design-and-implementation-of-a-rat-ex-vivo-lung-perfusion-model

Design and Implementation of a Rat <em>Ex Vivo</em> Lung Perfusion Model

Ex vivo lung preparations are a useful model that can be translated to many different fields of research, complementing corresponding in vivo and in vitro ...

Vanderbilt University Medical Center

University of Greifswald

: Cardiac arrest remains a worldwide health problem with very poor outcome. In the absence of bystander resuscitation, survival rates decrease by 10% per minute of arrest and global ischemia. Even the best manual chest compressions, however, can only produce a fraction of normal cardiac output and blood flow to vital organs. Physiological principles and current evidence for the use of mechanical devices to increase survival and quality of life after cardiac arrest are highlighted in this review article. : Mechanical adjuncts such as the Active Compression Decompression device, automated chest compressors and the use of a negative pressure valve (Impedance Threshold Device) can synergistically aid in improving quality of CPR and increasing cardiac output and vital organ perfusion. : The current conclusions that the use of mechanical adjunct devices in a preclinical setting is not recommended or neutral at best, need to be reevaluated, especially with regard to new advanced and promising treatments that require prolonged high-quality CPR during the transport to a hospital to improve the outcome of patients.

Mechanical adjuncts for cardiocerebral resuscitation.

Endotracheal intubation is a vital component of many rat in vivo experiments to secure the airway and allow controlled ventilation. Even in the hands of experienced researchers, however, the procedure remains technically challenging. The safest and most reliable way for human intubation is by video laryngoscopy. Previous attempts to apply this technique in rodents have been complicated and expensive. We, hereby, describe a novel, noninvasive method to safely intubate rats orally by video laryngoscopy, thus avoiding the need for a surgical tracheostomy. By repurposing a commercially available ear wax removal device, visualization of the rat larynx can be significantly enhanced. Because of its small diameter, integrated illumination, and a powerful camera with adequate focal length, the device has all of the necessary properties for exploring the upper airway of a rat. After identifying the vocal cords by video laryngoscopy, the insertion of an endotracheal tube (a 14G intravenous catheter) into the trachea under constant visual control is facilitated by using PE50 polyethylene tubing as a stylet (Seldinger technique). The procedure has been performed more than 60 times in our laboratory; all intubations were successful on the first attempt, and no adverse events were observed. We conclude that the described procedure is a simple and effective way to intubate a rat noninvasively, using inexpensive and commercially available equipment.

Video laryngoscopic oral intubation in rats: a simple and effective method.

Assessing intravascular hypovolemia due to hemorrhage remains a clinical challenge. Central venous pressure (CVP) remains a commonly used monitor in surgical and intensive care settings for evaluating blood loss, despite well-described pitfalls of static pressure measurements. The authors investigated an alternative to CVP, intravenous waveform analysis (IVA) as a method for detecting blood loss and examined its correlation with echocardiography.

Venous Waveform Analysis Correlates With Echocardiography in Detecting Hypovolemia in a Rat Hemorrhage Model.

Peripheral intravenous analysis (PIVA) has been shown to be more sensitive than central venous pressure (CVP) for detecting hemorrhage and volume overload. We hypothesized that PIVA is superior to CVP for detecting right ventricular (RV) failure in a rat model of respiratory arrest.

Venous waveform analysis detects acute right ventricular failure in a rat respiratory arrest model.

Due to its comorbidities type 2 diabetes mellitus (T2DM) and hypertension, the Zucker Spontaneous Hypertensive Fatty (ZSF1) rat is a clinically relevant animal model when assessing ischemia-reperfusion (IR) injury. Most IR studies in hearts isolated from diabetic animals have been conducted at normal glucose concentrations, providing a different environment compared to in-vivo. We hypothesized IR injury to be attenuated in isolated hearts of diabetic ZSF1 rats when adjusting the Krebs-buffer (KB) to their in-vivo, i.e., elevated blood glucose (BG) levels. Diabetic and non-diabetic ZSF1 rats were anesthetized, hearts isolated and Langendorff-prepared. While standard KB was used for the non-diabetic and diabetic unadjusted groups, KB with glucose levels increased to each rat's prior BG level was used for the adjusted diabetic group. All hearts underwent 30 min ischemia and 120 min reperfusion. Diastolic contracture during ischemia and early reperfusion was delayed and temporarily attenuated in the adjusted compared to the unadjusted diabetic and the non-diabetic groups. The decrease in coronary flow on reperfusion was attenuated in diabetic animals. Left ventricular developed pressure and contractility were not different among the three groups. Infarct size was significantly lower in non-diabetic animals; buffer adjustment made no difference in diabetic animals. In our study, T2DM did not worsen myocardial function in ZSF1 rat isolated hearts. Since our results reveal that hearts with an adjusted glucose level exhibit an at least temporary improvement of function following IR, further studies should consider adapting glucose levels to create more realistic conditions in isolated, perfused hearts.

Buffer glucose adjustment affects myocardial function after ischemia-reperfusion in long-term diabetic rat isolated hearts.

Increasing venous return during cardiopulmonary resuscitation (CPR) has been shown to improve hemodynamics during CPR and outcomes following cardiac arrest (CA). We hypothesized that a high central venous pressure amplitude (CVP-A), the difference between the maximum and minimum central venous pressure during chest compressions, could serve as a robust predictor of return of spontaneous circulation (ROSC) in addition to traditional measurements of coronary perfusion pressure (CPP) and end-tidal CO (etCO) in a porcine model of CA.

Article	Year
Mechanical adjuncts for cardiocerebral resuscitation. Expert review of medical devices\| PubMed ID: 31353970	2019
Video laryngoscopic oral intubation in rats: a simple and effective method. American journal of physiology. Lung cellular and molecular physiology\| PubMed ID: 32233786	2020
Venous Waveform Analysis Correlates With Echocardiography in Detecting Hypovolemia in a Rat Hemorrhage Model. Seminars in cardiothoracic and vascular anesthesia\| PubMed ID: 32957831	2021
Venous waveform analysis detects acute right ventricular failure in a rat respiratory arrest model. Pediatric research\| PubMed ID: 36042330	2022
Buffer glucose adjustment affects myocardial function after ischemia-reperfusion in long-term diabetic rat isolated hearts. Physiological reports\| PubMed ID: 36324287	2022
High Central Venous Pressure Amplitude Predicts Successful Defibrillation in a Porcine Model of Cardiac Arrest. Resuscitation\| PubMed ID: 36736947	2023

Claudius Balzer

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