Toward Functional Screening of Cardioactive and Cardiotoxic Drugs with Zebrafish <i>in Vivo</i> Using Pseudodynamic Three-Dimensional Imaging

Given the high mortality in patients with cardiovascular diseases and the life-threatening consequences of drugs with unforeseen adverse effects on hearts, a critical evaluation of the pharmacological response of cardiovascular function on model animals is important especially in the early stages of drug development. We report a proof-of-principle study to demonstrate the utility of zebrafish as an analytical platform to predict the cardiac response of new drugs or chemicals on human beings. With pseudodynamic 3D imaging, we derive individual parameters that are central to the cardiac function of zebrafish, including the ventricular stroke volume, ejection fraction, cardiac output, heart rate, diastolic filling function, and ventricular mass. We evaluate both inotropic and chronotropic responses of the heart of zebrafish treated with drugs that are commonly prescribed and possess varied known cardiac activities. We reveal deranged cardiac function of a zebrafish model of cardiomyopathy induced with a cardiotoxic drug. The cardiac function of zebrafish exhibits a pharmacological response similar to that of human beings. We compare also cardiac parameters obtained in this work with those derived with conventional 2D approximation and show that the latter tends to overestimate the cardiac parameters and produces results of greater variation. In view of the growing interest of using zebrafish in both fundamental and translational biomedical research, we envisage that our approach should benefit not only contemporary pharmaceutical development but also exploratory research such as gene, stem cell, or regenerative therapies targeting congenital or acquired heart diseases

Spatiotemporal Characterization of Phagocytic NADPH Oxidase and Oxidative Destruction of Intraphagosomal Organisms <i>in Vivo</i> Using Autofluorescence Imaging and Raman Microspectroscopy

Spatiotemporal Characterization of Phagocytic NADPH Oxidase and Oxidative Destruction of Intraphagosomal Organisms in Vivo Using Autofluorescence Imaging and Raman Microspectroscop

Features and interventions of cardiac arrest events by neurological status at hospital discharge.

Features and interventions of cardiac arrest events by neurological status at hospital discharge.</p

Data_Sheet_1_The CSP (Cardiogenic Shock Prognosis) Score: A Tool for Risk Stratification of Cardiogenic Shock.docx

BackgroundCardiogenic shock (CS) is a critical condition and the leading cause of mortality after acute myocardial infarction (AMI). Scores that predict mortality have been established, but a patient's clinical course is often nonlinear. Thus, factors present during acute care management may be explored. This study intended to develop a risk-predictive model for patients with CS.MethodsIn this observational study, adult patients who received inotropic support at the Emergency Room (ER) from January 2017 to August 2020 and were admitted to the cardiac care unit (CCU) with a diagnosis of CS were enrolled in this study. Patients with out-of-hospital cardiac arrest, inotropic support for bradycardia, and survival ResultsA history of coronary artery disease, multiple inotrope use, ejection fraction ConclusionsThe CSP score represents a risk-predictive model for in-hospital mortality in patients with CS in acute care settings. Patients identified as the high-risk category may have a poor prognosis.</p

Multivariate survival analysis for termination of cardiopulmonary resuscitation efforts using a Cox’s proportional hazards model.

Multivariate survival analysis for termination of cardiopulmonary resuscitation efforts using a Cox’s proportional hazards model.</p

Outcomes of Adult In-Hospital Cardiac Arrest Treated with Targeted Temperature Management: A Retrospective Cohort Study

<div><p>Aim</p><p>Targeted temperature management (TTM) for in-hospital cardiac arrest (IHCA) is given different recommendation levels within international resuscitation guidelines. We aimed to identify whether TTM would be associated with favourable outcomes following IHCA and to determine which factors would influence the decision to implement TTM.</p><p>Methods</p><p>We conducted a retrospective observational study in a single medical centre. We included adult patients suffering IHCA between 2006 and 2014. We used multivariable logistic regression analysis to evaluate associations between independent variables and outcomes.</p><p>Results</p><p>We included a total of 678 patients in our analysis; only 22 (3.2%) patients received TTM. Most (81.1%) patients met at least one exclusion criteria for TTM. In all, 144 (21.2%) patients survived to hospital discharge; among them, 60 (8.8%) patients displayed favourable neurological status at discharge. TTM use was significantly associated with favourable neurological outcome (OR: 3.74, 95% confidence interval [CI]: 1.19–11.00; <i>p</i>-value = 0.02), but it was not associated with survival (OR: 1.41, 95% CI: 0.54–3.66; <i>p</i>-value = 0.48). Arrest in the emergency department was positively associated with TTM use (OR: 22.48, 95% CI: 8.40–67.64; <i>p</i> value < 0.001) and having vasopressors in place at the time of arrest was inversely associated with TTM use (OR: 0.08, 95% CI: 0.004–0.42; <i>p</i>-value = 0.02).</p><p>Conclusion</p><p>TTM might be associated with favourable neurological outcome of IHCA patients, irrespective of arrest rhythms. The prevalence of proposed exclusion criteria for TTM was high among IHCA patients, but these factors did not influence the use of TTM in clinical practice or neurological outcomes after IHCA.</p></div

Impact of protocolized postarrest care with targeted temperature management on the outcomes of cardiac arrest survivors without temperature management

Protocolized postarrest care that includes targeted temperature management (TTM) improves survival and neurological outcomes in cardiac arrest survivors. Whether the accumulated experience regarding the use of the protocolized approach also benefits patients who did not undergo TTM has yet to be investigated. Adults (≥18 years old) with nontraumatic cardiac arrest and who survived to intensive care unit (ICU) admission were retrospectively recruited from a single tertiary medical centre from 2006 to 2009 and 2011 to 2017. Patients were excluded if they had traumatic injuries, were pregnant, did not survive to ICU admission, regained clear consciousness within 3 h after the return of spontaneous circulation, or underwent TTM. The sum of TTM cases since 2006 and before the cardiac arrest of each enrolled patient was used as a substitute index for the amount of experience accumulated from the use of protocolized TTM care. In total, 802 non-TTM patients were enrolled in the final analysis. The rate of survival to hospital discharge increased from 25.9% in 2006 to 33.3% in 2017. Regarding neurological recovery at hospital discharge, the incidence of favourable neurological function (cerebral performance category: 1 or 2) increased from 10.3% in 2006 to 23.5% in 2017. A multiple logistic regression indicated a significant association between the cumulative TTM case numbers and neurological outcomes in patients who did not receive TTM. The improvement of neurological outcomes in adult nontraumatic cardiac arrest survivors who did not receive TTM was associated with the cumulative number of cases receiving protocolized TTM care. In the era of TTM, the use of only historical control data might lead to bias, which is caused by overlooking the influence of a more refined protocolized postarrest care that includes TTM.KEY MESSAGEThe cumulative number of cases receiving protocolized TTM care, which we used as a substitute index for the amount of experience accumulated from the use of protocolized postarrest care that includes TTM, was associated with the improvement of neurological outcomes in adult nontraumatic cardiac arrest survivors who did not receive TTM. The cumulative number of cases receiving protocolized TTM care, which we used as a substitute index for the amount of experience accumulated from the use of protocolized postarrest care that includes TTM, was associated with the improvement of neurological outcomes in adult nontraumatic cardiac arrest survivors who did not receive TTM.</p

Baseline characteristics of study patients by neurological status at hospital discharge.

Baseline characteristics of study patients by neurological status at hospital discharge.</p

Validation of the Cardiac Arrest Survival Postresuscitation In-hospital (CASPRI) score in an East Asian population

BackgroundThe Cardiac Arrest Survival Postresuscitation In-hospital (CASPRI) score is a useful tool for predicting neurological outcome following in-hospital cardiac arrest (IHCA), and was derived from a cohort selected from the Get With The Guidelines-Resuscitation registry between 2000 and 2009 in the United States. In an East Asian population, we aimed to identify the factors associated with outcomes of resuscitated IHCA patients and assess the validity of the CASPRI score.MethodsA retrospective study was conducted in a single centre in Taiwan. Patients with IHCA between 2006 and 2014 were screened.ResultsAmong the 796 included patients, 94 (11.8%) patients achieved neurologically intact survival. Multivariable logistic regression analyses identified factors significantly associated with neurological outcome. Six of these factors were also components of the CASPRI score, including duration of resuscitation, neurological status before IHCA, malignant disease, initial arrest rhythms, renal insufficiency and age. In univariate logistic regression analysis, the CASPRI score was significantly associated with neurological outcome (odds ratio [OR]: 0.83, 95% confidence interval [CI]: 0.80–0.87); the area under the receiver operating characteristics curve was 0.79 (95% CI: 0.74–0.84).ConclusionIn this retrospective study conducted in a single centre at Taiwan, we identified the common prognosticators of IHCA shared by both East Asian and Western societies. As a composite prognosticator, CASPRI score predicts outcomes with excellent accuracy among successfully resuscitated IHCA patients in an East Asian population. This tool allows accurate IHCA prognostication in an East Asian population.</div

Kaplan–Meier plots depicting curves of time to termination of cardiopulmonary resuscitation.

CPR, cardiopulmonary resuscitation. Dotted line: Family present at the beginning of CPR. Solid line: Family absent at the beginning of CPR.</p