Treatment of intestinal ischemia with oxygenated intraluminal perfluorocarbons (original) (raw)
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Intraluminal oxygen can keep small bowel mucosa intact in a segmental ischemia model
Background. Intestinal preservation for transplantation is accompanied by hypoperfusion with long periods of ischemia with total blood cessation and absolute withdrawal of oxygen leading to structural damage. The application of intraluminal oxygen has been successfully tested in small-animal series during storage and transport of the organ but have been so far clinically unrelatable. In this study, we tested whether a simple and clinically approachable method of intraluminal oxygen application could prevent ischemic damage in a large animal model, during warm ischemia time. Methods. We utilised a local no-flow ischemia model of the small intestine in pigs. A low-flow and high-pressure intraluminal oxygen deliverance system was applied in 6 pigs and 6 pigs served as a control group. Mucosal histopathology, hypoxia and barrier markers were evaluated after two hours of no-flow conditions, in both treatment and sham groups, and in healthy tissue. Results. Macro- and microscopically, the...
Transintestinal Systemic Oxygenation Using Perfluorocarbon
Surgery Today, 2006
the patient's lungs, is thus desirable. Perfluorocarbon has an excellent oxygen-and carbon dioxide-carrying capacity (50 ml O 2 /dl and 160-210 ml CO 2 /dl, respectively), 10 and for this reason it has been studied and used in a novel mechanical ventilation Abstract Purpose. Perfluorocarbons have an excellent oxygenand carbon dioxide-carrying capacity. This prompted us to investigate the feasibility of transintestinal systemic oxygenation using perfluorocarbon. Methods. A rat hypoventilation model (room air, 20 breaths/min and a tidal volume of 10 ml/kg) was thus established, and FC-77 (Sumitomo-3M, Osaka, Japan) was used as a perfusate. Oxygenated FC-77 was perfused through the small intestine for 4 h. The rats were allocated into three groups as follows. Group 1 (n = 6): hypoventilation only; Group 2 (n = 6): saline was perfused instead of FC-77; Group 3 (n = 6): FC-77 was perfused. Arterial blood samples were drawn from the common iliac artery every 30 min until the end of perfusion. A standard blood gas analysis was performed. Results. The PaO 2 level in Group 3 was significantly higher than in Groups 1 or 2 (P = 0.006: at the end of perfusion, Group 1 = 58.6 ± 14.5 mmHg, Group 2 = 65.2 ± 29.4 mmHg, Group 3 = 84.0 ± 35.5 mmHg). The PaCO 2 level in Group 3 was significantly lower than that in Groups 1 or 2 (P = 0.014: at the end of perfusion, Group 1 = 56.8 ± 8.5 mmHg, Group 2 = 52.6 ± 5.7 mmHg, Group 3 = 44.4 ± 11.1 mmHg). Conclusion. Our findings indicate that transintestinal systemic oxygenation is indeed possible and could therefore become a useful new modality for respiratory assist.
American Heart Journal, 1988
Inadequate subendocardial oxygen delivery during perfluorocarbon perfusion in a canine model of ischemia Perfusion of the coronary artery distal to an occlusion was performed in 16 canine preparations to compare the mechanical perfusion of autologous blood to the perfluorocarbon fluosol DA, 20% emulsion (FDA-20). Both substances were perfused under similar conditions (30, 60, and 80 ml/min) and regional electrograms, contractility, and coronary perfusion were measured relative to native coronary perfusion. Autologous blood (60 and 80 ml/min) produced a significant increase in regional (epicardial, midmyocardial, and endocardial) and transmural flow, but not in the endocardial/epicardial perfusion ratio. No other significant changes were observed during autologous blood perfusion. In contrast, FDA-20 perfusion resulted in significant ST depression (-1.8 + 0.2,-1.7 t 0.2, and-1.3 ? 0.3 mm) at 30, 60, and 80 ml/min, respectively. FDA-20 also induced a significant decrease in distal diastolic coronary pressure and resistance, a significant decrease in the endocardial/epicardial perfusion ratio at all three perfusion rates, and a significant reduction in delivery of O2 to the subendocardium. These results indicate that autologous blood perfusion of the distal coronary artery during occlusion preserves myocardial function to a better degree than does FDA-20. (AM HEART J 1988;115:30.
Transplantation, 2008
Introduction. This study investigated the role of a novel nutrient-rich preservation solution in alleviating intestinal ischemia-reperfusion (IR) injury in a large animal model. Materials and Methods. Porcine intestines were treated in vivo with the following intraluminal flush solutions: group 1, none; group 2, University of Wisconsin solution; group 3, an amino acid-based solution, previously shown to be effective in reducing IR injury in rodent models. Intestinal ischemia was induced in vivo for 60 min, followed by 180 min reperfusion. Key metabolic aspects were assessed in relation to two fundamental kinase mechanisms that govern cell fate, AMP kinase, and Jun kinase. Results. After 180 min reperfusion, groups 1 and 2 exhibited clefting, denudation, and mucosal hemorrhage, whereas injury was markedly reduced in group 3 (median grades 4.5 and 5 vs. 0; PϽ0.05). In contrast to groups 1 and 2, group 3 tissues exhibited a full recovery of adenylates (ATP, total adenylates) and an effective control of oxidative stress throughout reperfusion. Neutrophil-mediated inflammation was abrogated in group 3. An up-regulation of two key enzymes (glutaminase and alanine aminotransferase) provided a mechanism for the superior recovery of energetics and the preservation of mucosal integrity in group 3. A strong activation of AMP-activated protein kinase resulting in the up-regulation of a primary proapoptotic kinase mechanism, Jun kinase, was evident in groups 1 and 2. Discussion. A strategy of intraluminal administration of a nutrient-rich solution represents a potential therapy for alleviating intestinal IR injury; these findings suggest a more effective method for the ischemic storage of intestine.
REVIEW: Ischemia—Reperfusion Injury of the Intestine and Protective Strategies Against Injury
Digestive Diseases and Sciences, 2004
Ischemia—Reperfusion injury of the intestine is a significant problem in abdominal aortic aneurysm surgery, small bowel transplantation, cardiopulmonary bypass, strangulated hernias, and neonatal necrotizing enterocolitis. It can also occur as a consequence of collapse of systemic circulation, as in hypovolemic and septic shock. It is associated with a high morbidity and mortality. This article is a comprehensive review of the current status of the molecular biology and the strategies to prevent Ischemia—Reperfusion injury of the intestine. Various treatment modalities have successfully been applied to attenuate reperfusion injury in animal models of reperfusion injury of the intestine. Ischemic preconditioning has been found to be the most promising strategy against reperfusion injury during the last few years, appearing to increase the tolerance of the intestine to reperfusion injury. Although ischemic preconditioning has been shown to be beneficial in the human heart and the liver, prospective controlled studies in humans involving ischemic preconditioning of the intestine are lacking. Research focused on the application of novel drugs that can mimic the effects of ischemic preconditioning to manipulate the cellular events during reperfusion injury of the intestine is required.
Transabdominal oxygenation using perfluorocarbons
Journal of Pediatric Surgery, 1999
Purpose: Evaluation of the intraabdominal (intraperitoneal and intraluminal) administration of oxygen-saturated perfluorocarbon on both portal and arterial blood oxygenation. Methods: Eight male rabbits were divided into the test (n = 5) and control (n = 3) groups. Each underwent intrajejunal, intraperitoneal, and intravascular (artery, portal vein) catheter placements along with ligation of the duodenum and the terminal ileum under general anesthesia. The test group received oxygen-saturated perfluorotripropylamine (FTPA), and the control group received oxygen desaturated FTPA. The oxygen delivery was assessed by serial blood gas measurements before and after the administration of FTPA. Results:The administration of oxygen-saturated FTPA significantly increased the partial pressure of oxygen within both the arterial and the portal venous blood (Pa02, Ppv02) without significant changes in Pco2 values. Oxygen desaturated FTPA failed to show any effects on blood gas values. Compared with oxygen desaturated FTPA, oxygen-saturated FTPA increased Pao2, Ppvo2, and oxygen saturation (artery, portal vein) significantly at some, but not all of the time-points measured. Conclusions:The intraabdominal administration of saturated FTPA improved both the portal venous and the arterial oxygenation. This new mode of oxygenation may be helpful as an adjunct to conventional oxygen delivery systems.
Pathophysiology of the intestinal ischemic reperfusion injury
Global Journal of Animal Scientific Research, 2014
The objective of this review is to approach current information about the ischemic reperfusion injury that affects the gastrointestinal system in animals, because it is classified as a complex event that can cause local and systemic injuries, leading to multiple organ failure. The deleterious events caused by the reperfusion process are greater when compared with the ischemia, due to the circulation of toxins released secondary to hypoxia, loss of cellular membrane integrity, release of free radical and endothelial injuries during reperfusion. It is known that in Veterinary Medicine most of the abdominal emergencies (acute abdomen) cause gastrointestinal microcirculatory dysfunctions and its diagnostic is still a challenge, because the clinical signs are similar to other diseases. The reperfusion injury is one of the reasons for the morbidity and mortality associated with intestinal ischemia, a common affection, especially in equines. The injuries on intestinal ischemia/reperfusion (I/R) are considerate of extreme importance due to its severity and the comprehension of the pathophysiological mechanism of these injuries is necessary to determine therapeutic strategies in the main domestic species.