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Asian Cardiovasc Thorac Ann 1998;6:188-194
© 1998 Asia Publishing EXchange Pte Ltd

ORIGINAL CONTRIBUTION

Antegrade-Retrograde Cardioplegia for Myocardial Protection During Coronary Artery Bypass Graft Surgery

Tarek A Abdel Aziz, MD, Najib Al Khaja, MD, PhD, Mohamed A Ali, MD, Ali S Maklad, MD1, Mohamed F Bassiouny, MD1, Murdo Turner, FRCS, Donald G Roberts, MD, PhD

Department of Cardiothoracic Surgery Dubai Hospital Dubai, United Arab Emirates
1 Department of Cardiothoracic Surgery Ain Shams University Cairo, Egypt
For reprint information contact: Najib Al Khaja, MD, PhD Department of Cardiothoracic Surgery Dubai Hospital P.O. Box 7272 Dubai, United Arab Emirates Tel: 971 4 71 4444 Fax: 971 4 71 9340

   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
This prospective randomized clinical study was designed to assess and compare the use of combined antegrade-retrograde cardioplegia versus antegrade cardioplegia in providing adequate myocardial preservation during coronary artery bypass graft surgery. Fifty patients undergoing elective coronary artery bypass grafting were randomly divided into 2 groups according to the route of cardioplegic delivery: group A (25 patients) received antegrade cold crystalloid cardioplegia; group B (25 patients) received combined antegrade-retrograde cold crystalloid cardioplegia. The groups were compared by clinical and electrocardiographic criteria and biochemical markers of ischemic myocardial damage. There was a highly significant statistical difference between the groups in terms of spontaneous recovery of sinus rhythm (40% of patients in group A versus 96% in group B). The use of direct current shock to restore sinus rhythm was higher in group A (60%) compared with group B (4%). Low cardiac output occurred in 20% of patients in group A and in 16% of patients in group B but this difference was not statistically significant. No bundle-branch block was found in group B whereas the incidence was 8% in group A. Significantly higher levels of biochemical markers of myocardial damage were obtained in group A at 10 minutes, 4 hours, and 12 hours after declamping. These results indicate that combined antegrade-retrograde cardioplegia is superior to antegrade cardioplegia for myocardial protection during coronary artery bypass graft surgery.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Effective intraoperative myocardial protection requires adequate distribution of cardioplegic solution to all myocardial segments to be accomplished in a safe, simple, and rapid fashion.1 In spite of the known advantages of antegrade cardioplegia, it is associated with a number of actual and theoretical limitations.2 Nonhomogenous distri-bution of cardioplegia in severe critical proximal coronary artery stenosis and in evolving myocardial infarction has been demonstrated experimentally.3 Coronary ostial injury has been reported during and after aortic valve surgery.4 Further limitations of antegrade cardioplegia include poor distribution in patients with aortic regurgitation unless the aorta is opened and the coronary ostia are perfused directly, and the need to interrupt the continuity of mitral valve procedures to remove the retractors and avoid aortic distortion during cardioplegic replenishment.1 In addition, antegrade infusion may not be technically possible in patients with type A aortic dissection.5 To obviate these limitations, retrograde coronary sinus perfusion has been proposed as an alternative method of providing myocardial protection.6 Retrograde cardioplegia leads to excellent protection of the left ventricle in cases of severe coronary artery stenosis and when internal mammary artery grafts are used.7 However, recent studies have documented that retrograde cardioplegia does not adequately perfuse the right ventricle.8 The possibility of delayed cardiac arrest due to the low flow rate used for retrograde cardioplegia has also been noted.9

This prospective randomized clinical study was designed to assess and compare the use of combined antegrade-retrograde cardioplegia versus antegrade cardioplegia in providing adequate myocardial preservation during coronary artery bypass graft surgery using clinical, hemodynamic, electrocardiographic, and biochemical parameters.


   PATIENTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
The two techniques of cardioplegia delivery were evaluated in 50 patients undergoing CABG. The criteria for exclusion of patients from this study included single-vessel disease, reoperation, combined procedures, an ejection fraction of less than 30%, or emergency CABG. Twenty-five patients were randomly assigned to receive antegrade cold crystalloid cardioplegia (group A) and the other 25 patients received combined antegrade-retrograde cold crystalloid cardioplegia (group B). Ethical approval and informed consent were obtained. In group A, there were 23 males and 2 females, the mean age was 51.8 ± 7.3 years. In group B, there were 24 males and 1 female, the mean age was 50.5 ± 6.6 years.

All patients had a history of chest pain and they were classified according to the Canadian Cardiovascular Society classification of angina.10 Routine laboratory investigations were carried out preoperatively, on the day of surgery, the 1st and 5th postoperative days, and before discharge. A standard 12-lead electrocardiogram (ECG) was obtained preoperatively, on the day of surgery, on the first 3 postoperative days, and repeated when needed. The ECG recordings were analyzed carefully by two independent cardiologists for dysrhythmias, conduction disturbances, and new ischemic changes according to the Minnesota code.11 All of the patients were diagnosed to have coronary artery disease based on selective coronary angiography. Left ventricular ejection fractions were calculated from angiography according to Simpson's method.12

Biochemical studies comprised serum levels of creatine kinase-MB isoenzyme (CK-MB), myoglobin, and troponin T. Samples were taken preoperatively (sample 1), intraoperatively from the right atrium 10 minutes after declamping (sample 2), and postoperatively from the radial artery 4 hours and 12 hours after declamping (samples 3 and 4). All samples were centrifuged immediately and the serum was stored at –80°C until analysis. The determination of CK-MB levels was carried out by the indirect immunological method.13 The latex agglutination method was used for determination of myoglobin levels.14 Semi-quantitative evaluation was performed by means of a dilution series. Lack of agglutination was considered to be a myoglobin level of 50 µg·L-1 for the purpose of calculation and statistical analysis.15 The enzyme-linked immunosorbent manual assay was used for estimation of cardiac troponin T.16

Standard anesthetic and operative procedures were used in all patients. The chest was entered through a median sternotomy incision. Both the aorta and right atrium were cannulated. A single double-stage venous cannula was used to cannulate the right atrium. After heparinization (usually 3 mg·kg-1 heparin sulfate) to achieve an activated clotting time of at least 400 seconds and 4 times the control time, the patient was connected to the heart-lung machine using a membrane blood oxygenator. Once bypass was established, systemic hypothermia was instituted and the temperature was lowered to 28°C rectal. The aorta was clamped, cardioplegia was infused, and the pericardium was irrigated with ice-cold saline. All distal anastomoses were performed during a single period of aortic cross-clamping and the proximal anastomosis were performed after declamping. After obtaining complete hemodynamic stability, decannulation was carried out and heparin was neutralized with protamine sulfate.

Data used for intraoperative evaluation included the aortic cross-clamping time, the cardiopulmonary bypass time, the ease with which the heart took over from the heart-lung machine, spontaneous reversion to sinus rhythm versus use of a defibrillator and number of direct current shocks, the rhythm after bypass, the use of inotropic support, and the use of a pacemaker. In the intensive care unit, hemodynamic parameters were obtained at 1, 2, 4, 8, 16, and 24 hours postoperatively and comprised: heart rate, rhythm, mean arterial pressure, urine output, and central venous pressure. The need for inotropic support and the use of pacemaker were recorded.

We used an antegrade cardioplegia cannula containing a side-port for venting and a side-arm for pressure monitoring in the aortic root (Research Medical, Inc., Midvale, UT, USA). The cannulation site was also used for de-airing after declamping and as a site for proximal anastomosis. For retrograde cardioplegia, we used a Buckberg Retroplegia cannula with a self-inflating balloon, semi-rigid stylet and a handle (Research Medical, Inc., Midvale, UT, USA). This cannula has a side-arm for pressure monitoring in the coronary sinus. The cannula was inserted in the coronary sinus through a 4/0 polypropylene pursestring suture placed low in the right atrium, near the junction with the inferior vena cava and it was withdrawn through a rubber tourniquet.

Cardioplegia was infused with a pneumatic pump inflated to 200 mm Hg. Pressure monitoring during cardioplegic infusion in both the aortic root and the coronary sinus was performed routinely using the transducer that was employed for routine central venous pressure monitoring. During antegrade infusion, aortic root pressure was kept between 80 and 100 mm Hg, while coronary sinus pressure was kept between 30 and 50 mm Hg. The pressure in the coronary sinus was not allowed to exceed 50 mm Hg. St. Thomas' Hospital solution no. 1 chilled to 4°C was infused in a dose of 15 mL per kg body weight initially and repeated every 15 minutes in a dose of 200 mL. In group B, half of the initial dose was given antegradely with aortic root pressure of 80 to 100 mm Hg and the other half was given retrogradely with coronary sinus pressure ranging between 30 and 50 mm Hg. All subsequent doses were given retrogradely through the coronary sinus. Cardioplegia was never given simultaneously by the two routes.

STATISTICAL ANALYSIS
Quantitative data were analyzed using the paired Student t test and qualitative data were analyzed using the standard error of differences between percentages (U test) and the chi-squared test where appropriate. A p value of less than 0.05 was considered significant. Data were expressed as mean values ± standard deviation.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
The two groups were similar with respect to age, sex, and angina class (Table 1Go). There were no significant differences between the groups in terms of risk factors, number of diseased vessels, ejection fraction, bypass parameters, number of grafts, myocardial support, the use of pacing and postoperative hemodynamic parameters (Tables 2 and 3GoGo). At the end of cardiopulmonary bypass, there were highly significant statistical differences between the groups in terms of the spontaneous recovery of sinus rhythm and the requirement of direct current shock to restore sinus rhythm, as shown in Table 4Go.


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  		Table 1. Preoperative Profile of Patients Given Antegrade (n = 25) or Combined Cardioplegia (n = 25)
 

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  		Table 2. Angiographic Findings in Patients Given Antegrade (n = 25) or Combined Cardioplegia (n = 25)
 

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  		Table 3. Operative Data in Patients Given Antegrade (n = 25) or Combined Cardioplegia (n = 25)
 

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  		Table 4. Myocardial Status after Declamping in Patients Given Antegrade (n = 25) or Combined Cardioplegia (n = 25)
 
ECG analysis showed that in group A, 16% of patients had new ischemic changes (ST-segment elevation of more than 2 mm, pathologic Q waves, or loss of R wave progression) on the day of surgery, which was persistent in 8% of patients up to the 3rd postoperative day. In group B, 12% had new ischemic changes on the day of surgery. These changes were persistent in 4% of patients up to the 3rd postoperative day. The difference was not statistically significant. No bundle-branch block was found in group B, while the incidence was 8% in group A (p < 0.05).

No differences were seen preoperatively between the two groups in terms of CK-MB levels (sample 1). There was a slight rise in both groups after declamping (sample 2), which reached a peak value after 4 hours (sample 3) and showed a tendency to decrease at 12 hours (sample 4). Samples 2, 3, and 4 had higher levels of CK-MB in group A compared to group B and the differences were significant for samples 2 and 4 (Figure 1Go).



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  		Figure 1. Creatine kinase MB-isoenzyme changes in patients given antegrade or combined retrograde-antegrade cardioplegia. Sample no. 1 = preoperative, 2 = 10 minutes after declamping, 3 = 4 hours after declamping, 4 = 12 hours after declamping.

 
Analyses of myoglobin showed that no agglutination was detected in the preoperative samples and they were empirically assumed to be 50 µg·L–1. In sample 2, there was a three-fold rise in both groups. The levels continued to rise in both groups and they were significantly higher in group A compared to group B for samples 3 and 4 (Figure 2Go).



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  		Figure 2. Myoglobin changes in patients given antegrade or combined retrograde-antegrade cardioplegia. Sample no. 1 = preoperative, 2 = 10 minutes after declamping, 3 = 4 hours after declamping, 4 = 12 hours after declamping.

 
Troponin T levels showed the same pattern as CK-MB. The preoperative samples were normal in both groups. In the intraoperative and postoperative samples, the levels started to rise in both groups to reach a peak in sample 3. The troponin T levels were significantly higher in sample 4 from group A compared to group B (Figure 3Go).



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  		Figure 3. Troponin T changes in patients given antegrade or combined retrograde-antegrade cardioplegia. Sample no. 1 = preoperative, 2 = 10 minutes after declamping, 3 = 4 hours after declamping, 4 = 12 hours after declamping.

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
The results of this study indicate that myocardial protection was better in the patients who received combined antegrade-retrograde cardioplegia as evidenced by cardiac rhythm, ECG changes, and the release of biochemical markers of myocardial injury. Although the standard technique of antegrade cardioplegic infusion is considered to be generally satisfactory, adequate myocardial protection cannot always be achieved. Experimental and clinical studies have demonstrated that critical stenosis of the coronary arteries may prevent homogenous distribution of cardioplegic solution when it is injected through the aortic root, which may contribute to the higher incidence of perioperative myocardial infarction observed in such patients.17–21

Retrograde coronary sinus perfusion was first introduced by Lillehei and colleagues22 in 1956 to facilitate surgery on the aortic valve. In the late 1970s, interest emerged in the coronary sinus as a route for delivery of cardioplegia. The adequacy of myocardial protection achieved by this retrograde technique was shown experimentally and clinically.2,23 However, concerns were raised that the sole use of retrograde perfusion creates inadequate preservation of the right ventricle on the basis of canine studies and on the observation that right ventricular venous drainage does not occur primarily via the coronary sinus.24,25 Furthermore, prolonged cardiac arrest due to the low flow rate used for retrograde cardioplegia was reported.9

The rationale for combined antegrade and retrograde routes of cardioplegic delivery is based on anatomic and experimental arguments.25,26 The coronary venous system is composed of two interrelated systems: the epicardial or superficial (greater) system and the endocardial or deep (lesser) system. The greater system includes the coronary sinus and its tributaries, the small cardiac vein, and the anterior cardiac vein that drain into the coronary sinus. The lesser system comprises the vessels that drain directly into the cardiac chambers. There is widespread anastomosis at all levels of the cardiac venous circulation.27,28 Thus, the myocardium may be adequately perfused retrogradely by this large venous network free of atherosclerotic changes.

Experimental studies have documented the nonhomogenicity of the distribution of coronary flow with either antegrade or retrograde cardioplegia alone, especially when there is coronary occlusion.29,30 It has been shown that antegrade blood cardioplegia provides homogeneous cooling and allows up to 4 hours of safe aortic clamping when all coronary arteries are patent. Conversely, there is delayed cooling and arrest of the anterolateral ventricle as well as poor early recovery of segmental shortening that impairs global recovery after 1 hour of ischemia following antegrade blood cardioplegia in the presence of an occluded left anterior descending coronary artery.17,31 On the other hand, retrograde coronary sinus cardioplegia leads to excellent hypothermia of the left ventricle and septum with complete return of contractile function in the anterior ventricle but inconsistent right ventricular wall cooling and 60% to 100% recovery of function. Antegrade cardioplegia distributes homogeneously throughout the heart but is redistributed away from the subendocardial muscle if there is coronary artery stenosis. Conversely, retrograde cardioplegia is distributed preferentially to subendocardial muscle, with or without coronary stenosis, but has a reduced distribution to the right ventricle and the septum, despite cooling these areas effectively.32 Advantages of using both routes of delivery of cardioplegia have been confirmed by the finding that left and right ventricular protection was achieved optimally by a combined antegrade-retrograde approach. The limitations of each method can be overcome by dividing the cardioplegic doses equally between antegrade and retrograde delivery.

In our study, retrograde cardioplegia was administered by the technique of transatrial blind cannulation of the coronary sinus. We used this technique to avoid bicaval cannulation and right heart isolation.9,33 There is no need for a right atriotomy for direct cannulation of the coronary sinus or cannula fixation using a pursestring suture around the orifice of the coronary sinus.34 We did not use the technique of right atrial cardioplegia.35 We share the opinion of others that although this technique is simple and obviates direct cannulation of the coronary sinus, it violates one of the most important principles of myocardial protection by inducing right ventricular distention in the arrested heart.36 Transatrial blind cannulation enabled us to use a single two-stage venous cannula. Hand-holding of the cannula with each dose was avoided and there was no need for balloon inflation or deflation by the surgeon as a self-inflating cannula was used according to the protocol described by Buckberg.37 We accomplished cannulation in most of the cases on a beating heart but used partial bypass when necessary to minimize hemodynamic changes.

No venous injury was detected among our patients. Menasché; and colleagues23 reported coronary sinus injury at the junction of the great cardiac vein in 2 patients in whom the coronary sinus pressure was not monitored during retrograde infusion for technical reasons. The principle sources of coronary sinus injury are forcible placement of the retrograde cannula into the coronary sinus and continued cardioplegic administration when coronary sinus pressure exceeds 50 to 60 mm Hg.37

In our study, the retrograde cannula was dislodged from the coronary sinus in 3 cases. We did not reinsert the stylet even if the retrograde cannula became dislodged into the right atrium. Rather, we removed the entire cannula and the stylet was reintroduced under direct vision to prevent inadvertent passage of the stylet through the larger holes in the balloon-containing portion of the cannula. Blind reinsertion risks advancing the stylet through these holes with possible coronary sinus perforation. It has been previously postulated that the proximity of the atrioventricular node to the coronary sinus orifice might lead to injury of the conduction system during cannulation of the coronary sinus.38 In our study, we did not encounter any cases of heart block after cannulation of the coronary sinus.

This study showed differences between the two groups with regard to spontaneous recovery of the myocardium and the need for direct current shock to restore sinus rhythm. Spontaneous heart contractions imply that high energy phosphate stores, nutrients, mitochondria, and cell membrane integrity were preserved during the period of potential ischemic injury.39 Although the need for intraoperative myocardial support was less in group B, the difference was not significant. These results confirm that combined antegrade-retrograde cardioplegia for CABG provides better myocardial preservation than the sole antegrade route. The incidence of low cardiac output needing myocardial support was also less in group B, although not statistically significant.

Bundle-branch block was less frequent in group B on the 3rd postoperative day (p < 0.05) and these patients had fewer ischemic ECG changes and arrhythmias (p > 0.05). Uchino and colleagues40 reported that the use of ECGs for diagnosis of perioperative myocardial infarction was disappointing because the ECG pattern is sometimes changed by bundle-branch block, rotation of the heart, or opening of the pericardium after surgery. It is difficult to establish the presence of a small infarction or to evaluate a new infarction in patients who have an old infarction or a pacemaker.

CK-MB and myoglobin are not absolutely specific to the heart, whereas troponin T is specific and sensitive for the diagnosis of myocardial injury.41,42 In our study, it was clear that the release of biochemical markers of myocardial damage was significantly less in group B, indicating superior myocardial preservation from combined antegrade-retrograde cardioplegia. Retrograde blind cannulation of the coronary sinus is a safe and simple procedure and we recommend that every cardiac surgeon should master this technique. Additional studies are necessary to ascertain the role of blood cardioplegia with the combined technique during routine cardiac surgery.

Presented at the Third International Cardiology Conference, Dubai, United Arab Emirates, April 1997.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Buckberg GD. Antegrade-retrograde blood cardioplegia to ensure cardioplegic distribution. Operative techniques and objectives. J Card Surg 1989;4:216–38.[Medline]

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  4. Chawla SR, Najafi M, David M, Serry C. Coronary obstruction secondary to direct cannulation. Ann Thorac Surg 1977;23:135–8.[Abstract]

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  14. Norregaard-Hansen K, Hangaard J, Norregard-Pederson B. A rapid latex agglutination test for detection of elevated levels of myoglobin in serum and its value in the early diagnosis of acute myocardial infarction. Scand J Clin Lab Invest 1984;44:90–103.

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  18. Shapira N, Lemole GM, Spagna PM, Bonner FG, Fernandez J, Morse D. Antegrade and retrograde infusion of cardioplegia: assessment by thermovision. Ann Thorac Surg 1987;43:92–7.[Abstract]

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  20. Quintilio C, Voci P, Bilotta F, et al. Risk factors of incomplete distribution of cardioplegic solution during coronary artery grafting. J Thorac Cardiovasc Surg 1995; 109:439–47.[Abstract/Free Full Text]

  21. Van der Salm TJ, Okike ON, Cutler BS, Parasakos JA, Ferulo J, Daggette M. Improved myocardial preservation by improved distribution of cardioplegic solutions. J Thorac Cardiovasc Surg 1982;83:767–71.[Abstract]

  22. Lillehei CW, Dewall RA, Gott VAL, Varco RL. The direct vision correction of calcific aortic stenosis by means of pump oxygenator and retrograde coronary sinus perfusion. Dis Chest 1956;30:123–7.[Medline]

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  24. Shiki K, Masuda M, Yonenaga K, Asou T, Tokunaga K. Myocardial distribution of retrograde flow through the coronary sinus of the excised normal canine heart. Ann Thorac Surg 1986;41:265–71.[Abstract]

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  29. Partington MT, Acar C, Buckberg GD, Julia P, Kofsky ER, Bugyi HI. Studies of retrograde cardioplegia. I. Capillary blood flow distribution to myocardium supplied by open and occluded arteries. J Thorac Cardiovasc Surg 1989; 97:605–12.[Abstract]

  30. Partington MT, Acar C, Buckberg GD, Julia P, Kofsky ER, Bugyi HI. Studies of retrograde cardioplegia. II. Advan-tages of retrograde/antegrade cardioplegia to optimize distribution in jeopardized myocardium. J Thorac Cardiovasc Surg 1989;97:613–22.[Abstract]

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  33. Menasché P, Subayi JB, Piwnica AH. Retrograde coronary sinus cardioplegia for aortic valve operations. A clinical report on 500 patients. Ann Thorac Surg 1990;49:556– 64.[Abstract]

  34. Guiraudon GM, Campbell CS, McLellan DG, et al. Retrograde coronary sinus versus aortic root perfusion with cold cardioplegia: randomized study of levels of cardiac enzymes in 40 patients. Circulation1986; 74(Suppl III):III-105–15.[Abstract/Free Full Text]

  35. Fabiani JN, Jebara V, Carpentier A. Right atrial cardio-plegia: a safe procedure for myocardial protection. Ann Thorac Surg 1989;47:331–2.[Medline]

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  40. Uchino T, Belbol A, Roberts D, Jagenberg R. Measurement of myosin light chain I and troponin T as markers of myocardial damage after cardiac surgery. J Cardiovasc Surg 1994;35:201–6.

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