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Original Article

Does Combined Antegrade–RetrogradeCardioplegia Have Any Superiority

Over Antegrade Cardioplegia?Hassan Radmehr, MD, Aliakbar Soleimani, MD ∗,

Hassan Tatari, MD and Mehrdad Salehi, MDCardiac Surgery Ward, Imam Khomeini Hospital, Medical Sciences/University of Tehran, Iran

Background: In a prospective randomised clinical study we assessed and compared antegrade vs. combinedantegrade–retrograde cardioplegia in patients who underwent elective coronary artery by pass grafting.

Methods: Between March 2006 and January 2007, 87 consecutive patients were randomly divided into two groups.Group A (n = 45) received antegrade cold (4 ◦C) blood cardioplegia. Besides antegrade cardioplegia, Group B (n = 42)received continuous retrograde cardioplegia passively by gravitational force. The need for cardiac support during andafter cardiopulmonary bypass, post-operative morbidity, ICU stay, hospital stay and mortality were compared in twogroups.

Results: There was no significant difference between the two groups in gender, age and pre-operative ejection fraction.Scap

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ixteen patients in Group A (35.5%) and eight patients in Group B (19%) needed inotropic support while weaning offardiopulmonary bypass (p = 0.04). Four patients in Group A (8.9%) and two patients in Group B (4.8%) needed intra-ortic balloon pump (p = 0.44) in the ICU. We found no statistically important difference between the two groups inost-operative morbidity and mortality.Conclusions: Retrograde continuous infusion of cardioplegia by gravitational force combined with antegrade car-

ioplegia, provides satisfactory myocardial protection and eliminates the need for inotropic support compared withntegrade technique alone.

(Heart, Lung and Circulation 2008;17:475–477)© 2008 Australasian Society of Cardiac and Thoracic Surgeons and the Cardiac Society of Australia and

New Zealand. Published by Elsevier Inc. All rights reserved.

eywords. Cardioplegia; Myocardium; Coronary disease

ntroduction

neven distribution of antegrade cardioplegia espe-cially in cases with severe proximal stenosis of

oronary arteries or severe myocardial hypertrophy istill a matter of concern. To resolve this problem somenvestigators have suggested retrograde administrationf cardioplegia via coronary venous system. Never-heless, retrograde cardioplegia has some limitations.his study was designed to determine if combinedntegrade–retrograde cardioplegia is associated withmproved clinical outcomes compared with antegradeechnique alone.

eceived 1 July 2007; received in revised form 27 April008; accepted 30 April 2008; available online 26 July 2008

Corresponding author at: Cardiac Surgery Ward, Imamhomeini Hospital, Keshavarz Blvd., Tehran 1419731351, Iran.el.: +98 912 1480625; fax: +98 216 6438634.-mail address: asoleimani@sina.tums.ac.ir (A. Soleimani).

Patients and Methods

This study was carried out on patients who underwentcoronary artery bypass graft surgery (CABG) betweenMarch 2006 and January 2007. A total of 87 patients metinclusion/exclusion criteria (Table 1) and agreed to partic-ipate in the study.

The patients were randomly allocated (by drawingpieces of paper from a bag) into two groups: Group A andGroup B. Two-dimensional transthoracic echocardiogra-phy was performed for all patients on the day before theoperation and before discharge from hospital. The opera-tions were performed through median sternotomy usingcardiopulmonary bypass (CPB). We performed moderatehaemodilution (Hct = 25%) CPB with mild hypothermia(30–32 ◦C). The left internal mammary artery was used forrevascularisation of left anterior descending artery, andsaphenous vein for the others.

After aortic cross-clamping, cardiac arrest was accom-plished in both groups with antegrade infusion of1000 ml of cold (4 ◦C) blood cardioplegic solution ata 4:1 blood:solution ratio. Each litre of the antegrade

2008 Australasian Society of Cardiac and Thoracic Surgeons and the Cardiac Society ofustralia and New Zealand. Published by Elsevier Inc. All rights reserved.

1443-9506/04/$30.00doi:10.1016/j.hlc.2008.04.009

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476 Radmehr et al. Heart, Lung and CirculationDoes Combined Antegrade–Retrograde Cardioplegia 2008;17:475–477

Table 1. Inclusion/Exclusion Criteria

Inclusion CriteriaSevere proximal stenosis of coronary arteriesa

Severe left main coronary stenosisa

Mild or moderate AISever left ventricular hypertrophySever left ventricular dysfunction

Exclusion CriteriaPreoperative unstable haemodynamic stateSingle vessel diseaseRecent MIb

CABG concomitant with other cardiac surgeriesDialysis patientsRedo operations

AI: aortic insufficiency, MI: myocardial infarction.a Stenosis ≥80% in diameter.b MI within the last 3 months.

cardioplegic solution we used contained potassium chlo-ride 20 mequiv., magnesium chloride 3.25 g and procainehydrochloride 272 mg. A 13Fr. retrograde coronary sinusperfusion catheter (Gundry®, Medtronic Inc., USA) witha manual-inflating balloon was inserted by palpation in tothe coronary sinus. Cardiac arrest was maintained in bothgroups by intermittent antegrade infusion of 500 ml of thesame cardioplegic solution every 20–30 min. In Group B,we hung the cardioplegia bag 100 cm above the patient toinfuse cardioplegia passively by gravitational force. Ret-rograde infusion was started at a flow rate of 50 ml/minand not interrupted during distal anastomosis until 10 minbefore aortic declamping. The retrograde cardioplegicsolution contained magnesium chloride 1.5 g, potassiumchloride 10 mequiv. and procaine hydrochloride 140 mg/l.

To obtain a good visualisation during distal anastomo-sis, CO2 was blown onto the field. Mean arterial pressuremaintained about 50–70 mmHg throughout CPB.

In both groups failure in weaning off CPB was managedprimarily by epinephrine 0.05–1 �g/(kg min). If difficultyin weaning continued, dopamine 5–15 �g/(kg min) wasadded to epinephrine. Intraaortic balloon pump (IABP)was used as the final strategy to wean the patients off CPB.For those patients with ST changes and/or systolic bloodpressure <80 mmHg who were suspicious for myocardialinfarction, blood samples were collected to measure cre-atine kinase-MB isoenzyme 4, 8, 12, 24 and 48 h after the

Table 2. Pre-operative Data

Group A(n = 45)

Group B(n = 42)

p-Value

Age (mean ± S.E.) 58.1 ± 1.69 56.6 ± 1.57 0.51Gender (M/F) 28/17 32/10 0.15AI 7 5 0.62AS 1 4 0.14Pre-op EF (mean ± S.E.) 39.1 ± 1.66 38.6 ± 2.00 0.87

AI: aortic insufficiency, AS: aortic stenosis, EF: ejection fraction, S.E.:standard error.

Table 3. Post-operative Morbidity and Mortality

Group A Group B Total

CVA 2 1 3MI 1 1 2Pleural effusion 2 0 2Renal failure 1 0 1ST-T changes 3 4 7Mediastinitis 0 1 1Mortality 3 3 6

CVA: cerebrovascular accident, MI: myocardial infarction.

or rising in serum creatinine more than 0.5 mg/dl com-pared with preoperative level.

Statistical Analysis

The data were expressed as proportions or as themean ± standard deviation (S.D.). Differences in categori-cal variables were analysed by χ2 analysis and differencesin continuous variables were analysed by student’s t-tests.All analyses were performed using the SPSS software, ver-sion 9.0 (SPSS, Inc. Chicago, IL). Results were consideredsignificant if p values were less than 0.05.

Results

Of 87 patients, 60 were male (69%) and 27 were female(27%). The demographic characteristics of patients in twogroups are summarised in Table 2. In preoperative coro-nary angiography, severe proximal stenosis was reportedin 40% of patients in Group A and 45.2% in Group B(p = 0.62).

Sixteen patients in Group A and eight patients in GroupB (35.5% vs. 19%) needed inotropic support while weaningoff CPB (p = 0.04). Five patients in Group A and one patientin Group B needed IABP support in addition to inotropicagents for CPB weaning (11.1% vs. 2.4%). Inotropic sup-port was established for 17 patients in Group A (41.5%)

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operation. Echocardiography was performed for all thesepatients as well. Diagnosis of myocardial infarction wasmade based on CK-MB levels greater than 25 IU/L ornew Q wave in ECG or new wall motion abnormalitydetected in echocardiography. Post-operative renal insuf-ficiency was defined as serum creatinine level >1.5 mg/dl

Table 4. Post-operative Data

Gro

Cross clamp time (min) (mean ± S.E.) 45.7 ±Pump time (min) (mean ± S.E.) 85.7 ±ICU stay (days) (mean ± S.E.) 1.9 ±Hospital stay (days) (mean ± S.E.) 6.0 ±Pre-discharge EF (mean ± S.E.) 38.5 ±EF: ejection fraction, S.E.: standard error.

and six patients in Group B (15%) postoperatively in the

Group B p-Value

7 44.5 ± 0.65 0.219 78.5 ± 2.56 0.040 2.3 ± 0.42 0.445 6.6 ± 0.50 0.334 38.4 ± 2.12 0.97

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2008;17:475–477 Does Combined Antegrade–Retrograde Cardioplegia

ICU (p = 0.008). Four patients in Group A (8.9%) and twopatients in Group B (4.8%) needed IABP and inotropic sup-port in the ICU for more than 24 h (P = 0.448). Table 3 showspost-operative morbidity in two groups.

Three patients in each group (6.7% in Group A vs. 7.1%in Group B) died in the ICU before discharge (p = 0.93).ICU stay, hospital stay and pre discharge ejection fractionare summarised in Table 4.

Discussion

Different strategies are being used for myocardial pro-tection. Indeed, myocardial protection is an art whichdepends largely on the surgeon’s experience and skills[1,2]. There is no consensus on using an optimal methodfor the protection of myocardium during ischaemic arrest,although it has been debated since the beginning of openheart surgery [3]. In patients with severe coronary steno-sis (>90%) there might be maldistribution of antegradecardioplegic solution in the myocardium. Thus, over-perfusion of patent coronary arteries and impairment ofmyocardial protection may occur.

In patients with severe left ventricular hypertrophia (forany reason) myocardial vascular network is not developedproportional to increased myocardial thickness. Conse-quently, this hypertrophied cardiac tissue will not beprotected adequately and there will be an increased pos-sm

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The flow rate that we used provided sufficient myocar-dial protection in our patients.

In this study, the probable disability of retrograde car-dioplegia in right ventricular protection was eliminated byadministration of antegrade cardioplegia.

The need for IABP was less in Group B (4.8% vs.8.9%).Although this finding was not found to be statisticallyimportant, we believe that, considering the expense ofinserting an IABP and potential peripheral vascular andhaemorrhagic complications arising from its use, thisreduction in number could be valuable.

ConclusionOn the basis of the results obtained from this clinicalstudy, we concluded that co-administration of retrogradeand antegrade cardioplegia has a great protective effecton myocardial cells and would diminish the need forinotropic support during and after CPB weaning.

References[1] Mentzer Jr RM, Salik Jahania M, Lasley RD. Myocardial pro-

tection. In: Cohn LH, Edmonds Jr LH, editors. Cardiac Surgeryin the Adult, NY. 2nd ed. McGraw-Hill Inc.; 2003. p. 413–38.

[2] Kouchoukos N. Cardiac Surgery. 3rd ed. Churchill Living-stone; 2003. pp. 131–162.

[3] Onoratio F, Renzulli A. Does antegrade cardioplegia aloneprovide adequate myocardial protection? J Thorac Cardiovasc

[1

[1

[1

[1

ibility of cardiac injury during aortic cross-clamping andyocardial ischaemia [4].In these patients, combined delivery of antegrade and

etrograde cardioplegia may provide a more homoge-eous distribution of cardioplegic solution. Some cardiacurgeons believe that leakage of retrograde cardioplegicolution through the coronary arteriotomy site duringistal coronary anastomosis obscures the surgical fieldnd results in prolongation of the operation [5–8]. Theylso propose that most portions of the right ventricle willot be protected effectively because there is no directommunication between the coronary sinus and anteriorardiac veins. This may particularly be problematic inatients with inadequate venous collaterals or right ven-

ricular dysfunction and can lead to incomplete recoveryf myocardium after CPB weaning [9–11].The appropriate pressure for retrograde continuous

dministration of cardioplegia is a matter of concern.coronary sinus pressure greater than 40 mmHg has

een reported to result in myocardial oedema as well asndothelial injuries. To avoid these complications, andnowing that 1 mmHg equals 1.36 cmH2O, we hung theardioplegia bag about 100 cm above the patient to be ableo infuse the cardioplegic solution passively by gravita-ional force with a pressure of about 37 mmHg.

Although in some studies the recommended flow rateor infusion of retrograde cardioplegia has been reportedbout 200 ml/min [12], we infused retrograde cardioplegiat a flow rate of 50 ml/min. We believe that with a flow ratef about 200 ml/min the pressure in coronary sinus willxceed 40 mmHg. Salerno and associates found that per-usion pressure in the coronary sinus would remain below0 mmHg if they keep the flow rate around 122 ml/min [13].

Surg 2003;126:1345–51.[4] Cook JE, James R. Does cardioplegia type affect outcome and

survival in patients with advanced left ventricular dysfunc-tion? Circulation 2000;102:84–9.

[5] Aronson S, Jacobsohn E, Savage R, Albertucci M. The influ-ence of collateral flow on the antegrade and retrogradedistribution of cardioplegia in patients with an occluded rightcoronary artery. Anesthesiology 1998;89:1099–107.

[6] Hilton CJ, Teubl W, Acker M. Inadequate cardioplegic pro-tection with obstructed coronary arteries. Ann Thorac Surg1979;28:323–4.

[7] Villanueva FS, Spotnitz WD, Glasheen WP. New insights intothe physiology of retrograde cardioplegia delivery. Am J Phys-iol 1995;268:H1555–66.

[8] Wranne B, Pinto FJ, Hammarstrom E. Abnormal right heartfilling after cardiac surgery: time course and mechanisms. BrHeart J 1991;66:435–42.

[9] Grondin CM, Helias J, Vouhe PR. Influence of a critical coro-nary artery stenosis on myocardial protection through coldpotassium cardioplegia. J Thorac Cardiovasc Surg 1981;82:608–15.

0] Aronson S, Lee BK, Liddicoat JR. Assessment of retrogradecardioplegia distribution using contrast echocardiography.Ann Thorac Surg 1991;52:810–4.

1] Caretta Q, Voci P, Acconcia MC. Collateral flow prevents unin-tentional myocardial ischemia during antegrade cardioplegiain patients undergoing coronary bypass grafting. J ThoracCardiovasc Surg 1997;113:585–93.

2] Ikonomidis JS, Yau TM, Weisel RD, Hayashida N, Fu X,Komeda M, Ivanov J, Carson S, Mohabeer MK, Tumiati L,Mickle DAG. Optimal flow rates for retrograde warm cardio-plegia. J Thorac Cardiovasc Surg 1994;107:510–9.

3] Salerno TA, Houck JP, Barrozo CA, Panos A, Christakis GT,Abel JG, Lichtenstein SV. Retrograde continuous warm bloodcardioplegia: a new concept in myocardial protection. AnnThorac Surg 1991;51:245–7.