Failing Hearts Are More Vulnerable to Sympathetic, but Not Vagal Stimulation-Induced, Atrial Fibrillation-Ameliorated with Dantrolene Treatment.

BACKGROUND: Both vagal (VS) and sympathetic (SS) stimulations can increase atrial fibrillation (AF) inducibility, with VS being known as more arrhythmogenic in normal hearts. Heart failure (HF) results in autonomic dysfunction (characterized by sympathetic activation and vagal withdrawal) and is associated with an increased AF incidence. This study investigated whether failing hearts, compared with normal control hearts, respond differently to autonomic stimulation-induced AF arrhythmogenesis and the effect of dantrolene on SS-enhanced AF in HF. METHODS AND RESULTS: A rat myocardial infarction (MI) HF model was used. In experiment 1, AF inducibility was compared in 9 MI-HF rats versus 10 sham-control animals at baseline, during VS, and during SS with isoproterenol infusion. In experiment 2, dantrolene treatment (n = 8) was compared with placebo-control (n = 9) on SS-induced AF inducibility in HF. Compared with the sham-control, baseline AF inducibility was higher in the MI-HF group. AF inducibility was augmented in both groups by autonomic stimulation. However, under VS the increased magnitude was less in the MI-HF group (49% ± 11% vs 80% ± 10%; P = .029), but under SS was significantly more (53% ± 8% vs 6% ± 7%; P < .001), compared with sham-control. Dantrolene significantly attenuated SS-enhanced AF in HF (69% ± 6% vs 29% ± 9%; P = .006). CONCLUSIONS: Failing hearts are less sensitive to VS, but more vulnerable to SS-induced AF compared with normal-control hearts. Dantrolene can significantly attenuate SS-enhanced AF in HF, indicating that cardiac ryanodine receptor dysfunction may play a critical role in SS-enhanced AF in HF, and stabilizing leaky ryanodine receptor with the use of dantrolene may be a new treatment option in this condition.

Electrical synaptic transmission in developing zebrafish: properties and molecular composition of gap junctions at a central auditory synapse.

In contrast to the knowledge of chemical synapses, little is known regarding the properties of gap junction-mediated electrical synapses in developing zebrafish, which provide a valuable model to study neural function at the systems level. Identifiable "mixed" (electrical and chemical) auditory synaptic contacts known as "club endings" on Mauthner cells (2 large reticulospinal neurons involved in tail-flip escape responses) allow exploration of electrical transmission in fish. Here, we show that paralleling the development of auditory responses, electrical synapses at these contacts become anatomically identifiable at day 3 postfertilization, reaching a number of ∼6 between days 4 and 9. Furthermore, each terminal contains ∼18 gap junctions, representing between 2,000 and 3,000 connexon channels formed by the teleost homologs of mammalian connexin 36. Electrophysiological recordings revealed that gap junctions at each of these contacts are functional and that synaptic transmission has properties that are comparable with those of adult fish. Thus a surprisingly small number of mixed synapses are responsible for the acquisition of auditory responses by the Mauthner cells, and these are likely sufficient to support escape behaviors at early developmental stages.

Hemodynamic Support With the Impella 5.5 Acute Mechanical Circulatory Support Device.

The Impella 5.5 is increasingly used as a bridge to recovery or heart replacement therapies despite lack of clinical trial evidence. We report real-world outcomes and hemodynamic effects of 150 consecutive patients from a single, high-volume center. Primary outcome was incidence of recovery, durable left ventricular assist device (LVAD), or heart transplant compared with incidence of death at 90 days. Secondary outcomes included hemodynamic trends and upgrade to veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support. The composite endpoint occurred in 59.3% and death in 18.8% of patients (incidence rate ratio: 8.1 [95% confidence interval {CI}: 5.4-12.2], p < 0.001). Decreases in pulmonary artery diastolic pressure (PADP) (p = 0.026), estimated pulmonary effective arterial elastance (Ea) (p < 0.001), and vasoactive-inotropic score (VIS) (p < 0.001) occurred during Impella 5.5 support. Pulmonary artery diastolic pressure correlated with estimated Ea (p < 0.001), suggesting improved right ventricle (RV) afterload with left ventricle (LV) unloading. Veno-arterial extracorporeal membrane oxygenation upgrade occurred in 11.3% of patients who had higher baseline right atrial pressure (RAP) (16.0 [9.0-20.5] vs. 9.0 [7.0-12.0], p = 0.022), PADP (28.5 [25.0-31.0] vs. 23.0 [18.0-28.0], p = 0.011), and lower pulmonary artery pulsatility index (PAPi) (1.45 [0.82-3.45] vs. 2.5 [1.65-3.86], p = 0.029). Upgrade patients had higher repeated measures trends in RAP (p < 0.001) and PADP (p = 0.015). The Impella 5.5 improved hemodynamics and effectively bridged to recovery or heart replacement therapies. Co-existing RV dysfunction can be supported on Impella 5.5 with careful hemodynamic trend monitoring.

Correlation between severity of obesity and mortality in cardiogenic shock.

INTRODUCTION: Cardiogenic shock (CS) is associated with high mortality despite the development of risk stratification tools and new treatment strategies. Obesity, although a risk factor for cardiovascular disease, is not included in current risk stratification tools for CS. A relationship between mortality and obesity has only been shown in subsets populations of CS; there is not yet a clear relationship between severity of obesity and all-cause CS. OBJECTIVES: In this study we evaluate the relationship between rising body mass index (BMI) and mortality in all-cause CS. METHODS: All patients with BMI measurements and hospitalizations complicated by CS from 2014 to 2019 at a single quaternary care institution were identified. Patients were grouped by obesity classification. Multivariate logistic regression was performed to determine a relationship between higher obesity classifications with 30-day mortality in patients with CS. RESULTS: Seventy-two patients were available for analysis. Mean BMI for those who survived compared to those who did not was 29.7 ± 8 kg/m2 vs 33.7 ± 7.6 kg/m2 (p = 0.04). The odds ratio for mortality with incremental increase in obesity classification was 1.6 (95% CI 1.1 - 2.6, p = 0.03) after adjusting for etiology of CS and other common associations with CS mortality. CONCLUSION: This study suggests that the higher mortality risk with incremental increases in BMI should be taken into account when risk stratifying these patients.

Cardiac implantable device interrogation in left ventricular systolic dysfunction reveals physiologic abnormalities prior to symptom onset in COVID-19: a case series.

Background: COVID-19 has affected individuals across the globe, and those with cardiac implantable electronic devices (CIEDs) likely represent a high-risk group. These devices can be interrogated to reveal information about the patient activity, heart rate parameters, and respiratory rate. Case summary: Four patients with CIEDs and left ventricular dysfunction were admitted to a single institution for COVID-19 infection. Each patient survived hospitalization, and none required intensive care. Retrospectively, CIED interrogation revealed each patient had decreased activity level prior to their reporting COVID-19 symptoms. Similarly, respiratory rate increased before symptom onset for three of the patients, while one did not have these data available. Of the three patients with heart rate variability (HRV) available, two had decreased HRV before they developed symptoms. After hospital discharge, these parameters returned to their baseline. Discussion: This case series suggests physiologic changes identifiable through interrogation of CIEDs may occur prior to the reported onset of COVID-19 symptoms. These data may provide objective evidence on which to base more sensitive assessments of infectious risk when performing contact tracing in communities.

Reduced epicardial vagal nerve density and impaired vagal control in a rat myocardial infarction-heart failure model.

BACKGROUND: Autonomic remodeling, characterized by sympathetic activation and vagal withdrawal, contributes to heart failure (HF) progression. However, the exact mechanism(s) responsible for vagal withdrawal in HF remain(s) unclear, and whether HF causes epicardial autonomic nerve remodeling is unknown. METHODS AND RESULTS: Myocardial infarction (MI) was produced in 14 Sprague-Dawley rats, and 10 sham surgery rats served as the control. MI-HF was confirmed 2 months after the surgery by echocardiography and hemodynamic measurement. Cervical vagal nerve stimulation was delivered to examine the heart rate slowing effect. Whole heart acetylcholinesterase histochemistry was used to examine the epicardial autonomic nerve remodeling at dorsal ventricles (remote from the infarcted area). Compared with the control animals, the same vagal nerve stimulation had less heart rate slowing effect in MI-HF group. Both epicardial nerve bundle length-density (2.56±0.60 µm/mm2 versus 1.68±0.46 µm/mm2, P=.001) and branching point-density (1.24±0.25 points/mm2 versus 0.66±0.18 points/mm2, P<.001) were lower in MI-HF rats. The chemically stained epicardial nerve bundles contain both sympathetic (tyrosine hydroxylase positive) and vagal (choline acetyltransferase positive) fibers. However, within the stained nerve bundle, the chemical color corresponds mainly with the vagal fibers. CONCLUSIONS: Whole heart acetylcholinesterase histochemistry revealed a decreased ventricular epicardial vagal nerve density in MI-HF rats, which may contribute to impaired cardiac vagal control in HF.

A Gram Stain Hands-On Workshop Enhances First Year Medical Students' Technique Competency in Comprehension and Memorization.

BACKGROUND: Laboratory diagnostic tests have an essential role in patient care, and the increasing number of medical and health professions schools focusing on teaching laboratory medicine to pre-clinical students reflects this importance. However, data validating the pedagogical methods that best influence students' comprehension and interpretation of diagnostic tests have not been well described. The Gram stain is a simple yet significant and frequently used diagnostic test in the clinical setting that helps classify bacteria into two major groups, Gram positive and negative, based on their cell wall structure. METHODS AND FINDINGS: We used this technique to assess which educational strategies may improve students' learning and competency in medical diagnostic techniques. Hence, in this randomized controlled study, we compared the effectiveness of several educational strategies (e.g. workshop, discussion, or lecture) in first year medical students' competency in comprehension and interpretation of the Gram stain procedure. We demonstrated that a hands-on practical workshop significantly enhances students' competency in memorization and overall comprehension of the technique. Interestingly, most students irrespective of their cohort showed difficulty in answering Gram stain-related analytical questions, suggesting that more emphasis should be allocated by the instructors to clearly explain the interpretation of the diagnostic test results to students in medical and health professional schools. CONCLUSION: This proof of principle study highlights the need of practical experiences on laboratory medical techniques during pre-clinical training to facilitate future medical doctors' and healthcare professionals' basic understanding and competency in diagnostic testing for better patient care.