Hemodynamic Effect of Repeated Epinephrine Doses Decreases With Cardiopulmonary Resuscitation Cycle Progression.

BACKGROUND: Epinephrine is administered to increase coronary perfusion pressure during advanced life support and promote short-term survival. Recent cardiopulmonary resuscitation (CPR) guidelines recommend an epinephrine dosing interval of 3 to 5 minutes during resuscitation; however, scientific evidence supporting this recommendation is lacking. Therefore, we aimed to investigate the hemodynamic effects of repeated epinephrine doses during CPR by monitoring augmented blood pressure after its administration in a swine model of cardiac arrest. METHODS AND RESULTS: A secondary analysis of data from a published study was performed using a swine cardiac arrest model. The epinephrine dose was fixed at 1 mg, and the first dose of epinephrine was administered after no-flow and low-flow times of 2 minutes and 8 minutes, respectively, and subsequently administered every 4 minutes. Four cycles of dosing intervals were defined because a previous study was terminated 26 minutes after the induction of ventricular fibrillation. Augmented blood pressures and corresponding timelines were determined. Augmented blood pressure trends following cycles and the epinephrine effect duration were also monitored. Among the 140 CPR cycles, the augmented blood pressure after epinephrine administration was the highest during the first cycle of CPR and decreased gradually with further cycle repetitions. The epinephrine effect duration did not differ between repeated cycles. The maximum blood pressure was achieved 78 to 97 seconds after epinephrine administration. CONCLUSIONS: Hemodynamic augmentation with repeated epinephrine administration during CPR decreased with cycle progression. Further studies are required to develop an epinephrine administration strategy to maintain its hemodynamic effects during prolonged resuscitation.

Distinguishing Protein Chemical Topologies Using Supercharging Ion Mobility Spectrometry-Mass Spectrometry.

A technique combining ion mobility spectrometry-mass spectrometry (IMS-MS) and supercharging electrospray ionization (ESI) has been demonstrated to differentiate protein chemical topology effectively. Incorporating as many charges as possible into proteins via supercharging ESI allows the protein chains to be largely unfolded and stretched, revealing their hidden chemical topology. Different chemical topologies result in differing geometrical sizes of the unfolded proteins due to constraints in torsional rotations in cyclic domains. By introducing new topological indices, such as the chain-length-normalized collision cross-section (CCS) and the maximum charge state (zM ) in the extensively unfolded state, we were able to successfully differentiate various protein chemical topologies, including linear chains, ring-containing topologies (lasso, tadpole, multicyclics, etc.), and mechanically interlocked rings, like catenanes.

Efficacy of Cardiopulmonary Resuscitation Using Automatic Compression-Defibrillation Apparatus: An Animal Study and A Manikin-Based Simulation Study.

BACKGROUND: Chest compression and defibrillation are essential components of cardiac arrest treatment. Mechanical chest compression devices (MCCD) and automated external defibrillators (AED) are used separately in clinical practice. We developed an automated compression-defibrillation apparatus (ACDA) that performs mechanical chest compression and automated defibrillation. We investigated the performance of cardiopulmonary resuscitation (CPR) with automatic CPR (A-CPR) compared to that with MCCD and AED (conventional CPR: C-CPR). METHODS: Pigs were randomized into A-CPR or C-CPR groups: The A-CPR group received CPR+ACDA, and the C-CPR group received CPR+MCCD+AED. Hemodynamic parameters, outcomes, and time variables were measured. During a simulation study, healthcare providers performed a basic life support scenario for manikins with an ACDA, MCCD, and AED, and time variables and chest compression parameters were measured. RESULTS: The animals showed no significant in hemodynamic effects, including aortic pressures, coronary perfusion pressure, carotid blood flow, and end-tidal CO2, and resuscitation outcomes between the two groups. In both animal and simulation studies, the time to defibrillation, time to chest compression, and hands-off time were significantly shorter in the A-CPR group than those in the C-CPR group. CONCLUSIONS: CPR using ACDA showed similar hemodynamic effects and resuscitation outcomes as CPR using AED and MCCD separately, with the advantages of a reduction in the time to compression, time to defibrillation, and hands-off time.

Development of an automatic device performing chest compression and external defibrillation: An animal-based pilot study.

BACKGROUND: Automatic chest compression devices (ACCDs) can promote high-quality cardiopulmonary resuscitation (CPR) and are widely used worldwide. Early application of automated external defibrillators (AEDs) along with high-quality CPR is crucial for favorable outcomes in patients with cardiac arrest. Here, we developed an automated CPR (A-CPR) apparatus that combines ACCD and AED and evaluated its performance in a pilot animal-based study. METHODS: Eleven pigs (n = 5, A-CPR group; n = 6, ACCD CPR and AED [conventional CPR (C-CPR)] group) were enrolled in this study. After 2 min observation without any treatment following ventricular fibrillation induction, CPR with a 30:2 compression/ventilation ratio was performed for 6 min, mimicking basic life support (BLS). A-CPR or C-CPR was applied immediately after BLS, and resuscitation including chest compression and defibrillation, was performed following a voice prompt from the A-CPR device or AED. Hemodynamic parameters, including aortic pressure, right atrial pressure, coronary perfusion pressure, carotid blood flow, and end-tidal carbon dioxide, were monitored during resuscitation. Time variables, including time to start rhythm analysis, time to charge, time to defibrillate, and time to subsequent chest compression, were also measured. RESULTS: There were no differences in baseline characteristics, except for arterial carbon dioxide pressure (39 in A-CPR vs. 33 in C-CPR, p = 0.034), between the two groups. There were no differences in hemodynamic parameters between the groups. However, time to charge (28.9 ± 5.6 s, A-CPR group; 47.2 ± 12.4 s, C-CPR group), time to defibrillate (29.1 ± 7.2 s, A-CPR group; 50.5 ± 12.3 s, C-CPR group), and time to subsequent chest compression (32.4 ± 6.3 s, A-CPR group; 56.3 ± 10.7 s, C-CPR group) were shorter in the A-CPR group than in the C-CPR group (p = 0.015, 0.034 and 0.02 respectively). CONCLUSIONS: A-CPR can provide effective chest compressions and defibrillation, thereby shortening the time required for defibrillation.

A single-domain protein catenane of dihydrofolate reductase.

A single-domain protein catenane refers to two mechanically interlocked polypeptide rings that fold synergistically into a compact and integrated structure, which is extremely rare in nature. Here, we report a single-domain protein catenane of dihydrofolate reductase (cat-DHFR). This design was achieved by rewiring the connectivity between secondary motifs to introduce artificial entanglement and synthesis was readily accomplished through a series of programmed and streamlined post-translational processing events in cells without any additional in vitro reactions. The target molecule contained few exogenous motifs and was thoroughly characterized using a combination of ultra-performance liquid chromatography-mass spectrometry, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, protease cleavage experiments and ion mobility spectrometry-mass spectrometry. Compared with the linear control, cat-DHFR retained its catalytic capability and exhibited enhanced stability against thermal or chemical denaturation due to conformational restriction. These results suggest that linear proteins may be converted into their concatenated single-domain counterparts with almost identical chemical compositions, well-preserved functions and elevated stabilities, representing an entirely new horizon in protein science.