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Ann Thorac Surg 2001;71:249-253
© 2001 The Society of Thoracic Surgeons

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Original article: cardiovascular

Retrograde versus antegrade crystalloid cardioplegia in coronary surgery: value of troponin-I measurement

^a Department of Thoracic and Cardiovascular Surgery, Medical School, Hannover, Germany
^b Department of Clinical Chemistry II, Medical School, Hannover, Germany

Accepted for publication May 10, 2000.

Address reprint requests to Dr Franke, Klinik für Herz-, Thorax-und Gefäß Chirurgie, Friedrich-Schiller-Universität, Postfach, D-07740 Jena, Germany
e-mail: ulrich.franke{at}med.uni-jena.de

	Abstract

Top Abstract Introduction Material and methods Results Comment References

 
Background. The optimal route for delivery of cardioplegia is still in debate in patients with ischemic heart disease. Cardiac troponin-I is a new marker with the potential for detection of minor differences in myocardial ischemia.

Methods. In a prospective randomized trial 58 patients undergoing elective coronary artery bypass grafting for two- or three-vessel coronary artery disease were divided into groups with antegrade (group A, n = 29) and retrograde (group R, n = 29) application of crystalloid cardioplegia (St. Thomas II). Patients with major risk factors were excluded. In addition to routine electrocardiogram monitoring, cardiac troponin-I and creatine kinase-MB activity were measured in all patients preoperatively at 2, 5, 8, 24, and 48 hours after aortic cross-clamp release, and at hospital discharge.

Results. In both groups, there were no differences regarding operative parameters. A significantly higher cardiac troponin-I concentration was observed in the antegrade group at 24 hours after cross-clamp (8.2 ± 8.5 µg/L vs 3.2 ± 3.1 µg/L; p = 0.02). Patients with subtotal stenosis or occlusion of one or more main coronary arteries showed significantly lower cardiac troponin-I levels after retrograde application.

Conclusions. Lower concentrations of the cardiac troponin-I marker after retrograde application of cardioplegia indicate advantages of myocardial protection in ischemic heart disease.

	Introduction

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The optimal delivery of cardioplegic solution in coronary artery bypass grafting is still controversial concerning optimal myocardial protection. In contrast to complex coronary reoperations in which the retrograde application of blood cardioplegia is widely accepted [1]. This issue has not been clarified for elective coronary artery bypass grafting. Applying antegrade cardioplegia, homogenous perfusion of all segments of the heart may be limited in cases of badly collateralized coronary artery stenoses. Retrograde administration through the coronary sinus seems to offer a solution for this problem. However, arteriosinusoidale shunts or rare anatomical problems in hearts with very short coronary sinus may well result in inhomogeneous cardiac protection with retrograde application of cardioplegia [2–4], which is especially true for the right heart. Thus far clinical studies could not clearly demonstrate the advantages of one or both procedures [5].

Cardiac troponin I (cTnI) is a new marker of myocardial ischemia. Whereas the other ischemic markers creatine kinase-MB (CK-MB) and troponin T can be expressed in injured striated muscles the cardiac isoform of troponin I is highly specific [6, 7]. Therefore, cTnI should be sensitive to discriminate injuries due to inhomogeneous myocardial protection.

We thus investigated whether the application of this new troponin measurement would be helpful to clarify the role of the route of cardioplegic administration in coronary artery bypass grafting.

	Material and methods

Top Abstract Introduction Material and methods Results Comment References

 
Patients
Fifty-eight patients admitted for elective coronary artery bypass grafting were prospectively randomized into two groups with antegrade (group A, n = 29) and retrograde (group R, n = 29) application of cristalloid cardioplegia (St. Thomas II). Patients with an ejection fraction of less than 35%, a forced end-expectory volume in the first second of less than 60%, chronic hemodialysis, or patients older than 80 years were excluded. Also candidates with a myocardial infarction within 4 weeks preoperatively were excluded.

Operative management
Standard anesthesia and monitoring were used in all patients. All operations were performed by two experienced cardiac surgeons (UF, TW). After median sternotomy the left internal mammary artery was dissected, harvesting of the saphenous vein was performed simultaneously. Cannulation for the cardiopulmonary bypass was carried out in the usual fashion with a two-stage venous cannulation technique. The systemic temperature of the patients was maintained at 31° to 33°C. A cardioplegia delivery cannula with separate vent line (DLP Medtronic, Grand Rapids, MI) was inserted into the ascending aorta of all patients. In patients of the retrograde group an additional coronary sinus catheter with autoinflating silicone cuff (DLP Medtronic) was positioned by a closed transatrial technique. After cross-clamping of the aorta cardioplegia was delivered depending of the group selection. Cold, hyperkalemic crystalloid St. Thomas II solution was applied at an initial volume of 1000 mL in all patients. A second or third shot of 300 to 500 mL was given to patients with restarting electrical heart activity or after 30 minutes of cross-clamp time after the previous application. It was used exclusively the initially randomized delivery route. No combinations were performed. After finalizing of the distal anastomoses aortic, the cross-clamp was removed. The proximal anastomoses were performed using a partial aortic clamping.

Electrocardiogram
Twelve-lead electrocardiograms were recorded preoperatively, postoperatively in the intensive care unit, on the first and second postoperative day, and at time of hospital discharge. Electrocardiographic analysis was performed by two independent cardiologists. Electrocardiograms were screened for new persistent Q waves and ST-segment deviations ( 1 mm ST-segment evaluation in two limb leads or more or 2 mm or more ST-segment elevation in two or more precordial leads).

Measurements
Serial venous blood samples were measured preoperatively and at 2, 5, 8, 24, and 48 hours after release of the aortic clamp and at the time of hospital discharge. The cTnI concentrations were measured by the Stratus II automated two-site fluorometric enzyme immunoassay (Dade Diagnostika, München, Germany), which uses mouse monoclonal antibodies. Normally, cTnI serum concentrations by this assay are below the detectable concentration of 0.6 ng/mL. The CK-MB activities were measured by the Vitros enzyme immunoassay (Ortho-Clinical Diagnostics, Neckargemünd, Germany). The normal concentration of CK-MB activity is below 10 U/L.

Statistical analysis
Statistical analysis was performed by the SPSS program for Windows, version 7.5.2 (SPSS Inc, Chicago, IL). The data are presented as the mean ± one standard deviation. Significance was assumed if the p value was less than 0.05. Qualitative variables were compared by ² test and quantitative variables using Mann-Whitney test or t test for independing samples. For comparison of the repeated measures of cTnI and CK-MB levels within the antegrade or retrograde cardioplegia groups we used the analysis of variance with repeated measures. Comparison of the mean cTnI and CK-MB levels between the antegrade and retrograde group at the same time points was performed using the t test for independent samples in connection with the Levene’s test. Pearson’s correlation was used for the calculation of the independence of cTnI and CK-MB values from predisposing indices of myocardial ischemia.

	Results

Top Abstract Introduction Material and methods Results Comment References

 
Patients
Both groups did not show significant differences regarding age, gender, ejection fraction, and incidence of insulin-dependent diabetes mellitus. The mean forced end-expiratory volume in the first second and the number of preoperative infarctions were the same in both groups (Table 1).

Ischemic markers
In Figure 1 the kinetic of the cTnI concentrations of both groups are depicted. The increase of cTnI levels between all time points was statistically significant in every group until the 24-hour measurement (p < 0.001 to p < 0.05). At the same investigation time the cTnI levels of the antegrade administration group were higher than those of the retrograde group for the first 24 hours. This difference was statistically significant only for the 24-hour measurement (8.2 ± 8.5 µg/L vs 3.2 ± 3.1 µg/L, p = 0.020). Forty-eight hours after aortic cross-clamp release, the cTnI concentration did not differ any more between groups.

View larger version (12K): [in this window] [in a new window]   Fig 1. Time course of cardiac troponin I (cTnI) concentration for antegrade and retrograde delivery group. *p < 0.05 between groups.

View larger version (12K): [in this window] [in a new window]   Fig 2. Time course of creatinine kinase-MB activity (CK-MB) concentration for antegrade and retrograde delivery group.

View larger version (13K): [in this window] [in a new window]   Fig 3. Cardiac troponin I (cTnI) concentration in patients with subtotal stenosis or occlusion of one or more main coronary arteries.

	Comment

Top Abstract Introduction Material and methods Results Comment References

 
The optimal application of myocardial protection has been discussed controversially for a long time. Although many cardiac surgeons suggest the retrograde route of administration [8–10], others prefer the antegrade [11, 12], or a combined route of application [13, 14]. Retrograde application has the potential disadvantage of less optimal protection of the right ventricle, as described by Allen and colleagues [3]. In addition the type of preservation solution applied and as well as application modalities remain controversial [3, 4, 13, 15]. However, with few exceptions [14, 16] all studies subjected only the blood cardioplegia solution.

Cardiac troponin I has been shown to be a specific marker of cardiac damage with a higher specificity and a wider diagnostic window as compared to CK-MB measurements [8, 17–22]. It has been demonstrated that cTnI is not influenced by peripheral muscular diseases and is unchanged after noncardiac operations [6]. Therefore, it is widely accepted that cTnI should be able to detect even minor differences of myocardial ischemia.

It was the aim of our study to evaluate differences in between two cardioplegia delivery routes with regard to protection of myocardium in elective coronary artery bypass grafting and the use of standard crystalloid cardioplegia (St. Thomas II).

The comparability of our study groups was excellent because of the performance of operations by only two surgeons and the absence of perioperative myocardial infarction. Also, major risk factors for increased myocardial ischemia such as emergency revascularization and poor left ventricular function were excluded. Moreover, using one internal mammary artery and 2.7 venous grafts, both the revascularization technique as well as bypass times and aortic cross-clamp times were uniform in all patients. As a consequence the pre- and intraoperative data showed no or only minor differences in between groups. In patients of the retrograde group slightly higher cardioplegia volume was applied, mainly because the time until complete cardiac arrest was longer. After cardiopulmonary bypass patients of the antegrade group needed significantly more frequent norepinephrine support. Clinical outcome was favorable in both groups of patients with no hospital deaths or perioperative infarction on electrocardiographic monitoring. These results clearly reflect the adequacy of myocardial protection by crystalloid cardioplegia applied either antegrade or retrograde in elective myocardial revascularization.

Whereas CK-MB did not show any differences between the study groups, cTnI levels in patients of the retrograde group were significantly lower. Because numerous studies [7, 18, 21] were able to demonstrate a higher sensitivity and specificity of cTnI compared to CK-MB these differences indicate a better myocardial protection by retrograde delivery of cardioplegia. The estimated improvement of protection for patients with left main coronary artery (LMCA) stenosis greater than 50% or patients with triple vessel disease could not be confirmed. Potential causes of this are the limited number of patients and the cut-off point for the definition of stenosis (> 50%), which may not be specific enough to describe stenosis disturbing coronary perfusion during administration of cardioplegia. Chocron and co-workers [14] found a better protection by combined cardioplegia compared to antegrade application in a similar study design in only patients with main stem stenosis. In our study patients with subtotal stenosis or occlusion of one or more main coronary arteries demonstrated the best benefit of retrograde application of crystalloid cardioplegia compared with the antegrade application.

Our study does not allow a differentiated evaluation of both ventricles, because cTnI and CK-MB levels will only detect global myocardial ischemia. Because the left ventricle mass is bigger, ischemic injuries of the right ventricle myocardium could be undetected. Kaukoranta and co-workers [4] demonstrated that mild hypothermic blood cardioplegia leads to an anaerobic metabolism in the right ventricular myocardium but tissue levels of high-energy phosphates were well preserved.

The results of our study suggest that retrograde delivery of crystalloid cardioplegia improves myocardial protection in elective coronary bypass grafting compared to the antegrade route. Although both types of deliveries allow for excellent clinical results, cTnI was able to confirm slightly better myocardial protection in patients after retrograde delivery of cardioplegia. Especially patients with subtotal stenosis or occlusion of one or more main coronary artery show the greatest benefit by the retrograde delivery route.

	References

Top Abstract Introduction Material and methods Results Comment References

 

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Thorsten Wahlers Axel Haverich Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Franke, U. Articles by Haverich, A. Search for Related Content PubMed PubMed Citation Articles by Franke, U. Articles by Haverich, A. Related Collections Cardiac - pharmacology Extracorporeal circulation