Skeletal Muscle Reperfusion Injury Research Articles

The development of the E. Stanley Crawford Critical Issues Forum

The development of the E. Stanley Crawford Critical Issues Forum

Reperfusion injury of ischemic skeletal muscle is mediated by natural antibody and complement.

Reperfusion of ischemic tissue induces an acute inflammatory response that can result in necrosis and irreversible cell injury to both local vascular endothelium and parenchyma. To examine the pathogenesis of ischemia/reperfusion injury, we have used mice deficient in complement components C3, C4, or serum immunoglobulin in a hindlimb model of ischemia. We found that mice homozygous deficient in C3 or C4 were equally protected against reperfusion injury based on a significant reduction in leakage of radiolabeled albumin out of the vasculature. This demonstrates that classical pathway complement is an important factor in the initiation of inflammation following reperfusion. Furthermore, mice deficient in serum immunoglobulin were equally protected and this protection could be reversed by reconstitution with serum from normal mice. Thus, this report describes a novel mechanism for reperfusion injury that involves antibody deposition and activation of complement leading to inflammation permeability.

Role of neutrophil-endothelial adhesion in skeletal muscle reperfusion injury

Role of neutrophil-endothelial adhesion in skeletal muscle reperfusion injury

Role of neutrophil-endothelial adhesion in skeletal muscle reperfusion injury

During postischaemic revascularization neutrophil-endothelial adhesion in the skeletal muscle microcirculation, promoted by the neutrophil adhesion molecule Mac-1, may impair muscle blood flow and release oxygen free radicals and proteolytic enzymes which causes further tissue injury. This study has assessed the effect of an anti-Mac-1 monoclonal antibody on the severity of skeletal muscle injury in a rat model of 6-h hindlimb ischaemia and 4-h reperfusion. In control animals a sustained impairment of muscle perfusion was associated with neutrophil sequestration, muscle infarction and muscle oedema (P < 0.001 versus normal rats). In contrast, intravenous administration of anti-Mac-1 monoclonal antibody before revascularization prevented neutrophil recruitment, reduced muscle necrosis and improved postischaemic muscle perfusion at 120 and 240 min (not significantly different from normal), thus confirming that neutrophils are important cellular mediators of skeletal muscle reperfusion injury. Monoclonal antibodies targeting neutrophil adhesion molecules may, therefore, have a role in the prevention of this complication of limb revascularization.

Effects of low dose intra-arterial monoclonal antibodies to ICAM-1 and CD11/CD18 on local and systemic consequences of ischaemia-reperfusion injury in skeletal muscle

The aim of this study was to investigate the effects of intra-arterial infusion of low doses of monoclonal antibodies (Mabs) against adhesion molecules (the neutrophil CD18 integrins, and the endothelial adhesion molecule, ICAM-1) on reperfusion injury in skeletal muscle. The rabbit rectus femoris muscle was rendered ischaemic for 22 1 hours. Mabs were infused (−0.5 mg/kg) commencing 20 minutes before the end of ischaemia and for the first hour of reperfusion. 24 hours after reperfusion, the muscle was assessed for viability, oedema and neutrophil infiltration (myeloperoxidase (MPO) levels). The results of the viability assessment (control—20.9 (0–47.5)% [median (range)], anti-CD18 — 30.5 (3.0–89.4)%, anti-ICAM-1 — 27.9 (7.8—78.1)% and anti-CD18 combined with anti-ICAM-1 — 45.2 (15.6–92.3)%) showed no significant differences between groups, while analysis of MPO in the postischaemic muscle showed that the anti-ICAM-1 Mab reduced neutrophil infiltration significantly. Furthermore, in contralateral unoperated muscles MPO levels were elevated 24 hours after ischaemia in the contralateral muscle. This increased neutrophil infiltration was prevented by pretreatment with anti-ICAM-1. These results suggest that low doses of anti-CD18 and anti-ICAM-1 Mabs do not reduce reperfusion injury in skeletal muscle but may help to protect against systemic effects of severe trauma. The evidence suggests that reperfusion injury in this skeletal muscle model may be largely independent of neutrophil involvement.

Efficacy of Recombinant Human Manganese Superoxide Dismutase Compared to Allopurinol in Protection of Ischemic Skeletal Muscle Against “No-Reflow”

A growing body of experimental data indicates that the "no-reflow" phenomenon is a type of reperfusion injury in skeletal muscle which may, in part, be mediated by oxygen free radicals, and thus may be attenuated by using agents that scavenge or inhibit formation of these reactive oxygen metabolites. This study was undertaken to assess the efficacy of recombinant human manganese superoxide dismutase (rhMnSOD) in reducing reperfusion injury in skeletal muscle. The specific advantage of this agent over other SOD types is a much longer plasma half-life (5 to 7 hr), allowing better equilibration between extra- and intracellular compartments. The rat cremaster model was used to study "no-reflow" in skeletal muscle. Reperfusion injury in the muscle was assessed by fluorescein dye perfusion, myocyte creatine phosphokinase (CPK) release, and contractile function in response to electrical field stimulation. Compared with untreated saline control animals, those treated with rhMnSOD after 5 hr of cremasteric ischemia, had a significantly higher percentage area of blood reflow (78 percent +/- 6 percent of normal), a greater percentage tetanic (66 percent +/- 9 percent of normal) and twitch (56 percent +/- 9 percent of normal) contractile strength, and less CPK release (21.5 percent higher than pre-reperfusion baseline CPK levels) (p < 0.05). Untreated saline control CPK release (21.5 percent higher than the prereperfusion level. Animals treated with allopurinol also had a significantly higher percentage twitch contraction (47 percent +/- 14 percent of normal) and a lower CPK release (11.1 percent of the prereperfusion value) 45 min after reperfusion than untreated saline controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduction of reperfusion injury in rat skeletal muscle following administration of cinnamophilin, a novel dual inhibitor of thromboxane synthase and thromboxane A2 receptor.

We used cinnamophilin, a novel dual inhibitor of thromboxane synthase and thromboxane A2 (TXA2) receptor, and superoxide dismutase (SOD) with catalase to examine their protective effect against reperfusion injury in rat skeletal muscle. In 5 groups of 6 wistar rats three hours of ischaemia were induced in one hind limb by application of a tourniquet to the proximal thigh; the contralateral limb served as an internal, nonischaemic control. The first group did not receive any drug nor was it reperfused. In the other four groups, normal saline (reperfusion control), dimethylsulphoxide (DMSO), cinnamophilin, or SOD with catalase was given before removal of the tourniquet and one hour of reperfusion followed. Skeletal muscle injury was measured by a quantitative spectrophotometric assay of triphenyltetrazolium chloride (TTC) reduction and by muscle weight gain. One hour of reperfusion significantly (p<0.05) lowered TTC reduction in ischaemic limbs in the reperfusion control group in comparison with the rats in 3h ischaemia alone. Among the four reperfusion groups, only the cinnamophilin group had significantly lower decrease of TTC reduction and significantly lower muscle weight gain. These results demonstrate the protective effect of cinnamophilin against reperfusion injury of the ischaemic skeletal muscle in rats.

The value and limitations of L-arginine infusion on glomerular and tubular function in the ischemic/reperfused kidney

The nitric oxide precursor, L-arginine, has been shown to have a salutary effect on ischemia and reperfusion injury in skeletal muscle, skin, and intestines. Because L-arginine also increases renal blood flow, glomerular filtration, and urine flow in experimental animals with normal renal function, we postulated that L-arginine may also improve renal function after renal ischemic injury. Eighteen adult New Zealand white rabbits weighing 3 to 3.5 kg were subjected to bilateral normothermic renal ischemia by clamping both renal pedicles for 1 hour followed by 2 hours of reperfusion. The animals were randomized into three groups: group I (control, n = 6) received no additional treatment; group II (pretreatment, n = 6) received systemic intravenous L-arginine at 150 mg/kg over 20 minutes before induction of ischemia; group III (posttreatment, n = 6) received systemic intravenous L-arginine at 150 mg/kg over 20 minutes from the onset of reperfusion. Urine flow, creatinine clearance (CCR), fractional excretion of sodium (FENa), and renal failure index (RFI) were calculated before ischemia and 2 hours after reperfusion, by use of standard formulas. The changes of the various renal parameters were compared among the three groups. Bilateral normothermic renal ischemia for 1 hour produced a significant deterioration of glomerular filtration as evidenced by a CCR decrease from 11.1 +/- 1.8 to 2.49 +/- 0.9 ml/min (p < 0.01), FENa increase from 2.9% +/- 1.0% to 20.8% +/- 1.5% (p < 0.01) and RFI increase from 4.0 +/- 1.3 to 28.8 +/- 2.6 (p < 0.01). Pretreatment with L-arginine (group II) minimized the deleterious effects caused by ischemia on glomerular filtration (CCR of 2.49 +/- 0.9 ml/min in group I vs 4.95 +/- 2.5 ml/min in group II, p < 0.05) and tubular function (FENa of 20.8% +/- 1.5% in group I vs 13.0% +/- 5.6% in group II and RFI of 28.8 +/- 2.6 in group I vs 18.6 +/- 8.0 in group II, p < 0.05). Infusion of L-arginine at the onset of reperfusion (group III) produced a significant diuretic effect (urine flow from 32.6 +/- 13.4 ml/hr in group I to 63.3 +/- 18.8 ml/hr in group III, p < 0.05) and also minimized glomerular damage (CCR from 2.49 +/- 0.9 ml/min in group I to 4.80 +/- 1.2 ml/min in group III, p < 0.05); however, no beneficial effect was observed on tubular function. Induction of nitric oxide production by systemic L-arginine infusion can best preserve glomerular and tubular function in the ischemic/reperfused kidney when given before the ischemic insult.

Role of Neutrophil Depletion and Elastase Inhibition in Modifying Skeletal Muscle Reperfusion Injury

This study investigated the effect of neutrophil depletion and neutrophil elastase inhibition on the severity of skeletal muscle reperfusion injury. In a rodent model, indices (experimental/ normal limb) of gastrocnemius muscle viability (hlstochemical staining), oedema (wet:dry weight ratio) and myeloperoxidase content (neutrophil recruitment) were assessed in normal (no ischaemia), ischaemic (6-h unilateral hindlimb ischaemia), control (6-h ischaemia and 4-h reperfusion), neutrophil-depleted rats (given antineutrophil serum) and rats receiving the neutrophil elastase inhibitor Elafln. Neutrophil recruitment muscle infarction and oedema did not occur in normal limbs, or in those subjected to ischaemia without reperfusion. In contrast increased muscle myeloperoxidase levels ( P&lt; 0.001), muscle infarction ( P&lt; 0.01) and oedema ( P&lt; 0.001) all occurred in the reperfused limbs of control animals compared with those of normal and ischaemic rats. Antineutrophil serum and Elafln both reduced neutrophil recruitment during reperfusion ( P&lt; 0.001 and P&lt; 0.01 respectively) and muscle viability was preserved. Reperfusion oedema still occurred however, suggesting that altered endothelial permeability is mediated by factors other than neutrophils.

Reperfusion injury in skeletal muscle: a prospective study in patients with acute limb ischaemia and claudicants treated by revascularization: Adiseshiah M, Round JM, Jones DA. Br J Surg 1992;79:1026–1029

Reperfusion injury in skeletal muscle: a prospective study in patients with acute limb ischaemia and claudicants treated by revascularization: Adiseshiah M, Round JM, Jones DA. Br J Surg 1992;79:1026–1029

Prevention of Reperfusion Injury in Skeletal Muscle

Annals of the New York Academy of SciencesVolume 723, Issue 1 p. 420-421 Prevention of Reperfusion Injury in Skeletal Muscle D. A. O'FARRELL, D. A. O'FARRELL Orthopedic Research Laboratory Duke University Medical Center Durham, North Carolina 27710Search for more papers by this authorL-E. CHEN, L-E. CHEN Orthopedic Research Laboratory Duke University Medical Center Durham, North Carolina 27710Search for more papers by this authorA. V. SEABER, A. V. SEABER Orthopedic Research Laboratory Duke University Medical Center Durham, North Carolina 27710Search for more papers by this authorJ. R. URBANIAK, J. R. URBANIAK Orthopedic Research Laboratory Duke University Medical Center Durham, North Carolina 27710Search for more papers by this author D. A. O'FARRELL, D. A. O'FARRELL Orthopedic Research Laboratory Duke University Medical Center Durham, North Carolina 27710Search for more papers by this authorL-E. CHEN, L-E. CHEN Orthopedic Research Laboratory Duke University Medical Center Durham, North Carolina 27710Search for more papers by this authorA. V. SEABER, A. V. SEABER Orthopedic Research Laboratory Duke University Medical Center Durham, North Carolina 27710Search for more papers by this authorJ. R. URBANIAK, J. R. URBANIAK Orthopedic Research Laboratory Duke University Medical Center Durham, North Carolina 27710Search for more papers by this author First published: June 1994 https://doi.org/10.1111/j.1749-6632.1994.tb36765.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume723, Issue1Cellular, Biochemical, and Molecular Aspects of Reperfusion InjuryJune 1994Pages 420-421 RelatedInformation

Neutrophils and Skeletal Muscle Reperfusion Injury

Neutrophils and Skeletal Muscle Reperfusion Injury

Controlled Reperfusion Reduces Reperfusion Injury in Skeletal Muscle After Incomplete Limb Ischemia

Systemic and local complications occur after revascularization of extremities exposed to prolonged complete ischemia. Recently the authors demonstrated in experimental and clinical studies that these deleterious effects after normal blood (uncontrolled) reperfusion could be reduced significantly by controlling the composition of the reper fusate (calcium, pH, amino acids, osmolarity, and glucose) and the circumstances of the reperfusion (time, temperature, and pressure; controlled reperfusion) after complete prolonged limb ischemia. In this study the authors test the hypothesis that controlled reperfusion also has a beneficial effect and is safe to apply after a period of six hours of incomplete limb ischemia. Ten adult German house swine were exposed to six hours of incomplete limb ischemia by occlusion of the left iliac artery. This resulted in a significant reduction of limb tissue temperature (P &lt; 0.0003, ANOVA), pH, (P &lt; 0.0003, ANOVA), and adenosine triphosphate (ATP) (P &lt; 0.0003, ANOVA), as well as in increased levels of (continued on next page) (Abstract continued) creatine kinase (CK) in the systemic venous (P &lt; 0.003, ANOVA) and in the femoral vein blood (P &lt; 0.03 ANOVA). To simulate the clinical situation of embolectomy in 5 pigs the authors released the occlusive snares after the ischemic period and let the normal blood flow with systemic pressure occur (uncontrolled reperfusion). In the other 5 pigs (controlled reperfusion) they delivered a controlled reperfusate by with drawing blood from the aorta and mixing it with a crystalloid solution (calcium reduced, hyperosmolaric, hyperglycemic, alkalotic, glutamate and aspartate enriched, and containing a free radical scavenger) under controlled conditions (ratio blood:crys talloid solution 6:1, for thirty minutes, reperfusion pressure &lt; 50 mmHg, and normoth ermia) before establishing normal blood reperfusion. During the initial reperfusion (measured at five minutes after start of reperfusion) the group with controlled reperfusion (as compared with the animals with uncontrolled reperfusion) showed higher oxygen consumption (32.7 ±3.4 vs 15.8 ±1.9 mL/100g/min, P &lt; 0.01, ANOVA), higher glucose consumption (439.0 ±115.7 vs 16.5 ±4.7 mg/100g/min, P &lt; 0.03, ANOVA), less vascular resistance (19.2 ±2.8 vs 31.4 ±2.1 dyn x sec/cm5, P &lt; 0.03, ANOVA) as well as less lactate dehydrogenase (LDH; 286.2 ±38.2 vs 604.6 ±30.7 U/L, P &lt; 0.0003, ANOVA) and creatine kinase (CK; 294.2 ±73.0 vs 602.8 ±85.5 U/L, P &lt; 0.03, ANOVA) concentration in the femoral vein blood. At the end of the observation period (measured at ninety minutes after start of reperfusion), the group with controlled reperfusion showed less tissue water content (81.8 ±0.7 vs 84.3 ±0.7%, P &lt; 0.05, ANOVA), higher tissue ATP content (17.0 ±2.4 vs 9.7 ±4.3 μ Mol/g protein, ns), higher tissue ATP increase as compared with end ischemic values (6.1 ±1.5 vs -2.5 ±1.8 μMol/g protein, P &lt; 0.03, ANOVA), higher tissue pH (7.2 ±0.1 vs 6.8 ±0.1, P &lt; 0.03, ANOVA), less temperature decrease (0.3 ±0.2 vs 1.2 ±0.3°C, P &lt; 0.05, ANOVA), less reduction of flow in the limb (0.2 ±0.2 vs -1.3 ±0.4 mL/100g/min, P &lt; 0.03, ANOVA), less vascular resistance (16.7 ±1.2 vs 22.8 ±1.5 dyn x sec/cm 5, P &lt; 0.03, ANOVA), less CK (355.0 ±87.5 vs 624.4 ±73.4 U/L, P &lt; 0.05, ANOVA) and LDH (369.5 ±42.5 vs 538.4 ±39.1 U/L, P &lt; 0.03, ANOVA) concentration in the femoral vein blood as well as less CK (335.0 ±89.0 vs 595.8 ±76.6, P &lt; 0.05) and LDH (356.5 ±48.9 vs 546.0 ±37.8 U/L, P &lt; 0.0003, ANOVA) concentration in the central venous blood. These data indicate that severe local and systemic damage occurs with uncontrolled (normal blood) reperfusion even after incomplete limb ischemia and that these reper fusion changes can be reduced significantly by delivering a controlled reperfusate under controlled conditions without any observable negative side effects. They confirm the results with controlled limb reperfusion after prolonged complete limb ischemia (aortic occlusion), and this concept has already been successfully applied in 15 patients with complete and incomplete limb ischemia as long as eighteen hours.

The effect of mannitol on reperfusion injury and postischaemic compartment pressure in skeletal muscle

Mannitol has previously been shown to reduce skeletal muscle reperfusion injury and postischaemic compartment pressure. The present study was designed to evaluate whether these effects result from hyperosmolarity or free radical scavenging. A rabbit hindlimb perfusion model was used to compare the effects of mannitol (n = 6), glucose (n = 6)--an isomer of mannitol without scavenging effect--and fasciotomy (n = 6) on oedema, compartment pressure, energy charge, and muscle injury after 4 hours of ischaemia and 2 hours of reperfusion. One limb from each animal received treatment, while the other limb served as an untreated control. Mannitol and glucose reduced (p < 0.05) muscle water content and decreased (p < 0.01) the compartment pressure. Fasciotomy had no effect on muscle water content but normalised compartment pressure. The increase in energy charge following reperfusion was improved (p < 0.05) and uptake of [Tc99]methylenediphosphonate--an indicator of muscle injury--was reduced (p < 0.05) by mannitol only. In conclusion, mannitol reduces postischaemic oedema mainly by its hyperosmolar property whereas restitution of energy production and reduction of muscle necrosis seem to be an effect of free radical scavenging. The compartment pressure is reduced by hyperosmolarity and free radical scavenging.

Salvage of Postischemic Skeletal Muscle by Monoclonal Antibody Blockade of Neutrophil Adhesion Molecule CD18

Reperfusion of ischemic skeletal muscle is associated with neutrophil (PMN) adherence to damaged endothelium and PMN-mediated tissue destruction. Neutrophils may attach to endothelium through surface adhesive molecules, such as CD18. The purpose of this study was to determine whether monoclonal antibody blockade of CD18 would reduce skeletal muscle necrosis associated with ischemia and reperfusion. In rabbits, an entire hindlimb was rendered ischemic for 4 hr, followed by 48 hr of in vivo reperfusion. Animals were allocated to one of five treatment groups: ischemia/reperfusion without treatment (I/R controls), I/R plus treatment with the anti-CD18 antibody IB4 (end-ischemic 2 mg/kg dose), I/R plus treatment with an identical dose of isotype-matched control Ig, I/R plus anterior compartment fasciotomy, or I/R plus both IB4 and fasciotomy. After 48 hr of reperfusion anterior tibial muscle necrosis was assessed (by tetrazolium staining and computerized planimetry), wet:dry muscle weights (W:D) were determined, and muscle PMN sequestration was measured by myeloperoxidase (MPO) activity. IB4-treated animals exhibited markedly reduced muscle MPO activity, compared to untreated animals. Although all interventions reduced edema formation (W:D ratios), none did so significantly. IB4 treatment reduced muscle necrosis when used alone (to 28 ± 7%, vs. 48% ± 6% in untreated controls), however this was not statistically significant ( P = 0.06). Fasciotomy significantly reduced necrosis (to 22 ± 2%, P <0.05); however, the addition of IB4 to fasciotomy resulted in necrosis that was significantly lower than that after fasciotomy alone (12 ± 4%, P < 0.05 vs fasciotomy group) and the least necrosis of any group. Taken together, these results indicate that CD18 plays a role in PMN-mediated reperfusion injury of skeletal muscle and that CD18 blockade may be an effective adjuvant treatment to fasciotomy in reducing muscle loss after ischemia.

Comparison of cytokines and human recombinant superoxide dismutase in a skeletal muscle reperfusion injury model

Comparison of cytokines and human recombinant superoxide dismutase in a skeletal muscle reperfusion injury model

Skeletal Muscle Reperfusion Injury: Pathophysiology and Clinical Considerations

Skeletal muscle reperfusion injury following revascularization of an acutely ischaemic limb undoubtedly contributes to the morbidity and mortality of this surgical emergency. This article reviews the experimental evidence which has defined the biochemical events responsible for the pathogenesis of this injury, with particular emphasis on the roles played by free radicals, neutrophils and products of lipid peroxidation. Finally, the clinical relevance of both the local and systemic effects of the injury is considered, together with suggestions for potential therapeutic strategies based on the results of laboratory work.

Studies of Reperfusion Injury in Skeletal Muscle: Controlled Limb Reperfusion to Reduce Post-Ischaemic Syndrome

Revascularization after prolonged complete limb ischaemia may result in both severe damage to skeletal muscle and various systemic manifestations of the postischaemic syndrome. Previous experimental studies performed by the authors have shown that these are caused, to a large extent, by normal reperfusion at normal systemic pressure and that this additional injury can be substantially reduced by controlled reperfusion of the revascularized limb before restoration of the normal circulation. This treatment includes control of the conditions of reperfusion and composition of the initial reperfusate. In the present study, this concept of controlled limb reperfusion was applied to patients with prolonged severe lower limb ischaemia. Controlled limb reperfusion was used in 11 patients after prolonged complete unilateral or bilateral ischaemia. The ischaemic interval ranged from 5 to 21 h. Two patients were in cardiogenic shock, ten had a history of associated cardiac disease and seven coexistent peripheral vascular disease. After systemic heparinization, thromboembolectomy was undertaken using a Fogarty catheter. Cannulas were placed in the iliac, profunda and superficial femoral arteries and connected to a reperfusion set. Oxygenated blood was drawn from the iliac artery and mixed with an asanguineous solution (ratio 6:1). This controlled reperfusate was returned to the profunda and superficial femoral arteries using a single roller pump. The system allows control of both the composition of the reperfusate (Ca2+, pH, osmolarity, glucose, substrate, PO2, free radical scavengers) and the conditions of reperfusion (pressure, flow, temperature). After 30 min of controlled limb reperfusion, the cannulas were removed, the arteriotomy closed and normal blood reperfusion started.(ABSTRACT TRUNCATED AT 250 WORDS)

Morphologic Analysis of the Microcirculation During Reperfusion of Ischemic Skeletal Muscle and the Effect of Hyperbaric Oxygen

The morphologic events in the microcirculation that lead to reperfusion injury of ischemic skeletal muscle remain incompletely understood. The purpose of this experiment was to evaluate leukocyte endothelial adherence characteristics and dynamic changes in microvessel caliber during reperfusion of an in vivo skeletal muscle ischemia preparation. In addition, the effect of hyperbaric oxygen treatment on these microcirculatory changes also was studied. An intravital microscopy preparation of a transilluminated gracilis muscle in 27 rats was used to observe a total of 101 arterioles and 63 venules (13 to 73 microns diameter). Baseline hemodynamics were videotaped for 30 minutes following muscle isolation. The animals were divided into six groups: (1) sham, no ischemia, (2) 4 hours of global ischemia only, (3) no ischemia plus hyperbaric oxygen (one 2.5 ATA/1 hour of treatment with 100% oxygen), (4) 4 hours of ischemia plus hyperbaric oxygen during ischemia, (5) 4 hours of ischemia plus hyperbaric oxygen immediately on reperfusion, and (6) 4 hours of ischemia plus hyperbaric oxygen 1 hour after reperfusion. Changes in arteriolar and venular diameters at specific times during 3 hours of reperfusion were recorded, and the number of adherent and slow-rolling leukocytes in 100-microns venular segments were counted and compared with baseline measurements. The proximity of arterioles to venules was classified as adjacent (< 15 microns) or distant (> 15 microns). No significant changes in leukocyte endothelial adherence or arteriolar diameter were noted in group 1 sham or group 3 nonischemic hyperbaric oxygen-treated rats when compared with baseline measurements. A significant increase in adherent leukocytes was observed in group 2 ischemic venules (+14.9 +/- 2.5) within 5 minutes of reperfusion, which was maintained for 3 hours. Reperfusion measurements of arteriolar diameter in group 2 ischemic muscle preparations demonstrated an initial vasodilation that was followed at 1 hour by a progressive and severe vasoconstriction (-46.9 +/- 11.3 percent at 3 hours) in arterioles adjacent to venules that was not seen in distant arterioles. The increase in adherent leukocytes seen in group 2 ischemic venules was significantly reduced by hyperbaric oxygen treatment given during ischemia (group 4) or up to 1 hour during reperfusion (groups 5 and 6). In addition, the progressive ischemic arteriolar vasoconstriction was inhibited in all groups (4, 5, and 6) treated with hyperbaric oxygen.(ABSTRACT TRUNCATED AT 400 WORDS)

Free Radicals in Reperfusion Injury After Acute Aortic Occlusion

This investigation aims to evaluate the role of free radicals and the influence of radical scavengers in reperfusion injury of the skeletal muscle in male Wistar rats. Various parameters, including tissue blood flow, serum and calf muscle tissue levels of thiobarbituric acid (TBA) reactants, and the water content of calf muscles, were measured in the experimental setting, where infrarenal abdominal aorta was occluded for two hours followed by reperfusion with and without intraperitoneal administration of radical scavengers (superoxide dismutase or catalase). The rats were divided into four groups: group A: single laparotomy; group B: two-hour occlusion; group C: two-hour occlusion with superoxide dismutase; group D: two-hour occlusion with catalase. The increases in both serum and calf muscle tissue levels of TBA reactants following reperfusion were diminished in groups C and D as compared with those in group B. The water content of calf muscles showed a significant increase after reperfusion in group B, whereas it did not change in group D. The calf muscle tissue blood flow after reperfusion was significantly lower in group C than that in group B. These results indicate that oxygen-derived free radicals may be responsible for reperfusion injury in the lower extremity and that the attenuated blood flow during reperfusion produced by these scavengers seems to play an important role in reducing lipid peroxidation . In a clinical setting, limiting the rate of reperfusion blood flow may reduce the reperfusion injury in skeletal muscle.