Intraluminal Intestinal Administration of Oxygenated Perfluorocarbon Improves Acid–Base and Cardiopulmonary Parameters After Acute Mesenteric Ischemia. An Experimental Study in Rabbits

Purpose The aim of this study was to evaluate the effects of the intraluminal intestinal administration of oxygenated perfluorocarbon, during experimental acute intestinal ischemia, on the acid–base blood status and the cardiopulmonary parameters. Methods Thirty-six rabbits were separated into three groups: (a) Control group (ischemia alone), (b) PFC-O₂ group (ischemia plus infusion of oxygenated F-Decalin in intraluminal intestinal administration), and (c) PFC group (ischemia plus infusion of nonoxygenated F-Decalin in intraluminal intestinal administration). An equal number of the animals was then subjected to 8 h of intestinal ischemia by ligation of the superior mesenteric artery (subgroups 1), the mesenteric vein (subgroups 2) or both vessels (subgroups 3). At 0, 2, 4, 6, and 8 h arterial blood samples were taken for acid–base status tests and the vital signs (heart and respiratory rate, pressure of inferior vena cava, and systolic arterial pressure) were noted. The statistical analysis was performed by the nonparametric Kruskal–Wallis test. Results There were no significant differences in any of the studied parameters (pH, base excess, respiratory gases, pressure of inferior vena cava, systolic arterial pressure, heart and respiratory rate) between animals of the same group and subgroup. In addition, the differences among Control and PFC groups and their equal subgroups were not significant. On the other hand, the measurements of the PFC-O₂ animals showed significant differences at 4, 6, and 8 h of ischemia (P < 0.05) in comparison with those from the Control and PFC groups. Conclusion We conclude that the intraluminal intestinal administration of oxygenated perfluorocarbons may thus be a useful adjunctive therapy in the treatment of patients with acute mesenteric ischemia.     

Intestinal energy metabolism after ischemia-reperfusion: Effects of moderate hypothermia and perfluorocarbons

Purpose: This study investigated the roles of moderate hypothermia and extraluminal oxygenated perfluorcarbon (PFC) on intestinal metabolism after ischemia-reperfusion. Methods: A model of 30-minute intestinal ischemia followed by 60 minutes of reperfusion was used. The animals were maintained at either normothermia (36.5 to 37.5[deg ]C) or moderate hypothermia (31 to 32[deg ]C). Four groups of adult rats were studied (n = 8 per group): (A) sham at normothermia, (B) ischemia-reperfusion at normothermia, (C) ischemia-reperfusion at hypothermia and, (D) ischemia-reperfusion with extraluminal oxygenated PFC perfusion during ischemia at normothermia. Intestinal phosphocreatine, ATP and lactate levels were measured. Histologic changes in the intestine were evaluated. Results: Intestinal ischemia-reperfusion at normothermia caused a marked reduction in phosphocreatine and ATP with an increase in lactate. Moderate hypothermia exerted beneficial effects by attenuating the depletion of high-energy phosphates and the elevation of lactate. Extraluminal PFC perfusion during ischemia failed to produce a protective effect on high-energy phosphates, although it reduced lactate accumulation. Moderate hypothermia significantly decreased the degree of mucosal damage. Conclusions: Whole-body moderate hypothermia protects the small intestine from reperfusion injury as measured both biochemically and histologically. Extraluminal oxygenated PFC administration during ischemia did not protect the intestine from reperfusion injury in this model.     

Effect of Prolonged Selective Intramesenteric Arterial Vasodilator Therapy on Intestinal Viability After Acute Segmental Mesenteric Vascular Occlusion

OBJECTIVE: To evaluate the effect of selective intramesenteric artery vasodilator infusion on intestinal viability in a rat model of acute segmental mesenteric vascular occlusion. SUMMARY BACKGROUND DATA: Although intramesenteric arterial vasodilator infusion may be an effective treatment for nonocclusive mesenteric ischemia, it has also been advocated to increase collateral blood flow after mesenteric vascular occlusion. However, the authors have previously found that intraarterial vasodilators actually reduce collateral blood flow acutely, by preferentially dilating the vasculature of adjacent, nonischemic mesenteric vascular beds, a phenomenon well established in other organs. METHODS: A segment of rat ileum was acutely devascularized, with blood flow provided only by collateral arterial vessels from adjacent, nonischemic bowel. Papaverine (30 or 40 microg/kg/min), isoproterenol (0.06 microg/kg/min), norepinephrine (0.1 or 0.2 microg/kg/min), or vehicle saline was continuously infused into the cranial (superior) mesenteric artery for 48 hours. Viability was then assessed using previously established, objective gross and microscopic criteria. RESULTS: Although papaverine increased total mesenteric blood flow in normally vascularized rats, it not only failed to improve but actually significantly reduced the length of the devascularized segment maintained viable by collateral blood flow after 48 hours. Isoproterenol had a similar effect. Norepinephrine infusion decreased both normal mesenteric blood flow and viable segment length. CONCLUSIONS: These findings suggest that intraarterial vasodilator therapy fails to improve intestinal viability after segmental mesenteric vascular occlusion.     

Treatment of intestinal ischemia with oxygenated intraluminal perfluorocarbons

Liquid perfluorocarbons are biologically inert compounds capable of dissolving up to 40 percent oxygen by volume. This remarkable and reversible oxygen solubility has encouraged investigations into therapeutic application in situations where tissue oxygen delivery is impaired. One such setting is intestinal ischemia. Identically prepared devascularized segments of rat intestine were treated with either intraluminal oxygenated perfluorocarbon (perfluorotributylamine) or physiologic saline solution. After timed sacrifice, blinded quantitative histologic evaluation for ischemic injury was performed. The perfluorotributylamine treatment groups had histologic scores indicative of less severe injury between 1 and 4 hours. These scores achieved statistical significance (p less than 0.05). We conclude that intraluminal oxygenated perfluorocarbons have a significant protective effect in this model of intestinal ischemia. This quantitative analysis is unique and is an important aspect of the preclinical evaluation of the perfluorocarbon preparations.     

Protection against experimental small intestinal ischaemia-reperfusion injury with oxygenated perfluorochemical

BACKGROUND: Intestinal ischaemia-reperfusion (IR) injury frequently occurs in abdominal surgery. Perfluorochemical (PFC) can be used to oxygenate intestinal organs directly and allows adenosine 5'-triphosphate (ATP) production within the submerged organs during ischaemia. This study was designed to evaluate the protective effect of PFC in IR injury, focusing on cytokine production in rat small intestine. METHODS: The superior mesenteric artery was occluded in rats for 60 min and the small bowel placed in an intestinal bag containing either normal saline (group 1), oxygenated saline (group 2) or oxygenated PFC (group 3). The arterial clip was subsequently removed, allowing reperfusion. The number of rats that survived for 7 days, tissue ATP levels, biochemical variables, tissue lipid peroxidation (LPO), bacterial cultures and histological changes were examined after reperfusion. RESULTS: The use of oxygenated PFC in group 3 improved survival compared with the other groups. Serum creatine phosphokinase and lactate dehydrogenase levels in groups 1 and 2 reflected small intestinal damage, and plasma levels of tumour necrosis factor alpha and interleukin 6 were raised. In contrast, oxygenated PFC decreased these levels, and reduced LPO, bacterial translocation and augmented apoptosis of the small intestine after reperfusion. CONCLUSION: An intestinal bag containing oxygenated PFC showed protective effects during bowel ischaemia.     

Intestinal luminal microdialysis: a new approach to assess gut mucosal ischemia

BACKGROUND: The authors developed a microdialysis method for sampling lactate from the gut lumen to evaluate the metabolic state of the intestinal mucosa. The aim of the study was to evaluate the method in vivo during nonischemic systemic hyperlactatemia and gut ischemia. METHODS: Microdialysis capillaries were inserted in the lumen of jejunum, in the jejunal wall, and in the mesenteric artery and vein in anesthetized, normoventilated pigs. In the first experiment, infusion of lactate was used to clamp the arterial blood lactate at 5 mM and 10 mM (n = 6). In the second experiment, 90 min of intestinal ischemia was induced by total (n = 6) or partial (n = 6) occlusion of the superior mesenteric artery followed by 60 min of reperfusion. Sham-operated animals were used as controls (n = 6). RESULTS: Gut luminal lactate increased only slightly during the nonischemic hyperlactatemia: from a median baseline value of 0.10 (range, 0.06-0.28) to 0.50 (range, 0.15-1.18) and 0.86 (range, 0.35-2.05) mM. Total occlusion of superior mesenteric artery increased luminal lactate from a median of 0.09 (range, 0.06-0.17) to 2.37 (range, 1.29-2.98) and further up to 3.80 (range, 2.55-6.75) mM during reperfusion. Partial occlusion of superior mesenteric artery induced an increase from a median of 0.09 (range, 0.06-0.51) to 1.66 (range, 0.07-3.97) mM. Gut wall microdialysate lactate in deep and superficial layers followed the arterial and mesenteric vein microdialysate lactate. CONCLUSIONS: Luminal lactate concentration, as measured by microdialysis, increases substantially during gut ischemia but does not respond to systemic hyperlactatemia per se. In contrast, gut wall microdialysis cannot distinguish between gut ischemia and systemic hyperlactatemia. Gut luminal microdialysis provides a method for the assessment of intestinal ischemia with a potential for clinical application.     

Intestinal Luminal Microdialysis: A New Approach to Assess Gut Mucosal Ischemia

Background: The authors developed a microdialysis method for sampling lactate from the gut lumen to evaluate the metabolic state of the intestinal mucosa. The aim of the study was to evaluate the method in vivo during nonischemic systemic hyperlactatemia and gut ischemia.

Methods: Microdialysis capillaries were inserted in the lumen of jejunum, in the jejunal wall, and in the mesenteric artery and vein in anesthetized, normoventilated pigs. In the first experiment, infusion of lactate was used to clamp the arterial blood lactate at 5 mM and 10 mM (n = 6). In the second experiment, 90 min of intestinal ischemia was induced by total (n = 6) or partial (n = 6) occlusion of the superior mesenteric artery followed by 60 min of reperfusion. Sham-operated animals were used as controls (n = 6).

Results: Gut luminal lactate increased only slightly during the nonischemic hyperlactatemia: from a median baseline value of 0.10 (range, 0.06-0.28) to 0.50 (range, 0.15-1.18) and 0.86 (range, 0.35-2.05) mM. Total occlusion of superior mesenteric artery increased luminal lactate from a median of 0.09 (range, 0.06-0.17) to 2.37 (range, 1.29-2.98) and further up to 3.80 (range, 2.55-6.75) mM during reperfusion. Partial occlusion of superior mesenteric artery induced an increase from a median of 0.09 (range, 0.06-0.51) to 1.66 (range, 0.07-3.97) mM. Gut wall microdialysate lactate in deep and superficial layers followed the arterial and mesenteric vein microdialysate lactate.     

Endothelin-A receptor antagonism improves small bowel graft perfusion and structure after ischemia and reperfusion

BACKGROUND: We hypothesized that endothelin-A (ET-A) receptor activation plays a central role in intestinal ischemia-reperfusion-induced hemodynamic changes and may trigger the process of mucosal barrier destruction. Our aims were to investigate and compare the effects of systemic and intragraft ET-A receptor antagonist therapy during the early revascularization phase of small bowel transplants. METHODS: In Groups 1, 2, and 3 orthotopic small bowel autotransplants were performed in anesthetized dogs. Group 4 served as sham-operated control. Group 2 was treated i.v. with the ET-A receptor antagonist ETR-p1/fl peptide at the onset of reperfusion. In Group 3, intragraft infusion of the ETR-p1/fl peptide was applied during cold ischemia. The mucosal myeloperoxidase activity and the free radical-producing capacity of the granulocytes passing the intestinal graft were determined, and the systemic hemodynamic features were recorded. The extent of the mucosal injury was determined from tissue biopsies taken after 4 hr of reperfusion. RESULTS: Reperfusion progressively decreased the mesenteric blood flow, increased the mesenteric vascular resistance, and enhanced the accumulation and free radical production capacity of the leukocytes. These changes were significantly inhibited in Group 2 with systemic (i.v.) administration of the ET-A receptor antagonist. The local, intragraft treatment improved the mesenteric hemodynamic changes and decreased the accumulation but not the activation of the circulating leukocytes. The structural injury of the graft was prevented in both treated groups. CONCLUSIONS: Endothelins are involved in the hemodynamic events leading to structural injury of the intestinal graft after ischemia-reperfusion. The antagonism of intestinal ET-A receptors by a combination of local and systemic drug delivery offers a rational treatment modality in these conditions.     

Intestinal diamine oxidase levels reflect ischemic injury

Mucosal diamine oxidase (DAO) decreases during intestinal ischemia and may be a useful marker of intestinal ischemic injury. Tissue DAO activity and histologic changes were studied in intestinal segments taken from the midpoint of the small intestine before and 2, 4, and 24 hr after manipulation of the intestinal blood supply in 24 mongrel dogs. Intestinal DAO activity decreased significantly (17 +/- 21% of control value) 24 hr after SMA ligation and was associated with abnormal histology (histology score 7.8 +/- 2.9 at 24 hr vs 0.3 +/- 0.5 at 0 hr). SMA occlusion for 2 hr resulted in a significant decrease in DAO activity (45 +/- 36% of control value) 4 hr after manipulation which returned to normal at 24 hr, as did the histologic injury. Ligation of both the mesenteric arteries and veins resulted in a more rapid decrease in DAO activity. Decreased DAO activity correlated with the extent of histologic injury. Intestinal ischemia is associated with decreased intestinal DAO activity, which is influenced by the mechanism and duration of intestinal ischemia.     

Intestinal ischemia after laparoscopic cholecystectomy.

OBJECTIVES: Intestinal ischemia is a rarely reported complication following laparoscopic cholecystectomy. We describe a case of massive small intestinal necrosis 3 days following this procedure. An autopsy determined the cause to be splanchnic hypoperfusion, likely due to the physiologic changes induced by the pneumoperitoneum necessary to conduct the surgery. We sought to determine whether all reported cases of intestinal ischemia following laparoscopic cholecystectomy (LC) shared the same etiology, and if faulty operative technique could be invoked. METHODS: A review of all known published cases of intestinal ischemia following LC was conducted to determine the underlying etiology of ischemia, and whether adequate operative technique had been observed. RESULTS: Multiple causes of intestinal ischemia following LC have been described: splanchnic hypoperfusion, thrombosis of the superior mesenteric artery, and thrombosis of the inferior mesenteric vein. All occurred despite correct operative technique. CONCLUSIONS: Intestinal ischemia following LC has diverse causes. Patient factors rather than faulty operative technique would appear to underlie the development of this rare complication.     

大鼠肝缺血及再灌注所致小肠过氧化损伤及丹参的保护作用

目的 观察大鼠肝缺血再灌注小肠过氧化损伤及丹参预处理的保护作用.方法 首先将SD大鼠随机分为正常对照组(CO组)、假手术组(SO组)、缺血再灌注组(IR组)、丹参预处理组(SM组),分别在肝缺血30、45、60 min时取上段空肠进行大体病理学检测;然后在肝缺血45 min条件下,动物亦随机分为4组(CO组、SO组、IR组、SM组),按再灌注后不同时间(0、3、12、24、72 h)分为5个亚组,每组5只.SM组在阻断第一肝门30 min前经尾静脉推注丹参注射液6 g/kg加生理盐水40 ml/kg,其余各组按40 ml/kg给予生理盐水尾静脉注入,SO组开腹后仅解剖肝门,不钳夹肝蒂.分别在再灌注0、3、12、24、72 h取上段空肠行病理学检查、丙二醛(MDA)含量测定、髓过氧化物酶(MPO)活性测定.结果 空肠黏膜损伤评分随肝缺血时限延长而加重;在肝缺血45 min再灌注不同时限点SM组空肠黏膜损伤较IR组明显减轻,且肠组织MDA含量、MPO活性均低于IR组(P<0.05).结论 肝缺血再灌注所致小肠明显淤血性损伤,MDA含量、MPO活性升高,丹参预处理对肝缺血再灌注所致小肠损伤具有保护作用.     

L-lactate after embolization of the superior mesenteric artery

BACKGROUND: Plasma markers for intestinal ischemia have not proven to be accurate. The value of L-lactate is unclear. Experimental models based on open surgery confound the effects of surgical trauma with that of ischemia. The aim was to create an endovascular model for acute superior mesenteric artery thromboembolism, and then to study L-lactate and lactate dehydrogenase (LD) activity in plasma and peritoneal fluid in pigs with extensive, high-grade intestinal ischemia. MATERIALS AND METHODS: Nine pigs underwent full superior mesenteric artery embolization with 4 h of intended intestinal ischemia, whereas six were control animals. Sampling of central venous and arterial blood was performed throughout the experiment, ending with laparotomy to collect peritoneal fluid and segmental intestinal biopsies. A pathologist, blinded to the performed interventions, graded the ischemic lesions. RESULTS: There were no differences in plasma L-lactate (P = 0.61) or LD activity levels (P = 0.69), measured at different time points from baseline to end of study, between animals with extensive, high-grade intestinal ischemia and sham. Intraperitoneal L-Lactate (P = 0.005) and LD activity (P = 0.018) levels were elevated compared with sham. There were differences in grades of ischemia in the duodenum (P = 0.003), small intestine (P < 0.001), proximal (P < 0.001), and sigmoid (P = 0.032) colon between experimental animals and sham. The grade of small bowel ischemia (n = 15) correlated to intraperitoneal fluid L-lactate (r = 0.80; P < 0.001) and LD activity levels (r = 0.72; P = 0.003). CONCLUSIONS: This endovascular study in a porcine model showed that L-lactate and LD activity levels in peritoneal fluid, not in plasma, reflect intestinal ischemia. The study suggests that plasma L-lactate not is a useful early marker in patients with suspicion of intestinal ischemia.     

Intestinal metabolism after ischemia-reperfusion

PURPOSE: This study explores the effects of ischemia-reperfusion on various metabolic aspects of the small intestine. METHODS: Intestinal ischemia-reperfusion was obtained by clamping and unclamping the superior mesenteric artery in adult rats. Four groups of animals were studied: (A) sham operation for 150 minutes, (B) 90-minute intestinal ischemia, (C) 150-minute intestinal ischemia, and (D) 90-minute intestinal ischemia followed by 60-minute reperfusion. Body temperature was maintained at normothermia (36.5 to 37.5 degrees C). Concentrations of intestinal glucose, succinate, lactate, amino acids, phosphocholine (PC), glycerophosphocholine (GPC), choline, and phosphoenergetics were measured using magnetic resonance spectroscopy of freeze-clamped small intestine extracts. RESULTS: Intestinal ischemia (groups B and C) alone caused a significant drop in glucose and phosphoenergetics but caused an increase in amino acids, succinate, and lactate. Ischemia and ischemia-reperfusion decreased PC and GPC but increased choline. After intestinal reperfusion (group D), no recovery of phosphoenergetics was observed, but there was partial recovery of glucose, succinate, lactate, and amino acids. CONCLUSIONS: There is no recovery of phosphoenergetics after 90 minutes of intestinal ischemia followed by 60 minutes of reperfusion. Partial recovery of glucose, succinate, lactate, and amino acids may reflect equilibration of these metabolites between damaged cells and extracellular fluid.     

Changes in intestinal motility and in the myenteric plexus in a rat model of intestinal ischemia-reperfusion

Background/Purpose

Early histologic changes induced by intestinal ischemia-reperfusion injury (IIRI) have been extensively studied using animal models. However, information regarding late effects on intestinal motility is lacking. The aim of this study was to investigate the late effects of IIRI on myenteric plexus histology and intestinal motility.

Materials and Methods

Thirty-two postweaning male mice weighing between 58 and 103 g were divided randomly into 4 groups: Control (unoperated), Sham (celiotomy), 30-minute ischemia (celiotomy and superior mesenteric artery ischemia for 30 minutes), and 45-minute ischemia (celiotomy and superior mesenteric artery ischemia for 45 minutes). Postoperative intestinal motility was assessed by weighing total fecal output for 24 hours on the 3rd, 7th, 14th, and 21st day after surgery. Segments of duodenum, jejunum, and ileum were examined at light microscopy for changes in the myenteric plexus.

Results

Three weeks after IIRI, the ganglion cells from the myenteric plexus appeared in light microscopy, spongy or foamy, containing many vacuoles in their cytoplasm. The neuronal nucleus became irregular, with degenerative signs. These alterations did not occur among animals from the control or sham groups. Although the animals of the 45-minute ischemia group showed a significant drop in fecal output in the 21st postoperative day, this appeared to have no effect on weight gain.

Conclusions

The results suggest that intestinal ischemia-reperfusion causes late neuronal damage. These changes resulted in alterations of intestinal motility, which, within the conditions of the present study, had no repercussion on general weight gain.     

Supraceliac aortic cross-clamping and declamping. Effects of dopexamine and dopamine on systemic and mesenteric hemodynamics, metabolism and intestinal tonometry in a rat model

BACKGROUND: The effects of dopexamine and dopamine on mesenteric ischemia during reperfusion following aortic cross-clamping are not known. We determined intramucosal tonometric PCO2 and PCO2 gap using a rat model of supraceliac aortic cross-clamping and declamping. METHODS: Under pentobarbital and fentanyl anesthesia, 24 rats were surgically instrumented with arterial, right atrial, and portal venous catheters, ultrasonic flowprobes for measurements of abdominal aortic, superior mesenteric and carotid artery blood flow, and a pediatric tonometer for intestinal mucosal PCO2 measurements. Rats were randomized to receive a continuous infusion of dopexamine (10 x microg(-1) x kg(-1) x min(-1), n=8), dopamine (10 microg x kg(-1) x min(-1), n=8 ), or physiologic saline (control, n= 8), infused at a rate of 4 ml x kg(-1) x h(-1), administered throughout the experimental protocol. After 30 min of drug infusion, the aorta was cross-clamped at the supraceliac level for 30 min. Reperfusion following declamping was observed for 180 min. RESULTS: Intestinal tonometric PCO2 remained unchanged during drug treatment before aortic cross-clamping, increased similarly in all groups following declamping during early reperfusion, and recovered to baseline within 30 min of reperfusion. Dopexamine treatment was associated with higher lactate levels and increased heart rate (P<0.05) during aortic cross-clamping. CONCLUSIONS: 1) Mesenteric ischemia, determined by intestinal tonometric PCO2 and PCO2 gap, recovers within 30 min of reperfusion following 30 min of aortic cross-clamping irrespective of drug treatment and, 2) dopexamine induced higher lactate levels and increased heart rate during aortic cross-clamping and should be carefully analyzed for potentially adverse effects on cardiac function.     

Glucagonlike peptide-2 analogue enhances intestinal mucosal mass and absorptive function after ischemia-reperfusion injury

BACKGROUND/PURPOSE: This study was designed to explore the efficacy of a synthetic analogue of glucagonlike peptide-2 (GLP-2a) in enhancing mucosal mass and absorptive function in a rat model of intestinal ischemia-reperfusion (I-R) injury. METHODS: Each of 20 Sprague-Dawley rats underwent placement of a jugular venous catheter connected to a subcutaneous osmotic pump designed to deliver its contents over 3 days. Rats were divided into 4 groups (n = 5 per group): (1) normal intestine/saline infusion; (2) 30-minute superior mesenteric artery occlusion/saline infusion, (3) normal intestine/ GLP-2alpha infusion, and (4) 30-minute superior mesenteric artery occlusion/GLP-2alpha infusion. Subsequently, mean mucosal 14C-galactose and 14C-glycine absorption and DNA content were determined for each group. RESULTS: In saline-treated rats, 30 minutes of mesenteric ischemia decreased mean mucosal galactose absorption by 29% (P < .05), glycine absorption by 22% (P = .12), and DNA content by 28% (P < .01) when compared with rats with uninjured intestine. In rats subjected to 30 minutes of intestinal ischemia, GLP-2alpha significantly improved galactose absorption by 46% (P < .05), glycine absorption by 84% (P < .01), and DNA content by 63% (P < .01) when compared with saline-treated control rats. In rats with mesenteric I-R injury treated with GLP-2a, galactose absorption was returned to normal. Glycine absorption and DNA content were increased significantly by 44% (P < .01) and 18% (P < .05), respectively, beyond the baseline for normal intestine. CONCLUSIONS: Thirty minutes of intestinal ischemia followed by immediate reperfusion significantly decreased mucosal mass and absorptive function, validating this rat model of I-R injury. After mesenteric I-R, GLP-2a significantly increased mucosal DNA content and absorption of 14C-galactose and 14C-glycine when compared with untreated control rats. After I-R injury, GLP-2a restored mucosal mass and absorptive function to normal or above-normal levels.     

Ameliorating Small Bowel Injury Using a Cavitary Two-Layer Preservation Method with Perfluorocarbon and a Nutrient-Rich Solution

The aim of this study was to improve small bowel (SB) quality during cold storage by combining two proven preservation strategies involving perfluorocarbon (PFC) and a novel luminal amino acid-rich solution. Rodent SB was flushed vascularly with UW solution and flushed luminally as follows: Group 1 (control)--no luminal flush, stored in UW; Group 2--luminal UW solution, stored in PFC; Group 3--luminal amino-acid (AA) solution, stored in PFC; and Group 4--luminal AA solution, stored in AA solution. Energetics, histology and mucosal function/electrophysiology were assessed over 24 h at 4 degrees C. ATP was consistently greater in Groups 2-4 than in the Control Group. Groups 3 and 4 exhibited significantly greater ATP, ATP/ADP ratios and energy charge levels after 12-h storage than in the other Groups. Histologic injury was generally lower in the AA-treated tissues (Groups 3 and 4); after 24 h, only minor epithelial clefting (Park's median grade 2) was present in Group 4; and consistent transmural infarction (grade 8) was evident in Groups 1 and 2. Combined treatment with luminal amino acid solution and oxygenated storage solution (PFC or AA solution) significantly improves energetics and mucosal function. This strategy may have implications for successful SB preservation in the clinic.     

Intramucosal pH and intestinal mucosal damage in ischemia-reperfusion injury

Small bowel transplantation (SBT) has become an increasingly promising treatment for short bowel syndrome. The evaluation of graft viability after SBT, however, has not been established, except by mucosal biopsy. We monitored intestinal mucosal acidity in order to detect small intestinal ischemia-reperfusion injury. Mongrel dogs were used in this study. After laparotomy, the small bowel was isolated with a vascular pedicle. A tonometer to measure intramucosal pH (pHi) was then positioned in the terminal ileum. The superior mesenteric artery was occluded with or without concomitant superior mesenteric vein occlusion for 60 or 120 min. The value of pHi was determined from laparotomy (baseline) to 12 h after reperfusion. Whole-thickness specimens of the ileum were taken before ischemia, just before reperfusion, and 1 h afterward. Mucosal injury was graded histopathologically. pHi decreased from baseline in relation to the degree of histopathological mucosal injury. There was a significant correlation between histological findings and the change in pHi. We conclude that monitoring intestinal mucosal acidity is a reliable way of determining graft viability after SBT. Received: 19 February 1998 Received after revision: 27 July 1998 Accepted: 15 September 1998     

Effects of Thalidomide and Pentoxyphylline Over Local and Remote Organ Injury After Intestinal Ischemia/Reperfusion

Objective

We investigated the effects of thalidomide alone or in combination with pentoxyphylline upon intestinal ischemia/reperfusion (I/R) injury in the rat.

Materials and Methods

Twenty male Wistar rats were randomized into 5 groups: sham-operated (SHAM), control (CTL), thalidomide (400 mg/kg) treatment (THAL), pentoxyphylline (50 mg/kg) treatment and a combination group (THAL + POX). I/R was induced by clamping the superior mesenteric artery for 45 minutes, followed by 120 minutes of reperfusion. We measured serum concentrations of aspartate-aminotransferase (AST), lactate dehydrogenase (LDH), tumor necrosis factor (TNF)-α as well as lipid peroxidation and antioxidant status. Intestinal samples were morphologically analyzed, and dry to wet (W/D) ratios calculated in intestinal, lung and liver samples, as a measurement of tissue edema.

Results

Serum concentrations of AST, LDH, and TNF-α were increased after I/R in the CTL compared with the SHAM group (P < .05). Lipid peroxidation was also increased, and antioxidant capacity in serum, decreased (P < .05). The W/D ratio was elevated in all tissue samples as well (P < .05). Both thalidomide and pentoxyphylline effectively reduced AST, LDH, TNF-α, and lipid peroxidation levels, as well as attenuated tissue edema and intestinal injury induced by I/R (P < .05). Combination treatment showed only modest additive effects on lung W/D ratio and TNF-α levels.

Conclusion

Both drugs protected the intestine, lungs, and liver against intestinal I/R injury, probably by inhibition of TNF-α and lipid peroxidation. However, combination treatment showed small, additive effects.     

Description of a New Model of Intestinal Denervation and In Situ Ischemia-Reperfusion Injury Using the Cecal Artery for Perfusion

Background

The main purpose of the present investigation was to describe a model of intestinal denervation and in situ intestinal ischemia-reperfusion injury in adult rats, with utilization of the distal branch of the superior mesenteric artery close to the cecum for perfusion.

Methods

In the root of the mesentery, the mesenteric artery and vein were completely isolated. Close to the cecal valve, a lymphatic node served as the reference point for the localization of the cecal artery, which was cannulated for perfusion with cold lactated Ringer's solution. One hundred adult male rats were utilized in the study.

Results

In a pilot study, we demonstrated that the cold ischemia time was sufficient to promote histopathologic intestinal changes characteristic of ischemia-reperfusion injury. Among 88 operated animals, 62 (70.5%) survived the procedure.

Conclusion

The experimental model described herein has the advantage of preserving the entire intestine, which makes it more suitable for studies of physiological and morphological alterations after intestinal transplantation.