A Clinically Applicable Porcine Model of Septic and Ischemia/Reperfusion-Induced Shock and Multiple Organ Injury

Kubiak, Brian D.; Albert, Scott P.; Gatto, Louis A.; Vieau, Christopher; Roy, Somnath C.; Snyder, Kathy; Maier, Kristopher G.; Nieman, Gary F.

doi:10.1016/j.jss.2010.10.014

Cited by 46 publications

(46 citation statements)

References 46 publications

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“…-abdominal ischemia-reperfusion 1839 .......................................................................................................................... A pathologic animal model of septic and ischemia/reperfusion-induced shock and multiple organ injury replicated systemic inflammation and major organ system dysfunction seen in trauma patients and those with sepsis. 21 Similar to our findings, progressive functional deterioration within organs (including histopathologic injury to the lungs, kidney, liver, and intestines of the animals) occurred due to changes in hemodynamic status associated with shock. The pathologic porcine model constructed in the present study was developed according to the hypothesis of ischemia/reperfusion injury as it occurs in human patients.…”

Section: Discussionsupporting

confidence: 89%

“…The evidence to prove the existence of Paneth cells in pigs remains controversial, which makes the study of regenerative events following reperfusion injury more complicated in pig model. 26 Also, domestic piglets may not have been the best choice of experimental animal since the majority of domestic piglets have pre-existing pulmonary infections, 20,21 which may have affected our results. In addition, the CO remained stable in our model, but the CVP increased gradually and significantly.…”

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confidence: 99%

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Original Research: Porcine model for observing changes due to ischemia/reperfusion injury secondary to intra-abdominal endovascular balloon occlusion

Chao

Tsai

Wang

et al. 2016

Exp Biol Med (Maywood)

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Compared with conventional aortic cross-clamping, endovascular balloon occlusion (EBO) is a valuable strategy in unstable ruptured abdominal aorta aneurysm patients; however, it is unclear how long the balloon may remain safely inflated. Using a porcine model, we evaluated the influence of different EBO time periods on intra-abdominal pressure (IAP) and the association between various pathophysiologic indicators and reperfusion time. Twelve healthy three-month-old domestic piglets were subjected to ischemia/reperfusion injury using EBO within the abdominal aorta. Animals were grouped as A, B, and C based on 30, 60, or 120 min of ischemic time, respectively. Changes in IAP, hemodynamic data, respiratory and renal function, and histology after reperfusion were compared with baseline measurements. All pigs gradually developed intra-abdominal hypertension after ischemia/reperfusion injury. IAP increased significantly after 4 h of reperfusion in all three groups (all P < 0.001) with maximal IAP reaching > 22 mmHg in 10 pigs. However, no significant intergroup differences were found. Cardiac output remained stable, but mixed venous oxygen saturation decreased significantly at 4 h after reperfusion (P < 0.05). The pH decreased significantly at 10 min in all three groups (all P < 0.001). Histological changes in the small intestine, lung, and kidney occurred secondary to aortic ischemia; however, no significant differences were noted between groups (P > 0.05). EBO within the abdominal aorta induced ischemia/reperfusion injury which led to intra-abdominal hypertension, pathological changes within multiple organs, and decreased mixed venous oxygen saturation after only 30 min of abdominal aortic ischemia.

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Section: Discussionsupporting

confidence: 89%

mentioning

confidence: 99%

Original Research: Porcine model for observing changes due to ischemia/reperfusion injury secondary to intra-abdominal endovascular balloon occlusion

Chao

Tsai

Wang

et al. 2016

Exp Biol Med (Maywood)

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“…We have employed a well-established translational porcine model of ARDS using gut ischemia reperfusion (I/R) injury and peritoneal sepsis (PS) induced by fecal clot implantation in large animals (18) and transferred genes four hours after injury. To our knowledge, this is the first time gene transfer has been used as therapy following injury (PS+I/R) in a clinically applicable large animal model suggesting this approach may have clinical therapeutic potential.…”

Section: Introductionmentioning

confidence: 99%

Electroporation-Mediated Gene Delivery of Na+,K+-ATPase, and ENaC Subunits to the Lung Attenuates Acute Respiratory Distress Syndrome in a Two-Hit Porcine Model

Emr¹,

Roy²,

Kollisch-Singule³

et al. 2015

Shock

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Introduction Acute Respiratory Distress Syndrome (ARDS) is a common cause of organ failure with an associated mortality rate of 40%. The initiating event is disruption of alveolar-capillary interface causing leakage of edema into alveoli. Hypothesis: Electroporation mediated gene delivery of epithelial sodium channel (ENaC) and Na+,K+-ATPase into alveolar cells would improve alveolar clearance of edema and attenuate ARDS. Methods Pigs were anesthetized, instrumented, and the superior mesenteric artery was clamped to cause gut ischemia/reperfusion injury (I/R) and peritoneal sepsis (PS) by fecal clot implantation. Animals were ventilated according to ARDSnet protocol. Four hours after injury animals were randomized into groups: 1.Treatment Na+,K+-ATPase/ENaC plasmid (n=5), 2.Control Empty plasmid (n=5). Plasmids were delivered to the lung using bronchoscope. Electroporation was delivered using 8 square wave electric pulses across chest. Following electroporation pigs were monitored 48 hrs. Results The PaO2/FiO2 ratio and lung compliance were higher in the treatment group. Lung Wet/Dry Ratio was lower in the treatment group. Relative expression of the Na+,K+-ATPase transgene was higher throughout lungs receiving treatment plasmids. Quantitative histopathology revealed a reduction in intra-alveolar fibrin in the Treatment group. Bronchoalveolar lavage showed increased surfactant protein B in the treatment group. Survival was improved in the treatment group. Conclusion Electroporation-mediated transfer of Na+,K+-ATPase/ENaC plasmids improved lung function, reduced fibrin deposits, decreased lung edema, and improved survival in a translational porcine model of ARDS. Gene therapy can attenuate ARDS pathophysiology in a high fidelity animal model suggesting a potential new therapy for patients.

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“…Kubiak et al, showed that the Multiple Organ Dysfunction Syndrome (MODS) comes from an alteration of the inflammatory cascade system where the source is a vicious circle with abdominal start (activation and release of physiological, cellular systems and chemical mediators triggered) that stars inflammation-damageinflammation, abdominal level first and then systemically [8].…”

Section: Introductionmentioning

confidence: 99%

Negative Pressure Therapy with Intraperitoneal Saline Instillation in the Open Septic Abdomen

Jiménez-Fuertes¹,

Ruíz-Tóvar²,

Durán-Poveda³

et al. 2016

IJSR

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A Clinically Applicable Porcine Model of Septic and Ischemia/Reperfusion-Induced Shock and Multiple Organ Injury

Cited by 46 publications

References 46 publications

Original Research: Porcine model for observing changes due to ischemia/reperfusion injury secondary to intra-abdominal endovascular balloon occlusion

Original Research: Porcine model for observing changes due to ischemia/reperfusion injury secondary to intra-abdominal endovascular balloon occlusion

Electroporation-Mediated Gene Delivery of Na+,K+-ATPase, and ENaC Subunits to the Lung Attenuates Acute Respiratory Distress Syndrome in a Two-Hit Porcine Model

Negative Pressure Therapy with Intraperitoneal Saline Instillation in the Open Septic Abdomen

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