Abstract
Carboxypeptidase N (CPN) is an inactivator of anaphylatoxins and kinins, peptides implicated in the pathogenesis of complications in extracorporeal circulation. To investigate whether the level of CPN is altered during cardiopulmonary bypass (CPB) we studied 15 patients undergoing cardiac surgery utilizing CPB. The concentration of CPN decreased to about 48% of the initial value upon initiation of CPB and remained low throughout the procedure. A similar decrease was observed in the level of alkaline phosphatase, an enzyme that was measured to assess the degree of haemodilution. When the data were normalized for dilution, no difference in the concentration of CPN was observed during CPB. Moreover, no changes in the concentration of CPN were observed when protamine was given to neutralize heparin and none of the 15 patients experienced any side-effects of protamine administration. We conclude that the decrease in CPN during CPB was due primarily to dilution and not to changes in CPN synthesis or catabolism. Protamine administration is not associated with significant changes in the level of CPN in patients who have an asymptomatic reversal of heparin anti-coagulation.
Résumé
La carboxypeptidase N (CPN) est un inactivateur des anaphylatoxines et des kinines impliqué dans la pathogénèse des complications lors d’une circulation extracorporelle. Afin d’investiguer si le niveau de CPN est altéré durant la CEC, on a étudié 15 patients devant subir une chirurgie cardiaque sous CEC. La concentration de CPN a diminué jusqu’à 48% de la valeur initiale au début de la CEC et est demeurée basse durant la procédure. Une diminution similaire fut observée au niveau des phosphatases alcalines, un enzyme qui s’est mesuré afin d’évaluer le degré d’hémodilution. Quand les données furent normalisées pour la dilution, aucune différence dans la concentration de CPM ne fut observée durant la CEC. De plus, aucun changement dans la concentration de CPN ne fut observé quand la protamine fut administrée afin de neutraliser l’héparine et aucun des 15 patients n ’a démontré des effets secondaires lors de l’administration de la protamine. On conclut que la diminution du CPN lors de la CEC était due principalement à la dilution et non aux changements de la synthèse de la CPN ou son catabolisme. L’administration de protamine n’est pas associée aux changements significatifs dans le niveau de CPN aux patients chez qui on a renversé l’anticoagulation due à l’héparine sans incident.
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References
Erdos EG, Sloane EM. An enzyme in human blood plasma that inactivates bradykinin and kallidins. Biochem Pharmacol 1962; 11: 585–92.
Erdos EG. Kininases.In: Erdos EG (Ed.). Bradykinin, Kallidin and Kallikrein. Handbook of Experimental Pharmacology, Vol. 25 (Suppl). Heidelberg: Springer-Verlag, 1979; 428–87.
Bokisch VA, Muller-Eberhard HJ. Anaphylatoxin inactivator of human plasma: its isolation and characterization as a carboxypeptidase. J Clin Invest 1970; 49: 2427–36.
Mathews KP, Curd JG, Hugli TE. Decreased synthesis of serum carboxypeptidase N (SCPN) in familial SCPN deficiency. J Clin Immunol 1986; 6: 87–91.
Kirkiin JK, Westaby S, Blackstone EH et al. Complement and the damaging effects of cardiopulmonary bypass. J Thorac Cardiovasc Surg 1983; 86: 845–57.
Colman RW. Humoral mediators of catastrophic reactions associated with protamine neutralization. Anesthesiology 1987; 66: 595–6.
Knudsen F, Andersen LW. Immunological aspects of cardiopulmonary bypass. Journal of Cardiothoracic Anesthesia 1990; 4: 245–58.
Tan F, Jackman H, Skidgel RA, Zsigmond EK, Erdos EG. Protamine inhibits plasma carboxypeptidase N, the inactivator of anaphylatoxins and kinins. Anesthesiology 1989; 70: 267–75.
Lock R, Hessel EA. Probable reversal of protamine reactions by heparin administration. Journal of Cardiothoracic Anesthesia 1990; 4: 604–8.
Skidgel RA, Erdos, EG. Carboxypeptidase N (arginine carboxypeptidase).In: Bergmeyer (Ed.). Methods in Enzymatic Analysis. Vol V Enzymes 3: Peptidases, proteinases and their inhibitors. Weinheim: Verlag Chemie Gmblt., 1984; 60–72.
Moss DW, Henderson AR, Kachmar JF. Enzymes.In: Tietz NW (Ed.). Textbook of Clinical Chemistry. Philadelphia: WB Saunders 1986; 609–774.
McPherson RA. Specific Proteins.In: Henry JB (Ed.). Todd, Sanford, Davidson. Clinical Diagnosis and Management by Laboratory Methods. Philadelphia: WB Saunders 1984; 204–16.
Neter J, Wasserman W. Applied Linear Statistical Models. Homewood, Ill., R.D. Irwin, Inc., 1974.
Byrick RJ, Noble WH. Postperfusion lung syndrome. Comparison of Travenol bubble and membrane oxygenators. J Thorac Cardiovasc Surg 1978; 76: 685–93.
Ratliff NB, Young WB, Hackel DB, Mikat E, Wilson JW. Pulmonary injury secondary to extracorporeal circulation. An ultrastructural study. J Thorac Cardiovasc Surg 1973; 65: 425–32.
Gralnick HR, Fischer RD. The hemostatic response to open-heart operations. J Thorac Cardiovasc Surg 1971; 13: 361–8.
Hennessy VL Jr,Hicks RE, Niewiarowski S, Edmunds LH Jr,Colman RW. Function of human platelets during extracorporeal circulation. Am J Physiol 1977; 232: H622-H628.
Harker LA, Malpass TW, Branson HE, Hessel EA II, Slichter SJ. Mechanisms of abnormal bleeding in patients undergoing cardiopulmonary bypass: acquired transient platelet dysfunction associated with selected alpha granule release. Blood 1980; 56: 824–34
Lowenstein E, Johnston EW, Lappas DG et al. Catastrophic pulmonary vasoconstriction associated with protamine reversal of heparin. Anesthesiology 1983; 59: 470–3.
Cavarocchi NC, Schaff HV, Orszulak TA, Homburger HA, Schnell WA Jr,Pluth JR. Evidence for complement activation by protamine-heparin interaction after cardiopulmonary bypass. Surgery 1985; 98: 525–31.
Westaby S, Turner MW, Stark J. Complement activation and anaphylactoid response to protamine in a child after cardiopulmonary bypass. Br Heart J 1985; 53: 574–6.
Chenoweth DE, Cooper SW, Hugli TE, Stewart RW, Blackstone EH, Kirklin JW. Complement activation during cardiopulmonary bypass. N. Engl J Med 1981; 304: 497–503.
Westaby S. Complement and the damaging effects of cardiopulmonary bypass. Thorax 1983; 38: 321–5.
Rent R, Ertel N, Eisenstein R, Gewurz H. Complement activation by interaction of polyanions and polycations. I. Heparin-protamine induced consumption of complement. J Immunol 1975; 114: 120–4.
Hugli TE. Complement anaphylatoxins as plasma mediators, spasmogens and chemotaxins.In: Bing DH (Ed.). The Chemistry and Physiology of Human Plasma Proteins. New York: Pergamon, 1979; 255–80.
Hugli TE The structural basis for anaphylatoxin and chemotactic functions of C3a, C4a, and C5a.In: Atassi MZ (Ed.). Critical Reviews in Immunology. Boca Raton, FL, Chemical Rubber, 1981; 321–66.
Morel DR, Zapol WM, Thomas SJ et al. C5a and thromboxane generation associated with pulmonary vaso- and broncho-constriction during protamine reversal of heparin. Anesthesiology 1987; 66: 597–604.
Johnson AR. Effects of kinins on organ systems.In: Erdos EG (Ed.). Bradykinin, Kallidin and Kallikrein. Handbook of Experimental Pharmacology, Vol. 25 (suppl). Heidelberg: Springer-Verlag, 1979; 357–99.
Skidgel RA. Basic carboxypeptidases: regulators of peptide hormone activity. Trends Pharmacol Sci 1988; 9: 299–304.
Erdos EG. Conversion of angiotensin I to angiotensin II. Am J Med 1976; 60: 749–58.
Gorin AB, Liebler J. Changes in serum angiotensin-converting enzyme during cardiopulmonary bypass in humans. Am Rev Respir Dis 1986; 134: 79–84.
Kreutzer DL, McCormick JR, Despins A et al.: Characterization of the anaphylatoxin inactivator and chemotactic factor inactivator activities during cardiopulmonary bypass. J Exp Pathol 1984; 1: 183–7.
Horrow JC. Protamine: a necessary evil.In: Ellison N, Jobes DR (Eds.). Effective Hemostasis in Cardiac Surgery. Philadelphia: WB Saunders, Co. 1988; 15–39.
Moorthy SS, Pond W, Rowland RG. Severe circulatory shock following protamine (an anaphylactic reaction). Anesth Analg 1980; 59: 77–8.
Chung F, Miles J. Cardiac arrest following protamine administration. Can Anaesth Soc J 1984; 31: 314–8.
Stewart WJ, McSweeney SM, Kellett MA et al. Increased risk of severe reactions in NPH insulin-dependent diabetics undergoing cardiac catheterization. Circulation 1984; 70: 788–92.
Weiss ME, Nyhan D, Peng Z et al. Association of protamine IgE and IgG antibodies with life-threatening reactions to intravenous protamine. N Engl J Med 1989; 320: 886–92.
Levy JH, Schwieger IM, Zaidan JR, Faraj BA, Weintraub WS. Evaluation of patients at risk for protamine reactions. J Thorac Cardiovasc Surg 1989; 98: 200–4.
Lowenstein E, Lynch K, Robinson DR et al. Incidence, severity and causation of adverse cardiopulmonary response to protamine reversal of heparin anticoagulation in man. Am Rev Respir Dis 1988; 137: A245.
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These studies were supported in part by National Institutes of Health grants DK 41431 and HL 36473.
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Rabito, S.F., Anders, R., Soden, W. et al. Carboxypeptidase N concentration during cardiopulmonary bypass in humans. Can J Anaesth 39, 54–59 (1992). https://doi.org/10.1007/BF03008673
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DOI: https://doi.org/10.1007/BF03008673