has been unsuccessful, likely secondary to the inherent impossibility of predicting (and therefore preconditioning) an ischemic event, as well as the discomfort that is associated with traditional, fully occlusive RIPC stimuli. Our laboratory has previously shown that non-occlusive banding (NOB) via wrapping of a leather band (similar to a traditional Jewish ritual) can elicit an RIPC response in healthy human subjects.

Bereaved Parents: Insights for the Antenatal Consultation.

Objective: The study aimed to explore experiences of extremely preterm infant loss in the delivery room and perspectives about antenatal consultation.

Study Design: Bereaved participants were interviewed, following a semi-structured protocol. Personal narratives were analyzed with a mixed-methods approach.

Fast skeletal myosin-binding protein-C regulates fast skeletal muscle contraction.

Fast skeletal myosin-binding protein-C (fMyBP-C) is one of three MyBP-C paralogs and is predominantly expressed in fast skeletal muscle. Mutations in the gene that encodes fMyBP-C, , are associated with distal arthrogryposis, while loss of fMyBP-C protein is associated with diseased muscle. However, the functional and structural roles of fMyBP-C in skeletal muscle remain unclear.

How to hold an effective NICU family meeting: capturing parent perspectives to build a more robust framework.

Objective: To record the content and parental perceptions of family meetings in a Neonatal Intensive Care Unit (NICU) to improve existing frameworks for facilitating these meetings.

Study Design: A prospective, mixed-methods study. NICU family meetings were audio-recorded, transcribed, and analyzed by an iteratively derived coding framework until thematic saturation.

Patterns of Urinary Neutrophil Gelatinase-Associated Lipocalin and Acute Kidney Injury in Neonates Receiving Cardiopulmonary Bypass.

Unlabelled: Elevated urinary neutrophil gelatinase-associated lipocalin (uNGAL) predicts acute kidney injury (AKI) in children following cardiopulmonary bypass (CPB) during cardiac surgery, but little is known about uNGAL's predictive ability in neonates in this setting. We sought to determine the relationship between AKI and post-CPB uNGAL in neonates in the first 72 post-operative hours.

Methods: Urine samples for uNGAL analysis were collected at preoperative baseline and serially post-operatively from 76 neonates undergoing CPB.

Autonomic dysfunction following traumatic brain injury: translational insights.

Although there is a substantial amount of research on the neurological consequences of traumatic brain injury (TBI), there is a knowledge gap regarding the relationship between TBI and the pathophysiology of organ system dysfunction and autonomic dysregulation. In particular, the mechanisms or incidences of renal or cardiac complications after TBI are mostly unknown. Autonomic dysfunction following TBI exacerbates secondary injury and may contribute to nonneurologial complications that prolong hospital length of stay.

V2a Neurons Constrain Extradiaphragmatic Respiratory Muscle Activity at Rest.

Breathing requires precise control of respiratory muscles to ensure adequate ventilation. Neurons within discrete regions of the brainstem produce oscillatory activity to control the frequency of breathing. Less is understood about how spinal and pontomedullary networks modulate the activity of respiratory motor neurons to produce different patterns of activity during different behaviors (i.

Acoustic droplet vaporization-mediated dissolved oxygen scavenging in blood-mimicking fluids, plasma, and blood.

Acoustic droplet vaporization (ADV) has been shown to reduce the partial pressure of oxygen (PO) in a fluid. The goals of this study were three-fold: 1) to determine the ADV pressure amplitude threshold in fluids that had physiologically relevant values for surface tension, protein concentration, and viscosity; 2) to assess whether these parameters and fluid mixing affect ADV-mediated PO reduction; and 3) to assess the feasibility of ADV-mediated PO reduction in plasma and whole blood. In vitro ADV experiments were conducted using perfluoropentane droplets (number density: 5 × 10 ± 0.

Ablation of the calpain-targeted site in cardiac myosin binding protein-C is cardioprotective during ischemia-reperfusion injury.

Cardiac myosin binding protein-C (cMyBP-C) phosphorylation is essential for normal heart function and protects the heart from ischemia-reperfusion (I/R) injury. It is known that protein kinase-A (PKA)-mediated phosphorylation of cMyBP-C prevents I/R-dependent proteolysis, whereas dephosphorylation of cMyBP-C at PKA sites correlates with its degradation. While sites on cMyBP-C associated with phosphorylation and proteolysis co-localize, the mechanisms that link cMyBP-C phosphorylation and proteolysis during cardioprotection are not well understood.

Human antigen R as a therapeutic target in pathological cardiac hypertrophy.

RNA binding proteins represent an emerging class of proteins with a role in cardiac dysfunction. We show that activation of the RNA binding protein human antigen R (HuR) is increased in the failing human heart. To determine the functional role of HuR in pathological cardiac hypertrophy, we created an inducible cardiomyocyte-specific HuR-deletion mouse and showed that HuR deletion reduces left ventricular hypertrophy, dilation, and fibrosis while preserving cardiac function in a transverse aortic constriction (TAC) model of pressure overload-induced hypertrophy.

Cardiac Dysfunction in the Sigma 1 Receptor Knockout Mouse Associated With Impaired Mitochondrial Dynamics and Bioenergetics.

Background The Sigma 1 receptor (Sigmar1) functions as an interorganelle signaling molecule and elicits cytoprotective functions. The presence of Sigmar1 in the heart was first reported on the basis of a ligand-binding assay, and all studies to date have been limited to pharmacological approaches using less-selective ligands for Sigmar1. However, the physiological function of cardiac Sigmar1 remains unknown.

NBCe1 Na-HCO3 cotransporter ablation causes reduced apoptosis following cardiac ischemia-reperfusion injury .

Aim: To investigate the hypothesis that cardiomyocyte-specific loss of the electrogenic NBCe1 Na-HCO cotransporter is cardioprotective during ischemia-reperfusion (IR) injury.

Methods: An NBCe1 ( gene) conditional knockout mouse (KO) model was prepared by gene targeting. Cardiovascular performance of wildtype (WT) and cardiac-specific NBCe1 KO mice was analyzed by intraventricular pressure measurements, and changes in cardiac gene expression were determined by RNA Seq analysis.

Provider Perceptions of Bubble Continuous Positive Airway Pressure and Barriers to Implementation in a Level III Neonatal Unit in South India.

Background: Bubble continuous positive airway pressure (bCPAP) is a simple, safe, and cost-effective strategy to provide respiratory support to newborns with respiratory distress syndrome in resource-limited settings.

Purpose: To understand whether implementation of bCPAP, relative to other modes of respiratory support in the care of newborns with respiratory distress syndrome, increases positive attitudes about its potential for consistent and widespread use among providers in neonatal intensive care units (NICUs) of lower middle-income countries.

Methods: Semistructured qualitative interviews with 14 healthcare providers, including 5 neonatal nurses, 2 respiratory therapists, 5 postgraduate trainees in pediatrics, and 2 attending physicians, were conducted at a level III NICU in south India where bCPAP had been in consistent use for 6 years.

You Can't Take Your Baby Home Yet: A Longitudinal Study of Psychological Symptoms in Mothers of Infants Hospitalized in the NICU.

Evidence suggests that mothers of infants hospitalized in the Neonatal Intensive Care Unit (NICU) experience elevated rates of psychological symptoms. However, previous studies of this population have been mainly cross-sectional and have focused on very preterm infants. Although moderate- to late-preterm infants generally thrive, the possible psychological toll on their mothers has not yet been sufficiently examined.

Tranilast Blunts the Hypertrophic and Fibrotic Response to Increased Afterload Independent of Cardiomyocyte Transient Receptor Potential Vanilloid 2 Channels.

Tranilast is clinically indicated for the treatment of allergic disorders and is also a nonselective blocker of the transient receptor potential vanilloid 2 (TRPV2) channel. Previous studies have found that it has protective effects in various animal models of cardiac disease. Our laboratory has found that genetic deletion of TRPV2 results in a blunted hypertrophic response to increased afterload; thus, this study tested the hypothesis that tranilast through cardiomyocyte TRPV2 blockade can inhibit the hypertrophic response to pressure overload in vivo through transverse aortic constriction and ex vivo through isolated myocyte studies.

Inhibiting Fibronectin Attenuates Fibrosis and Improves Cardiac Function in a Model of Heart Failure.

Background: Fibronectin (FN) polymerization is necessary for collagen matrix deposition and is a key contributor to increased abundance of cardiac myofibroblasts (MFs) after cardiac injury. We hypothesized that interfering with FN polymerization or its genetic ablation in fibroblasts would attenuate MF and fibrosis and improve cardiac function after ischemia/reperfusion (I/R) injury.

Methods: Mouse and human MFs were used to assess the impact of the FN polymerization inhibitor (pUR4) in attenuating pathological cellular features such as proliferation, migration, extracellular matrix deposition, and associated mechanisms.