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Quantitative analysis of microcirculatory disorders after prolonged ischemia in skeletal muscle

Therapeutic Effects of Prophylactic Isovolemic Hemodilution

  • Original Papers
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Research in Experimental Medicine

Summary

Reperfusion injury following prolonged ischemia is thought to be caused primarily by microvascular failure. The aim of the present study was to investigate whether prophylactic isovolemic hemodilution with Dextran 60 (hct 30%) could improve microvascular perfusion after 4h of pressure-induced ischemia in skeletal muscle.

In 28 Syrian golden hamsters (6–8 weeks/60–80 g b. wt.) a dorsal skinfold chamber and permanent arterial and venous catheters were implanted under Nembutal anesthesia (50 mg/kg b. wt.). Following a recovery period of 48 h pressure-induced ischemia was applied to the skeletal muscle within the skinfold chamber by means of a transparent stamp. Quantitative analyses of microhemodynamics were performed in the awake animal prior to and 15 min, 1, 2, 4 and 24 h after ischemia using vital fluorescence microscopy.

In non-treated animals, functional capillary density decreased after 4 h of ischemia to 30% of the initial values (P < 0.001); after 24-h reperfusion only 50% of the initially perfused capillaries were reperfused (P < 0.001). The heterogeneity of functional capillary density increased after ischemia to a maximum of 2.19 ± 0.94 as compared to 0.48 ± 0.11 prior to ischemia. Capillary RBC-velocity suffered a marked reduction in the early reperfusion phase and did not recover up to the 24-h observation time. In contrast, prophylactic isovolemic hemodilution was associated with only a small and reversible reduction of functional capillary density after 4-h ischemia. At 24-h reperfusion 90% of the initially perfused capillaries were reperfused. Capillary RBC-velocity was reduced in the early reperfusion phase, but returned to normal values within 24h. Thus, prophylactic isovolemic hemodilution resulted in a marked reduction of microvascular reperfusion failure in skeletal muscle. A hematocrit lower than normal prior to ischemia provides better conditions for capillary reperfusion after prolonged ischemia.

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References

  1. Ames A III, Wright RL, Kowada M, Thurston JM, Majno G (1968) Cerebral ischemia. II. The no-reflow phenomenon. Am J Pathol 52:437–452

    PubMed  Google Scholar 

  2. Bagge U, Blixt A, Strid KG (1983) The initiation of postcapillary margination of leucocytes: Studies in vitro on the influence of erythrocyte concentration and flow velocity. Int J Microcirc Clin Exp 2:215–227

    PubMed  Google Scholar 

  3. Bailey MJ, Johnston CLW, Yates CJP, Sommerville PG (1979) Preoperative haemoglobin as predictor of outcome of diabetic amputations. Lancet 2:168–170

    PubMed  Google Scholar 

  4. Baldinger V (1986) Mikroangiodynamik und Gewebeoxygenierung bei normovolämischer Hämodilution mit kristalloiden und kolloidalen Lösungen. Vet med Dissertation, Universität Giessen, Giessen, FRG

    Google Scholar 

  5. Bartlett R, Funk W, Hammersen F, Arfors KE, Messmer K, Nemir P (1986) Effect of superoxide dismutase on skin microcirculation after ischemia and reperfusion. Surg Forum 37:599–601

    Google Scholar 

  6. Bouhoutsos J, Morris T, Chavatzas D, Martin P (1974) The influence of haemoglobin and platelet levels on the results of arterial surgery. Br J Surg 61:984–986

    PubMed  Google Scholar 

  7. Damon DH, Duling BR (1984) Distribution of capillary blood flow in the microcirculation of the hamster: An in vivo study using epifluorescent microscopy. Microvasc Res 27:81–95

    PubMed  Google Scholar 

  8. Driessen G, Schweiger B, Pohl I, Inhoffen W, Haest CVM, Heidtmann H, Scheidt H, Schmid-Schönbein H (1981) Einfluß veränderter Fließeigenschaften des Blutes auf die Perfusion der Mikrozirkulation. In: Messmer K, Fagrell B (Hrsg) Mikrozirkulation und arterielle Verschlußkrankheiten. Karger, Basel, S 39–44

    Google Scholar 

  9. Dunant JH, Edwards WS (1973) Small vessel occlusion in the extremity after various periods of arterial obstruction: An experimental study. Surgery 73:240–245

    PubMed  Google Scholar 

  10. Endrich B, Asaishi K, Götz A, Messmer K (1980) Technical report — A new chamber technique for microvascular studies in unanesthetized hamsters. Res Exp Med (Bul) 177:125–134

    Google Scholar 

  11. Endrich B, Messmer K (1984) Quantitative analysis of the microcirculation in the awake animal. In: Olszewski W (ed) Handbook of microsurgery. CRC Press, Miami, Fla, USA, pp 79–105

    Google Scholar 

  12. Engler RL, Schmid-Schönbein GW, Dahlgren MD, Morris DD, Peterson MA (1986) Role of leucocytes in myocardial ischemia and reflow in the dog. Int J Microcirc Clin Exp [Abstr] 5:283

    Google Scholar 

  13. Eriksson E, Anderson WA, Replogle RL (1974) Effects of prolonged ischemia on muscle microcirculation in the cat. Surg Forum 25:254–255

    PubMed  Google Scholar 

  14. Fischer EG, Ames A III (1972) Studies on mechanisms of impairment of cerebral circulation following ischemia: Effect of hemodilution and perfusion pressure. Stroke 3:538–542

    PubMed  Google Scholar 

  15. Flores J, DiBona DR, Beck CH, Leaf A (1972) The role of cell swelling in ischemic renal damage and the protective effect of hypertonic solute. J Clin Invest 51:118–126

    PubMed  Google Scholar 

  16. Fritzsche A, Pries AR, Ley K, Gaehtgens P (1986) Effect of isovolemic hemodilution on hematocrit distribution in the rat mesenteric microcirculation. Int J Microcirc Clin Exp [Abstr] 5:278

    Google Scholar 

  17. Gelin LE (1956) Studies in anemia of injury. Acta Chir Scand [Suppl] 210:1–130

    Google Scholar 

  18. Gidlöf A, Hammersen F, Larsson J, Lewis DH, Liljedahl SO (1982) Is capillary endothelium in human skeletal muscle an ischemic shock tissue? In: Lewis DH (ed) Induced skeletal muscle ischemia in man. Karger, Basel, pp 63–79

    Google Scholar 

  19. Granger DN, Höllwarth ME, Parks DA (1986) Ischemia-reperfusion injury: Role of oxygen-derived free radicals. Acta Physiol Scand [Suppl] 548:47–63

    Google Scholar 

  20. Haljamäe H, Jennische E, Medegard A (1977) Transmembrane potential measurements as an indicator of heterogeneous distribution of nutritive blood flow in skeletal muscle during shock. Acta Physiol Scand 101:458–464

    PubMed  Google Scholar 

  21. Hardaway RM (1966) Syndromes of disseminated intravscular coagulation. With special reference to shock and hemorrhage. Thomas, Springfield

    Google Scholar 

  22. Harman JW (1948) The significance of local vascular phenomena in production of ischemic necrosis in skeletal muscle. Am J Pathol 24:625–641

    Google Scholar 

  23. Hellberg O, Källskog Ö (1986) Influence of hematocrit in post-ischemic kidney damage. Int J Microcirc Clin Exp [Abstr] 5:279

    Google Scholar 

  24. Hint H (1968) The pharmacology of dextran and the physiological background for the clinical use of rheomacrodex and macrodex. Acta Anaesthesiol Belg 19:119–138

    PubMed  Google Scholar 

  25. Ivanov KP, Kalinina MK, Levkovich YUI (1985) Microcirculation velocity changes under hypoxia in brain, muscles, liver, and their physiological significance. Microvasc Res 30:10–18

    PubMed  Google Scholar 

  26. Kayar SR, Banchero N (1985) Sequential perfusion of skeletal muscle capillaries. Microvasc Res 30:298–305

    PubMed  Google Scholar 

  27. Kloner RA, Ganote CE, Jennings RB (1974) The “no-reflow” phenomenon after temporary coronary occlusion in the dog. J Clin Invest 54:1496–1508

    PubMed  Google Scholar 

  28. Kniseley MH (1963) Intravascular erythrocyte aggregation (blood sludge) In: Hamilton WF, Dow P (eds) Handbook of physiology, sect 2: Circulation, vol 3. Williams and Wilkins, Baltimore, pp 2249–2292

    Google Scholar 

  29. Kovacs K, Carrol R, Tapp E (1966) Temporary ischemia of the adrenal gland. J Pathol Bacteriol 91:235–240

    PubMed  Google Scholar 

  30. Krug A, du Mesnil de Rochemont W, Korb G (1966) Blood supply of the myocardium after temporary coronary occlusion. Circ Res 19:57–62

    PubMed  Google Scholar 

  31. Lewis DH (1984) The response of the microvasculature in skeletal muscle to hemorrhage, trauma, and ischemia. In: Hammersen F, Messmer K (eds) Skeletal muscle microcirculation. Prog Appl Microcirc 5:127–138

    Google Scholar 

  32. Laughlin MH, Armstrong RB (1980) Muscular blood flow distribution patterns as a function of running speed in rats. Am J Physiol 243:H296-H306

    Google Scholar 

  33. Lindbom L, Arfors KE (1983) Effect of acute normovolemic hemodilution on microvascular blood flow distribution in skeletal muscle. Int J Microcirc Clin Exp [Abstr] 2:260–261

    Google Scholar 

  34. Matrai A, Kollar L (1987) Importance of the preoperative haemoglobin concentration in arterial surgery. Eur Surg Res 19:1–5

    Google Scholar 

  35. McCord JM (1985) Oxygen-derived free radicals in postischemic tissue injury. N Engl J Med 312:159–163

    PubMed  Google Scholar 

  36. Messmer KFW (1987) Acceptable hematocrit levels in surgical patients. World J Surg 11:41–46

    PubMed  Google Scholar 

  37. Messmer K, Lewis DH, Sunder-Plassmann L, Klövekorn WP, Mendler N, Holper K (1972) Acute normovolemic hemodilution. Changes of central hemodynamics and microcirculatory flow in skeletal muscle. Eur Surg Res 4:55–70

    PubMed  Google Scholar 

  38. Messmer K, Sunder-Plassmann L, Klövekorn WP, Holper K (1972) Circulatory significance of hemodilution. Rheological changes and limitations. Adv Microcirc 4:1–77

    Google Scholar 

  39. Messmer K, Sunder-Plassmann L, Jesch F, Görnandt L, Sinagowitz E, Kessler M (1973) Oxygen supply to the tissues during limited normovolemic hemodilution. Res Exp Med 159:152–166

    Google Scholar 

  40. Messmer K, Kreimeier U, Intaglietta M (1986) Present state of intentional hemodilution. Eur Surg Res 18:254–263

    PubMed  Google Scholar 

  41. Mirhashemi S, Ertefai S, Messmer K, Intaglietta M (1987) Model analysis of the enhancement of tissue oxygenation by hemodilution due to increased microvascular flow velocity. Microvasc Res 34:290–301

    PubMed  Google Scholar 

  42. Mirhashemi S, Messmer K, Intaglietta M (1987) Tissue perfusion during normovolemic hemodilution investigated by a hydraulic model of the cardiovascular system. Int Microcirc Clin Exp 6:123–136

    Google Scholar 

  43. Oude Vrielink HHE, Slaaf DW, Tangelder GJ, Reneman RS (1987) Does capillary recruitment exist in young rabbit skeletal muscle? Int J Microcirc Clin Exp 6:321–332

    PubMed  Google Scholar 

  44. Parks DA, Bulkley GB, Granger DN, Hamilton SR, McCord JM (1982) Ischemic injury in the cat small intestine: Role of superoxide radicals. Gastroenterology 82:9–15

    PubMed  Google Scholar 

  45. Poche R, Arnold G, Nier H (1969) Die Ultrastruktur der Muskelzellen und der Blutkapillaren des isolierten Rattenherzens nach diffuser Ischämie und Hyperkapnie. Virchows Arch [Pathol Anat] 346:239–268

    Google Scholar 

  46. Renkin EM, Gray SD, Dodd LR (1981) Filling of microcirculation in skeletal muscles during timed india ink perfusion. Am J Physiol 241:H174-H186

    PubMed  Google Scholar 

  47. Romanus M, Stenqvist O, Haljamäe H, Seifert F (1977) Pressure-induced ischemia. I. An experimental model for intravital microscopic studies in hamster cheek pouch. Eur Surg Res 9:444–459

    PubMed  Google Scholar 

  48. Sack FU, Funk W, Hammersen F, Messmer K (1987) Microvascular injury of skeletal muscle and skin after different periods of pressure induced ischemia. Prog Appl Microcirc 12:282–288

    Google Scholar 

  49. Santavirta S, Luoma A, Arstila AU (1978) Ultrastructural changes in striated muscle after experimental tourniquet ischemia and short reflow. Eur Surg Res 10:415–424

    PubMed  Google Scholar 

  50. Schmid-Schönbein H, Rieger H (1981) Why hemodilution in low flow states? Bibl Haematol 47:99–121

    PubMed  Google Scholar 

  51. Sheehan HL, Davis JC (1959) Renal ischemia with failed reflow. J Pathol Bacteriol 78:105–120

    PubMed  Google Scholar 

  52. Slaaf DW, Tangelder GJ, Teirlinck HC, Oude Vrielink HHE, Reneman RS (1986) Flow cessation pressures in the rabbit tenuissimus muscle. Int J Microcirc Clin Exp 5:3–9

    PubMed  Google Scholar 

  53. Strock PE, Majno G (1969) Microvascular changes in acutely ischemic rat muscle. Surg Gynec Obstet 129:1213–1224

    PubMed  Google Scholar 

  54. Stücker O, Trouvé R, Vicaut E, Charansonney O, Teisseire B, Duruble M, Duvelleroy M (1983) Effects of different hematocrits on the isolated working rabbit heart reperfused after ischemia. Int J Microcirc Clin Exp 2:325–335

    PubMed  Google Scholar 

  55. Summers WK, Jamison RL (1971) The no-reflow in renal ischemia. Lab Invest 25:635–643

    PubMed  Google Scholar 

  56. Vicaut E, Trouvé R, Stücker O, Duruble M, Duvelleroy M (1985) Effects of changes in hematocrit on red cell flows at capillary bifurcations. Int J Microcirc Clin Exp 4:351–362

    PubMed  Google Scholar 

  57. Zeintl H, Tompkins WR, Messmer K, Intaglietta M (1986) Static and dynamic microcirculatory video image analysis applied to clinical investigations. In: Mahler F, Messmer K, Hammersen F (eds) Techniques in clinical capillary microscopy. Prog Appl Microcirc 11:1–10

    Google Scholar 

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Menger, M.D., Sack, F.U., Barker, J.H. et al. Quantitative analysis of microcirculatory disorders after prolonged ischemia in skeletal muscle. Res. Exp. Med. 188, 151–165 (1988). https://doi.org/10.1007/BF01852316

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