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J Thorac Cardiovasc Surg 1996;111:29-35
© 1996 Mosby, Inc.

CARDIOPULMONARY BYPASS,
MYOCARDIAL MANAGEMENT, AND SUPPORT TECHNIQUES

ATTENUATION OF CARDIOPULMONARY BYPASS–DERIVED INFLAMMATORY REACTIONS REDUCES MYOCARDIAL REPERFUSION INJURY IN CARDIAC OPERATIONS

Yoshiki Sawa, MD, Yasuhisa Shimazaki, MD, Keishi Kadoba, MD, Takashi Masai, MD, Hirotsugu Fukuda, MD, Toshihiro Ohata, MD, Kazuhiro Taniguchi, MD, Hikaru Matsuda, MD


Osaka, Japan

From the First Department of Surgery, Osaka University Medical School, Osaka, Japan.

Received for publication Dec. 22, 1994. Accepted for publication March 17, 1995. Address for reprints: Hikaru Matsuda, MD, First Department of Surgery, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka 565, Japan.

Abstract

In cardiac operations endopeptidase (protease) inhibitor may be beneficial in reducing myocardial injury when administered in the cardiopulmonary bypass prime. Nafamostat mesilate was evaluated in 20 patients who underwent coronary artery bypass grafting. The patients were divided into a control group (n = 10) and a nafamostat group (n = 10). Nafamostat (2 mg/kg per hour) was continuously given during cardiopulmonary bypass in the nafamostat group. The age, number of grafts, cardiopulmonary bypass time, and aortic crossclamp time were similar between groups. In the control group, neither tumor necrosis factor-{alpha}nor interleukin-1 levels showed any significant change during cardiopulmonary bypass, whereas interleukin-6 and interleukin-8 levels, percent expression of adhesion molecule (CD18) on neutrophils, and CH50 assay results increased significantly during cardiopulmonary bypass. As compared with the control group, the nafamostat group showed significantly lower levels of interleukin-6 (123 ± 57 versus 40 ± 22 pg/ml, respectively) and interleukin-8 (96 ± 13 versus 66 ± 14 pg/ml, respectively). The nafamostat group showed a significantly lower difference of CH50 assay results and malondialdehyde levels between coronary sinus blood and arterial blood and peak values of creatine kinase MB (43 ± 12 IU/L versus 19 ± 6 IU/L) during the postoperative course compared with findings in the control group. These results demonstrated that inflammatory reactions induced by cardiopulmonary bypass had adverse effects on myocardial recovery after aortic crossclamping and that nafamostat mesilate given during cardiopulmonary bypass appeared to reduce myocardial reperfusion injury by attenuating such inflammatory reactions. Attenuation of inflammatory reactions of cardiopulmonary bypass should be considered in the strategy of myocardial protection. (J THORAC CARDIOVASC SURG 1996;111:29-35)

Although the safety of cardiopulmonary bypass (CPB) has been elevated remarkably in recent years, prevention of postreperfusion syndrome including injuries to various organs after CPB has not yet been adequately achieved.Go Go 1-3 Recent studies suggested that complement is activated by CPB for cardiac operationsGo Go 4,5 and that neutrophils and inflammatory cytokines, which are closely involved in inflammation, can injure lungs and other organs during the course of CPB.Go Go 4-8 It is therefore plausible to imagine that inflammatory cytokines, in addition to CPB-activated complement and neutrophils, are closely related to the onset of reperfusion injury in myocardium.Go Go 9-11

We previously reported that nafamostat mesilate (FUT-175), which is a serine endopeptidase (protease) inhibitor, suppressed the activation of complement and of the clotting and fibrinolytic system during CPB.Go 7 The present study was undertaken to analyze changes in inflammatory cytokines, as well as complement consumption and neutrophil activation, during cardiac operations and to examine whether the antiinflammatory action of FUT-175 would suppress changes in these cytokines and reduce myocardial injury.

Patients and methods

The study subjects were 20 patients who underwent coronary artery bypass grafting at the Osaka University Hospital in 1993. All subjects gave informed consent, and the study was performed according to the guidelines of our internal review board. The subjects were blindly divided at random into two groups: group C (10 control patients who did not receive FUT-175 treatment) and group F (10 patients given FUT-175). Neither the surgeon nor the patient was informed as to the group to which the patient belonged. For group F patients, administration of FUT-175 was continued during CPB at a dosage of 2 mg/kg per hour. In terms of patient age, number of grafts, during of CPB, and duration of aortic crossclamping, there was no significant difference between the two groups Go(Table I). Arterial blood was sampled at five points (1 hour and 2 hours after the start of CPB and immediately, and 2 and 12 hours after the end of CPB).


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  		Table I. Comparison of the preoperative basic data between control and FUT-175 groups
 
The basic method of myocardial protection was the use of cold potassium crystalloid cardioplegic solution as described before.Go 12 The initial dose of cardioplegic solution was 10 ml/kg body weight, and a further half dose was infused every 30 minutes. Myocardial temperature was monitored at the ventricular septum and maintained at less than 15º C with topical cooling. The blood temperature of CPB was maintained at 28º C, and a membrane oxygenator (Capiox-E, Terumo Co., Tokyo, Japan) primed without blood was used in all cases.

Tumor necrosis factor-{alpha} (TNF-{alpha}), interleukin-1ß (IL-1ß), IL-6, and IL-8 levels in the blood were measured by an enzyme-linked immunosorbent assay method using commercial kits (TNF-{alpha} and IL-1ß kits, Otsuka Pharmaceutical Co., Tokushima, Japan; IL-6 and IL-8 kits, Toray Fujibionics, Tokyo, Japan). The prevalence of adhesion molecule (CD18) expression on neutrophils was measured by flow cytometry. For this measurement, fluorescein isothiocyanate–labeled monoclonal antibody anti-CD18 (MA-7953, Becton Dickinson, San Jose, Calif.) and flow cytometry (FACScan, Becton Dickinson) were used. Before aortic crossclamping and 10 minutes after the release of the aortic crossclamp, CH50 assay levels by the one-point method (Kyowa Pharmaceutical Co., Tokyo, Japan) and the level of the indicator of lipid peroxidation, malondialdehyde, by the fluorescence methods (Wako Pharmaceutical, Osaka, Japan) were measured in coronary sinus and arterial blood. The value of each of these two parameters in arterial blood was subtracted from that in coronary sinus blood to yield the amount of total complement activity and malondialdehyde originating from the myocardium.Go 12 Furthermore, creatine kinase (CK) MB levels were measured. The maximum value of CK-MB level, recorded during the first 24 hours after operation, was compared between the two groups.Go 13

As for the clinical data, the rate of spontaneous defibrillation at the release of the aortic crossclamp and the maximum dose of dopamine required at weaning from CPB (expressed in micrograms per kilogram per minute) to maintain the arterial pressure higher than 80 mm Hg were compared; no other drugs including catecholamine and vasodilators were used during these periods. Moreover, the percentage of ST segment elevation (more than 1 mm) during the postoperative period and the duration of catecholamine support in the postoperative period were compared for the two groups.

Results were expressed as mean plus or minus the standard deviation. For comparison of the significance of the difference between the two groups or of the data with the baseline data, a two-tailed unpaired t test was used. For comparison of multiple data within the group, the Newman-Keuls test was used. For the percentage rate of spontaneous defibrillation and ST segment elevation, the {chi}2 test was used. A value of p < 0.05 was regarded as statistically significant.

Results

Clinical results
All patients tolerated the surgical procedures and survived without significant complication related to this study.

Inflammation caused by CPB
When the course of CH50 assay results and CD18 expression on neutrophils in group C was followed, starting during CPB and ending 12 hours after completion of CPB, CD18 expression increased significantly and CH50 assay results decreased significantly during CPB. Both parameters had returned to baseline levels by 12 hours after the end of CPB (Fig. 1).



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  		Fig. 1. Course of CH50 assay results and CD18 expression on neutrophils during CPB.

 
When the course of IL-6 and IL-8 levels in group C was followed for the same period, both increased during CPB and had returned to baseline levels by 12 hours after CPB (Fig. 2). IL-1ß and TNF-{alpha} levels in group C showed no significant changes during CPB (Fig. 3).



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  		Fig. 2. Course of IL-6 and IL-8 levels during CPB.

 


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  		Fig. 3. Course of IL-1ß and TNF-{alpha} levels during CPB.

 
Suppression of CPB-caused inflammation by FUT-175
When the time course of IL-6 and IL-8 levels was compared between group C and group F, both parameters, measured 2 hours after the start of CPB, were significantly lower in group F (IL-6, 41 ± 14 pg/ml; IL-8, 18 ± 13 pg/ml) than in group C (IL-6, 79 ± 16 pg/ml; IL-8, 49 ± 21 pg/ml) (Fig. 4).



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  		Fig. 4. Comparison of IL-6 and IL-8 levels between groups C and F.

 
Myocardial protection by FUT-175
The differences in both CH50 assay finding and levels of malondialdehyde between coronary venous blood and arterial blood, as measured after the release of aortic occlusion, were significantly lower in group F than in group C (F versus C: CH50, 0.4 ± 0.1 IU/ml versus 2.2 ± 0.1 IU/ml; malondialdehyde, 0.8 ± 0.2 nmol/ml versus 1.4 ± 0.2 nmol/ml) (Fig. 5).



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  		Fig. 5. Comparison of differences in CH50 assay results and malondialdehyde (MDA) levels between coronary venous blood and arterial blood between groups F and C.

 
The maximal CK-MB level within the first 24 hours after operation was significantly lower in group F (19 ± 6 IU/L) than in group C (43 ± 12 IU/L) (Fig. 6).



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  		Fig. 6. Comparison of maximal CK-MB levels (max CPK-MB) within first 24 hours after operation between groups F and C.

 
Other clinical results
Go(Table II). Group F had a significantly higher percentage of patients with spontaneous defibrillation after the release of the aortic crossclamp than group C. However, there was no significant difference in maximum dosage of dopamine required at weaning from CPB, percentage of ST segment elevation, and duration of catecholamine support in the postoperative period between the two groups.


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  		Table II. Comparison of the results in clinical data between control and FUT-175 groups
 
Discussion

The results of the present study demonstrated that IL-6 and IL-8 levels increased during CPB and decreased after the end of CPB, that CH50 assay results decreased and CD18 expression increased throughout CPB until CPB was completed, and that FUT-175 treatment suppressed the CPB-stimulated production of these cytokines, myocardial complement consumption, and MDA production resulting in a decrease of CK-MB loss from the myocardium and an increase in rate of spontaneous defibrillation after release of the aortic crossclamp. These results indicate that CPB causes activation of complement and neutrophils and enhances cytokine production and that endopeptidase (protease) inhibitors reduce CPB-caused injury to the myocardium by suppressing these changes. These inflammatory reactions during CPB coincided with those described in previous reports.Go Go 14-19

Gillinov and associatesGo 15 reported that neutrophils are more likely to be activated and express CD18 during CPB because of some potent chemotactic factors such as C5a, platelet activating factor, and leukotriene B4. However, no clinical reports of CPB-associated neutrophil activation have been reported. In the present study, the increase in CD18 expression during CPB was parallel to the change observed in CH50 assay results. This finding is identical with the finding reported by Gillinov and associates.Go 15

Various reports have been published concerning CPB-caused enhancement of inflammatory cytokine production. Kawamura and associatesGo 16 and Steinberg and associatesGo 17 reported that IL-6 levels increased during CPB and deceased after the end of CPB. Similar changes in levels of IL-8 have also been reported by Kawamura,Go 16 Finn,Go 18 Laouar,Go 19 and their associates. These findings indicate that these inflammatory cytokines involved in the acute-phase reactions serve as promoters of CPB-associated inflammation.

The relationship of the increase of these cytokines to CPB-associated injury of organs in the clinical situation had only been reported by Laouar and co-workers,Go 19 who reported that even when IL-8 levels were reduced by methylprednisolone, neutrophil infiltration into lungs could not be suppressed. In the present study, FUT-175 reduced the level of inflammatory cytokines with attenuation of reperfusion injury in myocardium. These results endorse our hypothesis that these cytokines may be related to reperfusion injury in myocardium. However, these clinical investigations have limitation and further experimental studies appear to be needed to obtain direct evidence of the accuracy of our hypothesis.

Regarding the mechanism by which FUT-175 suppresses cytokine production, it has been reported that FUT-175 inhibits the endopeptidase (protease) involved in the release of cytokines from cytokine-producing cells.Go 20 It is also known that FUT-175 directly suppresses the activity of complementGo 21 and neutrophils.Go 22 On the other hand, FUT-175 protected reperfusion injury in myocardium in an experiment that used isolated hearts perfused with crystalloid solution,Go 23 which suggests that it also inhibits proteases of a lysosome origin.Go 24 In the present study, FUT-175 was found to suppress inflammatory reactions that involve complement consumption and decreased lipid peroxydation. It is plausible to imagine that suppression of these inflammatory reactions resulted in decreased complement consumption and decreased oxygen free radical production by neutrophils in the heart after reperfusion, thus leading to a reduction of myocardial injury.

Menaschè and colleaguesGo 25 reported that IL-1ß and TNF-{alpha} production is induced by CPB and that their levels reach a peak 2 hours after CPB. However, Butler,Go 26 Steinberg,Go 17 Finn,Go 18 and their associates reported that neither IL-1ß nor TNF-{alpha} levels showed any significant increase during CPB, which is similar to the results we obtained. This discrepancy may be associated with some factors such as the magnitude of surgical stress and the length of CPB or the difference in the assay method. It is also possible that IL-1ß and TNF-{alpha} are produced in the late phase of the reaction, unlike IL-6 and IL-8, which increase during the acute phase, so that the production mechanism and origin of IL-1ß and TNF-{alpha} may differ from those of IL-6 and IL-8.

In summary, the present study suggests that (1) neutrophil activation and increases in complement consumption and levels of IL-6 and IL-8 were observed during CPB, (2) myocardial malondialdehyde production and complement consumption increased after reperfusion after CPB, and (3) the increase in these inflammatory reactions in CPB and the leak of CK-MB from the myocardium were reduced when a protease inhibitor was administered during CPB. These results allow us to conclude that because inflammatory cytokine production is enhanced during CPB and causes aggravation of myocardial injury, suppression of inflammatory cytokine production is important in reducing reperfusion injury in myocardium.

References

  1. Bear DM, Osborn JJ. The postperfusion pulmonary congestion syndrome. Am J Clin Pathol 1960;34:442-5.
  2. Osborn JJ, Popper RW, Kerth WJ, Gerbode F. Respiratory insufficiency following open heart surgery. Ann Surg 1962;156:638-47.[Medline]
  3. Miller DR, Kuenzig MC. Pulmonary changes following normothermic and profound hypothermic perfusion in dog. J THORAC CARDIOVASC SURG1968;56:717-31.
  4. 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.[Abstract]
  5. Hammerschmidt DE, Stroneck DF, Bowers TK. Complement activation and neutropenia occurring during cardiopulmonary bypass. J THORAC CARDIOVASC SURG1981;81:370-7.
  6. Kirklin JK, Westerby S, Blackstone EH, Kirklin JW, Chenoweth DE, Pacifico AD. Complement and the damaging effects of cardiopulmonary bypass. J THORAC CARDIOVASC SURG1983;86:845-57.
  7. Miyamoto Y, Hirose H, Matsuda H. Analysis of complement activation profile during cardiopulmonary bypass and its inhibition by FUT-175. Trans Am Soc Artif Intern Organs 1985;31:508-11.[Medline]
  8. Howard RJ, Crain C, Franzini DA, Hood CI, Hugli TE. Effects of cardiopulmonary bypass on pulmonary leukostasis and complement activation. Arch Surg 1988;123:1496-501.[Abstract/Free Full Text]
  9. Engler RL, Schmidt-Schonbein GW, Parelec RS. Leukocyte capillary plugging in myocardial ischemia and reperfusion in the dog. Am J Pathol 1983;111:98-111.[Abstract]
  10. Crawford MH, Grover FL, Kolb WP, et al. Complement and neutrophil activation in the pathogenesis of ischemic myocardial injury. Circulation 1988;78:1449-58.[Abstract/Free Full Text]
  11. Kilgore KS, Friedrichs GS, Homeister JW, Lucchesi BR. The complement system in myocardial ischemia/reperfusion injury. Cardiovasc Res 1994;28:437-44.[Free Full Text]
  12. Sawa Y, Matsuda H, Shimazaki Y, et al. Evaluation of leukocyte-depleted terminal blood cardioplegia in patients undergoing elective and emergency coronary artery bypass grafting. J THORAC CARDIOVASC SURG 1994;108:1125-31.[Abstract/Free Full Text]
  13. Matsuda H, Maeda S, Hirose H, et al. Optimum dose of cold potassium cardioplegia for patients with chronic aortic valve disease: determination by left ventricular mass. Ann Thorac Surg 1986;41:22-6.[Abstract]
  14. Kuratani T, Matsuda H, Sawa Y, Kaneko M, Nakano S, Kawashima Y. Experimental study in a rabbit model of ischemia-reperfusion lung injury during cardiopulmonary bypass. J THORAC CARDIOVASC SURG 1988;103:564-8.[Abstract]
  15. Gillinov AM, Redmond JM, Winkelstein JA, et al. Complement and neutrophil activation during cardiopulmonary bypass: a study in the complement deficient dog. Ann Thorac Surg 1994;57:345-52.[Abstract]
  16. Kawamura T, Wakusawa R, Okada K, Inada S. Evaluation of cytokines during open heart surgery with cardiopulmonary bypass: participation of interleukin 8 and 6 in reperfusion injury. Can J Anaesth 1993;40:1016-21.[Medline]
  17. Steinberg JB, Kapelanski DP, Olson J, Weiler JM. Cytokine and complement levels in patients undergoing cardiopulmonary bypass. J THORAC CARDIOVASC SURG 1993;106:1008-16.[Abstract]
  18. Finn A, Naik S, Klein N, Levinsky RJ, Strobel S, Elliott M. Interleukin-8 release and neutrophil degranulation after pediatric cardiopulmonary bypass. J THORAC CARDIOVASC SURG 1993;105:234-41.[Abstract]
  19. Laouar A, Villiers C, Sanceau J, et al. Inactivation of interleukin-6 in vitro by monoblastic U937 cell plasma membranes involves both protease and peptidyl-transferase activities. Eur J Biochem 1993;215:825-31.[Medline]
  20. Issekutz AC, Roland DM, Patrick RA. The effect of FUT-175 on C3a, C4a and C5a generation in vitro and inflammation reactions in vivo. Int J Immunopharmacol 1990;12:1-9.[Medline]
  21. Inagi R, Miyata T, Maeda K, Sugiyama S, Miyama A, Nakashima I. FUT-175 as a potent inhibitor of C5/C3 convertase activity for production of C5a and C3a. Immunol Lett 1991;27:49-52.[Medline]
  22. Kato H, Inoue M, Yamamura Y, et al. Mechanism of polymorphonuclear leukocytes accumulation examined using inhibitors of complement and arachidonic acid cascade in rats treated with OK-432. Nat Immun Cell Growth Regul 1989;8:290-300.[Medline]
  23. Homeister JW, Satoh P, Lucchesi BR. Effects of complement activation in the isolated heart: role of the terminal complement components. Circ Res 1992;71:303-19.[Abstract/Free Full Text]
  24. Decker RS, Wildenthal K. Sequential lysosomal alterations during cardiac ischemia: II–ultrastructural and cytochemical changes. Lab Invest 1978;83:662-73.
  25. Menaschè P, Haydar S, Peynet J, et al. A potential mechanism of vasodilation after warm heart surgery: the temperature-dependent release of cytokines. J THORAC CARDIOVASC SURG 1994;107:293-9.[Abstract/Free Full Text]
  26. Butler J, Chong GL, Baigie RJ, Pillai R, Westaby S, Rocker GM. Cytokine responses to cardiopulmonary bypass with membrane and bubble oxygenation. Ann Thorac Surg 1992;53:833-8.[Abstract]



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