Effects of resuscitation with polymerized porcine hemoglobin (pPolyHb) on hemodynamic stability and oxygen delivery in a rat model of hemorrhagic shock

Introduction: Experimental models of hemorrhagic shock (HS) in rats are important to test new treatments that may improve outcomes in humans, and general anesthesia is required during these experiments. The volatile anesthetic Isoflurane is known for its beneficial effects in rat HS models. Focusing on cardiovascular compensatory mechanisms, we wanted to evaluate Isoflurane versus the injectable anesthetic Pentobarbital in our rat model of mild HS (class 2). We hypothesize that Isoflurane during development of HS improves hemodynamics compared to Pentobarbital. Methods: Twelve Sprague-Dawley rats were initially anesthetized with an intraperitoneal (IP) injection of Pentobarbital (45 mg/kg) and intubated (1 L/min, FiO 2 0.25); heart rate (HR) was monitored by subcutaneous ECG needles. Femoral artery and vein were cannulated for continuous blood pressure measurement and delivery of fluids, respectively. In one group (n=7), anesthesia was continued with repeated IP injections of Pentobarbital (dose mg/kg), the other group (n=5) received continuous Isoflurane (1%). After 30 min of stabilization and administration of Heparin (100 IU/kg), HS was induced by removal of 1 ml of blood over 1 min via the femoral vein, repeated every 3 min until a volume of 5 ml of blood was removed. Mean arterial blood pressure (MAP) and HR were recorded and analyzed in LabChart. Results: During baseline, rats showed no significant differences in HR and MAP between both groups. After 5 ml of hemorrhage, both groups showed significant changes compared to baseline, with significantly higher MAP and HR in rats given only Pentobarbital. Conclusions: In our rat model of HS, Isoflurane dampens the physiologic response to compensate for mild hemorrhage. The cardiovascular response of rats in the Isoflurane group was a decrease of HR and MAP to every ml of hemorrhage, while rats given only Pentobarbital were able to maintain their MAP by raising their HR until decompensation.

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Blood-Based Brain and Global Biomarker Changes after Combined Hypoxemia and Hemorrhagic Shock in a Rat Model of Penetrating Ballistic-Like Brain Injury

Neurotrauma Reports ◽

10.1089/neur.2021.0006 ◽

2021 ◽

Vol 2 (1) ◽

pp. 370-380

Author(s):

Xue Li ◽

Kevin Pierre ◽

Zhihui Yang ◽

Lynn Nguyen ◽

Gabrielle Johnson ◽

...

Keyword(s):

Brain Injury ◽

Hemorrhagic Shock ◽

Rat Model

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Cytochrome c limits oxidative stress and decreases acidosis in a rat model of hemorrhagic shock and reperfusion injury

Journal of Trauma and Acute Care Surgery ◽

10.1097/ta.0000000000001257 ◽

2017 ◽

Vol 82 (1) ◽

pp. 35-41 ◽

Cited By ~ 8

Author(s):

Rebecca D. Powell ◽

Donna A. Goodenow ◽

Hannah V. Mixer ◽

Iain H. Mckillop ◽

Susan L. Evans

Keyword(s):

Oxidative Stress ◽

Cytochrome C ◽

Hemorrhagic Shock ◽

Reperfusion Injury ◽

Rat Model

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Cremaster muscle perfusion, oxygenation, and heterogeneity revealed by a new automated acquisition system in a rodent model of prolonged hemorrhagic shock

Journal of Applied Physiology ◽

10.1152/japplphysiol.00570.2019 ◽

2019 ◽

Vol 127 (6) ◽

pp. 1548-1561

Author(s):

Ivo P. Torres Filho ◽

David Barraza ◽

Kim Hildreth ◽

Charnae Williams ◽

Michael A. Dubick

Keyword(s):

Hemorrhagic Shock ◽

Oxygen Delivery ◽

Repeated Measurements ◽

Laser Speckle ◽

Automated System ◽

Cremaster Muscle ◽

Tissue Oxygen ◽

Hypoxia Ischemia ◽

Tissue Oxygen Delivery ◽

Muscle Homeostasis

Local blood flow/oxygen partial pressure (Po2) distributions and flow-Po2 relationships are physiologically relevant. They affect the pathophysiology and treatment of conditions like hemorrhagic shock (HS), but direct noninvasive measures of flow, Po2, and their heterogeneity during prolonged HS are infrequently presented. To fill this void, we report the first quantitative evaluation of flow-Po2 relationships and heterogeneities in normovolemia and during several hours of HS using noninvasive, unbiased, automated acquisition. Anesthetized rats were subjected to tracheostomy, arterial/venous catheterizations, cremaster muscle exteriorization, hemorrhage (40% total blood volume), and laparotomy. Control animals equally instrumented were not subjected to hemorrhage/laparotomy. Every 0.5 h for 4.5 h, noninvasive laser speckle contrast imaging and phosphorescence quenching were employed for nearly 7,000 flow/Po2 measurements in muscles from eight animals, using an automated system. Precise alignment of 16 muscle areas allowed overlapping between flow and oxygenation measurements to evaluate spatial heterogeneity, and repeated measurements were used to estimate temporal heterogeneity. Systemic physiological parameters and blood chemistry were simultaneously assessed by blood samplings replaced with crystalloids. Hemodilution was associated with local hypoxia, but increased flow prevented major oxygen delivery decline. Adding laparotomy and prolonged HS resulted in hypoxia, ischemia, decreased tissue oxygen delivery, and logarithmic flow/Po2 relationships in most regions. Flow and Po2 spatial heterogeneities were higher than their respective temporal heterogeneities, although this did not change significantly over the studied period. This quantitative framework establishes a basis for evaluating therapies aimed at restoring muscle homeostasis, positively impacting outcomes of civilian and military trauma/HS victims. NEW & NOTEWORTHY This is the first study on flow-Po2 relationships during normovolemia, hemodilution, and prolonged hemorrhagic shock using noninvasive methods in multiple skeletal muscle areas of monitored animals. Automated flow/Po2 measurements revealed temporal/spatial heterogeneities, hypoxia, ischemia, and decreased tissue oxygen delivery after trauma/severe hemorrhage. Hemodilution was associated with local hypoxia, but hyperemia prevented a major decline in oxygen delivery. This framework provides a quantitative basis for testing therapeutics that positively impacts muscle homeostasis and outcomes of trauma/hemorrhagic shock victims.

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Caspase-(8/3) activation and organ inflammation in a rat model of resuscitated hemorrhagic shock

Journal of Trauma and Acute Care Surgery ◽

10.1097/ta.0000000000002152 ◽

2019 ◽

Vol 86 (3) ◽

pp. 431-439 ◽

Cited By ~ 1

Author(s):

Kim Gilbert ◽

Guy Rousseau ◽

Caroline Bouchard ◽

Sophie Dunberry-Poissant ◽

Frédérique Baril ◽

...

Keyword(s):

Hemorrhagic Shock ◽

Rat Model ◽

Caspase 8

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A high‐efficiency MUF method benefits postoperative hemodynamic stability and oxygen delivery in neonates with transposition of great arteries

Journal of Cardiac Surgery ◽

10.1111/jocs.14065 ◽

2019 ◽

Vol 34 (6) ◽

pp. 468-473

Author(s):

Jia Shen ◽

Wei Wang ◽

Wei Zhang ◽

Lei Jiang ◽

Yin Yu Yang

Keyword(s):

Oxygen Delivery ◽

High Efficiency ◽

Hemodynamic Stability ◽

Transposition Of Great Arteries

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Alda-1 Prevents Pulmonary Epithelial Barrier Dysfunction following Severe Hemorrhagic Shock through Clearance of Reactive Aldehydes

BioMed Research International ◽

10.1155/2019/2476252 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Tianfeng Hua ◽

Min Yang ◽

Yangyang Zhou ◽

Limin Chen ◽

Huimei Wu ◽

...

Keyword(s):

Lung Injury ◽

Hemorrhagic Shock ◽

Rat Model ◽

Weight Ratio ◽

Dry Weight ◽

Epithelial Barrier ◽

Lung Edema ◽

Epithelial Tissue ◽

Diffuse Infiltration ◽

Reactive Aldehydes

Severe hemorrhagic shock and resuscitation (HS/R) can lead to lung injury, resulting in respiratory insufficiency. We investigated whether treatment with Alda-1, an ALDH2 activator, decreased lung injury induced by severe HS/R in a rat model. Male Sprague-Dawley rats were randomized into three groups, hemorrhagic shock + placebo, hemorrhagic shock + Alda-1, and sham. All animals were heparinized, and then 50% of the total calculated blood volume was collected over 60 minutes. After 40 minutes of hemorrhagic shock, animals were reinfused with the shed blood over 40 minutes and then observed for an additional 2 hours. Concentrations of 4-HNE, TNF-α, IL-6, and ALDH2 activity were detected; lung injury and lung wet-to-dry weight ratios were assessed. Expression of occludin and ZO-1 proteins in lung tissues was also determined. At 2 hours after resuscitation, lung injury was significantly reduced and the wet-to-dry weight ratio was notably decreased in the Alda-1 group compared with placebo (P<0.05). Alda-1 treatment also significantly increased the activity of ALDH2 and decreased the levels of toxic 4-HNE (P<0.05). In the Alda-1 group, IL-6 and TNF-α were dramatically decreased compared with placebo-treated animals (P<0.05). Expression of occludin and ZO-1 proteins was significantly decreased in the placebo group compared with the Alda-1 group (P<0.05). Thus, in a rat model of severe HS/R, treatment with Alda-1 increased the activity of ALDH2, significantly accelerated the clearance of reactive aldehydes, and concomitantly alleviated lung injury through improvement of pulmonary epithelial barrier integrity resulting in decreased alveolar epithelial tissue permeability, lung edema, and diffuse infiltration of inflammatory cells.

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