Lower limb ischaemia-reperfusion injury alters gastrointestinal structure and function

Yassin, M. M. I.; D’Sa, Aires A.B. Barros; Parks, T. G.; McCaigue, M. D.; Leggett, P. L.; Halliday, M. I.

doi:10.1002/bjs.1800841023

Cited by 36 publications

(17 citation statements)

References 22 publications

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“…Despite the vast number of experimental studies to assess the effects of IR on organ structure and function (4,7,16,29,30,36), there is only limited information on the rapid response of intestinal tissue to halted blood flow. We have developed a new in vivo mouse model to assess the early effects of IR in real-time on intestinal structure and function.…”

Section: Discussionmentioning

confidence: 99%

“…There is abundant information on the compromising effects of IR on many processes in the intestine, such as capillary blood flow (13,23), villus structure (4,36), mucosal permeability (29,30), and mitochondrial activity (7,16). Present protective treatments of IR damage include the application of various extracellular signaling molecules and the manipulation of a variety of intracellular signaling pathways (3,31), but relatively little is known about the early events that trigger the switch from reversible mucosal injury to the irreversible damage that leads to necrosis of epithelial villus cells in the intestine (3).…”

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confidence: 99%

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Intestinal ischemia-reperfusion injury: reversible and irreversible damage imaged in vivo

Guan

Worrell

Pritts

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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The early events in an intestinal ischemic episode have been difficult to evaluate. Using in vivo microscopy we have analyzed in real-time the effects of short (15 min) and long (40-50 min) ischemia with subsequent reperfusion (IR), evaluating structure, integrity, and functioning of the mouse jejunal mucosa while monitoring blood flow by confocal microscopy. IR was imposed by inflation/deflation of a vascular occluder, and blood flow was monitored and confirmed with scanning confocal imaging. After short ischemia, villus tip cells revealed a rapid increase (23%) in the intracellular NAD(P)H concentration (confocal autofluorescence microscopy), and the pH-sensitive probe BCECF showed a biphasic response of the intracellular pH (pH(i)), quickly alkalinizing from the resting value of 6.8 +/- 0.1 to 7.1 +/- 0.1 but then strongly acidifying to 6.3 +/- 0.1. Upon reperfusion, values returned toward control. In contrast, results were heterogeneous after long IR. During long ischemia, one-third of the epithelial cells remained viable with reversible changes upon reperfusion, but remaining cells lost membrane integrity (Lucifer Yellow uptake, LY) and had membrane blebs during ischemia. These effects became more pronounced as the reperfusion interval progressed when cells exhibited more severely affected NAD(P)H and pH(i) values, larger blebs, and more LY uptake and eventually were shed from the villus. Results from stereo microscopy suggest that these irreversible effects of IR may have occurred as a result of incomplete restorations of local blood flow, especially at the antimesenteric side of the intestine. We conclude that the adverse effects of short ischemia on the jejunum epithelium are fully reversible during the reperfusion interval. However, after long ischemia, reperfusion cannot restore normal structure and functioning of a majority of cells, which deteriorate further. Our results provide a basis for defining the cellular events that cause tissue to transit from reversible to irreversible damage during IR.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Intestinal ischemia-reperfusion injury: reversible and irreversible damage imaged in vivo

Guan

Worrell

Pritts

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…This observation first occurred in the literature in 1992, since then it has been demonstrated that lower limb ischemia causes an increment in intestinal permeability (Corson et al, 1992;Edrees et al, 2003;Harkin et al, 2001Harkin et al, , 2007Yassin et al, 1997), intestinal proinflammatory cytokine expression (Scott et al, 2009), and systemic endotoxin concentration (Cabie et al, 1993;Corson et al, 1992;Foulds et al, 1997;Lau et al, 2000;Yassin et al, 1996Yassin et al, , 1998. It has also been demonstrated that lower limb IR can influence the elements of small bowel microcirculation evaluated by intravital videomicroscopy.…”

Section: Discussionmentioning

confidence: 89%

“…Previous animal and human studies demonstrated that lower limb ischemicreperfusion injuries could lead to intestinal mucosal damage (Leng et al, 2011;Weeks et al, 2007;Yassin et al, 1996Yassin et al, , 1997Zhang et al, 2011), increased intestinal permeability (Corson et al, 1992;Edrees et al, 2003;Harkin et al, 2001Harkin et al, , 2007Yassin et al, 1997), endotoxemia (Cabie et al, 1993;Corson et al, 1992;Foulds et al, 1997;Lau et al, 2000;Yassin et al, 1996Yassin et al, , 1998, as well as bacterial translocation (Willoughby et al, 1996;Yassin et al, 1998). The increased intestinal permeability facilitates the entrance of endotoxin and gut flora into the circulation which aggravates the already existing systemic inflammation therefore possibly increasing mortality rates (Doig et al, 1998;Keel and Trentz, 2005).…”

Section: Introductionmentioning

confidence: 96%

Improvement of small intestinal microcirculation by postconditioning after lower limb ischemia

Turóczi

Fülöp

Czigány

et al. 2015

Microvascular Research

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“…Acute lung injury and acute respiratory distress syndrome (ARDS) as a remote sequela of severe lower torso ischemia-reperfusion have been demonstrated experimentally8 and clinically 9. The gastrointestinal system is also commonly targeted for injury after ischemia-reperfusion below the infrarenal aorta 11-13…”

Section: Discussionmentioning

confidence: 99%

Risk Factors for Postoperative Complications after Open Infrarenal Abdominal Aortic Aneurysm Repair in Koreans

et al. 2011

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PurposeOpen infrarenal abdominal aortic aneurysm (AAA) repair is performed without event in most cases. However, some patients suffer major morbidities such as renal failure, myocardial infarction, paraplegia, acute respiratory distress syndrome, or hepatic dysfunction. Predicting what kinds of patient populations are more prone to develop such complications may keep the clinicians more attentive to the patients, possibly leading to better prognoses. In this retrospective study, we searched the incidence of and risk factors for postoperative complications and their predictive equations in 162 patients who underwent open infrarenal AAA repair.Materials and MethodsPostoperative complications were observed within 30 days. Patient characteristics, types of aneurysm and surgery, and hemodynamic and metabolic variables during the periclamp period were analyzed in relation to postoperative complications using multiple logistic regression analysis.ResultsPostoperative complications involved the cardiac (20%), pulmonary (14%), renal (13%), gastrointestinal (6%), hepatic (3.1%), and neurologic (2.5%) systems, and bleeding occurred in 1.2% of cases. The mortality rate was 5.6%. The risk factors were age [> 67 yrs, odds ratio (OR) 2.6], clamp duration (> 110 min, OR 4.7), volume of blood transfusion (> 1,280 mL, OR 4.4), emergency operation (OR 1.4), and vasopressor infusion during clamp (OR 1.4). The prediction model was: P(x) = exp(α)/[1 + exp(α)] α;-2.2 + 0.9 × age + 1.5 × clamp duration + 1.5 × transfusion + 0.3 × emergency + 0.4 × vasopressor infusion [insert 1 if risk factors exist, otherwise, insert 0 to each variable].ConclusionA significant number of complications occurred after infrarenal AAA repair. Therefore, creating a protocol to identify and monitor high risk patients would improve postoperative care.

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Lower limb ischaemia-reperfusion injury alters gastrointestinal structure and function

Abstract: These data suggest that reperfusion of acutely ischaemic extremities produces structural and functional changes in the small intestine, although these changes are not associated with increased neutrophil infiltration within the bowel wall.

Cited by 36 publications

References 22 publications

Intestinal ischemia-reperfusion injury: reversible and irreversible damage imaged in vivo

Intestinal ischemia-reperfusion injury: reversible and irreversible damage imaged in vivo

Improvement of small intestinal microcirculation by postconditioning after lower limb ischemia

Risk Factors for Postoperative Complications after Open Infrarenal Abdominal Aortic Aneurysm Repair in Koreans

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