Michele Finotti , Maria Barahona , Renee M. Maina , Taras Lysyy , Raghav Agarwal , Phillip Schmitt , Giorgio Caturegli , Chiara Di Renzo , Alessandro Anselmo , David Mulligan , John P. Geibel , Francesco D'Amico
{"title":"在离体灌注模型中,l -精氨酸可预防离体大鼠肠区缺血损伤","authors":"Michele Finotti , Maria Barahona , Renee M. Maina , Taras Lysyy , Raghav Agarwal , Phillip Schmitt , Giorgio Caturegli , Chiara Di Renzo , Alessandro Anselmo , David Mulligan , John P. Geibel , Francesco D'Amico","doi":"10.1016/j.tpr.2022.100096","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>The small intestine is one of the most sensitive organs to ischemia. L-arginine has been shown to reduce damage from ischemia and reperfusion injury. We hypothesize that explanted intestinal segments from rats will demonstrate reduced susceptibility to ischemic injury when perfused with l-arginine.</p></div><div><h3>Methods</h3><p>45 small intestinal segments were harvested from male Sprague-Dawley rats and connected to an ex vivo intestinal perfusion device. Ischemic damage was induced by perfusing the extraluminal side with Ringer-HEPES buffer saturated with 100% N2. All segments were then perfused intraluminally with and without l-arginine. We conducted a set of experiments with intraluminal perfusion with both l-arginine and N-nitroarginine methyl ester (L-NAME), an inhibitor of the nitric oxide – arginine pathway. Control segments were perfused extraluminally under non-ischemic conditions and intraluminally with and without l-arginine. The intraluminal perfusate contained FITC-inulin, and the fluorescence signal of FITC-inulin was measured to calculate average fluid secretion, which directly corresponds to the extent of ischemic injury.</p></div><div><h3>Results</h3><p>Intestinal segments perfused with l-arginine had significantly decreased secretion over time in comparison to intestinal segments perfused without l-arginine (p<0.0001). Perfusion with L-NAME abrogated the protective effect of l-arginine.</p></div><div><h3>Conclusion</h3><p>Intraluminal perfusion with l-arginine reduced ischemic damage to harvested intestine.</p></div>","PeriodicalId":37786,"journal":{"name":"Transplantation Reports","volume":"7 2","pages":"Article 100096"},"PeriodicalIF":0.0000,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2451959622000051/pdfft?md5=825054dc528742035dccee8f8bb93798&pid=1-s2.0-S2451959622000051-main.pdf","citationCount":"1","resultStr":"{\"title\":\"L-arginine prevents ischemic injury in explanted rat intestinal regions in an ex vivo perfusion model\",\"authors\":\"Michele Finotti , Maria Barahona , Renee M. Maina , Taras Lysyy , Raghav Agarwal , Phillip Schmitt , Giorgio Caturegli , Chiara Di Renzo , Alessandro Anselmo , David Mulligan , John P. Geibel , Francesco D'Amico\",\"doi\":\"10.1016/j.tpr.2022.100096\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>The small intestine is one of the most sensitive organs to ischemia. L-arginine has been shown to reduce damage from ischemia and reperfusion injury. We hypothesize that explanted intestinal segments from rats will demonstrate reduced susceptibility to ischemic injury when perfused with l-arginine.</p></div><div><h3>Methods</h3><p>45 small intestinal segments were harvested from male Sprague-Dawley rats and connected to an ex vivo intestinal perfusion device. Ischemic damage was induced by perfusing the extraluminal side with Ringer-HEPES buffer saturated with 100% N2. All segments were then perfused intraluminally with and without l-arginine. We conducted a set of experiments with intraluminal perfusion with both l-arginine and N-nitroarginine methyl ester (L-NAME), an inhibitor of the nitric oxide – arginine pathway. Control segments were perfused extraluminally under non-ischemic conditions and intraluminally with and without l-arginine. The intraluminal perfusate contained FITC-inulin, and the fluorescence signal of FITC-inulin was measured to calculate average fluid secretion, which directly corresponds to the extent of ischemic injury.</p></div><div><h3>Results</h3><p>Intestinal segments perfused with l-arginine had significantly decreased secretion over time in comparison to intestinal segments perfused without l-arginine (p<0.0001). 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L-arginine prevents ischemic injury in explanted rat intestinal regions in an ex vivo perfusion model
Background
The small intestine is one of the most sensitive organs to ischemia. L-arginine has been shown to reduce damage from ischemia and reperfusion injury. We hypothesize that explanted intestinal segments from rats will demonstrate reduced susceptibility to ischemic injury when perfused with l-arginine.
Methods
45 small intestinal segments were harvested from male Sprague-Dawley rats and connected to an ex vivo intestinal perfusion device. Ischemic damage was induced by perfusing the extraluminal side with Ringer-HEPES buffer saturated with 100% N2. All segments were then perfused intraluminally with and without l-arginine. We conducted a set of experiments with intraluminal perfusion with both l-arginine and N-nitroarginine methyl ester (L-NAME), an inhibitor of the nitric oxide – arginine pathway. Control segments were perfused extraluminally under non-ischemic conditions and intraluminally with and without l-arginine. The intraluminal perfusate contained FITC-inulin, and the fluorescence signal of FITC-inulin was measured to calculate average fluid secretion, which directly corresponds to the extent of ischemic injury.
Results
Intestinal segments perfused with l-arginine had significantly decreased secretion over time in comparison to intestinal segments perfused without l-arginine (p<0.0001). Perfusion with L-NAME abrogated the protective effect of l-arginine.
Conclusion
Intraluminal perfusion with l-arginine reduced ischemic damage to harvested intestine.
期刊介绍:
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