The protective effect of hyperbaric oxygenation on the small intestine in ischemia-reperfusion injury

Hyperbaric oxygenation has been used as the method of treatment in several ischemic diseases, but its effectiveness still remains controversial. The authors investigated the effect of hyperbaric oxygenation on ischemia-reperfusion injury of the small intestine using a rat model. Wistar King A Makino (WKAM) rats were subjected to 120 minutes of superior mesenteric artery occlusion before reperfusion, with 90 minutes of hyperbaric oxygenation (two absolute atmospheric pressure in an experimental hyperbaric chamber) during ischemia in group A and immediately after reperfusion in group B, and no hyperbaric oxygen was provided to group C. Jejunal samples 1.5 cm in length were taken at the end of ischemia in all groups, at 30 minutes after reperfusion in groups A and C, and at 120 minutes after reperfusion in groups B and C, for the measurement of adenine nucleotides (high-performance liquid chromatography method) and for histological examination (hematoxylineosin [HE] staining). The survival rate was significantly higher in group A than in group C. The amount of adenosine triphosphate in the samples was not significantly different among the three groups, whereas the energy charge at the end of ischemia was significantly higher in group A than in group C. Histologically, the damage to the mucosa and the longitudinal muscle layer decreased in group A compared with that observed in groups B and C. These results suggest that hyperbaric oxygenation during ischemia is able to ameliorate ischemia-reperfusion injury in the rat small intestine.     

Vitamin C reduces ischemia-reperfusion injury in a rat epigastric island skin flap model

We have examined the effects of lumbar extradural administration of 1% etidocaine 10 ml on somatosensory evoked potentials to posterior tibial nerve stimulation measured in the cervical extradural space. Eight patients, anaesthetized with propofol and nitrous oxide, were studied before hysterectomy and a control group received a similar anaesthetic and 0.9% sodium chloride solution 10 ml in the lumbar extradural space. Etidocaine decreased significantly overall amplitude of the evoked potentials and the amplitudes of all peaks, between 30 and 50 min after extradural injection. The effects of etidocaine on spinal cord conduction were greater than those found previously for lignocaine and bupivacaine, suggesting that it is the local analgesic of choice for inhibiting afferent conduction.     

Protective effect of salvianolic acid a on ischemia-reperfusion induced injury in isolated rat heart

BACKGROUND: Recognition of advanced abdominal pregnancy and care of the patient afflicted with it may present formidable challenges. Aside from the difficulty of diagnosing the problem and thereby delaying necessary intervention, management can be difficult at best, even when the condition is relatively uncomplicated. When it is compounded by a life-threatening complication, such as uncontrollable hemorrhage, it challenges the skills of the most experienced obstetrician and the resources of the best-equipped facility and its personnel. CASE: Partial placental separation was encountered at surgery; it progressed intraoperatively despite the care taken to avoid disturbing the placental implantation site. Severe hemorrhage was controlled by a combination of aortic compression, packing and use of large "liver" sutures incorporating the uterine wall for tamponade of the principal placental implantation site, on the mesentery. CONCLUSION: It is important to be prepared to deal with the complication of intense intraabdominal bleeding in the course of intraoperative management of abdominal pregnancy.     

Mediators of ischemia-reperfusion injury of rat lung

In rats, we characterized the mediators of lung reperfusion injury after ischemia. Animals underwent left lung ischemia. After 90 minutes of ischemia, reperfusion for up to 4 hours was evaluated. Lung injury, as determined by vascular leakage of serum albumin, increased in ischemic-reperfused animals when compared with time-matched sham controls. Injury was biphasic, peaking at 30 minutes and 4 hours of reperfusion. The late but not the early phase of reperfusion injury is known to be neutrophil dependent. Bronchoalveolar lavage of ischemic-reperfused lungs at 30 minutes and 4 hours of reperfusion demonstrated increased presence of serum albumin, indicative of damage to the normal vascular/airway barrier. Lung mRNA for rat monocyte chemoattractant protein-1 and tumor necrosis factor-alpha peaked very early (between 0.5 and 1.0 hour) during the reperfusion process. Development of injury was associated with a decline in serum complement activity and progressive intrapulmonary sequestration of neutrophils. Administration of superoxide dismutase before reperfusion resulted in reduction of injury at 30 minutes of reperfusion. Complement depletion decreased injury at both 30 minutes and 4 hours of reperfusion. Requirements for tumor necrosis factor-alpha, interferon-gamma, and monocyte chemoattractant protein-1 for early injury were shown whereas only tumor necrosis factor-alpha was involved at 4 hours. We propose that acute (30-minute) lung injury is determined in large part by products of activated lung macrophages whereas the delayed (4-hour) injury is mediated by products of activated and recruited neutrophils.     

The effect of alpha-tocopherol and pentoxyfilline on ischemia-reperfusion induced liver injury in rats

BACKGROUND/AIM: In the present study our purpose was to investigate the effect of pentoxyfilline, that plays a role in microcirculation and tissue oxygenation, alone and in combination with an antioxidant vitamin E on tissue damage in the rat liver induced by ischemia-reperfusion. METHODOLOGY: Thirty-one albino rats were divided into four groups. Rats in group I (n= 7), group II (n= 8) and group III (n= 8) were given, respectively, pentoxyfilline (25 mg/kg), pentoxyfilline and vitamin E in combination (25 mg/kg and 50 mg/kg, respectively) and equal volume of saline solution intraperitoneally for 7 days. Rats in group IV (n= 8) served as controls and received no treatment. On day 7 ischemia was induced by cross-clamping the hepatic artery, portal vein and left branch of the biliary duct for 30 minutes. Malondialdehyde (MDA) and catalase activity were assessed in tissue sample, and the level of ALT was measured in serum obtained after reperfusion for 30 minutes. Histological examination of tissue sample was also carried out. RESULTS: There was no significant difference in ALT level between three study groups. Group I and group II had significant lower MDA and catalase levels than those of group III. The results of histopathologic examination in group I and group II were better than that of group III. CONCLUSION: Our findings suggested that the treatment of pentoxyfilline alone and in combination with vitamin E decreased liver damage induced by ischemia-reperfusion and that the effect of latter was more effective but the difference between the two treatment patterns was not statistically significant.     

In vitro and in vivo protective effect of honokiol on rat liver from peroxidative injury

Honokiol, a compound extracted from the Chinese medicinal herb Magnolia officinalis, has a strong antioxidant effect on the inhibition of lipid peroxidation in rat heart mitochondria. To investigate the protective effect of honokiol on hepatocytes from peroxidative injury, oxygen consumption and malondialdehyde formation for in vitro iron-induced lipid peroxidation were assayed, and the mitochondrial respiratory function for in vivo ischemia-reperfusion injury were evaluated in rat liver, respectively. The inhibitory effect of honokiol on oxygen consumption and malondialdehyde formation during iron-induced lipid peroxidation in liver mitochondria showed obvious dose-dependent responses with a concentration of 50% inhibition being 2.3 x 10(-7) M and 4.96 x 10(-7) M, respectively, that is, 550 times and 680 times more potent than alpha-tocopherol, respectively. When rat livers were introduced with ischemia 60 min followed by reperfusion for 60 min, and then pretreated with honokiol (10 micrograms/kg BW), the mitochondrial respiratory control ratio (the quotient of the respiration rate of State 3 to that of State 4) and ADP/O ratio from the honokiol-treated livers were significantly higher than those of non-treated livers during reperfusion. The dose-dependent protective effect of honokiol on ischemia-reperfusion injury was 10 microgram-100 micrograms/Kg body weight. We conclude that honokiol is a strong antioxidant and shed insight into clinical implications for protection of hepatocytes from ischemia-reperfusion injury.     

The protective effect of vitamin E, idebenone and reduced glutathione on free radical mediated injury in rat brain synaptosomes

In the present study the effect of ascorbate (0.8 mM)/iron (2.5 microM) on lipid and protein oxidation, in Synaptosomes isolated from rat brain cortex, was evaluated. Vitamin E, idebenone and reduced glutathione were used as free radicals scavengers, in order to analyze the mechanism involved in ascorbate/iron-induced oxidative stress. An increased formation of reactive oxygen species (ROS) in the cytosol and in the mitochondria was observed, in ascorbate/iron treated synaptosomes. Idebenone (50 microM) prevented the increased formation of ROS in both synaptosomal compartments, vitamin E (150 microM) protected partially this formation in mitochondria, whereas reduced glutathione (250 microM) (GSH) was ineffective. After ascorbate/iron treatment an increase in lipid peroxidation occurred as compared to control, which was completely inhibited by idebenone. A decrease in protein-SH content was also observed, and it was prevented by Vitamin E, idebenone and GSH. When synaptosomes were treated with ascorbate/iron the levels of GSH decreased, and the levels of oxidized glutathione (GSSG) increased as compared to controls under these conditions. Glutathione peroxidase activity was unchanged, whereas an inhibition of glutathione reductase activity was observed. These data suggest that the increased formation of free radicals in synaptosomes leads to lipid and protein oxidation, the role of the endogenous GSH being essential to protect protein thiol-groups against oxidative damage in order to maintain enzyme activity.     

Use of a nitric oxide precursor to protect pig myocutaneous flaps from ischemia-reperfusion injury

Nitric oxide is a radical with vasodilating properties that protects tissues from neutrophil-mediated ischemia-reperfusion injury in the heart and intestine. Previous studies in our laboratory suggested that L-arginine, a nitric oxide precursor, can protect skin flaps from ischemia-reperfusion injury. In this study, we examined the effects of L-arginine on the survival of myocutaneous flaps in a large animal model and established whether this effect was mediated by nitric oxide and neutrophils. Two superiorly based 15 x 7.5 cm epigastric myocutaneous island flaps were dissected in 15 Yorkshire pigs weighing 45 to 50 kg. One of the flaps was subjected to 6 hours of arterial ischemia and then reperfused for 4 hours (ischemia-reperfusion flaps), whereas the other flap was used as a non-ischemic control (non-ischemia-reperfusion flaps). The flaps were divided into four groups: control non-ischemia-reperfusion flaps that received only saline (group I); ischemia-reperfusion flaps that were treated with saline (group II); and flaps treated with either L-arginine (group III) or Nomega-nitro-L-arginine methylester (L-NAME), a nitric oxide synthase competitive inhibitor, plus L-arginine in equimolar amounts (group IV). These drugs were administered as an intravenous bolus 10 minutes before the onset of reperfusion, followed by a 1-hour continuous intravenous infusion. Full-thickness muscle biopsies were taken at baseline, 3 and 6 hours of ischemia, and 1 and 4 hours of reperfusion. The biopsies were evaluated by counting neutrophils and measuring myelo-peroxidase activity. At the end of the experiment, skeletal muscle necrosis was quantified using the nitroblue tetrazolium staining technique, and a full-thickness biopsy of each flap was used for determination of water content. Statistical analysis was performed using analysis of variance and the Newman-Keuls test. Non-ischemia-reperfusion flaps showed no muscle necrosis. Ischemia-reperfusion flaps treated with saline had 68.7 +/- 9.1 percent necrosis, which was reduced to 21.9 +/- 13.6 percent with L-arginine (p < 0.05). L-NAME administered concomitantly with L-arginine demonstrated a necrosis rate similar to that of saline-treated ischemia-reperfusion flaps (61.0 +/- 17.6 percent). Neutrophil counts and myeloperoxidase activity after 4 hours of reperfusion were significantly higher in ischemia-reperfusion flaps treated with L-NAME and L-arginine as compared with the other three groups (p < 0.05). Flap water content increased significantly in ischemia-reperfusion flaps treated with saline and L-NAME plus L-arginine versus non-ischemia-reperfusion flaps (p < 0.02) and L-arginine-treated ischemia-reperfusion flaps (p < 0.05). There was no difference in flap water content between ischemia-reperfusion flaps treated with L-arginine and non-ischemia-reperfusion flaps. Administration of L-arginine before and during the initial hour of reperfusion significantly reduced the extent of flap necrosis, neutrophil accumulation, and edema due to ischemia-reperfusion injury in a large animal model. This protective effect is completely negated by the use of the nitric oxide synthase blocker L-NAME. The mechanism of action seems to be related to nitric oxide-mediated suppression of ischemia-reperfusion injury through neutrophil activity inhibition.     

Hypertensive nephrosclerosis in the Dahl/Rapp rat. Initial sites of injury and effect of dietary L-arginine supplementation

BACKGROUND: The Dahl/Rapp strains of salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) rat were developed to examine pathogenetic mechanisms that produce hypertension in response to an increase in dietary salt. We have shown that providing SS/Jr rats with L-arginine, the metabolic precursor of nitric oxide, acutely prevented salt-sensitive hypertension, suggesting that SS/Jr rats developed hypertension because of inadequate nitric oxide production while on a high-salt diet. EXPERIMENTAL DESIGN: Male 23-day SS/Jr and SR/Jr rats were placed on chow that contained 8% sodium chloride. One group of SS/Jr rats also received L-arginine, 1.25 g/liter, in their drinking water. These three groups were examined at weekly intervals for 4 weeks. RESULTS: SS/Jr rats rapidly developed hypertension when placed on the high-salt chow. After 2 weeks on this diet, inulin clearance dramatically decreased, and albumin excretion rate increased. By the fourth week of study, SS/Jr rats on the high-salt diet had died or were dying. Coincident with the progressive decline in inulin clearance, renal morphologic analysis confirmed development of myointimal thickening, fibrinoid necrosis, and glomerulosclerosis. In contrast, over the 4 weeks of study, SS/Jr rats supplemented with oral L-arginine did not develop hypertension and any of the associated renal complications seen in age-matched SS/Jr rats on the high-salt diet. L-Arginine also corrected hypertension in SS/Jr rats exposed to the high-salt chow for 2 weeks before the inception of L-arginine. L-Arginine administration after 3 weeks on this chow, however, failed to reverse hypertension and the depressed inulin clearance and morphologic renal damage. CONCLUSIONS: Along with previous work (Chen PY, Sanders PW, J Clin Invest 88:1559-67), these studies were consistent with the hypothesis that hypertension and hypertensive nephrosclerosis developed in SS/Jr rats because, while on a high-salt diet, substrate (L-arginine) became a rate-limiting factor in the synthesis of nitric oxide.     

The role of xanthine dehydrogenase (xanthine oxidase) in ischemia-reperfusion injury in rat kidney

Xanthine dehydrogenase (XDH) and xanthine oxidase (XO) are enzymes involved in the metabolism of purines in various organisms. XO produces superoxide radicals, suggesting that is responsible for tissue ischemia-reperfusion injury. To test this notion further studies were performed on rat kidneys and the time course of changes in purine nucleotides, oxypurines and XDH and XO activity was determined. At 24 hours after reperfusion subsequent to 30-minute ischemia, serum creatinine increased to 0.83 +/- 0.74 mg/dl from 0.28 +/- 0.06 mg/dl (the level prior to ischemia, the control). Renal ATP and ADP contents were reduced after ischemia lasting for 30 minutes and restored 10 minutes after reperfusion following 30 minutes of ischemia. The renal AMP content increased after 30 minutes of ischemia and recovered within 10 minutes after reperfusion. The total adenine nucleotide (TAN) content was reduced gradually during ischemia-reperfusion in the rat kidney. Although the energy charge was reduced following 30 minutes of ischemia, it was restored to the control level 10 minutes following reperfusion. Hypoxanthine (HX) and xanthine (X), which had accumulated at 30 minutes after ischemia, were reduced to the control levels 10 minutes after reperfusion. There were no significant changes in the pre-ischemia values of total XDH and XO activities or XDH/XO ratio during the period nor at various time intervals (up to 24 hours) during reperfusion. It was shown that HX and X accumulate without significant conversion of XDH to XO during ischemia. Therefore the putative role of XO in ischemia-reperfusion injury seems to more complex than initially predicted.     

Endothelial protective effect of stobadine on ischaemia/reperfusion-induced injury

A pedagogical network has been developed at University Hospital of Rennes from 1996. The challenge is to give medical information and informatics tools to all medical students in the clinical wards of the University Hospital. At first, nine wards were connected to the medical school server which is linked to the Internet. Client software electronic mail and WWW Netscape on Macintosh computers. Sever software is set up on Unix SUN providing a local homepage with selected pedagogical resources. These documents are stored in a DBMS database ORACLE and queries can be provided by specialty, authors or disease. The students can access a set of interactive teaching programs or electronic textbooks and can explore the Internet through the library information system and search engines. The teachers can send URL and indexation of pedagogical documents and can produce clinical cases: the database updating will be done by the users. This experience of using Web tools generated enthusiasm when we first introduced it to students. The evaluation shows that if the students can use this training early on, they will adapt the resources of the Internet to their own needs.     

The effects of thyroid hormone modulation on rat liver injury associated with ischemia-reperfusion and cold storage

We investigated the effects of thyroid hormone modulation on liver injury associated with ischemia-reperfusion (I-R) and cold storage in rats. First, euthyroid and thyroxine (T4)-pretreated rats were exposed in vivo to 20-min global liver ischemia, then 30-min reperfusion. Liver injury was assessed by measuring serum alanine aminotransferase (ALT) levels. Liver concentrations of adenine nucleotides, reduced glutathione (GSH), and oxidized glutathione were evaluated. Second, rats were given the antithyroid drug propylthiouracil (PTU). Livers stored at 0-1 degrees C in Euro-Collins' solution for 20 h were reperfused at 37 degrees C for 15 min. Lactate dehydrogenase (LDH) in the effluent perfusate and bile flow were evaluated during reperfusion. Serum ALT levels increased after ischemia and I-R. ALT increased significantly more in T4-pretreated than in euthyroid rats after ischemia and I-R. Preischemic levels of adenosine triphosphate (ATP) were significantly lower in livers from T4-pretreated than in euthyroid rats (6.22 +/- 0.7 and 11 +/- 0.9 nmol/mg protein, respectively; P < 0.05). After ischemia, liver ATP was similarly reduced in T4-pretreated and euthyroid rats. After reperfusion, ATP partially recovered in euthyroid rats but remained low in T4-pretreated rats (6.7 +/- 1.0 and 1.91 +/- 0.7 nmol/mg protein, respectively; P < 0.05). Preischemic levels of liver GSH decreased to 44% in T4-pretreated rats. After ischemia, GSH decreased similarly in euthyroid and T4-pretreated rats. GSH recovered promptly after reperfusion in euthyroid rats but remained low in T4-pretreated rats (13.9 +/- 3.3 and 3.9 +/- 0.9 nmol/mg protein, respectively; P < 0.02). During reperfusion after cold storage, LDH in effluent perfusate was significantly lower and bile flow higher in livers from PTU-pretreated rats than from euthyroid rats. The histopathological changes observed after I-R and cold storage confirmed the biochemical findings. Our results suggest that T4 administration exacerbates pretransplant liver damage by increasing liver susceptibility to I-R, whereas PTU administration reduces the liver injury associated with cold storage. Implications: We studied the effects of thyroid hormone modulation on liver injury associated with ischemia-reperfusion and cold storage in rats. Thyroxine administration increased susceptibility to ischemia-reperfusion injury, whereas the antithyroid agent propylthiouracil reduced the deleterious effects associated with cold storage.     

Contraction of experimental skin flaps

BACKGROUND AND PURPOSE: Some types of radiation therapy have been associated with an increased risk of cardiac mortality and morbidity in patients with early-stage breast cancer. A relationship has been observed between cardiac radiation dose-volume and the level of excess risk of cardiac mortality. However, relatively few data are available on the morbidity from myocardial infarction associated with adjuvant radiotherapy. PATIENTS AND METHODS: From 1971 to 1976, a total of 960 patients with operable breast cancer were randomly allocated to preoperative radiation therapy, postoperative radiation therapy or to surgery alone. A previous analysis of the cardiac dose-volumes with the treatment techniques used in the trial indicated that the irradiated patients could roughly be divided into three groups. Information on the number of myocardial infarctions was obtained through computerized record linkage with a population-based registry of myocardial infarctions in Stockholm County. Information on cause-specific mortality was obtained from the Swedish Cause-of-Death Registry. The median follow-up was 20 years (range 17-23 years). RESULTS: A total of 58 patients developed an acute myocardial infarction during the period of follow-up. The number of myocardial infarction cases was not significantly different between the three treatment groups. When analyzed according to estimated cardiac radiation dose-volumes, patients in the highest dose-volume subgroup exhibited a hazard of myocardial infarction of 1.3 (95% CI 0.7-2.6) relative to that of the surgical controls, whereas the corresponding relative hazard for the intermediate and low dose-volume subgroups was below unity. Data on death due to cardiovascular disease showed that patients in the high dose-volume group exhibited a hazard of 2.0 (95% CI 1.0-3.9, P = 0.04) relative to that of the surgical controls. Concerning death due to ischemic heart disease, the relative hazard for the same subgroup was 2.5 (95% CI 1.1-5.7, P = 0.03). The difference between the groups was established after 4-5 years. The cumulative incidence curves continued to diverge up to about 10-12 years. No further divergence appeared after 12 years, but the number of events was low. CONCLUSIONS: This analysis confirms and extends previous results from the trial. Cardiac mortality was positively correlated with the cardiac dose-volume. Patients receiving high dose-volumes exhibited an increased mortality of ischemic heart disease, but not of myocardial infarction, which implies another mechanism, e.g. radiation-induced microvascular damage to the heart.     

The role of endogenous nitric oxide in modulating ischemia-reperfusion injury in the isolated, blood-perfused rat lung

Ischemia-reperfusion (IR) lung injury occurs after various clinical procedures, including cardiopulmonary bypass. It is not clear whether endogenous nitric oxide (NO) is protective or injurious in lungs subjected to IR. Thus, in this study we examined the contribution of endogenous NO to IR injury in isolated, blood-perfused rat lungs. Lungs of male Wistar rats (300 g) were subjected to 30 min ischemia and 180 min reperfusion (I30R180). Lungs were sampled for inducible nitric oxide synthase (i-NOS) mRNA expression (each n = 3) and NOS enzyme activity (each n = 4) at different time points. NOS inhibitors NG-nitro-L-arginine-methyl ester (10[-4] M) and aminoguanidine (10[-4] M) were used to study the contribution of NO to IR injury in lungs subjected to I30R30 and I30R180. The contribution of i-NOS to IR lung injury was studied by inducing i-NOS enzyme with Salmonella lipopolysaccharide, followed by I30R30. We found that ischemia-reperfusion alone can upregulate i-NOS mRNA and i-NOS enzyme activity (p < 0.05, ANOVA), but downregulate constitutive NOS enzyme activity over 180 min reperfusion. Endogenously produced NO is protective against lung injury in I30R180 in normal rats and lung injury in I30R30 in septic rats. NO is also pivotal in maintaining pulmonary vascular homeostasis in septic rat lungs undergoing IR.     

Delayed effect of denervation on wound contraction in rat skin

Neuronal supply in soft tissues may be an important part of cutaneous wound healing. In order to observe the effect of denervation on wound contraction, rectangular full-thickness skin defects were created on the dorsum of two groups of Wistar rats. In the experimental group (n = 20), spinal nerves corresponding to the area of the open wound (T11 to L2) were isolated and divided bilaterally. In the control group (n = 20), the same pairs of spinal nerves were dissected but left intact. Limits of denervation were verified by the pinprick test. Wound healing, which is primarily in the form of wound contraction in this model, was evaluated by tracing wound margins onto millimetric paper weekly. Wound contraction was delayed significantly in the experimental group (p < 0.05) at all follow-up periods when compared with the controls. Loss of neuropeptide secretion from the nerve endings in denervated tissues may be responsible for the retarded wound contraction, since neuropeptides are thought to exert trophic effects on skin wound healing.     

L-arginine treatment in ischemia/reperfusion injury

We tested whether treatment with exogenous L-arginine, the precursor of nitric oxide (NO), could protect the skeletal muscle from ischemia/reperfusion (I/R) injury. A rabbit hindlimb I/R model (2.5 h ischemia/2 h reperfusion) was used. Morphological changes were elucidated by morphometry. Plasma concentrations of malondialdehyde (pMDA), as well as L-arginine and L-citrulline content in the plasma and skeletal muscle were measured. I/R injury in the skeletal muscle was manifested by development of prominent interstitial edema (fraction of interfiber area was 26.23% vs 15.09% in sham operated control, p < .005) and severe microvascular constriction (capillary area was 11.41 microns2 vs 16.92 in control, p <.005). These changes were accompanied by increased pMDA levels, indicating a process of lipid peroxidation in the cell membranes. L-arginine treatment (4 mg/kg/min intravenously, for 1 h, infusion initiated 30 min before reperfusion) caused an intracellular accumulation of this amino acid in the SM. Intracellular concentrations of L-citrulline increased (201.0 mumol/dm3 after reperfusion vs 176.0 before ischemia onset, p < .005), suggesting stimulated endogenous NO synthesis. L-arginine treatment protected capillary constriction (capillary area was 17.64 microns2 vs 11.41 in the untreated animals, p < .0005) and reduced interstitial edema after reperfusion (fraction of interfiber area was 17.80% vs 26.23 in untreated animals, p < 0.005). The protective effect of L-arginine treatment on I/R injury of SM may be related to its ability to prevent microvascular constriction and reduce permeability disorders by the stimulation of endogenous NO production.     

Anatomy of upper extremity skin flaps

This article reviews some recent applications of time and frequency domain cross-correlation techniques to human motor unit recording. These techniques may be used to examine the pre-synaptic mechanisms involved in control of motoneuron activity during on-going motor tasks in man without the need for imposed and artificial perturbations of the system. In this review we examine, through several examples, areas in which insights have been gained into the basic neurophysiological processes that bring about motoneuron firing in man and illustrate how these processes are affected by central nervous system pathology. We will demonstrate that synchronization and coherence may be revealed between human motor unit discharges and give examples that support the hypothesis that these phenomena are generated by activity in a focused common corticospinal input to spinal motoneurons. Disruption of central motor pathways due to diseases of the nervous system leads to pathophysiological alterations in the activity of these pre-synaptic motoneuron inputs that can be revealed by cross-correlation analysis of motor unit discharges. The significance of these studies and outstanding questions in this field are discussed.     

Participation of nitric oxide in the mucosal injury of rat intestine induced by ischemia-reperfusion

The dual role of nitric oxide as a cytoprotective or a cytotoxic free radical gas has been noted in various types of pathophysiological conditions, including the digestive system. The aim of this study was to examine the role of nitric oxide in the mucosal injury induced by ischemia-reperfusion in the rat small intestine. A transient intestinal ischemia was produced in the catheterized ileal segments of rats by occluding the anterior mesenteric artery for 60 min. Nitric oxide metabolites (NO2- and NO3-) and lactate dehydrogenase activity in perfusates of the intestinal lumen were measured over 5 hr periods. The time-course of histological changes in small intestine was also observed. After ischemia-reperfusion, nitric oxide release in the intestinal lumen increased significantly and the dynamics of nitric oxide release correlated with that of lactate dehydrogenase leakage. The administration of NG-nitro-L-arginine methyl ester (1.0-2.5 mg/kg) inhibited this increased nitric oxide release and the lactate dehydrogenase leakage and afforded protection against the mucosal injury induced by ischemia-reperfusion. In conclusion, the nitric oxide production that was accelerated by ischemia-reperfusion of small intestine may possibly participate in the breakdown of intestinal mucosa after ischemia-reperfusion insult.