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Right arrow Myocardial protection

Ann Thorac Surg 2004;77:664-671
© 2004 The Society of Thoracic Surgeons

Original article: cardiovascular

Continuous cold blood cardioplegia improves myocardial protection: a prospective randomized study

Yves A. G. Louagie, MD, PhDa*, Jacques Jamart, MDb, Manuel Gonzalez, MDc, Edith Collard, MDd, Serge Broka, MDd, Laurence Galanti, MD, PhDe, André Gruslin, MSf

a Cardiovascular and Thoracic Unit, Mont Yvoir, Belgium
b Biostatistics, Mont Yvoir, Belgium
c Intensive Care Unit, Mont Yvoir, Belgium
d Anesthesiology, Mont Yvoir, Belgium
e Laboratory of Clinical Biology, Mont Yvoir, Belgium
f Perfusion Team, University Clinics of Mont Godinne, Université Catholique de Louvain, Mont Yvoir, Belgium

Accepted for publication August 6, 2003.

* Address reprint requests to Dr Louagie, Cardiovascular and Thoracic Surgery, University Clinics of Mont Godinne, 1 av Therasse, B-5530 Mont Yvoir, Belgium
e-mail: louagie{at}chir.ucl.ac.be


   Abstract
Top
 Abstract
Introduction
 Patients and methods
 Results
 Comment
 Acknowledgments
 References
 
BACKGROUND: To assess the influence on myocardial protection of the rate of infusion (continuous vs intermittent) of cold blood cardioplegia administered retrogradely during prolonged aortic cross-clamping. The end-points were ventricular performance and biochemical markers of ischemia.

METHODS: Seventy patients undergoing myocardial revascularization for three-vessel disease were prospectively randomized to receive intermittent or continuous retrograde cold blood cardioplegia. Hemodynamic measurements were obtained using a rapid-response thermodilution catheter and included right ventricular ejection fraction, cardiac output, left and right ventricular stroke work index, and systemic and pulmonary vascular resistance. Blood samples were obtained from the coronary sinus before cross-clamp application and immediately after cross-clamp removal for determinations of lactate and hypoxanthine.

RESULTS: The left ventricular stroke work index trend was significantly superior (p = 0.038) by repeated-measures analysis in continuous cardioplegia. Other hemodynamic measurements revealed a similar trend. The need for postoperative inotropic drugs support was reduced in continuous cardioplegia. The release of lactate in the coronary sinus after unclamping was 2.30 ± 0.12 mmol/L after intermittent cardioplegia and 1.97 ± 0.09 mmol/L after continuous cardioplegia (p = 0.036). The release of hypoxanthine was 20.47 ± 2.74 µmol/L in intermittent cardioplegia and 11.77 ± 0.69 µmol/L in continuous cardioplegia (p = 0.002).

CONCLUSIONS: Continuous cold blood cardioplegia results in improved ventricular performance and reduced myocardial ischemia in comparison with intermittent administration.


   Introduction
Top
 Abstract
 Introduction
Patients and methods
 Results
 Comment
 Acknowledgments
 References
 
Continuous retrograde infusion might potentiate the effect of cold blood cardioplegia administered intermittently, reduce ischemia and result in improved ventricular performance. In 1981, Bomfim [1] demonstrated that myocardial protection during aortic valve replacement afforded by continuous blood cardioplegia was superior to that of a singly administered group. The results were based on myocardial biopsies of the left ventricle for assessment of cardiac metabolism and enzyme release. Khuri [2] reported no change in myocardial pH during aortic clamping with continuous blood cardioplegia, but a decline with multidose perfusion. In a series of 1225 consecutive patients undergoing isolated coronary artery bypass grafting in our institution, we demonstrated that the use of cold blood cardioplegia reduced fourfold the risk of operative mortality in comparison with a standard crystalloid cardioplegia solution [3]. Thereafter, we reported [4] in a study, including 298 patients, that continuous retrograde cold blood cardioplegia resulted in better left and right ventricular stroke work index during the first 20 hours after coronary artery bypass compared with historical controls using intermittent antegrade or retrograde cold blood cardioplegia and, consequently, that there was a reduced incidence of major adverse cardiac events.

This comparative study had to be corroborated by a prospective randomized study. We undertook the present study involving patients undergoing coronary artery surgery for triple-vessel coronary artery disease, using cold blood retrograde cardioplegia administered either intermittently or continuously as myocardial protection. The end-points were ventricular hemodynamic performance and biochemical markers of ischemia.


   Patients and methods
Top
 Abstract
 Introduction
 Patients and methods
Results
 Comment
 Acknowledgments
 References
 
Study design
Seventy patients undergoing myocardial revascularization were prospectively randomized to receive intermittent or continuous retrograde cold blood cardioplegia. The size of the study groups was determined by statistical power analysis. We selected left ventricular stroke work index (LVSWI) as the primary variable. Knowing from previous studies the standard deviation of LVSWI (± 14 gm/beat/m2), we estimated that, if an {alpha} error of 0.05, a ß error of 0.20 (power 0.80), and a {delta} (minimal difference considered as clinically significant) of 10 gm/beat/m2 were accepted, a minimal number of 31 patients per group was required. The study protocol was approved by the Ethics Committee of the hospital on April 9, 1996, and informed, documented consent was obtained from all patients. To evaluate myocardial protection over prolonged aortic cross-clamping times, only patients undergoing multiple coronary bypass grafting for triple-vessel disease or left main stem disease were studied. Unstable patients requiring emergent surgery were not included.

All of the patients underwent isolated coronary operations under the care of the same surgeon (Y.L.). Patients were randomly assigned, using an envelope technique of randomization, to one of the cardioplegic strategies just before the start of cardiopulmonary bypass. The period of inclusion extended from March 1997 to October 2000. Two groups were compared: in the first group (n = 35) cold blood cardioplegia was administered intermittently in a retrograde manner (IBC); in the second group (n = 35) the same type of cardioplegia was administered continuously (CBC).

Techniques of cardioplegia
The conduct of the operation, apart from the technique of cardioplegia, did not differ among the groups. The procedure was completed at 28°C hypothermia. All anastomoses were realized with 8-0 monofilament using 6x optical magnification. If necessary, a microblower (Visuflo; Research Medical, Inc, Midvale, UT) delivering 6 L/min of compressed air passed through a 20-µm filter was used while completing the distal anastomoses. Thanks to that device, cardioplegia administration had never to be interrupted during the construction of the distal anastomoses in the CBC group.

The technique of cold blood cardioplegia used has been described in detail in a previous report [4]. Cardiac arrest was obtained by an initial bolus of 500 mL of antegrade 4°C crystalloid cardioplegia followed by a bolus of 500 mL of retrograde 8°C blood cardioplegia. Topical ice slush was applied in both groups. Thereafter, only in the continuous group, cold blood cardioplegia was administered retrogradely and continuously at a rate of 50 mL/min. The solution was delivered through a catheter inserted into the coronary sinus (94115ST Gundry RCSP Cannula; DLP Inc, Grand Rapids, MI). The catheter was inserted beyond the origin of the middle cardiac vein and the distal balloon was inflated before the start of retrograde cardioplegia administration. The temperature of the infusate was set at 8°C using a heater/cooler (Bentley HE-30 Gold Heat Exchanger; Baxter Healthcare Corporation, Bentley Division, Irvine, CA). To avoid hemodilution due to the large amounts infused, a cardioplegic delivery system consisting of disposable tubing with an 8:1 blood/cardioplegic ratio (Bentley Custompac Cardioplegic Set; Bentley Laboratories Europe, Ad Uden, The Netherlands) was used in both groups. The potassium concentration of the crystalloid solution was adapted to obtain a similar infusate kalemia of 10 to 12 mEq/L.

In both groups, after each completed distal anastomosis, a bolus of retrograde blood cardioplegia was administered at a rate of 250 mL/min during 2 minutes. While the last anastomosis was completed, the temperature of the perfusate was gradually increased to 37°C. Before unclamping the aorta, a final bolus of 37°C noncardioplegic blood was administered retrogradely at a rate of 250 mL/min for 4 minutes.

The characteristics of cardioplegia administration were assessed by monitoring coronary sinus pressure and septal temperature. If necessary, the retrograde cardioplegia catheter balloon was reinflated. In this way, there was no need to reposition the catheter during the procedure. In the CBC group, the administration of cardioplegia was easily assessed by the return of blood while completing the distal anastomoses.

Hemodynamic measurements
The following hemodynamic data were obtained: mean arterial and pulmonary arterial pressures, pulmonary capillary wedge pressure (PCWP), right atrial pressure (RAP), and heart rate. Thermodilution cardiac output was measured in triplicate using a Hellige CO computer (Hellige GMBH, Freiburg im Breisgau, Germany). Ventricular function was monitored with the insertion of a right ventricular (RV) rapid-response thermodilution REF-1 catheter (Baxter Healthcare Corp, Edwards Critical Care Division, Santa Ana, CA). Hemodynamic measurements (in triplicate) included RV ejection fraction, cardiac output, RV and pulmonary artery pressures, and right atrial and PCWP. Systemic pressures were measured through a radial arterial line. Indices of ventricular function calculated according to standard formulas included right and left ventricular stroke work index (RVSWI, LVSWI), and systemic and pulmonary vascular resistance. The hemodynamic measurements were repeated before aortic cannulation (pericardial incision); at the end of the operation; after reversal of heparin therapy; at chest closure; and at 3, 6, 12, 24, and 36 hours after the end of the cardiopulmonary bypass.

Serum biochemical markers
Lactate and hypoxanthine concentrations were measured in blood samples obtained from the coronary sinus cannula before application of the cross clamp and immediately after cross-clamp removal. The method used for lactate determinations was radiative energy attenuation technology (Abbott, North Chicago, IL) and high-pressure liquid chromatography (HPLC; Waters, Milford, MA) for hypoxanthine.

Venous blood samples were taken for measurement of CK-MB mass and troponin I at the following times: at the time of opening of the pericardium; during aortic cannulation; at aortic unclamping; at chest closure; and at 3, 6, 12, 24, and 36 hours after the end of the cardiopulmonary bypass. CK-MB mass and troponin I concentrations were measured using specific fluorometric enzyme immunoassays (Dade, Miami, FL).

Statistical analysis
Values are presented as means ± the standard error of the mean. In addition, median and 95% confidence limits are presented for skewed data such as amounts of inotropic drugs administered. Clinical data were compared by {chi}2 tests, Fischer's exact test, unpaired t tests, paired t tests, or Mann-Whitney nonparametric U tests as appropriate. Data obtained repeatedly, such as hemodynamic and enzymatic determinations, were compared by analysis of variance (ANOVA) for repeated measurements or by regression analysis using generalized estimating equations (GEE) as described by Liang and Zeger [5]. The latter analysis allowed us to take into account simultaneously the influence of the initial value, time, and between-subject categorical variable(s). For these reasons the GEE analysis was used for hemodynamic determinations, the influence of the initial value being taken into account. Repeated measures analyses evaluate the influence of time and of between-subject categoric variables. Only the p values related to the latter comparisons will be reported. All statistical analyses were performed with use of the SPSS 10.0 software package (SPSS Inc, Chicago, IL), except regression analysis of repeated measures, for which the RMGEE program was used [6].


   Results
Top
 Abstract
 Introduction
 Patients and methods
 Results
Comment
 Acknowledgments
 References
 
The clinical profile and intraoperative data are shown in Tables 1 and 2. The two groups were similar with respect to all measured preoperative and intraoperative variables. The distribution of the arterial grafts was identical among the groups.


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  		Table 1. Patient Demographics

 

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  		Table 2. Operative Data

 
Characteristics of cardioplegia
During cardioplegic arrest, the septal temperature trend was higher in the intermittent group (ANOVA, p < 0.001; Fig 1). . The overall mean septal temperature was 15.9 ± 0.4°C for IBC and 13.2 ± 0.4°C for CBC (p < 0.001). The mean temperature of the cardioplegia infusate was 7.7 ± 0.1°C. The average duration of cardioplegia administration in the IBC group was 11.3 ± 0.2 minutes.



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  		Fig 1. Cardioplegia was assessed by measurement of (top) septal temperature and coronary sinus pressure (bottom). Bolus n represents the averaged data obtained during 250 mL/min infusion of cold blood cardioplegia every 20 minutes. Interval (Interv) n represents the averaged data measured during the intervals used to realize the distal anastomoses. During cardioplegic arrest, the mean septal temperature trending was higher in the intermittent group (p < 0.001). The coronary sinus pressure trending was lower in the intermittent group (p = 0.003). —{blacksquare}— = continuous; – – {blacktriangleup} – – = intermittent.

 
The pressure measured in the coronary sinus demonstrated less variability in the continuous group (Fig 1). The minimal pressure was lower in IBC patients than in CBC: 5.4 ± 1.0 mm Hg versus 16.9 ± 1.5 mm Hg (p = 0.004).

The total volume of crystalloids infused during CBC was significantly higher than in IBC (1026 ± 159 mL vs 724 ± 27 mL, p < 0.001). The kaliemia increased from 3.63 ± 0.05 mEq/L before aortic cross-clamping to 4.58 ± 0.08 mEq/L after aortic clamp release (p = 0.000). However, there was no difference among the cardioplegia groups: 4.47 ± 0.11 mEq/L in the IBC group and 4.68 ± 0.10 mEq/L in the CBC group (p = 0.157).

Hemodynamic measurements
There were no significant differences among the groups regarding heart rate, mean arterial pressure, pulmonary capillary wedge pressure, and central venous pressure. The cardiac index, RV ejection fraction, and RVSWI were constantly higher in the continuous cardioplegia patients, but the differences did not reach significance by the repeated measures analysis (Figs 2–4). . . . However, the LVSWI was significantly superior (GEE p = 0.038) in the CBC group. Student's t tests revealed significant differences at time points 12 and 24 hours, p = 0.032 and 0.050, respectively. An influence of afterload is unlikely because mean arterial pressure and calculated systemic vascular resistance were similar among the groups. Nevertheless, to ascertain whether the superior LVSWI trend evidenced in the CBC group was related either to improved myocardial protection or to the combination of higher preop EF, initial LVSWI and unequal hemodynamic conditions, GEE testing was repeated on that measurement, looking for confounding covariates. Thus, besides the initial LVSWI value and time (included in the standard GEE analysis), we added to the model the following covariates: preoperative EF, MAP, PCWP, and SVR. The GEE analysis confirmed the independent influence of cardioplegia groups, the CBC being associated with superior LVSWI outcome (p = 0.031), of initial LVSWI (p = 0.045), and of time (p < 0.001). Furthermore, it indicated an independent influence of MAP (p < 0.001) and SVR (p < 0.001). By contrast, no influence could be demonstrated for PCWP and preoperative EF.



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  		Fig 2. Trend in (top) cardiac index and right ventricular ejection fraction (bottom). The procedure time (Proc.) is represented by a hatched bar. The other time intervals represent hours following the end of cardiopulmonary bypass. There was no significant difference between the groups. Student's posthoc t test revealed a p value of 0.04 at 3 hours for cardiac index (asterisk). —{blacksquare}— = continuous; – – {blacktriangleup} – – = intermittent.

 


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  		Fig 3. Trend in mean AP, LVSWI, SVR, and PCWP. The procedure time (Proc.) is represented by a hatched bar. The other time intervals represent hours following the end of cardiopulmonary bypass. The LVSWI was significantly better (p = 0.038) in the continuous cardioplegia group of patients by generalized estimating equation analysis. Student's t tests were significantly different at times 12 hours and 24 hours (p = 0.032 and 0.050, respectively, asterisk). The other variables did not differ significantly. —{blacksquare}— = continuous cardioplegia; – – {blacktriangleup} – – = intermittent cardioplegia. (LVSWI = left ventricular stroke work index; mean AP = mean arterial pressure; PCWP = pulmonary capillary wedge pressure; SVR = systemic vascular resistance.)

 


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  		Fig 4. Trends in mean PAP, RVSWI, PVR, and CVP. The duration of the procedure (Proc.) is represented by a hatched bar. These variables did not differ significantly among the groups by generalized estimating equation analysis. Student's t tests were significantly different at times 12 hours and 36 hours (p = 0.029 and 0.039, respectively) for CVP (asterisk). —{blacksquare}— = continuous cardioplegia; – – {blacktriangleup} – – = intermittent cardioplegia. (CVP = central venous pressure; PAP = pulmonary arterial pressure; PVR = pulmonary vascular resistance; RVSWI = right ventricular stroke work index.)

 
The inotropic and vasoactive drugs administered during the same period were considered. The total amounts of dopamine administered were 713 ± 411 {gamma}/kg (median 0; 95% CI, -158–1953) in the IBC group of patients, and 182 ± 182 {gamma}/kg (median 0; 95% CI, -222–648) in the CBC group (p = 0.286). The total amounts of dobutamine administered were 3287 ± 1109 {gamma}/kg (median 640; 95% CI, 1320–6897) in the IBC group, and 1827 ± 667 {gamma}/kg (median 0; 95% CI, 504–3394) in the CBC group (p = 0.283). The total amounts of epinephrine administered were 5536 ± 2134 {gamma}/kg (median 35; 95% CI, 1452–11671) in the IBC group, and 993 ± 489 {gamma}/kg (median 0; 95% CI, -3–2187) in the CBC group (p = 0.251). Although there was a marked tendency for a reduced administration of inotropic drugs in the CBC group, this did not reach statistical significance given the wide variation of the amounts of drugs infused.

Serum biochemical markers
The release of lactate in the coronary sinus after unclamping was 2.30 ± 0.12 mmol/L in the IBC group and 1.97 ± 0.09 mmol/L in the CBC group (p = 0.036; Fig 5). . The arterial blood lactate concentration was 1.35 ± 0.19 mmol/L in the IBC group and 1.36 ± 0.16 mmol/L in the CBC group (not significant [NS]). The release of hypoxanthine in the coronary sinus was 20.47 ± 2.74 µmol/L in the IBC group and 11.77 ± 0.69 µmol/L in the CBC group (p = 0.002; Fig 5). The release of CK-MB mass and of troponin I did not differ among the groups of patients (Fig 6). .



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  		Fig 5. Lactate (left) and hypoxanthine (right) concentrations were measured in the coronary sinus before aortic cross clamping and immediately after aortic clamp release. These markers of ischemia were markedly lower in the continuous cardioplegia group of patients. ({blacksquare} = continuous cardioplegia; {square} = intermittent cardioplegia.)

 


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  		Fig 6. Plasma levels of the MB mass isoenzyme of creatine kinase (CK-MB) and of troponin I. The duration of the procedure (Proc.) is represented by a hatched bar. —{blacksquare}— = continuous cardioplegia; – – {blacktriangleup} – – = intermittent cardioplegia.

 
Clinical outcomes
The total amount of blood lost in the drains was 1542 ± 129 mL in the IBC group of patients, and 1552 ± 164 in the CBC group (NS). The total amount of heterologous blood transfused was 437 ± 67 mL in the IBC group, and 402 ± 101 mL in the CBC group (NS). There was no reexploration required for bleeding.

The incidence of adverse events did not differ among the groups: the incidence of atrial fibrillation was 23% in the CBC group of patients, and 29% in the IBC group, while the incidence of respiratory tract infection was 6% in the CBC group and 14% in the IBC group. A 74-year-old man died on the fourth postoperative day of irreversible low cardiac output syndrome, despite the use of intraaortic balloon counter-pulsation and extracorporeal membrane oxygenation. He had undergone a quintuple bypass grafting under continuous cardioplegia. Two other patients belonging to the IBC group had low postoperative cardiac output. One of these required intraaortic balloon counterpulsation to be weaned from cardiopulmonary bypass. The other patient sustained a perioperative inferior myocardial infarction.

The mean stay in the intensive care unit was 73 ± 10 hours for the IBC patients, and 54 ± 3 hours for those in the CBC group (NS). The median hospital stay was 11 days for both groups of patients.


   Comment
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
Acknowledgments
 References
 
Much attention has been given to the use of continuous warm blood cardioplegia. However, the majority of experimental and clinical studies failed to demonstrate a clear superiority of this approach administered continuously in comparison with intermittent cold blood cardioplegia. Experimental studies have reported that continuous warm blood cardioplegia is inferior to cold blood cardioplegia [7, 8], that it could be harmful to the right ventricle [9], or that warm or cold continuous blood cardioplegia provide similar myocardial protection [10, 11]. In the clinical setting, continuous warm cardioplegia offered no better myocardial preservation over intermittent cold blood or crystalloid cardioplegia in the hypertrophied left ventricle [12, 13], in isolated coronary bypass grafting [14, 15], in ischemic myocardium during urgent coronary revascularization [16, 17], or in stunned myocardium [18]. Only Honkonen and colleagues [19] demonstrated that the recovery of right ventricular function after coronary surgery was better in terms of ejection fraction and preload-related stroke work with warm continuous cardioplegia compared with intermittent cold cardioplegia.

Warm blood cardioplegia leads to some difficulty in the visualization of distal anastomoses. There is always a possibility of ceasing cardioplegia, but multiple intervals of warm ischemia may have cumulative damaging effects. By contrast, continuous cold blood cardioplegia has many advantages: hypothermia provides superior ischemic tolerance, and the rate of administration of cold blood cardioplegia can be markedly reduced, which allows precise surgery. Surprisingly, recent clinical studies on the subject are sparse.

Rao and colleagues [20] advocated the use of continuous retrograde tepid cardioplegia and antegrade infusions at a high flow rate of 200 mL/min. Jasinski and coworkers [21] reported that the viability of the myocardium, as assessed by oxygen utilization and functional recovery, were better preserved with simultaneous antegrade and retrograde cold blood cardioplegia administered continuously than by retrograde administration alone.

In the present study, a specific influence of continuous cardioplegia was evident: CBC was associated with a permanently lower septal temperature and with a significant reduction of the pressure variations in the coronary sinus. Whether lower septal temperature is responsible per se of a better myocardial protection is difficult to assess. We compared three techniques of cold blood cardioplegia delivery [4]: intermittent antegrade, intermittent retrograde, and continuous retrograde. In the latter group of continuous cardioplegia, two subgroups differed by the temperature of cardioplegia that was set either at 8°C or 18°C. There was no difference among these subgroups regarding postoperative LVSWI expressed as percentage of pre-CPB value.

Regarding left ventricular performance, LVSWI was significantly higher for patients receiving CBC, particularly at 12 and 24 hours postoperatively. This improved hemodynamic situation was not related to a reduction in afterload and preload because the mean arterial pressure, SVR, and PCWP trends did not differ. Furthermore, these differences are not explained by a different inotropic drug regimen because the CBC patients received less dopamine and dobutamine than the IBC group. Concerning measurements of RV performance, EF RV, RVSWI, PVR, and CVP did not differ among the groups. This is apparently in contradiction with our previous work [4] where RVSWI was superior in patients receiving CBC administered at 18°C compared with IBC administered anterogradely or retrogradely. However, CBC administered at 8°C, as in the present study, did not differ.

Assessment of right ventricular function by repeated measurements over a 48-hour time interval is difficult because volume estimates are necessary. Radionuclide ventriculography and echocardiography provide estimates of right ventricular volumes but are difficult to realize in the early postoperative period. Furthermore, the assymetrical right ventricle shape renders the volume estimation inaccurate by the latter means and only magnetic resonance based methods are able to estimate right ventricular volume properly. Therefore, many investigators have used rapid-response thermodilution catheters to provide estimates of right ventricular function [22, 23]. Although not ideal, measurements are reproducible, thus allowing for comparison between groups. Despite their methodology limitations, these methods correlate well with the clinical outcome. Indeed, we studied [24] risk factors in unstable angina patients and found a highly significant (p < 0.0001) intergroup difference in the LVSWI and PVR between the control group and the group of patients who experienced a poor hospital outcome. A possible bias resulting from unequal distribution of initial hemodynamic values was addressed by using repeated measures generalized estimating equations that take into account simultaneously the influence of the initial value, time, and between-subject categoric variable(s).

Myocardial ischemia was assessed by lactate and adenine nucleotide degradation product concentrations measured in the coronary sinus immediately after aortic cross-clamp release. These variables are very sensitive markers of myocardial ischemia [25–27]. Yau and coworkers [27, 28] compared five techniques of cardioplegia and reported that lactate production is greatest during cardioplegia and increases with time during the aortic cross-clamp interval. The most important difference among the groups in that study was at the cross-clamp removal. However, lactate production could persist after 10 minutes of reperfusion in those patients receiving warm retrograde cardioplegia. Likewise, the hypoxanthine concentrations differed maximally among the groups at the time of cross-clamp removal, but no difference persisted after 20 minutes of reperfusion. In the present study, markedly lower concentrations of lactate and hypoxanthine were found in the CBC group of patients at the time of cross-clamp removal. Troponin I concentration and CK-MB mass are reliable markers of myocardial injury. Clinically, troponin I has the advantage over CK-MB, in that it is not influenced by autotransfusion [29]. Although troponin I release was lower in the CBC group of patients until 12 hours, this did not achieve statistical difference. Likewise, there were no differences regarding CK-MB mass determinations. In a previous study [4], we observed that the release of CK-MB isoenzymes was not influenced by any technique of blood cardioplegia delivery. Thus, biochemical samples in the coronary sinus detected reduced ischemia in the CBC group in the early postoperative phase. However, less sensitive serum markers such as troponin I and CK-MB mass were unable to detect such subtle differences. A further explanation would be that IBC causes reversible ischemia without significant myocardial cell necrosis or damage.

The clinical course is not a reliable indicator for distinguishing between different forms of delivery of cardioplegia unless patient numbers are very high. This study lacked sufficient statistical power to detect differences in clinical outcomes attributable to cardioplegic technique, but we have reported those data for the sake of completeness. We demonstrated in a previous study [4], on 298 consecutive patients undergoing isolated coronary artery bypass grafting, that CBC was associated with a significantly reduced incidence of major cardiac events (combination of hospital death and postcardiopulmonary bypass intraaortic balloon pump implantation).

To conclude, this prospective and randomized study corroborates the results of our previous comparative study [4]. It demonstrates a better LV performance and reduced myocardial ischemia associated with CBC in comparison with IBC in patients receiving multiple coronary artery bypass surgery.


   Acknowledgments
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 Acknowledgments
References
 
We wish to thank Brigitte Malhomme for data collection in this project.


   References
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 Acknowledgments
 References
 

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