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Research Article| Volume 164, ISSUE 3, P194-198, September 1992

Reduction of the extent of ischemic skeletal muscle necrosis by perfusion with oxygenated perfluorocarbon

  • Author Footnotes
    1 From the Division of Vascular Surgery, Maimonides Medical Center,SUNY Health Science Center of Brooklyn, Brooklyn, New York. This work was supported by a grant from the Maimonides Medical Center Research and Development Foundation.
    Chittur Mohan
    Footnotes
    1 From the Division of Vascular Surgery, Maimonides Medical Center,SUNY Health Science Center of Brooklyn, Brooklyn, New York. This work was supported by a grant from the Maimonides Medical Center Research and Development Foundation.
    Affiliations
    Brooklyn, New York, USA
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  • Author Footnotes
    1 From the Division of Vascular Surgery, Maimonides Medical Center,SUNY Health Science Center of Brooklyn, Brooklyn, New York. This work was supported by a grant from the Maimonides Medical Center Research and Development Foundation.
    Mark Gennaro
    Footnotes
    1 From the Division of Vascular Surgery, Maimonides Medical Center,SUNY Health Science Center of Brooklyn, Brooklyn, New York. This work was supported by a grant from the Maimonides Medical Center Research and Development Foundation.
    Affiliations
    Brooklyn, New York, USA
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  • Author Footnotes
    1 From the Division of Vascular Surgery, Maimonides Medical Center,SUNY Health Science Center of Brooklyn, Brooklyn, New York. This work was supported by a grant from the Maimonides Medical Center Research and Development Foundation.
    Corrado Marini
    Footnotes
    1 From the Division of Vascular Surgery, Maimonides Medical Center,SUNY Health Science Center of Brooklyn, Brooklyn, New York. This work was supported by a grant from the Maimonides Medical Center Research and Development Foundation.
    Affiliations
    Brooklyn, New York, USA
    Search for articles by this author
  • Author Footnotes
    1 From the Division of Vascular Surgery, Maimonides Medical Center,SUNY Health Science Center of Brooklyn, Brooklyn, New York. This work was supported by a grant from the Maimonides Medical Center Research and Development Foundation.
    Enrico Ascer
    Correspondence
    Requests for reprints should be addressed to Enrico Ascer, MD,Maimonids Medical Center, Division of Vascular Surgery, 4802 Tenth Avenue, Brooklyn, New York 11219.
    Footnotes
    1 From the Division of Vascular Surgery, Maimonides Medical Center,SUNY Health Science Center of Brooklyn, Brooklyn, New York. This work was supported by a grant from the Maimonides Medical Center Research and Development Foundation.
    Affiliations
    Brooklyn, New York, USA
    Search for articles by this author
  • Author Footnotes
    1 From the Division of Vascular Surgery, Maimonides Medical Center,SUNY Health Science Center of Brooklyn, Brooklyn, New York. This work was supported by a grant from the Maimonides Medical Center Research and Development Foundation.
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      Oxygenated perfluorocarbon emulsion has been shown to preserve feline cerebral function after ischemia. The postulated protective effects of perfluorocarbons include improvement of blood rheology and prevention of neutrophil adherence by nonchemical inhibition of surface receptors. In this study, we used a well-described gracilis muscle model to investigate whether oxygenated perfluorocarbon can minimize skeletal muscle necrosis by mitigating the degree of leukosequestration. In eight adult mongred dogs, both gracilis muscles were weighted and then subjected to 6 hours of normothermic ischemia followed by 48 hours of normothermic reperfusion. However, one randomly selected side (experimental side) was infused with oxygen (O2) Fluosol-DA 20% (4.4±0.2 mL O2/100 mL) intra-arterially at 12 mL/min for 40 minutes immediately after ischemia. Muscle biopsy specimens were obtained before ischemia and after 1 hour and 48 hours of reperfusion to estimate myeloperoxidase (MPO) activity, a marker of neutrophil infiltration. After 48 hours, both gracilis muscles were harvested and weighted in all animals. Muscle necrosis was measured by serial transections, nitroblue tetrazolium staining, and computerized planimetry. The transmuscular oxygen tension (pO2) of the gracilis muscle on the experimental side increased from 2 to 4 mm Hg during ischemia to 315±50 mm Hg during O2 Fluosol-DA 20% infusion. The percentage of muscle necrosis on the control side was 48.08%±8.46%, compared with 27.62%±6.96% on the experimental side (p <0.001). MPO activity was significantly higher at 48 hours of reperfusion compared with pre-ischemic and 1-hour reperfusion values (5.46±1.52 U/mg tissue protein versus 0.06±0.01 U/mg tissue protein and 0.16±0.06 U/mg tissue protein, respectively, in the control group; 1.78±0.60 U/mg tissue protein versus 0.16±0.08 U/mg tissue protein and 0.27±0.10 U/mg tissue protein, respectively, in the experimental group, p<0.05). However, MPO activity at 48 hours of reperfusion in the experimental group was significantly lower than in the control group (p<0.05). There was no difference in the percentage of weight gain between the control and the experimental groups (38.31%± 9.36% and 28.34%±7.35%, respectively, p >0.05). These data show that perfluorocarbons minimize the extent of skeletal muscle necrosis in this canine model. Based on our data on MPO activity, we believe that the protective effect of perfluorocarbons is in part due to the decreased leukosequestration in the muscle during the periods of ischemia and reperfusion. The potential for clinical application of this new treatment modality is very attractive, since high mortality and morbidity rates continue to be reported in patients with acute limb ischemia.
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      References

        • Haimovici H.
        Metabolic complications of acute arterial occlusions.
        J Cardiovasc Surg. 1979; 20 (Torino): 349-357
        • Haimovici H.
        Arterial embolism with acute massive ischemic myopathy and myoglobinuria.
        Surgery. 1960; 116: 414-421
        • Quinones-Baldrich WJ
        The role of fibrinolysis during reperfusion of ischemic skeletal muscle.
        Microcirc Endothelium Lymphatics. 1989; 5: 299-314
        • Little JR
        Implanted device for middle cerebral artery occlusion in conscious cats.
        Stroke. 1977; 8: 258-260
        • Boschenstein FK
        • Reilly JA
        • Yahr MD
        • Correll JW
        Effect of low molecular weight dextran on cortical blood flow.
        Arch Neurol. 1966; 14: 288-293
        • Little JR
        Modification of acute ischemia by treatment with mannitol.
        Stroke. 1978; 9: 4-9
        • Ames III, A
        • Wright RL
        • Kowada M
        • Thurston JM
        • Majno G
        Cerebral ischemia. The no-reflow phenomenon.
        Am J Pathol. 1968; 52: 437-453
        • Little JR
        Microvascular alterations and edema in focal cerebral ischemia.
        in: Pappius H Feindel W Dynamics of brain edema. Springer-Verlag, New York1976: 236-243
        • Chiang J
        • Kowada M
        • Ames III, A
        • Wright RL
        • Majno G
        Cerebral ischemia III. Vascular changes.
        Am J Pathol. 1968; 52: 455-476
        • Romson J
        • Hook BG
        • Kunkel SL
        • Abrams GD
        • Schork MA
        • Luchessi BR
        Reduction of the extent of ischemic myocardial injury by neutrophil depletion in the dog.
        Circulation. 1983; 67: 1016-1023
        • Engler R
        • Dahlgren M
        • Morris D
        • Peterson M
        • Schmid-Schonbein G
        Role of leukocytes in response to acute myocardial ischemia and reflow in dogs.
        Am J Physiol. 1986; : H314-H322
        • McCord JM
        Oxygen-derived free radicals in post-ischemic tissue injury.
        N Eng J Med. 1985; 312: 159-163
        • Novelli GP
        • Livi P
        • Ghinassi L
        • Lisi L
        • Brunelleschi S
        • Fantozzi R
        Superoxide generation by granulocytes during superior mesenteric artery occlusion shock in rabbits.
        in: Novelli GP Ursini F Oxygen radicals in shock. International workshop. Karger, Basel1986: 487-493
        • Simpson PJ
        • Todd RF
        • Fantone JC
        • et al.
        Reduction of experimental canine myocardial reperfusion injury by a monoclonal antibody (anti-Mol, anti-CD 11b) that inhibits leukocyte adhesion.
        J Clin Invest. 1988; 81: 624-629
        • Osterholm JL
        • Alderman JB
        • Triolo AJ
        • D'Amore BR
        • Williams HD
        • Frazer G
        Severe cerebral ischemia treatment by ventriculosubarachnoid perfusion with an oxygenated fluorocarbon emulsion.
        Neurosurgery. 1983; 13: 381-387
        • Peerless SJ
        • Ishikawa R
        • Hunter IG
        • Peerless MJ
        Protective effect of Fluosol-DA in acute cerebral ischemia.
        Stroke. 1981; 12: 558-563
        • Kuzon WM
        • Walker PM
        • Mickle DAG
        • Harris KA
        • Pynn BR
        • McKee NH
        An isolated skeletal muscle model suitable for acute ischemia studies.
        J Surg Res. 1986; 41: 24-32
        • Suzuki K
        • Ota H
        • Sasagawa S
        • Sakatani T
        • Fujikura T
        Assay method for myeloperoxidase in human polymorphonuclear leukocytes.
        Anal Biochem. 1982; 132: 345-352
        • Bradford M
        A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of proteindye binding.
        Anal Biochem. 1976; 72: 248-254
        • Novikoff AB
        • Shin W
        • Drucker JJ
        Staining results with two tetrazolium salts.
        J Biophys Biochem Cytol. 1961; 9: 47-61
        • Labbe R
        • Lindsay T
        • Walker PM
        The extent and distribution of skeletal muscle necrosis after graded periods of complete ischemia.
        J Vasc Surg. 1987; 6: 152-157
        • Chait LA
        • May Jr, JW
        • O'Brian BM
        • Hurley JV
        The effects of the perfusion of various solutions on the no reflow phenomenon in experimental free flaps.
        Plast Reconstr Surg. 1978; 61: 421-430
        • Leaf A
        Cell swelling. A factor in ischemic tissue injury.
        Circulation. 1973; 48: 455-458
        • Strock PE
        • Majno G
        Microvascular changes in experimental tourniquet ischemia.
        Surg Gynecol Obstet. 1969; 129: 1213-1223
        • Wells RE
        Rheology of blood in the microvasculature.
        N Engl J Med. 1964; 270: 832-839
        • Edstrom RFS
        • Essex HE
        Swelling of the brain induced by anoxia.
        Neurology. 1956; 6 (Minneapolis): 118-124
        • Van Harreveld A
        Changes in volume of cortical neuronal elements during asphyxiation.
        Am J Physiol. 1957; 191: 233-242
        • Leaf A
        On the mechanism of fluid exchange of tissues in vitro.
        Biochem J. 1957; 62: 241-248
        • Forman MB
        • Bingham SE
        • Kopelman HA
        • et al.
        Reduction of infarct size with intracoronary perfluorochemical in a canine preparation of reperfusion.
        Circulation. 1985; 71: 1060-1068
        • Forman MB
        • Puett DW
        • Bingham SE
        • et al.
        Preservation of endothelial cell structure and function by intracoronary perfluoro-chemical in a canine preparation of reperfusion.
        Circulation. 1987; 76: 469-479
        • Bajaj AK
        • Cobb MA
        • Virmani R
        • Gay JC
        • Light RT
        • Forman MB
        Limitation of myocardial reperfusion injury by intravenous perfluorochemicals; role of neutrophil activation.
        Circulation. 1989; 79: 645-656
        • Forman MB
        • Puett DW
        • Wilson BH
        • et al.
        Beneficial longterm effect of intracoronary perfluorochemical on infarct size and ventricular function in a canine reperfusion model.
        J Am Coll Cardiol. 1987; 9: 1082-1090
        • Kolodgie FD
        • Virmani R
        • Farb A
        Limitation of no reflow injury by blood-free reperfusion with oxygenated perfluorochemical (Fluosol-DA 20%).
        J Am Coll Cardiol. 1991; 18: 215-223
        • Rubin BB
        • Smith A
        • Liauw S
        • Isenman D
        • Romaschin AD
        • Walker PM
        Complement activation and white cell sequestration in postischemic skeletal muscle.
        Am J Physiol. 1990; 259: H525-H531
        • Mohan C
        • Ascer E
        • Marini CP
        • Maughan R
        • Gennaro M
        Does iloprost mediate thromboxane release and polymorphonuclear leukocyte sequestration in ischemic skeletal muscle?.
        J Cardiovasc Surg. 1992; (in press)
        • Ascer E
        • Mohan C
        • Gennaro M
        • Cupo S
        Interleukin-1 and thromboxane release after skeletal muscle ischemia and reperfusion.
        Ann Vasc Surg. 1992; 6: 69-73