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Eur J Cardiothorac Surg 1999;16:337-341
© 1999 Elsevier Science NL

Cardiac troponin T release during coronary surgery using intermittent cross-clamp with fibrillation, on-pump and off-pump beating heart

Michal Krejca, Jacek Skiba, Przemyslaw Szmagala, Tadeusz Gburek, Andrzej Bochenek

1st Cardiac Surgery Department, Silesian Heart Center, ul. Ziolowa 47, 40-635 Katowice, Poland

Corresponding author. Tel.: +48-32-2527041, ext. 1640


    Abstract
 Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 References
 
Objective: Troponin T is a unique marker which might be particularly useful in assessing myocardial cell damage in patients undergoing cardiac surgery. The aim of the study was a comparison between intra-operative release of troponin T (TnT) during three different myocardial protection strategies. Methods: Thirty-eight PTS undergoing myocardial revascularization were randomised into 3 groups in whom procedure was performed with intermittent cross-clamp (Group I; n=13), beating-heart on pump without aortic cross-clamp (Group II; n=12), beating-heart without use of extracorporeal circulation (Group III; n=13). Serial venous blood samples were collected for TnT measurement prior surgery, 1, 4, 12, 24, 48, 72 h after the procedure. Haemodynamic measurements were made using a thermodilution PA catheter. Results: The groups were similar with respect to age, sex, preoperative LV function, number of grafts, potential risk factors. There were no hospital deaths and no myocardial infarction (MI) in three groups, postoperative haemodynamic measurements showed no significant differences. TnT serum levels were significantly higher in group I when compared to groups II and III. TnT levels were significantly lower in group III when compared to group II following 48-h post-operation. Conclusions: Coronary bypass grafting without aortic cross-clamping and without CPB offers superior myocardial protection.

Key Words: Tropinin T • Coronary surgery • Cross-clamp • On-pump • Off-pump • Beating heart


    1. Introduction
 Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 References
 
The diagnosis of myocardial infarction during the peri- and postoperative period is very difficult. There is no chest pain under general anesthesia and predominantly subendocardial ischemia is diagnosed by continuous analysis of the ST segment only. Assays of serum enzymes: aspartate aminotransferase (AST), lactate dehydrogenase (LD), creatine kinase (CK) and isoenzyme MB are widely performed in the early phase of acute myocardial infarction [1]. An ideal marker of myocardial injury would be a cardiac specific biological marker in serum very early after myocardial infarction or ischemic damage. The contractile and regulatory proteins of the myocardium provide such a useful diagnostic tool [2]. Unlike CK-MB and myoglobin, skeletal muscle isoforms of troponin are structurally different and do not cross-react with antibodies raised against cardiac isotypes [3]. The TnT is a sensitive marker and it presents a diagnostic interest in unstable angina, cardiac surgery and reperfusion. This protein allow to affirm its very good cardiac specificity, making of it a first choice marker of myocardial lysis, particularly in the postoperative follow-up [4].

There are many strategies for intraoperative protection of the heart. Current cardioplegic techniques do not consistently avoid myocardial ischemic damage in patients undergoing coronary artery bypass grafting. Potassium cardioplegic arrest and myocardial cooling are common adjuncts for myocardial protection during cardiac operations [5].

Crystalloid vs. blood cardioplegia, warm vs. cold blood cardioplegia, antegrade vs. retrograde delivery and intermittent vs. continuous perfusion are the main methods currently used. In hearts with relatively normal preoperative ventricular performance, hypothermic potassium cardioplegia provides adequate protection during aortic cross-clamping, even when cardioplegic arrest is prolonged. Complete recovery of ventricular performance and metabolism even in the arrested hypothermic heart is not always achieved because anaerobic metabolism is not completely adequate to satisfy metabolic demand during ischemia [69]. Alternatively, revascularization without cardiopulmonary bypass is not always technically feasible.

Currently noncardioplegic technique is our initial consideration for all patients who require coronary arteries bypass grafting (CABG) regardless of the presence of severe left ventricular dysfunction, ventricular aneurysm, advanced age, or the need for an emergency operation.

The purpose of this study, therefore, was to investigate the role of cardiac TnT in the diagnosis of minor myocardial tissue damage in noncardioplegic CABG surgery. Besides our routine myocardial protection method which is an intermittent aortic cross-clamp with ventricular fibrillation we took into consideration a group of patients operated on beating heart. This group of patients was operated with conventional sternotomy as a pilot group to minimally invasive CABG with minithoracotomy which is routinely being carried out at our department nowadays.


    2. Materials and methods
 Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 References
 
Thirty-eight male patients suffered from one or two vessel coronary heart disease undergoing elective coronary artery bypass grafting with left ventricular ejection fraction greater than 40% were consecutively enrolled in this study. The patients with critical lesions in circumflex artery were excluded from the study. All patients were on standard antianginal treatment and they all discontinued aspirin 7 days prior to surgery. After approval by the local ethic committee and written informed consent the patients were randomly assigned to one of three groups.

In group I the myocardial protection consisted of intermittent aortic cross-clamp technique with ventricular fibrillation while distal anastomoses were completed. Proximal anastomosis was performed on beating heart with an aortic side clamp. All operations were performed using cardiopulmonary bypass with ascending aorta cannulation and two-stage venous cannula and moderate hypothermia 32°C. Systemic rewarming was started during the completion of the last distal anastomosis.

In group II no special myocardial protection technique was used. The beating heart without aortic cross-clamp was unloaded on conventional normothermic cardiopulmonary bypass. The left ventricle was consistently vented through the right superior pulmonary vein. The target vessel was occluded proximally and distally using a 4-0 Prolene suture passed beneath the artery. The grafts were anastomosed distally to the target coronary vessel and than to the aorta with the aid of a side clamp.

In group III no cardiopulmonary bypass was used and after median sternotomy, anastomoses were completed on beating heart with the same surgical strategy like in group II.

All distal anastomoses were performed with running sutures 7-0 distally and 6-0 proximally (Prolene, Ethicon).

A standard anaesthesiological regimen was applied. Anaesthesia was induced with Fentanyl 0.005–0.01 mg/kg b.w. and Pancuronium 0.1 mg/kg body wt. and maintained after intubation with Isoflurane with an inspiratory concentration of 0.5–1.0% as required.

In all patients perioperative haemodynamic measurements: heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), pulmonary wedge pressure (PWP), cardiac index (CI), systemic vascular resistance (SVR), left ventricle stroke work index (LVSWI) with use of a Swan-Ganz catheter were made.

Serial venous blood samples were drawn just before sternotomy, 1, 4, 12, 24, 48 and 72 h after the end of the ischemic time. Blood samples for the measurement of TnT were collected in tubes with no preservatives and were centrifuged immediately for 5 min. The plasmas were aliquoted into tubes and subsequently frozen and stored at -20°C until determination. TnT concentration was measured in plasma by an enzyme immunoassay (Boehringer, Mannheim, Germany) which is highly specific for TnT and was developed by Katus et al. [3]. The cross-reactivity of the antibody combination of the assay with purified skeletal TnT is below 1% [10].

Data was analysed with Statistica PL ’97 statistical program (Stat Soft, Tulusa, USA). Student's t-test, Mann–Whitney test, {chi}2 and Fisher's exact test were used when appropriate. The two-factor ANOVA followed by the Duncans multiple range test was carried out to compare mean serum Troponin levels in the three groups. Results were expressed as mean±standard deviation, P-values less than 0.05 were considered significant.


    3. Results
 Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 References
 
The study groups were uniform as far as preoperative risk factors were concerned. The characteristics of patients in the ventricular fibrillation (VF), beating heart and off-pump groups are shown in Table 1. Each patient received an average of 1.8 grafts (range 1–2) with the time of coronary occlusion/aortic cross-clamp time ranging between 6 and 22 min. There were no deaths and no patient had MI by electrocardiographic criteria or TnT release. No patient in any group had need of an intraaortic balloon pump. One patient in the group I had mediastinal bleeding requiring reexploration. Postoperative haemodynamic measurements showed no significant differences between groups.


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Table 1. Preoperative clinical data

 
Fig. 1 shows mean serum concentrations of TnT time courses in three groups (two factor ANOVA shows significant difference (P<0.001). Serum concentrations of TnT increased as early as 1 h after the end of the ischemic time. The peak level of TnT was reached at 48 h after the end of ischemic time in group I and 4 h after the end of ischemic time in group II and III (no cross-clamp groups). TnT levels subsequently declined with time following 4 h peak level in groups II and III, and appeared lower than preoperative values at 72 h in group III (no pump) only. In group I serum TnT level on third postoperative day remained much higher than preoperative level.



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Fig. 1. Time course of cardiac troponin T concentrations in group I (intermittent aortic cross-clamp), group II (beating heart without aortic cross-clamp on CPB), group III (beating heart without CPB).

 
Table 2 shows time changes of mean±SD serum troponin concentrations in three groups. The TnT postischemic serum concentrations in group I were significantly higher in all assessed time periods than those observed in group II and III. Following 48 postischemic h there were significantly higher TnT levels noted in group II when compared to group III in which TnT concentrations started to decline more rapidly.


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Table 2. Comparison between time changes of median±SD serum troponin concentrations in three groups

 

    4. Discussion
 Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 References
 
Ischemic arrest with antegrade cold crystalloid cardioplegia is at present probably the most widely used technique of myocardial protection during coronary artery bypass surgery. In recent years a few studies at least showed no differences in time courses of cardiac troponin concentrations between different cardioplegic protection techniques. These markers did not detect any significant difference in myocardial protection as long as cold crystalloid and cold blood cardioplegia or route of delivery of cardioplegic solution were considered [1113].

There are many potential reasons why cardiac troponins failed to detect differences between different cardioplegic protection strategies. First of all despite the type or the route of cardioplegia being used, the myocardial protection was always adequate thus having its reflection in low troponin concentration levels. On the other hand one should remember that the aortic cross-clamping, the fact of the cardiopulmonary bypass use, reperfusion injury following prolonged cardioplegic ischemia may all influence same myocardium cell damage [14].

This study was designed to compare three different noncardioplegic myocardial protection techniques. Since all operated patients were at low operative risk and intermittent aortic cross-clamping with ventricular fibrillation is our routine cardioprotection method we had no technical problems with anastomoses. The most frequent procedure was LIMA to LAD anastomosis accompanied by saphenous vein graft either to RCA or Dl (intermediate artery in one case only). As the octopus technique was not available for us at that time we elevated the heart using towels and the manoeuvres with pericardial sutures. In our opinion the heart manoeuvres as well as same tissue damage caused by sutures passed beneath targeted artery are reflected in early 4 h postischemic peak of TnT in both group II and group Ill operated on beating heart.

Surprisingly there were significant differences in TnT levels following 48 postoperative h between group II and group III. Does it really mean that cardiopulmonary bypass itself causes same minor myocardial damage which can be detected by TnT serum concentration? We rather think that despite present statistical differences myocardial cell damage was very low in both beating heart groups. It is probably worth considering a beating heart surgery either on or without cardiopulmonary bypass as a routine technique of myocardial protection or rather a technique of no myocardial endanger in low left ventricle ejection fraction/high risk patients [15]. We believe, there is a place for beating-heart coronary arteries operation with sternotomy especially in patients with very poor left ventricular function. When feasible we use this technique in patients with LVEF 20–25% which is now quite common in our practice.

Certainly in such a group of patients the invasiveness of coronary artery operation is determined more by myocardial ischemia during the cross-clamp period and the inflammatory response to cardiopulmonary bypass (CPB) than by the type of incision.

There were significantly higher TnT concentration levels observed in group I (cross-clamp group) in contrast to group II and group III. However, even the highest observed TnT serum concentration level was far below 3.5 ng/ml which is usually considered as a border level of significant myocardial ischemia [3]. The TnT postischemic levels in group I correspond well with data from other authors comparing different types of cardioplegic protection techniques [4,11,12]. This may suggest that aortic cross-clamping itself and even intermittent however total ischemia of myocardium plays the major role in myocardial cell damage.

The time courses of TnT serum concentration level were roughly monophasic in fact in all three groups studied, with only one peak during 4 h after the end of ischemia in group II and group III and one peak during 48 h following end of ischemia in group I. Some kind of biphasic release of TnT observed is probably the result of a rapid loss of the cytoplasmic pool superimposed on prolonged myofibrillar degradation [3]. This may explain why the peak TnT level seems to depend on the aortic cross-clamp use. The detection of TnT could be short-dated and long-dated during the postoperative period, but ends in our study at 72 h post ischemia and make us doubt whether 48 h TnT level in group I represents a real peak level.

We know that this study showing our initial experience with beating heart surgery has many limitations and that it is focused to troponin T release mainly in patients with good LV function and one or two vessel disease only. Much larger study comparing different beating heart operative techniques (Octopus, CTS, thoracoscopic-video) is now being carried out at our department.

In conclusion we believe that measuring troponin T in the early postoperative period is very useful for detecting myocardial injury or evaluating different regimens of myocardial protection. The beating heart technique offers superior myocardial protection and may be an acceptable alternative in selected high-risk patients.


    References
 Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 References
 

  1. Adams J.E., Abendschein D.R., Jaffe A.S. Biochemical markers of myocardial injury: is MB creatine kinase the choice for the 1990s?. Circulation 1993;88:750-763.[Free Full Text]
  2. Ohinan E.M., Armstrong P.W., Christenson R.H., Gragner C.B., Katus H.A., Hamm C.W., O'Hanesian M.A., Wagner G.S., Kleiman N.S., Harrell F.E., Califf R.M., Topol E.J. Cardiac troponin T levels for risk stratification in acute myocardial ischemia. New Engl J Med 1996;335:1333-1341.[Abstract/Free Full Text]
  3. Katus H.A., Schoeppenthau M., Tanzeem A., Bauer H.G., Saggau W., Diederich K.W., Hagl S., Kuebler W. Non-invasive assessment of perioperative myocardial cell damage by circulating cardiac troponin T. Br Heart J 1991;65:259-264.[Abstract/Free Full Text]
  4. Mair P., Mair J., Seibt I., Weiser C., Furtwaengler W., Waldenberger F., Puschendorf B., Balogh D. Cardiac troponin T: a new marker of myocardial tissue damage in bypass surgery. J Cardiothorac Vasc Anesth 1993;7:674-678.[Medline]
  5. Hendry P.J., Masters R.G., Haspect A. Is there a place for cold crystalloid cardioplegia in the 1990s?. Ann Thorac Surg 1994;58:1690-1694.[Abstract]
  6. Loop F.D., Higgins T.L., Panda R., Pearce G., Estafanous F.G. Myocardial protection during cardiac operations: decreased morbidity and lower cost with blood cardioplegia and coronary sinus perfusion. J Thorac Cardiovasc Surg 1992;104:608-618.[Abstract]
  7. Barner H.B., Laks H., Codd J.E. Cold blood as the vehicle for potassium cardioplegia. Ann Thorac Surg 1979;28:509-521.[Abstract]
  8. Follette D., Fey K., Becker H., Foglia R., Steed D., Mulder D.G., Buckberg G.D. Superiority of blood cardioplegia over asanguineous cardioplegia: experimental and clinical study. Chir Forum Exp Klim Forsch 1980:279-283.
  9. Chitwood W.R. Retrograde cardioplegia: current methods. Ann Thorac Surg 1992;53:352-355.[Abstract]
  10. Katus H.A., Looser S., Hallermayer K., Remppis A., Scheffold T., Borgya A., Essig U., Geuss U. Development and in vitro characterization of a new immunoassay of cardiac troponin T. Clin Chem 1992;38:386-393.[Abstract/Free Full Text]
  11. Caputo M., Dihmis W., Birdi I., Reeves B., Suleiman M.S., Angelini G.D., Bryan A.J. Cardiac troponin T and troponin I release during coronary artery surgery using cold crystalloid and cold blood cardioplegia. Eur J Cardiothorac Surg 1997;12:254-260.[Abstract]
  12. Cohen A.S., Hadjinikolaou L., McColl A., Richmond W., Sapsford R.A., Glenville B.E. Lipid peroxidation, antioxidant status and troponin-T following cardiopulmonary bypass: a comparison between intermittent cross-clamp with fibrillation and crystalloid cardioplegia. Eur J Cardiothorac Surg 1997;12:248-253.[Abstract]
  13. Chocron S., Alwan K., Toubin G., Clement F., Kaili D., Taberlet C., Cordier A., Etievent J.P. Crystalloid cardioplegia route of delivery and cardiac troponin I release. Ann Thorac Surg 1996;62:481-485.[Abstract/Free Full Text]
  14. Valen G., Sellei P., Owall A., Eriksson E., Kallner A., Waldum H., Risberg B., Vaage J. Release of markers of myocardial and endothelial injury following cold cardioplegic arrest in pigs. Scand Cardiovasc J 1997;31:45-50.[Medline]
  15. Perrault L.P., Menasche P., Peynet J., Faris B., Bel A., de Chaumaray T., Gatecel C., Touchot B., Bloch G., Moalic J.M. On-pump, beating-heart coronary artery operations in high-risk patients: an acceptable trade-off?. Ann Thorac Surg 1997;64:1368-1373.[Abstract/Free Full Text]
Received January 26, 1999; received in revised form June 14, 1999; accepted June 22, 1999.




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