Biology subjects

Ward, K. R.

Publications and source records attributed to Ward, K. R..

3 recordsLinked to original sources

bioRxiv2023

Effect of percutaneous ventricular assisted device on post-cardiac arrest myocardial dysfunction in swine model with prolonged cardiac arrest

BackgroundPercutaneous left ventricular assist device (pLVAD) can provide hemodynamic support during and after cardiac arrest, but it remains unclear if pLVAD reduces post-cardiac arrest myocardial dysfunction. MethodsThis is an analysis of a subset of animals that achieved return of spontaneous circulation (ROSC) in a study comparing pLVAD, transient aortic occlusion (AO), or both during cardiopulmonary resuscitation (CPR) after prolonged cardiac arrest. pLVAD, AO, or both were initiated after 24 minutes of ventricular fibrillation cardiac arrest (8 min no-flow and 16 min mechanical CPR). AO was discontinued post-ROSC, and pLVAD support or standard care were continued. Beginning 60 minutes post-ROSC, pLVAD support was weaned to <1.0 L/min while maintaining a mean arterial pressure >70 mmHg, and subsequently removed at 240 minutes when feasible. The primary outcome was the recovery of cardiac index (CI), stroke volume index (SVI), and left ventricular ejection fraction (LVEF) at 240 minutes post-ROSC. Data are shown as mean (standard error). ResultsSeventeen animals achieved ROSC without complication and were included in this analysis (pLVAD group, n = 11 and standard care group, n = 6). For the primary outcome, the pLVAD group had significantly higher CI of 4.2(0.3) vs. 3.1(0.4) L/min/m2 (p=0.043) and LVEF 60(3) vs. 49(4) % (p=0.029) at 240 minutes after ROSC, respectively, when compared with the standard care group, while SVI was not significant difference (2[3] vs. 23[4] mL/min/m2, p=0.054). During the first 60 minutes after ROSC with maximum pLVAD flow, the pLVAD group had significantly higher coronary perfusion pressure (62[4] vs. 47[5] mmHg, p=0.019), lower LV stroke work index (3.9[3.0] vs. 14.9[4.4] cJ/m2, p=0.043), and lower total pulmonary resistance index (13.2[4.8] vs. 21.5[14.4] Wood Unit, p=0.001). ConclusionThese results suggest that early pLVAD support after ROSC is associated with better recovery myocardial function compared to standard care after prolonged cardiac arrest.

physiology↗

bioRxiv2021

A Novel Swine Model of the Acute Respiratory Distress Syndrome Using Clinically-Relevant Injury Exposures

To date, existing animal models of the acute respiratory distress syndrome (ARDS) have failed to translate preclinical discoveries into effective pharmacotherapy or diagnostic biomarkers. To address this translational gap, we developed a high-fidelity swine model of ARDS utilizing clinically-relevant lung injury exposures. Fourteen male swine were anesthetized, mechanically ventilated, and surgically instrumented for hemodynamic monitoring, blood, and tissue sampling. Animals were allocated to one of three groups: 1) Indirect lung injury only: animals were inoculated by direct injection of E. coli into the kidney parenchyma, provoking systemic inflammation and distributive shock physiology; 2) Direct lung injury only: animals received volutrauma, hyperoxia, and bronchoscope-delivered gastric particles; 3) Combined indirect and direct lung injury: animals were administered both above-described indirect and direct lung injury exposures. Animals were monitored for up to 12 hours, with serial collection of physiologic data, blood samples, and radiographic imaging. Lung tissue was acquired post-mortem for pathological examination. In contrast to indirect lung injury only and direct lung injury only groups, animals in the combined indirect and direct lung injury group exhibited all of the physiological, radiographic, and histopathologic hallmarks of human ARDS: impaired gas exchange (mean PaO2/FiO2 ratio 124.8 {+/-} 63.8), diffuse bilateral opacities on chest radiographs, and extensive pathologic evidence of diffuse alveolar damage. Our novel porcine model of ARDS, built on clinically-relevant lung injury exposures, faithfully recapitulates the physiologic, radiographic, and histopathologic features of human ARDS, and fills a crucial gap in the translational study of human lung injury.

pathology↗

bioRxiv2019

Rapid breath analysis for acute respiratory distress syndrome diagnostics using a portable 2-dimensional gas chromatography device

Acute respiratory distress syndrome (ARDS) is the most severe form of acute lung injury, responsible for high mortality and long-term morbidity. As a dynamic syndrome with multiple etiologies its timely diagnosis is difficult as is tracking the course of the syndrome. Therefore, there is a significant need for early, rapid detection and diagnosis as well as clinical trajectory monitoring of ARDS. Here we report our work on using human breath to differentiate ARDS and non-ARDS causes of respiratory failure. A fully automated portable 2-dimensional gas chromatography device with high peak capacity, high sensitivity, and rapid analysis capability was designed and made in-house for on-site analysis of patients breath. A total of 85 breath samples from 48 ARDS patients and controls were collected. Ninety-seven elution peaks were separated and detected in 13 minutes. An algorithm based on machine learning, principal component analysis (PCA), and linear discriminant analysis (LDA) was developed. As compared to the adjudications done by physicians based on the Berlin criteria, our device and algorithm achieved an overall accuracy of 87.1% with 94.1% positive predictive value and 82.4% negative predictive value. The high overall accuracy and high positive predicative value suggest that the breath analysis method can accurately diagnose ARDS. The ability to continuously and non-invasively monitor exhaled breath for early diagnosis, disease trajectory tracking, and outcome prediction monitoring of ARDS may have a significant impact on changing practice and improving patient outcomes.

bioengineering↗