World Journal of Cardiovascular Diseases, 2013, 3, 454-457 WJCD
http://dx.doi.org/10.4236/wjcd.2013.37071 Published Online October 2013 (http://www.scirp.org/journal/wjcd/)
Tepid antegrade intermittent blood cardioplegia as an
alternative for intermittent crossclamping with Lidoflazine
Sofia Kalantary1, Anouk de Bruyn1, Steven Laga2, Inez Rodrigus2
1University of Antwerp, Antwerp, Belgium
2Department of Cardiac Surgery, Antwerp University Hospital, Antwerp, Belgium
Email: email@example.com, firstname.lastname@example.org, Steven.Laga@uza.be, Inez.Rodrigus@uza.be
Received 27 July 2013; revised 29 August 2013; accepted 9 September 2013
Copyright © 2013 Sofia Kalantary et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background: Blood cardioplegia is a technique with
many variations in its use. Intermittent cross clamp-
ing with Lidoflazine has proven to deliver good car-
dioprotection in our center. Question: Is tepid (32˚C)
antegrade intermittent blood cardioplegia an efficient,
safe and easy-to-use alternative to intermittent cross-
clamping with Lidoflazine in elective isolated CABG
in low-risk patients? Primary outcomes are heart en-
zymes (cTnI, CK-MB). Secondary outcomes are op-
eration times, length of hospital stay, major compli-
cations and in-hospital mortality. Methods: From
January 2012 until November 2012, 40 patients with
LVEF ≥50%, EuroSCORE II <3.5% and no severe
systemic disease underwent elective CABG and were
consecutively randomized to intermittent cross-clamp-
ing (ICC; n = 20) or blood cardioplegia (BCP; n = 20).
All were operated on by the same surgeon. Results:
There were no significant differences in age (BCP
65.34 ± 9.76; ICC 65.25 ± 8.42) and EuroSCORE II
(BCP 1.25 ± 0.72; ICC 1.04 ± 0.71). There was a sig-
nificant difference in cross clamp time (BCP 61.10 ±
23.07; ICC 41.30 ± 13.10). No significant differences
in ECC-time (BCP 95.85 ± 27.04; ICC 113.80 ± 34.47)
and number of distal anastomoses (BCP 2.70 ± 0.73;
ICC 2.90 ± 0.72) were found. Values of cTnI 1-day
postoperative (BCP 1.50 ± 0.76; ICC 4.50 ± 3.90),
maximum cTnI (BCP 2.85 ± 1.73; ICC 6.40 ± 4.30)
and maximum CK-MB (BCP 21.10 ± 22.30; ICC 31.35
± 24.39) differed significantly. No significant differ-
ences in postoperative parameters were found: length
of hospital stay (BCP 7.95 ± 1.40; ICC 8.25 ± 1.71),
atrial fibrillation (BCP 0.20 ± 0.41; ICC 0.45 ± 0.51),
major complications (BCP 0.35 ± 0.49; ICC 0.30 ±
0.47). There was no in-hospital mortality. Conclusion:
Primary outcomes defined by the cardiac enzymes
(cTnI, CK-MB) favour the use of tepid antegrade in-
termittent blood cardioplegia in low-risk patients
undergoing elective CABG-operations. Regarding se-
condary outcomes, ICC showed shorter cross clamp
Keywords: Blood Cardioplegia; Intermittent Cross
Clamping; Lidoflazine; Myocardial Protection
Worldwide, there is a great variation in the techniques
used for optimization of myocardial protection during
CABG-operations. Despite much research on this topic,
no specific protocol has proven superiority [1-3]. For
more than 20 years, the use of intermittent cross-clamping
with Lidoflazine in our center has proven to deliver good
myocardial protection. Blood cardioplegia, on the other
hand, is a well-known cardioplegic technique, with many
variations in its use regarding the temperature, site and
frequency of its injection and composition of the solution.
Common principle is the mixture of a cardioplegic solu-
tion with blood of the patient.
Is tepid (32˚C) antegrade intermittent blood cardioplegia
an efficient, safe and easy-to-use alternative to intermit-
tent crossclamping with Lidoflazine in elective isolated
CABG-operations in low-risk patients? Primary out-
comes are values of postoperative heart enzyme values
(cTnI and CK-MB). Secondary outcomes are operation
times (extra-corporal circulation time (ECC), cross clamp
time (XTC) and total duration of surgery), post-operative
length of hospital stay, occurrence of postoperative atrial
fibrillation, major in-hospital complications and in-hos-
3. METHODS AND MATERIALS
From January 2012 until November 2012 forty low risk
S. Kalantary et al. / World Journal of Cardiovascular Diseases 3 (2013) 454-457 455
patients underwent an elective CABG-operation by one
Inclusion criteria were:
two or three vessels disease with a stenosis >70%.
Exclusion criteria were:
Severe renal insufficiency with a GFR <30 ml/min.
Age <18 years.
Patients were consecutively randomized to intermittent
cross clamping (ICC; n = 20) or blood cardioplegia (BCP;
n = 20). In the ICC-group, the patients received Li-
doflazine (1 mg/kg) systemically after induction of an-
esthesia [4,5]. The patient’s blood was cooled down by
the heater-cooler, to a bladder temperature of 28˚C -
30˚C, so hypothermia was another protective measure.
Repetitively, the aortic cross clamp was placed in order
to perform the distal anastomoses, with a maximum time
of 15 minutes for each single anastomosis to limit the
time of myocardial ischemia. In the BCP-group, patients
were operated on with the use of a modified Calafiore-
solution (KCl 1.7 mmol/ml, MgSO4 0.17 mmol/ml, aqua
pi ad 50 ml) with a temperature of 32˚C. This solution
was mixed with blood every 15 minutes and 400 cm3
was delivered into the aortic root during 2 minutes. Other
pump characteristics were a declining concentration of
the Modified Calafiore solution, starting at a rate of 120
ml/min and a maximum aortic root pressure of 100
mmHg. Postoperative follow up consisted of repetitive
measurements of cTnI and CK-MB. In addition, occur-
rence of major postoperative complications (cfr. infra),
atrial fibrillation and length of postoperative hospital stay
With the use of SPSS Statistics 20, statistical analyses
were performed. All values are expressed as mean ±
standard deviation. Using the Shapiro-Wilk test, normal-
ity was examined. After confirmation, the parameters
were analyzed using anunpaired T-test. The parameters
where normality was not found were analyzed using the
Mann-Whitney U-test. A probability level of 0.05 was
chosen as the criterion for statistical significance.
As shown in Table 1, there were no significant differ-
ences in demographic characteristics. The number of
patients is identical in both groups (BCP 20; ICC 20).
Fewer women than men undergo CABG, which explains
the male predominance in this study (sex ratio M/F: BCP
16/4; ICC 17/3). Since coronary heart diseases are mainly
a concern for middle-aged or older patients, both groups
Table 1. Demographic data.
with lidoflazine p-value
Number of patients20 20
Sexratio: M/F 16/4 17/3 0.681
Age (years) 65.34 ± 9.76 65.25 ± 8.42 0.695
EuroSCOREII 1.25 ± 0.72 1.04 ± 0.71 0.304
consist of patients aged 65 years and older (BCP 65.34 ±
9.76; ICC 65.25 ± 8.42). One of the inclusion criteria for
this study was a EuroSCORE II < 3.5%, as can be seen
in both study arms (BCP 1.25 ± 0.72; ICC 1.04 ± 0.71).
The peroperative parameters that were considered im-
portant were the number of distal anastomoses, ECC
time and aortic crossclamp time. These are shown in Ta-
ble 2. The number of distal anastomoses was comparable
(BCP 2.70 ± 0.73; ICC 2.90 ± 0.72). The mean value of
the ECC-time was higher in the Lidoflazine-group,
which can be explained by the deeper cooling used with
this technique and therefore longer reheating times. This
difference however did not prove to be of significance
(BCP 95.85 ± 27.04; ICC 113.80 ± 34.47; p-value 0.123).
The crossclamp time was significantly longer with blood
cardioplegia due to the placement of a single aortic cross
clamp compared with the intermittent cross clamping
method used with Lidoflazine (BCP 61.10 ± 23.07; ICC
41.30 ± 13.10).
There was no in-hospital mortality. Table 3 shows the
heart enzymes that were followed, cTnI and CK-MB.
These enzymes were repetitively measured and the 24-
hour postoperative and maximum values during the
whole postoperative course were determined. Most of
these heart enzyme values showed significant differences,
as shown in the following table.
As shown in Table 4, other important parameters such
as postoperative length of hospital stay and occurrence of
atrial fibrillation showed no significant differences. The
incidence of major complications was comparable. These
included: low cardiac output, arrhythmias, pulmonary-
complications (pneumonia, pulmonary embolism, pneu-
mothorax, ARDS), stroke, sternal dehiscence and wound
complications, severe renal insufficiency and infections.
Statistical analysis confirmed the comparability of both
groups considering patient characteristics (age, Euro-
SCORE II) and number of distal anastomoses, thus lim-
The efficiency of myocardial protection was measured
by postoperative levels of heart enzymes (cTnI, CK-MB),
which have proven to relate to the degree of myocardial
damage and are easily detectable [6,7].
Copyright © 2013 SciRes. OPEN ACCESS
S. Kalantary et al. / World Journal of Cardiovascular Diseases 3 (2013) 454-457
Table 2. Peroperative parameters.
Number of distal
anastomoses 2.70 ± 0.73 2.90 ± 0.72 0.363
ECC-time (min) 95.85 ± 27.04 113.80 ± 34.47 0.123
Crossclamp time (min) 61.10 ± 23.07 41.30 ± 13.10 0.002
Table 3. Levels of heart enzymes.
cTnI 1 day postoperative
(mmol/l) 1.50 ± 0.76 4.50 ± 3.90 0.000
Max. cTnI (mmol/l) 2.85 ± 1.73 6.40 ± 4.30 0.002
CK-MB 1 day postoperative
(mmol/l) 16.95 ± 18.63 26.05 ± 25.850.132
Max. CK-MB (mmol/l) 21.10 ± 22.30 31.35 ± 24.390.041
Table 4. Postoperative parameters.
Postoperative length of
hospital stay 7.95 ± 1.408.25 ± 1.71 0.499
Occurrence of atrial
fibrillation (%) 20 ± 41 45 ± 51 0.096
Major complications 0.35 ± 0.490.30 ± 0.47 0.739
Regarding the results of this study, the significant
lower value of postoperative cardiac enzymes with blood
cardioplegia can be addressed to different mechanisms.
Theoretical advantages of blood cardioplegia are the ca-
pacity to augment oxygen delivery by the presence of
hemoglobin to prevent ischemic injury and the presence
of buffers and radical scavengers .
Secondly, the hyperkalemia of the solution will lead to
a diastolic cardiac arrest making manipulation of the
heart easier for the surgeon, thus limiting the periopera-
tive damage to the heart. The cross clamp times however
have proven to be significantly longer with the use of
blood cardioplegia since this technique requires a single
aortic cross clamp. The coronary arteries are derived of
blood during the whole operation time, even when it is
not strictly required for the surgeon. The main benefit of
intermittent crossclamping with Lidoflazine is that the
aortic clamp is only placed when making an anastomosis,
providing the coronary arteries with blood in between.
This limits the ischemia times of the myocardium, which
is a target on itself during CABG-operations.
The theoretical downside of this repetitive cross-
clamping is the greater risk for cerebral embolisms if
plaques in the aorta are present. In some institutions
however, including ours, this higher incidence of strokes
using intermittent crossclamping with Lidoflazine was
not seen . Myocardial protection with intermittent
aortic crossclamping is economically advantageous when
compared to any cardioplegic solution .
Tepid blood cardioplegia is defined as a blood car-
dioplegia solution infused at a temperature of 32˚C. This
will lead to hypothermia of the heart and thus a reduced
metabolism of the myocytes. Secondarily, a certain de-
gree of systemic hypothermia will be reached, which will
vary dependant on the duration of the ECC-time, and the
settings of the heater-cooler.
Despite the existence of a protocol for the use of the
Modified Calafiore solution in our institution, difficulties
in applying this strictly in a clinical setting remains an
important issue. This is for example the case when the
amount of the cardioplegia solution needs to be adjusted
to the myocardial needs in case of remaining or resuming
heart activity. The lack of a standardized protocol in
these circumstances leads to great individual differences
depending on the perfusionist’s preferences.
A disadvantage of blood cardioplegia is the longer
preparation time needed by the perfusionist. These min-
utes can be of critical importance in urgent CABG-op-
erations where the damaged myocardium will benefit
from early connection to the heart-lung machine because
of the reduced workload. Another potential disadvantage
of blood cardioplegia is the possible damage by the high
potassium concentration to the endothelium of the coro-
nary arteries .
A limitation of this study is the small amount of in-
cluded patients. We expect more pronounced differences
in a larger study population. Furthermore, it would be
interesting to include high-risk patients in the study de-
sign, since they will benefit more from efficient myocar-
Primary outcomes defined by the cardiac enzymes (cTnI,
CK-MB) favour the use of tepid antegrade intermittent
blood cardioplegia in low-risk patients undergoing elec-
tive CABG-operations. Regarding secondary outcomes,
ICC with Lidoflazineonly showed shorter cross clamp
times, but other secondary outcomes were comparable.
 Hendrikx, M., Jiang, H., Gutermann, H., Toelsie, J., Re-
nard, D., Briers, A., Pauwels, J.L. and Mees, U. (1999)
Release of cardiac troponin I in antegrade crystalloid
versus cold blood cardioplegia. Journal of Thoracic and
Cardiovascular Surgery, 118, 452-459.
 Pichon, H., Chocron, S., Alwan, K., Toubin, G., Kaili, D.,
Copyright © 2013 SciRes. OPEN ACCESS
S. Kalantary et al. / World Journal of Cardiovascular Diseases 3 (2013) 454-457
Copyright © 2013 SciRes.
Falcoz, P., Latini, L., Clement, F., Viel, J.F. and Etievent,
J.P. (1997) Crystalloid versus cold blood cardioplegia and
cardiac troponin I release. Circulation, 96, 316-320.
 Elwatidy, A.M., Fadalah, M.A., Bukhari, E.A., Aljubair,
K.A., Syed, A., Ashmeg, A.K. and Alfagih, M.R. (1999)
Antegrade crystalloid cardioplegiavsantegrade/retrograde
cold and tepid blood cardioplegia in CABG. Annals of
Thoracic Surgery, 68, 447-453.
 Flameng, W. (1988) Myocardial protection. Annals of the
New York Academy of Sciences, 522, 600-610.
 Flameng, W., Borgers, M., Van der Vusse, G.J., De-
meyere, R., Vandermeersch, E., Thone, F., et al. (1983)
Cardioprotective effects of lidoflazine in extensive aorta-
coronary bypass grafting. Journal of Thoracic and Car-
diovascular Surgery, 85, 758-768.
 Sadony, V., Korber, M., Albes, G., Podtschaske, V.,
Etgen, T., Trosken, T., et al. (1998) Cardiac troponin I
plasma levels for diagnosis and quantitation of periopera-
tive myocardial damage in patients undergoing coronary
artery bypass surgery. European Journal of Cardio-
Thoracic Surgery, 13, 57-65.
 Costa, M.A., Carere, R.G., Lichtenstein, S.V., Foley, D.P.,
de Valk, V., Lindenboom, W., et al. (2001) Incidence,
predictors, and significance of abnormal cardiac enzyme
rise in patients treated with bypass surgery in the arterial
revascularization therapies study (ARTS). Circulation,
 Martin, J. and Benk, C. (2006) Blood Cardioplegia. Mul-
timedia Manual of Cardiothoracic Surgery, 1009, 1510.
 Boethig, D., Minami, K., Lueth, J.U., El-Banayosy, A.,
Breymann, T. and Koerfer, R. (2004) Intermittent aortic
cross-clamping for isolated CABG can save lives and
money: Experience with 15307 patients. Thoracic and
Cardiovascular Surgeon, 52, 147-151.
 He, G.W. and Yang, C.Q. (1996) Hyperkalemia alters
endothelium-dependent relaxation through non-nitric ox-
ide and noncy-clooxygenase pathway: A mechanism for
coronary dysfunction due to cardioplegia. Annals of Tho-
racic Surgery, 61, 1394-1399.
BCP: blood cardioplegia
CABG: coronary artery bypass grafting
XCT: cross clamp time
ECC: extracorporeal circulation
EuroSCORE: European System for Cardiac Operative
ICC: intermittent cross-clamping
LVEF: left ventricular ejection fraction