Abstract
Purpose
This study compares the effects of stored red cells, freshly donated blood and ultrapurified polymerized bovine haemoglobin (HBOC) on haemodynamic variables, oxygen transport capacity and muscular tissue oxygenation after acute and almost complete isovolaemic haemodilution in a canine model.
Methods
Following randomization to one of three groups, 24 anaesthetized Foxhounds underwent isovolaemic haemodilution with 6% hetastarch to haematocrit levels of 20%, 15% and 10% before they received isovolaemic stepwise augmentation of 1 g · dl−1 haemoglobin. In Group 1, animals were given autologous stored red cells which they had donated three weeks before. In Group 2, animals received freshly donated blood harvested during haemodilution. In Group 3, animals were infused with HBOC. Skeletal muscle tissue oxygen tension was measured with a polarographic 12 μ needle probe.
Results
In all groups, heart rate and cardiac index were increased with decreasing vascular resistance during haemodilution (P < 0.05). Haemodynamic variables showed a reversed trend during transfusion when compared to haemodilution but remained below baseline (P < 0.05). Arterial and venous oxygen content were changed in parallel to changes of haematocrit and haemoglobin concentrations but were lower in Group 3 than in Groups 1 and 2 (P < 0.05) during transfusion. In contrast, the oxygen extraction ratio was higher in Group 3 (59 ± 8%, P < 0.01) at the end of transfusion than in Group 1 (37 ± 13%) and 2 (32 ± 5%). In Group 3, mean tissue oxygen tension increased from 16 ± 5 mmHg after haemodilution to 56 ± 11 mmHg after transfusion (P < 0.01) and was higher than in Group 1 (41 ± 9, P < 0.01) and Group 2 (29 ± 11, P < 0.01). While in Group 3 an augmentation of 0.7 g · dl−1 haemoglobin resulted in restoring baseline tissue oxygenation, higher doses of 2.7 g · dl−1 and 2.1 g · dl−1 were needed in Groups 1 and 2 to reach this level (P < 0.01).
Conclusion
The results show a higher oxygenation potential of HBOC than with autologous stored red cells because of a more pronounced oxygen extraction.
Résumé
Objectif
Cette étude compare les effets des hématies conservées, du sang fraîchement prélevé et de l’hémoglobine bovine polymérisée ultrapurifiée (HBOC) sur les variables hémodynamiques, la capacité de transport en oxygène et l’oxygénation du tissu musculaire après hémodilution isovolémique aiguë et presque complète sur un modèle canin.
Méthodes
Après randomisation en trois groupes, 24 fox-hounds ont subi, une hémodilution isovolémique en paliers avec de l’hétastarch à 6% pour réaliser des hématocrites de 20%, 15% et 10% avant de recevoir une augmentation iso-volémique en paliers de 1 g · dl−1 d’hémoglobine. Dans le groupe 1, les chiens ont reçu les hématies autologues conservées prélevées trois semaines auparavant. Dans le groupe 2, les animaux ont reçu de sang frais recueilli au moment de l’hémodilution. Dans le groupe 3, les animaux ont été perfusés avec HBCO. La tension en oxygène du tissus musculaire a été mesurée avec une sonde polarographique.
Résultats
Dans tous les groupes, la fréquence et l’index cardiaques ont augmenté avec la baisse de la résistance vasculaire pendant l’hémodilution (P < 0,05). Pendant la transfusion, les variables hémodynamiques ont révélé une tendance inverse de celle de l’hémodilution mais sont demeurées sous la ligne de base (P < 0,05). Pendant la transfusion, les contenus artériels et veineux eh oxygène ont changé parallèlement aux changements de l’hématocrite et de la concentration de l’hémoglobine mais étaient plus bas dans le groupe 3 que dans les groupes 1 et 2 (P < 0,05). Par contre, à la fin de la transfusion, l’extraction de l’oxygène a été plus grande dans le groupe 3 (59 ± 8%, P < 0,01) que dans les groupes 1 (37 ±13%) et 2 (31 ± 5%). Dans le groupe 3, après la transfusion, la tension tissulaire moyenne en oxygène a augmenté de 16 ±5 mmHg à 56 ± 11 mmHg (P < 0,01) et était plus élevée que dans les groupes 1(41 ± 9, P < 0,01) et 2 (29 ± 11,P < 0,01). Alors que dans le groupe 3, une augmentation de 0,7 g · dl−1 a permis de ramener l’oxygénation tissulaire à la ligne de base, des quantités plus grandes (2,7 g · dl−1 et de 2,2 g · dl−1) ont été requises pour atteindre ce niveau dans les groupes 1 et 2.
Conclusion
Ces résultats montrent un potentiel d’oxygénation plus élevé avec HBCO qu ’avec des hématies autologues conservées en raison d’une extraction plus prononcée de l’oxygène.
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References
Chang TMS, Varma R. Assessment of blood substitutes: I. Efficacy studies in anesthetized and conscious rats with loss of 1/3, 1/2 and 2/3 blood volume. Artif Cells Blood Substit Immobil Biotechnol 1994; 22: 159–69.
Harringer W, Hodakowski GT, Svizzero T, Jacobs EE, Vlahakes GJ. Acute effects of massive transfusion of a bovine hemoglobin blood substitute in a canine model of hemorrhagic shock. Eur J Cardiothorac Surg 1992; 6: 649–54.
Looker D, Abbott-Brown D, Cozarf P, et al. A human recombinant haemoglobin designed for use as a blood substitute. Nature 1992; 356: 258–60.
Lee R, Atsumi N, Jacobs EE Jr, Austen WG, Vlahakes GJ. Ultrapure, stroma-free, polymerized bovine hemoglobin solution: evaluation of renal toxicity. J Surg Res 1989; 47: 407–11.
Urbaitis BK, Razynska A, Corteza Q, Fronticelli C, Bucci E. Intravascular retention and renal handling of purified natural and intramolecularly cross-liked hemoglobins. J Lab Clin Med 1990; 117: 115–21.
Fronticelli C, Bucci E, Orth C. Solvent regulation of oxygen affinity in hemoglobin. J Biol Chem 1984; 259: 10841–4.
Bosman RJ, Minten J, Lu HR, Van Aken H, Flameng W. Free polymerized hemoglobin versus hydroxyethyl starch in resuscitation of hypovolemic dogs. Anesth Analg 1992; 75: 811–7.
Vlahakes GJ, Lee R, Jacobs EE Jr, LaRaia PJ, Austen WG. Hemodynamic effects and oxygen transport properties of a new blood substitute in a model of massive blood replacement. J Thorac Cardiovasc Surg 1990; 100: 379–88.
Hobbhahn J, Vogel H, Kothe N, Brendel W, Peter K, Jesch F. Hemodynamics and oxygen transport after partial and total blood exchange with pyridoxalated polyhemoglobin in dogs. Acta Anaesthesiol Scand 1985; 29: 537–43.
Jesch FH, Peters W, Hobbhahn J, Schoenberg M, Messmer K. Oxygen-transporting fluids and oxygen delivery with hemodilution. Crit Care Med 1982; 10: 270–4.
Standl Th, Reeker W, Kochs E, Schulte am Esch J. Tissue oxygenation changes in skeletal muscle during complete isovolumic haemodilution with a bovine haemoglobin solution compared with 6% hydroxyethyl starch 200,000/0.5. (German) Anaesthesist 1994; 43 (Suppl): 800–1.
Federspiel WJ, Popel AS. A theoretical analysis of the effect of the paniculate nature of blood on oxygen release in capillaries. Microvasc Res 1986; 32: 164–89.
Honig CR, Frierson JL, Gayeski TEJ. Anatomical determinants of 02 flux density at coronary capillaries. Am J Physiol 1989; 256: 375–82.
Fleckenstein W, Weiss Ch. A comparison of pO2 histograms from rabbit hind-limb muscles obtained by simultaneous measurements with hypodermic needle electrodes and with surface electrodes. Adv Exp Med Biol 1984; 169: 447–55.
Fleckenstein W, Schäffler A, Heinrich R, Petersen C, Günderoth-Palmowski M, Notiert G. On the differences between muscle pO2 measurements obtained with hypodermic needle probes and with multiwire surface probes. Part 1: Differences between tissue pO2 and tissue surface pO2 observed in dog gracilis muscle.In: Ehrly AM, Hauss J, Huch R (Eds.). Clinical Oxygen Pressure Measurement I. Berlin: Blackwell Ueberreuter Wissenschaft, 1990: 256–67.
Boekstegers P, Weidenhöfer S, Kapsner T, Werdan K. Skeletal muscle partial pressure of oxygen in patients with sepsis. Crit Care Med 1994; 22: 640–50.
Schulte am Esch J, Bause HW, Kochs E. Influences of various respiratory and circulatory conditions on muscle tissue oxygenation in critically ill patients.In: Vincent J-L (Ed.). Yearbook of Intensive Care and Emergency Medicine. Berlin: Springer-Verlag, 1992: 303–9.
Breepoel PM, Kreuzer F, Hazevoet M. Interaction of organic phosphates with bovine hemoglobin. I. Oxylabile and phosphate-labile proton binding. Pflügers Arch 1981; 389: 219–25.
Brewer GJ, Eaton JW. Erythrocyte metabolism: interaction with oxygen transport. Science 1971; 171: 1205–11.
Walker WH, Netz M, Gänshirt KH. 49 day storage of erythrocyte concentrates in blood bags with the PAGGS-mannitol solution. (German). Beitraege zur Infusionstherapie 1990; 26: 55–9.
Simon ER. Red cell preservation: further studies with adenine. Blood 1962; 20: 485–91.
Valtis DJ, Kennedy AC. Defective gas-transport function of stored red blood-cells. Lancet 1954; 1: 119–24.
Chapman RG, Rettberg WAH, Dougherty S. Effect of initial storage at room temperature on human red blood cell ATP, 2,3-DPG, and viability. Transfusion 1977; 17: 147–50.
Hamasaki N, Hirota C, Ideguchi H, Ikehara Y. Regeneration of 2,3-bisphosphoglycerate and ATP of stored erythrocytes by phosphoenolpyruvate, a new preservative for blood storage. Prog Clin Biol Res 1981; 55: 577–94.
Beutler E, Meul A, Wood LA. Depletion and regeneration of 2,3-diphosphoglyceric acid in stored red cells. Transfusion 1969; 9: 109–14.
Federspiel WJ. Pulmonary diffusing capacity: implications of two-phase blood flow in capillaries. Respir Physiol 1989; 77: 119–34.
Biro GP, Taichmann GC, Lada B, Keon WJ, Rosen AL, Sehgal LR. Coronary vascular actions of stroma-free hemoglobin preparations. Artif Organs 1988; 12: 40–50.
Vogel WM, Dennis RC, Cassidy G, Apstein CS, Valeri CR. Coronary constrictor effect of stroma-free hemoglobin solutions. Am J Physiol 1986; 251: H413–20.
Gilroy D, Shaw C, Parry E, Olding-Smee W. Detection of a vasoconstrictor factor in stroma-free haemoglobin solutions. J Trauma 1988; 28: 1312–6.
Hodakowski GT, Page RD, Harringer W, et al. Ultra-pure polymerized bovine hemoglobin blood substitute: effects on the coronary circulation. Biomaterials Artificial Cells, & Immobilization Biotechnology 1992; 20: 669–72.
Kreuger A, Akerblom O. Adenine consumption in stored citrate-phosphate-dextrose-adenine blood. Vox Sang 1980; 38: 156–60.
Åkerblom O, Kreuger A. Studies on citrate-phosphatedextrose (CPD) blood supplemented with adenine. Vox Sang 1975; 29: 90–5.
Sputtek A, Singbartl G, Langer R, Schleinzer W, Henrich HA, Khnl P. Cryopreservation of red blood cells with the non-penetrating cryoprotectant hydroxyethyl starch. Cryo-Letters 1995; 16: 283–8.
Brückner UB, Messmer K. Organ blood supply and oxygénation during limited isovolemic hemodilution with 6% HES 200/0.62 and 6% dextran-70. (German). Anaesthesist 1991; 40: 434–40.
Cole DJ, Schell RM, Drummond JC, Reynolds L. Focal cerebral ischemia in rats. Effect of hypervolemic hemodilution with diaspirin cross-linked hemoglobin versus albumin on brain injury and edema. Anesthesiology 1993; 78: 335–42.
Gonzalez P, Hackney AC, Jacobs EE, Hughes GS, Orringer EP. A phase I/II study of polymerized bovine hemoglobin (PBH) in adult patients with sickle cell disease (SCD) not in crisis. Blood 1994; 84: 413a.
Hughes G Jr, Jacobs E Jr, Yancey B, et al. Hemoglobinbased oxygen carrier preserves oxygen delivery and exercise capacity in humans. Crit Care Med 1995; 23: A86.
Hughes G Jr, Jacobs E Jr, Antal E, et al. Pharmacokinetics of a novel hemoglobin-based oxygen carrier in humans. Crit Care Med 1995; 23: A257.
Monk T, Goodnough L, Hughes G Jr, Jacobs E Jr. Evaluation of the safety and tolerance of hemoglobinbased oxygen carrier-201. Anesthesiology 1995; 83: A285.
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Standl, T., Horn, P., Wilhelm, S. et al. Bovine haemoglobin is more potent than autologous red blood cells in restoring muscular tissue oxygenation after profound isovolaemic haemodilution in dogs. Can J Anesth 43, 714–723 (1996). https://doi.org/10.1007/BF03017957
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DOI: https://doi.org/10.1007/BF03017957