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.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
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
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
Bailey MJ, Johnston CLW, Yates CJP, Sommerville PG (1979) Preoperative haemoglobin as predictor of outcome of diabetic amputations. Lancet 2:168–170
Baldinger V (1986) Mikroangiodynamik und Gewebeoxygenierung bei normovolämischer Hämodilution mit kristalloiden und kolloidalen Lösungen. Vet med Dissertation, Universität Giessen, Giessen, FRG
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
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
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
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
Dunant JH, Edwards WS (1973) Small vessel occlusion in the extremity after various periods of arterial obstruction: An experimental study. Surgery 73:240–245
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
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
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
Eriksson E, Anderson WA, Replogle RL (1974) Effects of prolonged ischemia on muscle microcirculation in the cat. Surg Forum 25:254–255
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
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
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
Gelin LE (1956) Studies in anemia of injury. Acta Chir Scand [Suppl] 210:1–130
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
Granger DN, Höllwarth ME, Parks DA (1986) Ischemia-reperfusion injury: Role of oxygen-derived free radicals. Acta Physiol Scand [Suppl] 548:47–63
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
Hardaway RM (1966) Syndromes of disseminated intravscular coagulation. With special reference to shock and hemorrhage. Thomas, Springfield
Harman JW (1948) The significance of local vascular phenomena in production of ischemic necrosis in skeletal muscle. Am J Pathol 24:625–641
Hellberg O, Källskog Ö (1986) Influence of hematocrit in post-ischemic kidney damage. Int J Microcirc Clin Exp [Abstr] 5:279
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
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
Kayar SR, Banchero N (1985) Sequential perfusion of skeletal muscle capillaries. Microvasc Res 30:298–305
Kloner RA, Ganote CE, Jennings RB (1974) The “no-reflow” phenomenon after temporary coronary occlusion in the dog. J Clin Invest 54:1496–1508
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
Kovacs K, Carrol R, Tapp E (1966) Temporary ischemia of the adrenal gland. J Pathol Bacteriol 91:235–240
Krug A, du Mesnil de Rochemont W, Korb G (1966) Blood supply of the myocardium after temporary coronary occlusion. Circ Res 19:57–62
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
Laughlin MH, Armstrong RB (1980) Muscular blood flow distribution patterns as a function of running speed in rats. Am J Physiol 243:H296-H306
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
Matrai A, Kollar L (1987) Importance of the preoperative haemoglobin concentration in arterial surgery. Eur Surg Res 19:1–5
McCord JM (1985) Oxygen-derived free radicals in postischemic tissue injury. N Engl J Med 312:159–163
Messmer KFW (1987) Acceptable hematocrit levels in surgical patients. World J Surg 11:41–46
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
Messmer K, Sunder-Plassmann L, Klövekorn WP, Holper K (1972) Circulatory significance of hemodilution. Rheological changes and limitations. Adv Microcirc 4:1–77
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
Messmer K, Kreimeier U, Intaglietta M (1986) Present state of intentional hemodilution. Eur Surg Res 18:254–263
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
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
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
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
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
Renkin EM, Gray SD, Dodd LR (1981) Filling of microcirculation in skeletal muscles during timed india ink perfusion. Am J Physiol 241:H174-H186
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
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
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
Schmid-Schönbein H, Rieger H (1981) Why hemodilution in low flow states? Bibl Haematol 47:99–121
Sheehan HL, Davis JC (1959) Renal ischemia with failed reflow. J Pathol Bacteriol 78:105–120
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
Strock PE, Majno G (1969) Microvascular changes in acutely ischemic rat muscle. Surg Gynec Obstet 129:1213–1224
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
Summers WK, Jamison RL (1971) The no-reflow in renal ischemia. Lab Invest 25:635–643
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
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
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01852316