Name: standardized hemorrhagic shock induction guided by cerebral oximetry and extended hemodynamic monitoring in pigs
Uploaded: 2019-05-21T13:00:00
Description: Watch this Scientific Journal Video about Standardized Hemorrhagic Shock Induction Guided by Cerebral Oximetry and Extended Hemodynamic Monitoring in Pigs at JoVE.com

The authors want to thank Dagmar Dirvonskis for her excellent technical support.

The experiments in this protocol were approved by the State and Institutional Animal Care Committee (Landesuntersuchungsamt Rheinland-Pfalz, Koblenz, Germany; Chairperson: Dr. Silvia Eisch-Wolf; reference number: 23 177-07/G 14-1-084; 02.02.2015). The experiments were conducted in accordance with the Animal Research&#160;Reporting of In Vivo Experiments (ARRIVE) guidelines. The study was planned and conducted between November 2015 and March 2016. After extended literature research, the pig model was chosen as a well-esta...

The protocol describes one method of inducing hemorrhagic shock via controlled arterial bleeding in pigs that is guided by systemic hemodynamics, as well as by cerebral microcirculatory impairment. Shock conditions were achieved by a calculated blood withdrawal of 25-35 mL kg-1 and confirmed by the mentioned composite of surrogate parameters indicating considerable cardio-circulatory failure. If untreated, this procedure was lethal within 2 h in 66% of the animals, which underlines the severity and reproducibi...

Massive blood loss is among the main causes of injury-related deaths1,2,3. The loss of circulatory fluid and oxygen carriers leads to hemodynamic failure and severe oxygen undersupply and can cause irreversible organ failure and death. The severity level of shock is influenced by additional factors like hypothermia, coagulopathy, and acidosis4. Particularly the brain, but also the kidneys lack compensation capacity due to high oxygen demand and the incapability of adequate anaerobic energy generation5,6. For therapeutic purposes, fast and immediate action is pivotal. In clinical practice, fluid resuscitation with a balanced electrolyte solution is the first option for treatment, followed by the administration of red blood cell concentrates and fresh frozen plasma. Thrombocyte concentrates, catecholamines, and the optimization of coagulation and the acid-base status support the therapy to regain normal physiological conditions after sustained trauma. This concept focuses on the restoration of hemodynamics and macrocirculation. Several studies, however, show that microcirculatory perfusion does not recover simultaneously with the macrocirculation. Especially, cerebral perfusion remains impaired and further oxygen undersupply may occur7,8.
The use of animal models allows scientists to establish novel or experimental strategies. The comparable anatomy, homology, and physiology of pigs and humans enable conclusions on specific pathological factors. Both species have a similar metabolic system and response to pharmacologic treatments. This is a great advantage in comparison to small animal&#160;models where differences in blood volume, hemodynamics, and overall physiology make it almost impossible to mimic a clinical scenario9. Furthermore, authorized medical equipment and consumables can be easily used in porcine models. Additionally, it is easily possible to obtain pigs from commercial suppliers, which allows a high diversity of genetics and phenotypes and is cost reducing10. The model of blood withdrawal via vessel cannulation is quite common11,12,13,14,15.
In this study, we extend the concept of hemorrhagic shock induction via arterial blood withdrawal with an exact titration of hemodynamic failure and cerebral oxygenation impairment. Hemorrhagic shock is achieved if the cardiac index and mean arterial pressure drops below 40% of the baseline value, which has been shown to cause considerable deterioration of the cerebral regional oxygenation saturation8. Pulse contour cardiac output (PiCCO) measurement is used for continuous hemodynamic monitoring. First, the system has to be calibrated by transpulmonary thermodilution, which enables the calculation of the cardiac index of the extravascular lung water content and the global end-diastolic volume. Subsequently, the continuous cardiac index is calculated by pulse contour analysis and also provides dynamic preload parameters like pulse pressure and stroke volume variation.
This technique is well established in clinical and experimental settings.Near-infrared spectroscopy (NIRS) is a clinically and experimentally established method to monitor changes in cerebral oxygen supply in real-time. Self-adherent sensors are attached to the left and right forehead and calculate the cerebral oxygenation non-invasively in the cerebral frontal cortex. Two wavelengths of infrared light (700 and 900 nm) are emitted and detected by the sensors after being reflected from the cortex tissue. To assess the cerebral oxygen content, contributions of arterial and venous blood are calculated in 1:3 relations and updated in 5 s intervals. The sensitivity in depth of 1-4 cm is exponential decreasing and influenced by the penetrated tissue (e.g., skin and bone), although the skull is translucent to infrared light. The technique facilitates quick therapeutic actions to prevent patients from adverse outcomes like delirium or hypoxic cerebral injury and serves as the target parameter in case of impaired cardiac output16,17. The combination of both techniques during experimental shock enables an exact titration of macrocirculation, as well as cerebral microcirculatory impairment, to study this life-threatening event.

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standardized hemorrhagic shock induction guided by cerebral oximetry and extended hemodynamic monitoring in pigs

Hemorrhagic shock ranks among the main reasons for severe injury-related death. The loss of circulatory volume and oxygen carriers can lead to an insufficient oxygen supply and irreversible organ failure. The brain exerts only limited compensation capacities and is particularly at high risk of severe hypoxic damage.This article demonstrates the reproducible induction of life-threatening hemorrhagic shock in a porcine model by means of calculated blood withdrawal. We titrate shock induction guided by near-infrared spectroscopy&#160;and extended hemodynamic monitoring to display systemic circulatory failure, as well as cerebral microcirculatory oxygen depletion. In comparison to similar models that primarily focus on predefined removal volumes for shock induction, this approach highlights a titration by means of the resulting failure of macro- and microcirculation.

After starting the shock induction, a short time of compensation can be registered. With ongoing blood removal, the aforementioned cardio-circulatory decompensation, as monitored by a significant decrease of crSO2, the cardiac index, the intrathoracic blood volume index, and the global end-diastolic volume index (Figure 2, Figure 3, and Figure 4), occurs. Furthermore, significant tachycard...

Watch this Scientific Journal Video about Standardized Hemorrhagic Shock Induction Guided by Cerebral Oximetry and Extended Hemodynamic Monitoring in Pigs at JoVE.com

Standardized Hemorrhagic Shock Induction Guided by Cerebral Oximetry and Extended Hemodynamic Monitoring in Pigs

Hemorrhagic shock is a severe complication in seriously injured patients, which leads to life-threatening oxygen undersupply. We present a standardized method to induce hemorrhagic shock via blood withdrawal in pigs that is guided by hemodynamics and microcirculatory cerebral oxygenation.

Hemorrhagic shock ranks among the main reasons for severe injury-related death. The loss of circulatory volume and oxygen carriers can lead to an ...

This standardized model of hemorrhagic shock induction guided by cerebral oxymetry and external hemodynamic monitoring can be used to simulate a realistic clinical scenario. The main advantage of this model is its simple and highly flexible design, which allow various levels of cardio cellulatory impairment to be easily selected. This techniques allows the evaluation of different therapy concepts of hemorrhagic shock such as fluid resuscitation, coagulation, and catecholamine therapy.This technique provides insight into the different pathophysiological aspects of hemorrhagic shock and hemodynamic effects on cerebral regional oxygenation, as assessed by near infrared spectroscopy. Visualization of hemorrhagic shock can be critical because the compensation mechanisms of the animals can disguise hemodynamic instability for long period of time. Before beginning covering the inguinal area, apply ultrasound gel to the ultrasound probe and cover the inguinal of an anesthetized approximately 28 kilogram two to three month old pig with a sterile fenestrated drape.Scan the right femoral vessels with ultrasound using the doppler technique to distinguish between the artery and the vein. Visualize the longitudinal axis of the right femoral artery and puncture the right femoral artery under ultrasound visualization with a Seldinger needle under permanent aspiration with a five milliliter syringe. Bright red, pulsating blood confirms correct positioning of the aspired needle position.After disconnecting the syring, insert the guide wire and retract the Seldinger needle. Visualize the right femoral vein before rotating the probe 90 degrees to switch to a longitudinal view of the vein. Next, puncture the right femoral vein under ultrasound visualization with the Seldinger needle under permanent aspiration with the five milliliter syringe.A high oxygen level is indicative of arterial blood and a low oxygen level is a sign of venous blood. After disconnecting the syringe, insert the guide wire and retract the Seldinger needle. Visualize both right vessels under ultrasound to control the correct wire position and push a two millimeter arterial introducer sheath over the guide wire into the right artery and the central venous line into the right femoral vein.Then aspirate all of the ports and flush the ports with saline solution. For a pulse contour cardiac output, or PiCCO measurement, insert the PiCCO catheter into the right arterial introducer sheath and connect the catheter with the arterial wire of the PiCCO system and the arterial transducer directly to the PiCCO port. Next connect the venous measuring unit of the PiCCO system with the right venous introducer sheath.Switch the three way stopcocks of both transducers open to the atmosphere to calibrate the systems to zero, according to the manufacturer's instructions. Turn on the PiCCO system and confirm that a new patient is being measured. To calibrate the continuous cardiac output measurement, click TD for thermo dilution and load four degree Celsius physiological saline solution into a 10 milliliter syringe.Click start and quickly and steadily inject 10 milliliters of the cold saline solution into the venous measuring unit. Then wait until the measurement is complete and the system requests a repetition before repeating the procedure two more times. For cerebral regional oxygenation monitoring, first stick two self adherent near infrared spectroscopy sensors to the forehead of the pig and connect the pre-amplifier to the monitor and the color coded sensor cable connectors to the pre-amplifier.Close the pre-amp locking mechanism and attach the sensors to the sensor cables. After switching on the monitor, click new patient, enter the study name, and click done. Check the incoming signal.When the signal is stable, click baseline menu and set baselines. If the baseline has already been entered, click yes and event mark to confirm the new baseline. Then use the arrow buttons on the keyboard under next event to select the three induction event followed by select event.For hemorrhagic shock induction, connect the left arterial introducer sheath with a three way stopcock and equip one port of the three way stopcock with a 50 milliliter syring and one with an empty infusion bottle. Measure and document the exact hemodynamic parameters and calculate 40%of the cardiac index and mean arterial pressure as hemodynamic targets. Select the 93 blood loss event in the near infrared spectroscopy system and aspirate 50 milliliters of blood into the syringe.Switch the tree way stopcock and push the blood into the empty bottle. Note the removed blood volume and monitor the arterial blood pressure, cardiac index, and the cerebral regional oxygenation saturation closely. Then, select the 97 hypotension event.Using hemorrhagic shock has challenging critical aspects and should performed with caution, as hemodynamic instability can lead to sudden death. With ongoing blood removal, cardio circulatory decompensation as monitored by a significant decrease in the cerebral regional oxygen saturation, cardiac index, intrathoracic blood volume index and global end diastolic volume index occur. Furthermore, significant tachycardia and a decrease in arterial blood pressure are common manifestations of hemorrhagic shock.The stoke volume variation increases significantly while extravascular lung water content and systemic vascular resistance are usually unaffected. After ending the blood withdrawal, the hemodynamic values and cerebral regional oxygenation saturation typically remain at a critically low level. The hemoglobin content and hematocrit do not directly decrease during hemorrhagic shock induction, but lactate levels rise and the central venous oxygen saturation decreases.Hemorrhagic shock is a serious complication in severely injured patients that can lead to life threatening oxygen under supply. A fast and effective therapy is required to avoid serious organ damage. This procedure can be expanded hemodynamic therapy concept like fluid resuscitation or catecholamine administration.To investigate different methods for optimizing treatment. This new model paves the way for the evaluation of new therapy concepts of hemorrhagic shock because it simulates a realistic scenario similar to clinical emergency situations. Working with human and animal blood can be hazardous.Always wear gloves, a face mask, and safety glasses to avoid infectious disease contamination.

standardized-hemorrhagic-shock-induction-guided-cerebral-oximetry

Research

JoVE Journal

Medicine

Monitoring of Systemic and Hepatic Hemodynamic Parameters in Mice

The use of mouse models in experimental research is of enormous importance for the study of hepatic physiology and pathophysiological disturbances. However, due to the small size of the mouse, technical details of the intraoperative monitoring procedure suitable for the mouse were rarely described. Previously we have reported a monitoring procedure to obtain hemodynamic parameters for rats. Now, we adapted the procedure to acquire systemic and hepatic hemodynamic parameters in mice, a species ten-fold smaller than rats. This film demonstrates the instrumentation of the animals as well as the data acquisition process needed to assess systemic and hepatic hemodynamics in mice. Vital parameters, including body temperature, respiratory&#160;rate&#160;and heart&#160;rate were recorded throughout the whole procedure. Systemic hemodynamic parameters consist of carotid artery pressure (CAP) and central venous pressure (CVP). Hepatic perfusion parameters include portal vein pressure (PVP), portal flow rate as well as the flow rate of the common hepatic artery (table 1). Instrumentation and data acquisition to record the normal values was completed within 1.5 h. Systemic and hepatic hemodynamic parameters remained within normal ranges during this procedure.
This procedure is challenging but feasible. We have already applied this procedure to assess hepatic hemodynamics in normal mice as well as during 70% partial hepatectomy and in liver lobe clamping experiments. Mean PVP after resection (n= 20), was 11.41&#177;2.94 cmH2O which was significantly higher (P&#60;0.05) than before resection (6.87&#177;2.39 cmH2O). The results of liver lobe clamping experiment indicated that this monitoring procedure is sensitive and suitable for detecting small changes in portal pressure and portal flow rate. In conclusion, this procedure is reliable in the hands of an experienced micro-surgeon but should be limited to experiments where mice are absolutely needed.

This film demonstrates how to acquire systemic and hepatic hemodynamics in mice. The whole monitoring includes acquisition of vital parameters, systemic blood pressure, central venous pressure, common hepatic artery flow rate, and portal vein pressure as well as the portal flow rate in mice.

The use of mouse models in experimental research is of enormous importance for the study of hepatic physiology and pathophysiological disturbances. ...

Uncontrolled Hemorrhagic Shock Modeled via Liver Laceration in Mice with Real Time Hemodynamic Monitoring

Uncontrolled hemorrhage is an important cause of preventable deaths among trauma patients. We have developed a murine model of uncontrolled hemorrhage via a liver laceration that results in consistent blood loss, hemodynamic alterations, and survival.
Mice undergo a standardized resection of the left-middle lobe of the liver. They are allowed to bleed without mechanical intervention. Hemostatic agents can be administered as pre-treatment or rescue therapy depending on the interest of the investigator. During the time of hemorrhage, real-time hemodynamic monitoring via a left femoral arterial line is performed. Mice are then sacrificed, blood loss is quantified, blood is collected for further analysis, and organs are harvested for analysis of injury. Experimental design is described to allow for simultaneous testing of multiple animals.
Liver hemorrhage as a model of uncontrolled hemorrhage exists in the literature, primarily in rat and porcine models. Some of these models utilize hemodynamic monitoring or quantify blood loss but lack consistency. The present model incorporates quantification of blood loss, real-time hemodynamic monitoring in a murine model that offers the advantage of using transgenic lines and a high-throughput mechanism to further investigate the pathophysiologic mechanisms in uncontrolled hemorrhage.

Uncontrolled hemorrhage, an important cause of mortality among trauma patients, can be modeled using a standard liver laceration in a murine model. This model results in consistent blood loss, survival, and allows for testing hemostatic agents. This article provides the step-by-step process to perform this valuable model.

Uncontrolled hemorrhage is an important cause of preventable deaths among trauma patients. We have developed a murine model of uncontrolled hemorrhage via ...

Complete and Partial Aortic Occlusion for the Treatment of Hemorrhagic Shock in Swine

Hemorrhage remains the leading cause of preventable deaths in trauma. Endovascular management of non-compressible torso hemorrhage has been at the forefront of trauma care in recent years. Since complete aortic occlusion presents serious concerns, the concept of partial aortic occlusion has gained a growing attention. Here, we present a large animal model of hemorrhagic shock to investigate the effects of a novel partial aortic balloon occlusion catheter and compare it with a catheter that works on the principles of complete aortic occlusion. Swine are anesthetized and instrumented in order to conduct controlled fixed-volume hemorrhage, and hemodynamic and physiological parameters are monitored. Following hemorrhage, aortic balloon occlusion catheters are inserted and inflated in the supraceliac aorta for 60 min, during which the animals receive whole-blood resuscitation as 20% of the total blood volume (TBV). Following balloon deflation, the animals are monitored in a critical care setting for 4 h, during which they receive fluid resuscitation and vasopressors as needed. The partial aortic balloon occlusion demonstrated improved distal mean arterial pressures (MAPs) during the balloon inflation, decreased markers of ischemia, and decreased fluid resuscitation and vasopressor use. As swine physiology and homeostatic responses following hemorrhage have been well-documented and are like those in humans, a swine hemorrhagic shock model can be used to test various treatment strategies. In addition to treating hemorrhage, aortic balloon occlusion catheters have become popular for their role in cardiac arrest, cardiac and vascular surgery, and other high-risk elective surgical procedures.

Here, we present a protocol demonstrating a hemorrhagic shock model in swine that uses aortic occlusion as a bridge to definitive care in trauma. This model has application in testing a wide range of surgical and pharmacological therapeutic strategies.

Hemorrhage remains the leading cause of preventable deaths in trauma. Endovascular management of non-compressible torso hemorrhage has been at the ...

Complete and Partial Resuscitative Endovascular Balloon Occlusion of the Aorta for Hemorrhagic Shock

Resuscitative endovascular balloon occlusion of the aorta (REBOA) devices grew out of a military-civilian partnership to develop new capabilities for hemorrhage control. With the advent of purpose-built devices, REBOA has become increasingly common in civilian trauma and acute care settings. Currently available REBOA catheters were designed as complete aortic occlusion devices. However, the therapeutic window for complete aortic occlusion is time-limited due to ischemia-reperfusion injury. The partial procedure allows blood flow past the level of occlusion while maintaining targeted proximal pressure, which has been shown to reduce distal ischemia and adjunctive resuscitation requirements in preclinical studies with prolonged occlusion times as compared to traditional complete occlusion.
pREBOA-PRO is the first catheter designed to enable partial and complete aortic occlusion and is currently in limited market release at seven Level I trauma centers in North America. This paper will focus on procedural considerations for REBOA, including patient selection criteria and a comparison of complete and partial aortic occlusion in a simulator, along with highlighting critical steps to improve clinical outcomes. Additionally, this paper reviews a contrast-enhanced CT scan from a trauma patient that shows distal perfusion after 2 h of partial aortic occlusion using this newly designed catheter and discusses representative results from the limited market release to highlight the profound effect of technological innovation on outcomes in vascular emergencies.

A commercial catheter was designed to facilitate true partial resuscitative endovascular balloon occlusion of the aorta (REBOA) and address the complications associated with complete aortic occlusion. Initial clinical reports indicate that partial REBOA improves transition to reperfusion, reduction of distal ischemia, and extension of safe occlusion time compared to complete occlusion.

Resuscitative endovascular balloon occlusion of the aorta (REBOA) devices grew out of a military-civilian partnership to develop new capabilities for ...

Description of a Swine Infant Model of Volume-Controlled Hemorrhagic Shock

Hemorrhagic shock is a leading cause of morbidity and mortality in pediatric patients. Interpretation of the clinical indicators validated in adults to guide resuscitation and comparison between different therapies is difficult in children due to the inherent heterogeneity of this population. As a result, compared to adults, appropriate management of pediatric hemorrhagic shock is still not well established. In addition, the scarcity of pediatric patients with hemorrhagic shock precludes the development of clinically relevant studies. For this reason, an experimental pediatric animal model is necessary to study the effects of hemorrhage in children as well as their response to different therapies. We present an infant animal model of volume-controlled hemorrhagic shock in anesthetized young pigs. Hemorrhage is induced by withdrawing a previously calculated blood volume, and the pig is subsequently monitored and resuscitated with different therapies. Here, we describe a precise and highly reproducible model of hemorrhagic shock in immature swine. The model yields hemodynamic data that characterizes compensatory mechanisms that are activated in response to severe hemorrhage.

This article aims to provide researchers with a detailed and accessible guide to set up an infant porcine model of hemorrhagic shock.

Hemorrhagic shock is a leading cause of morbidity and mortality in pediatric patients. Interpretation of the clinical indicators validated in adults to ...

Dosage-Dependent Induction of Endotoxemia in Pigs via LPS Infusion

Lipopolysaccharide Infusion as a Porcine Endotoxemic Shock Model

Sepsis and septic shock are frequently encountered in patients treated in intensive care units (ICUs) and are among the leading causes of death in these patients. It is caused by a dysregulated immune response to an infection. Even with optimized treatment, mortality rates remain high, which makes further insights into the pathophysiology and new treatment options necessary. Lipopolysaccharide (LPS) is a component of the cell membrane of gram-negative bacteria, which are often responsible for infections causing sepsis and septic shock. 
The severity and high mortality of sepsis and septic shock make standardized experimental studies in humans impossible. Thus, an animal model is needed for further studies. The pig is especially well suited for this purpose as it closely resembles humans in anatomy, physiology, and size. 
This protocol provides an experimental model for endotoxemic shock in pigs by LPS infusion. We were able to reliably induce changes frequently observed in septic shock patients, including hemodynamic instability, respiratory failure, and acidosis. This will allow researchers to gain valuable insight into this highly relevant condition and evaluate new therapeutic approaches in an experimental setting.

Author Spotlight: Induction of Experimental Endotoxemic Shock in Pigs for Studying Hemodynamic and Respiratory Failure

We provide a protocol for an experimental endotoxemic shock model in pigs by infusion of lipopolysaccharide.

Sepsis and septic shock are frequently encountered in patients treated in intensive care units (ICUs) and are among the leading causes of death in these ...

Oleic Acid&amp;#45;Induced Acute Respiratory Decompensation in Pigs

A Porcine Model of Acute Respiratory Failure with a Continuous Infusion of Oleic Acid

This protocol outlines an acute respiratory distress model utilizing centrally administered oleic acid infusion in Yorkshire pigs. Prior to experimentation, each pig underwent general anesthesia, endotracheal intubation, and mechanical ventilation, and was equipped with bilateral&#160;jugular vein central vascular access catheters. Oleic acid was administered through a dedicated pulmonary artery catheter at a rate of 0.2 mL/kg/h. The infusion lasted for 60-120 min, inducing respiratory distress. Throughout the experiment, various parameters including heart rate, respiratory rate, arterial blood pressure, central venous pressure, pulmonary artery pressure, pulmonary capillary wedge pressure, end-tidal carbon dioxide, peak airway pressures, and plateau pressures were monitored. Around the 60 min mark, decreases in partial arterial oxygen pressure (PaO2) and fraction of oxygen-saturated hemoglobin (SpO2) were observed. Periodic hemodynamic instability, accompanied by acute increases in pulmonary artery pressures, occurred during the infusion. Post-infusion, histological analysis of the lung parenchyma revealed changes indicative of parenchymal damage and acute disease processes, confirming the effectiveness of the model in simulating acute respiratory decompensation.

Author Spotlight: Exploring Venous Waveforms for Non&amp;#45;Invasive Respiratory Monitoring in Pigs

Infusing oleic acid continuously into the pulmonary artery of an anesthetized adult pig induces acute respiratory failure, enabling controlled experimentation during acute respiratory decompensation.

This protocol outlines an acute respiratory distress model utilizing centrally administered oleic acid infusion in Yorkshire pigs. Prior to ...

Vascular Cannulation with Hemorrhagic Shock Induction in Rats

Developing a Clinically Relevant Hemorrhagic Shock Model in Rats

Over the recent decades, the development of animal models allowed us to better understand various pathologies and identify new treatments. Hemorrhagic shock, i.e., organ failure due to rapid loss of a large volume of blood, is associated with a highly complex pathophysiology involving several pathways. Numerous existing animal models of hemorrhagic shock strive to replicate what happens in humans, but these models have limits in terms of clinical relevance, reproducibility, or standardization. The aim of this study was to refine these models to develop a new model of hemorrhagic shock. Briefly, hemorrhagic shock was induced in male Wistar Han rats (11-13 weeks old) by a controlled exsanguination responsible for a drop in the mean arterial pressure. The next phase of 75 min was to maintain a low mean arterial blood pressure, between 32 mmHg and 38 mmHg, to trigger the pathophysiological pathways of hemorrhagic shock. The final phase of the protocol mimicked patient care with an administration of intravenous fluids, Ringer Lactate solution, to elevate the blood pressure. Lactate and behavioral scores were assessed 16 h after the protocol started, while hemodynamics parameters and plasmatic markers were evaluated 24 h after injury. Twenty-four hours post-hemorrhagic shock induction, the mean arterial and diastolic blood pressure were decreased in the hemorrhagic shock group (p&#160;&#60; 0.05). Heart rate and systolic blood pressure remained unchanged. All organ damage markers were increased with the hemorrhagic shock (p &#60; 0.05). The lactatemia and behavioral scores were increased compared to the sham group (p &#60; 0.05). In conclusion, we demonstrated that the protocol described here is a relevant model of hemorrhagic shock that can be used in subsequent studies, particularly to evaluate the therapeutic potential of new molecules.

Author Spotlight: Developing Innovative Therapeutic Strategies for Hemorrhagic Shock Research

Hemorrhagic shock kills 1.9 million people worldwide every year. Small animals are frequently used as hemorrhagic shock models but are associated with issues of standardization, reproducibility, and clinical significance, thus limiting their relevance. This article describes developing a new clinically relevant hemorrhagic shock model in rats.

Over the recent decades, the development of animal models allowed us to better understand various pathologies and identify new treatments. Hemorrhagic ...

Shock Induction and Treatment of Hemodynamic Instability in a Porcine Model Using LPS Infusion and PiCCO Monitoring

After inserting the Swan-Ganz catheter into the pulmonary artery, allow the anesthetized pig to stabilize for 30 minutes. Then obtain the baseline hemodynamic measurements. Administer 150 micrograms per kilogram of lipopolysaccharide or LPS for 30 minutes.Monitor the hemodynamic parameters such as arterial and pulmonary arterial blood pressure, heart rate, and ventilation. Then monitor the hemodynamic parameters at an LPS infusion rate of 15 micrograms per kilogram per hour. On the PiCCO monitor, press the thermodilution button, then press the button for central venous pressure or CVP input, and enter the current CVP value before pressing the Start button.When prompted, inject 10 milliliters of cold saline solution into the injectate temperature sensor connected to the Swan-Ganz catheter. After measuring cardiac index, global end-diastolic index, and extravascular lung water index, apply hemodynamic instability treatment according to the flow chart. In case of volume loading, rapidly infuses 200 milliliters of balanced electrolyte solution.For catecholamine therapy, increase the norepinephrine infusion rate by one microgram per kilogram per hour. Mean arterial blood pressure decreased following LPS infusion, but was maintained above 60 millimeters of mercury through fluid resuscitation or norepinephrine infusion. The animals demonstrated a decrease in cardiac index and an increase in heart rate, indicating hemodynamic instability during the shock state.Lung damage was indicated by a decrease in the partial pressure of oxygen and the arterial blood inspiratory oxygen fraction ratio, and an increase in pulmonary artery pressure. Cerebral oxygenation also decreased following the induction of shock. The animals also exhibited acidosis and increasing lactate levels.

Surgical Technique for Jugular Vein Thermodilution Catheter Placement in Pigs

Determination of Cardiac Output in a Porcine Model for Ex Vivo Pulmonary Perfusion

Due to their physiological similarities to humans, pigs are used as experimental models for ex vivo lung perfusion (EVLP). EVLP is a technique that perfuses lungs that are not suitable for transplantation via an extracorporeal circulation pump to improve their function and increase their viability. Existing EVLP protocols are differentiated by the type of perfusion solution and perfusion flow, which varies from 40%-100% of the estimated cardiac output (CO) according to the body surface area (BSA). Devices for measuring CO use simple physical principles and other mathematical models. Thermodilution in animal models continues to be the reference standard for estimating CO because of its simplicity and ease of reproduction. Therefore, the objective of this study was to reproduce the measurement of CO by thermodilution in pigs and compare its precision and accuracy with those obtained by the BSA, weight, and Fick's method, to establish perfusion flow during EVLP. In 23 pigs, a thermodilution catheter was placed in the right jugular vein, and the carotid artery on the same side was cannulated. Blood samples were obtained for gasometry, and CO was estimated by thermodilution, adjusted body surface area, Fick's principle, and per body weight. The CO obtained by the BSA was greater (p = 0.0001, ANOVA, Tukey) than that obtained by the other methods. We conclude that although the methods used in this study to estimate CO are reliable, there are significant differences between them; therefore, each method must be evaluated by the investigator to determine which meets the needs of the protocol.

Author Spotlight: Assessment of Cardiac Output Calculation by Thermodilution in Pigs for Effective Perfusion Flow During EVLP

This protocol describes the surgical technique used for the placement of a thermodilution catheter through the jugular vein in pigs to estimate cardiac output and ensure adequate lung perfusion during ex vivo lung perfusion (EVLP).

Due to their physiological similarities to humans, pigs are used as experimental models for ex vivo lung perfusion (EVLP). EVLP is a technique that ...