Awake Prone Positioning Strategy for Nonintubated Hypoxic Patients with COVID-19: A Pilot Trial with Embedded Implementation Evaluation.

Prone positioning is an appealing therapeutic strategy for nonintubated hypoxic patients with coronavirus disease (COVID-19), but its effectiveness remains to be established in randomized controlled trials. To identify contextual factors relevant to the conduct of a definitive clinical trial evaluating a prone positioning strategy for nonintubated hypoxic patients with COVID-19. We conducted a cluster randomized pilot trial at a quaternary care teaching hospital.

Pharmacologic resuscitation for hemorrhagic shock combined with traumatic brain injury.

Background: We have previously demonstrated that valproic acid (VPA), a histone deacetylase inhibitor, can improve survival after hemorrhagic shock (HS), protect neurons from hypoxia-induced apoptosis, and attenuate the inflammatory response. We have also shown that administration of 6% hetastarch (Hextend [Hex]) after traumatic brain injury (TBI) decreases brain swelling, without affecting size of the lesion. This study was performed to determine whether addition of VPA to Hex would decrease the lesion size in a clinically relevant large animal model of TBI + HS.

Heat resistance and salt hypersensitivity in Lactococcus lactis due to spontaneous mutation of llmg_1816 (gdpP) induced by high-temperature growth.

During construction of several gene deletion mutants in Lactococcus lactis MG1363 which involved a high-temperature (37.5°C) incubation step, additional spontaneous mutations were observed which resulted in stable heat resistance and in some cases salt-hypersensitive phenotypes. Whole-genome sequencing of one strain which was both heat resistant and salt hypersensitive, followed by PCR and sequencing of four other mutants which shared these phenotypes, revealed independent mutations in llmg_1816 in all cases.

Histone deacetylase inhibitor suberoylanilide hydroxamic acid attenuates Toll-like receptor 4 signaling in lipopolysaccharide-stimulated mouse macrophages.

Objective: We have previously demonstrated that pretreatment and posttreatment of animals with suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, can improve survival in a mouse model of lipopolysaccharide (LPS)-induced severe shock. This study was designed to assess whether SAHA affects LPS/Toll-like receptor 4 signaling through acetylation of heat shock protein 90 (HSP90) and degradation of its client protein interleukin-1 receptor-associated kinase 1 (IRAK1).

Methods: RAW264.

Traumatic brain injury and hemorrhagic shock: evaluation of different resuscitation strategies in a large animal model of combined insults.

Traumatic brain injury (TBI) and hemorrhagic shock (HS) are the leading causes of trauma-related mortality and morbidity. Combination of TBI and HS (TBI + HS) is highly lethal, and the optimal resuscitation strategy for this combined insult remains unclear. A critical limitation is the lack of suitable large animal models to test different treatment strategies.

Increased cycle length during long-duration ventricular fibrillation is caused by decreased upstroke velocity as well as prolonged refractoriness.

Background: Cycle length (CL) increases as ventricular fibrillation (VF) progresses.

Objective: The purpose of this study was to test the hypotheses that increased CL is due to increased diastolic interval (DI), not increased action potential duration (APD), and that the DI increase is not solely due to increased postrepolarization refractoriness.

Methods: In 10 swine, VF was recorded for 20 minutes using a floating microelectrode through a hole in a 504-electrode epicardial plaque.

Transmural recording of shock potential gradient fields, early postshock activations, and refibrillation episodes associated with external defibrillation of long-duration ventricular fibrillation in swine.

Background: Knowledge of the shock potential gradient (nablaV) and postshock activation is limited to internal defibrillation of short-duration ventricular fibrillation (SDVF).

Objective: The purpose of this study was to determine these variables after external defibrillation of long-duration VF (LDVF).

Methods: In six pigs, 115-20 plunge needles with three to six electrodes each were inserted to record throughout both ventricles.

Chemical ablation of the Purkinje system causes early termination and activation rate slowing of long-duration ventricular fibrillation in dogs.

Endocardial mapping has suggested that Purkinje fibers may play a role in the maintenance of long-duration ventricular fibrillation (LDVF). To determine the influence of Purkinje fibers on LDVF, we chemically ablated the Purkinje system with Lugol solution and recorded endocardial and transmural activation during LDVF. Dog hearts were isolated and perfused, and the ventricular endocardium was exposed and treated with Lugol solution (n = 6) or normal Tyrode solution as a control (n = 6).

Intracoronary infusion of catecholamines causes focal arrhythmias in pigs.

Background: Acute ischemia causes myriad changes including increased catecholamines. We tested the hypothesis that elevated catecholamines alone are arrhythmogenic.

Methods And Results: A 504 electrode sock was placed over both ventricles in six open-chest pigs.

Effects of procainamide and sotalol on restitution properties, dispersion of refractoriness, and ventricular fibrillation activation patterns in pigs.

Background: Interest in combining antiarrhythmic drugs has been prompted by the lack of efficacy of monotherapies and the toxicity resulting from high doses of individual agents.

Objectives: We tested the hypothesis that procainamide and sotalol combined have greater beneficial effects on restitution, on the dispersion of refractoriness, and on decreasing the complexity of ventricular fibrillation (VF) than either drug alone.

Methods: Six open-chest pigs received intravenous procainamide (15 mg/kg load and 50 microg/kg/min maintenance) followed by sotalol (1.

Linear electrode arrays for stimulation and recording within cardiac tissue space constants.

In this paper, we document a fabrication process that yields linear arrays of rectangular platinum black electrodes spaced 25 mum apart with edge-to-edge separation of 20 microm. The spatial arrangement is therefore sufficiently fine to insure stimulation and recording within cardiac tissue space constants, as six electrodes with dimensions of either 5 x 100 microm2, 5 x 250 microm2, or 5 x 500 microm2 were positioned in a 130-microm2 span in the arrays. Despite the small electrode sizes and available surface areas, favorable impedance characteristics were identifed.

Optical measurements of intramural action potentials in isolated porcine hearts using optrodes.

Background: Measurements of intramural membrane potential (Vm) would greatly increase knowledge of cardiac arrhythmias and defibrillation. Optrodes offer the possibility for three-dimensional Vm mapping, but their signal quality has been inadequate.

Objective: The purpose of this work was to improve optrode signal quality and use optrodes to measure intramural distribution of action potentials and shock-induced Vm changes in porcine hearts.

Printed circuit board electrodes for transmural cardiac mapping.

Plunge needle recording techniques have provided valuable insights into transmural activation in cardiac tissue. Construction of plunge needles has been a costly and time intensive endeavor. Plunge needles constructed with standard printed circuit board (PCB) technology and methods are outlined.

Guidelines for plunge needle recording for effective detection of purkinje activation.

Direct recording of Purkinje fiber activity may lead to a better understanding of the role of the specialized conduction system in pathological cardiac conditions. Two studies were conducted in pigs to determine guidelines for effective plunge needle recording techniques. In the first experiment, Purkinje fiber activations were recorded at 16 KHz with 3 bipolar electrodes (2 mm spacing) on epoxy plunge needles, and were later lowpass filtered and downsampled to determine the rate required for effective identification of Purkinje activation.

The transmural activation sequence in porcine and canine left ventricle is markedly different during long-duration ventricular fibrillation.

Background: Humans are more similar in transmural Purkinje and cardiac ion channel distributions to dogs than pigs. The Purkinje network in pigs is transmural but confined to the endocardium in dogs. Little is known about intramural activation during long-duration ventricular fibrillation (LDVF) given these differences.

Role of maximum rate of depolarization in predicting action potential duration during ventricular fibrillation.

During ventricular fibrillation (VF) only 39% of the variation in action potential duration (APD) is accounted for by the previous diastolic interval [DI((n-1))], i.e., restitution, and the previous APD [APD((n-1))], i.

Activation patterns of Purkinje fibers during long-duration ventricular fibrillation in an isolated canine heart model.

Background: The roles of Purkinje fibers (PFs) and focal wave fronts, if any, in the maintenance of ventricular fibrillation (VF) are unknown. If PFs are involved in VF maintenance, it should be possible to map wave fronts propagating from PFs into the working ventricular myocardium during VF. If wave fronts ever arise focally during VF, it should be possible to map them appearing de novo.

Transmural and endocardial Purkinje activation in pigs before local myocardial activation after defibrillation shocks.

Background: Earliest recorded postshock myocardial activations in pigs originate in the subepicardium of the apex and lateral free wall of the left ventricle (LV) 30-90 ms after the shock.

Objective: The purpose of this study was to determine whether the Purkinje system is a candidate for the source of postshock activations by performing endocardial and transmural postshock activation mapping.

Methods: In five pigs, 32 plunge needles with 12 electrodes (1-mm spacing) were inserted into the LV apex and lateral free wall.

A semi-implantable multichannel telemetry system for continuous electrical, mechanical and hemodynamical recordings in animal cardiac research.

We have developed an eight-channel telemetry system for studying experimental models of chronic cardiovascular disease. The system is an extension of a previous device that has been miniaturized, reduced in power consumption and provided with increased functionality. We added sensors for ventricular dimension, and coronary artery blood flow and arterial blood pressure that are suitable for use with the system.

Improving performance of HVAC systems to reduce exposure to aerosolized infectious agents in buildings; recommendations to reduce risks posed by biological attacks.

The prospect of biological attacks is a growing strategic threat. Covert aerosol attacks inside a building are of particular concern. In the summer of 2005, the Center for Biosecurity of the University of Pittsburgh Medical Center convened a Working Group to determine what steps could be taken to reduce the risk of exposure of building occupants after an aerosol release of a biological weapon.

Chronic myocardial infarction is a substrate for bradycardia-induced spontaneous tachyarrhythmias and sudden death in conscious animals.

Introduction: Patients with bradycardia can have severe tachyarrhythmias but it is unclear whether bradycardia alone can induce arrhythmias or whether an additional substrate is necessary. While several animal models of ventricular tachycardia (VT) exist, no model has been reported to mimic the clinical condition of spontaneous VT and sudden cardiac death (SCD) in the presence of bradycardia and chronic myocardial infarction (MI) in large animals without manipulation of the autonomic nervous system. We tested the hypothesis that MI and bradycardia cause more spontaneous sustained VT than does bradycardia alone.

Evidence that activation following failed defibrillation is not caused by triggered activity.

Background: Earliest postshock activation following failed defibrillation shocks slightly lower than the defibrillation threshold (DFT) in large animals appears to arise from a focus. We tested the hypothesis that these foci are caused by early or delayed afterdepolarizations (EADs or DADs) by performing epicardial electrical mapping and giving the EAD inhibitor pinacidil or the DAD inhibitor flunarizine to see if the foci were extinguished or altered in timing or location.

Methods And Results: A sock containing 504 electrodes was placed over the entire ventricular epicardium of 12 open-chested pigs.