Open Journal of Thoracic Surgery, 2012, 2, 5-9 Published Online March 2012 ( 5
Single Dose Inamrinone in Terminal Warm Cardioplegia
in On-Pump Coronary Artery Bypass Patients
Aarne Jyrala1*, Nicole M. Gatto2, Gregory L. Kay1
1Department of Cardiothoracic Surgery, The Heart Institute at Good Samaritan Hospital, Los Angeles, USA; 2School of Public
Health, Department of Biostatistics, University of California, Los Angeles, USA.
Email: *
Received December 11th, 2011; revised January 28th, 2012; accepted February 4th, 2012
Background: Phosphodiesterase inhibitors (PDI) are used in cardiac surgery to improve and stabilize cardiac function
after surgery. The aim of this study is to evaluate changes in hemodynamics and early outcomes when PDI (Inocor/
inamrinone) is given in terminal warm blood cardioplegia to on-pump CABG only patients and compare results with
patients who did not receive the drug. Material and Methods: From April 2003 through September 2004 241 pts under-
went elective on-pump CABG only surgery. 141 pts received Inocor in the terminal warm blood cardioplegia (Group 1)
and 100 pts did no t (Group 2). Result s: Demographic data, preoperative EuroSCORE risk scores and operative details
were similar. Of pts preoperatively in sinus rhythm (SR) 80.15% in Group 1 and 69.79% in Group 2 regained spontaneous
SR (p = 0.07) after release of crossclamp. Ino tropic support was need ed in 5 pts in Group 1 and in 12 pts in Group 2, p
= 0.02. Post cardiopu lmona ry b y-p ass ( CPB) IABP suppor t was ne eded for 4 p ts in Gr oup 2 and non e for Group 1 pts, p
= 0.01. There was no operative mortality in either Group and hospital/30 day mortality was similar (3/2.13% vs
3/3.00%, p = 0.69). There w ere no statistical difference in stay in postoperative inten sive care unit (p = 0 .15), total hos-
pital stay (p = 0.07), appearance of postoperative atrial fibrillation (p = 0.23) or appearance of postoperative kidney
injury (p = 0.27). Post CPB cardiac index improved 16.90% in Group1but decreased 1.49% in Group 2, p < 0.0001.
Mean arterial pressure decreased 7.46% in Group 1 pts and 5.08% in Group 2 pts, p = 0.002, but no pts in either Group
needed medication for too low blood pr essure. Systemic vascular resistance decr eased 28.40% in Group 1 and 9.02% in
Group 2, p < 0.0001. Conclusions: Inamrinone in terminal warm blood cardioplegia (hot shot) is safe and effective way
to improve and stabilize cardiac function after on-pump CABG surgery but does not affect short-term outcomes.
Keywords: Phosphodiesterase Inhibitors; Postop erative Cardiac Function
1. Introduction
Phosphodiesterase (PDE) III inhibitors (PDI) are widely
used in cardiac surgery [1] to facilitate weaning from
cardiopulmonary bypass (CPB) and to stabilize the pa-
tient after surgery. Mostly used is Primacor® (milrinone,
Sanofi-Aventis, Bridgewater, NJ, USA), which is a de-
rivative of Inocor® (inamrinone, Bedford Laboratories,
Bedford, OH, USA) and has several times greater ino-
tropic and vasodilatory properties on weight basis than
Inocor but is short-lived (half life approx 30 min) and
needs initial bolus dose and continued intravenous admini-
stration which often leads to low systemic blood pressure
and subsequent ne ed for drugs to increase blood pressur e
[2,3] Inocor has a half-life of 3.6 hours and is able to
sustain its effect for the critical early postoperative hours
when given in a single dose before or after release of cross-
clamp [4-7]. The hemodynamic effects of both drugs are
similar [8].
We hypothesized that giving a PDI directly into the
coronaries rather than intravenously or into CPB would
result in better cardiac recovery and performance after
CPB and possibly have less vasodilatory effects than
systemic delivery. Intracoronary administration has been
studied with CHF patients and shown to be effective in
increasing cardiac performance acutely [9]. There are no
earlier reports available about intracoronary use of PDI’s
in combination with cardiac surgery. The PDI was given
preemptively to all pts operated with cardiopulmonary
by-pass by two surgeons. One surgeon did not give PDI to
any patient, so we were able to compare two groups of
elective on-pump CABG surgery patients for differences
which may be achieved by giving preemptive Inocor
intracoronary with the hot shot.
The aim of this study is to evaluate the safety and ef-
fects of intracoronary administration of Inocor after elec-
*Corresponding a uthor.
Copyright © 2012 SciRes. OJTS
Single Dose Inamrinone in Terminal Warm Cardioplegia in On-Pump Coronary Artery Bypass Patients
tive on-pump CABG surgery. The effects are compared
with a matching population of patients who did not re-
ceive Inocor.
The study was approved by the hospital’s research
2. Material and Methods
From April 2003 through September 2004 510 pts under-
went on-pump cardiac surgery at our institute. Only elec-
tive on-pump CABG patients were included into the study.
Patients with concomitant cardiac procedures, valve or
aortic procedures, emergency operations, patients with
ongoing inotrope infusions and pts with preoperative
IABP support were excluded leaving 241 pts for the
At the time of the study two surgeons gave preemptive
Inocor to every pt and one surgeon did not give it to any
pt and did not contribute in the preparation of manuscript.
This created two groups of pts: Inocor group ( Group 1) n =
141 pts and no In ocor group (Gr ou p 2) n = 100 pts.
25 - 50 mg Inocor was given into the terminal warm
cardioplegia (hot shot) by perfusionist. The dose was de-
pendent on the size of the patient. Pts with a BSA > 2 m2
were given 50 mg and smaller pts 25 mg. The dose is about
two thirds of the manufacturer recommended starting
Cardiac output, cardiac index (CI), arterial pressure
were measured and systemic vascular resistance (SVR)
calculated when pts were anesth etized but before open ing
the chest and again 30 - 45 minutes after cross-clamp had
been released and the patient weaned from CPB. The
results were documented on the anesthesia sheet. Mean
arterial pressures (MAP) were calculated using formula
MAP = (Syst BP + 2 × Diast BP)/3. Operative and perfu-
sion reports were analyzed for nu mber of graf ts, len g th of
CPB, length of aortic cross-clamp, need for cathechola-
mines at the time of separation from CPB and need for
IABP support. Spontaneous return of sinus rhythm (SR)
of pts preoperatively in SR were documented.
Early outcomes [stay in the postoperative intensive
care unit (ICU)], length of hospitalization (LOS), occur-
rence of postoperative atrial fibrillation (AF) and acute
kidney injury (AKI), operative and hospital/30 day mor-
tality) were obtained from hospital charts of all pts.
3. Statistical Analysis
Variables were examined in their continuous form and
categorized as follows: baseline serum creatinine (>2.2
mg/dl, <2.25 mg/dl) and left ventricular ejection fraction
(<0.3, >0.3). Demographic characteristics, EuroSCORE
variables, operative factors and short-term follow-up
measures were summarized by administration of PDI in
the hot shot (Group 1-Inocor n = 141, Group 2-no Inocor,
n = 100). Variables were compared between Groups us-
ing simple parametric t-test or chi = square test and a
p-value < 0.05 was regarded as statistically significant.
All analyses used SAS version 9.2 (SAS Institute Inc.
Cary, NC, USA).
4. Surgical Technique
All pts were operated through standard median sternotomy.
Ascending aorta was cannulated when feasible and single
venous cannulation with vacuum assistance was used for
venous return. Moderate hypothermia to 34˚C was used
during CPB.
Cold whole blood cardioplegia was used given ante-
gradely and retrogradely. Retrograde cardioplegia was given
continuously during cross-clamp time stopping only when
it interfered with visualization and for maximum of 10
minutes at a time. Pts were rewarmed in the later stages
of the procedure and when the pts temperature was
>36˚C, 500 ml of warm blood was given retrogradely
(hot shot). Inocor 25 - 50 mg was added to this by the
perfusionist to Group 1 pts. Cross-clamp was removed
when the hot shot was completed.
Anesthesia was conducted according to hospital ap-
proved protocol in all cases.
5. Results
The demographic variables and ES risk scores were equal
between the groups and no single variable had a statistic-
cally significant difference. The data is summarized in
Tables 1 an d 2.
Comparing operative details the number of grafts, CPB
and cross-clamp times were equal. Appearance of spon-
taneous sinus rhythm in pts in preoperative SR after re-
lease of cross-clamp was quite similar between the Groups:
Group 1 pts (109/80.15% vs 67/69.79%, p = 0.07). Need
for cathecholamines for weaning and stabilization the pa-
tient was lower in Group 1 pts (5/3.55% vs 12/12.00%,
P = 0.01). No pt needed IABP support after CPB in
Group 1 but 4 pt s in Group 2, p = 0.01.
Postoperative outcomes did not differ statistically al-
though there was a tendency for longer ICU and LOS
and higher incid ence of postoperativ e AF in Group 2 pts.
There were no difference in appearance of AKI (defined
as postoperative rise in s-crea > 2.2 mg/dl). Outcomes are
summarized in Table 3.
Mean pre CPB CI, MAP and SVR did not differ be-
tween the groups. CI improved after CPB in Group 1
with 16.90%, p < 0.0001, while in Group 2 CI decreased
by 1.49%, p = 0.64.
MAP decreased sign ificantly in bo th groups, 7.46% v s
4.82%, p < 0.0001 for Group 1 pts and p = 0.002 for
Group 2 pts. There was no pt in either Group who needed
drugs for too low blood pressure.
Copyright © 2012 SciRes. OJTS
Single Dose Inamrinone in Terminal Warm Cardioplegia in On-Pump Coronary Artery Bypass Patients
Copyright © 2012 SciRes. OJTS
Table 1. Demographics of Groups 1 and 2 patients.
Variable Group 1, n = 141
m ± SD/n (%) Group 2, n = 100
m ± SD/n (%) p
Age, years 66.76 ± 9.56 66.31 ± 11.36 0.71
Females 50 (35.50) 32 (32.00) 0.58
NYHA 2.71 ± 0.62 2.78 ± 0.76 0.48
LVEF 0.48 ± 0.14 0.48 ± 0.14 0.93
LVEF < 0.3 11 (7.81) 13 (13.00) 0.19
CHF 34 (24.11) 22 (22.00) 0.76
DIABETES 53 (37.58) 49 (49.00) 0.08
PTS IN PREOP SR 136 (96.45) 96 (96.00) 0.86
S-CREA 1.27 ± 1.03 1.28 ± 1.04 0.96
S-CREA > 2.2 mg/dl 7 (4.96) 6 (6.00) 0.73
RE-DO 14 (9.93) 10 (10.00 %) 0.99
3VD 78 (67.38) 68 (68.00) 1.00
2VD 36 (25,53) 18 (18.00) 0.21
1VD 10 (7.09) 14 (14.00) 0.09
LM > 70% 31 (21.99) 13 (13.00) 0.09
AES 5.48 ± 3.31 5.23 ± 3.26 0.57
LES 7.80 ± 10.02 7.44 ± 9.08 0.77
NYHA: New York Heart Association functional classification; LVEF: left ventricular ejection fraction; CHF:
congestive heart failure; SR: sinus rhythm; S-CREA: serum creatinine concentration in mg/dl; RE-DO: reopera-
tion on the heart; 3VD: triple vessel coronary artery disease; 2VD: double vessel disease; 1VD: single vessel dis-
ease; LM: l eft main coronary artery stenosis; AES: additi v e EuroSCORE points; LES: logistic EuroSCORE %.
Table 2. Operative details.
Variable Group 1
m ± SD/n (%) Group 2
m ± SD/n (%) p
Grafts/patient 3.51 ± 0.99 3.52 ± 1.11 0.92
CPB 1 21 .72 ± 34.71 115.90 ± 34.78 0.20
X-clamp 102.50 ± 28.72 95.27 ± 27.20 0.05
Spont SR 109 (80.15) 67 (69.79) 0.07
Inotropes1 5 (3.55) 12 (12.00) 0.01
IABP support 0 4 (4.00) 0.01
Oper. mortality 0 0
CPB: cardiopulmonary bypass time, minutes; X-clamp: aortic cross clamp time, minutes; SR: sinus rhythm;
IABP: intra-aortic balloon pulsation device; ¹Cathecolamines, dopamine, adrenaline or noradrenaline for weaning
off CPB and continued to intensive care unit.
Table 3. Postoperative outcomes.
Variable Group 1
m ± SD/n (%) Group 2
m ± SD/n (%) p
Hospital/30 day mortality 3 (2.13) 3 (3.00) 0.67
ICU days 1.53 ± 1.66 2.12 ± 4.38 0.15
LOS days 7.79 ± 5.43 9.16 ± 6.24 0.08
Postop AF1 13 (10.74) 16 (16.67) 0.11
Postop AKI2 11 (8.21) 12 (12.77) 0.28
ICU: stay in postoperative intensive care unit; LOS: total hospital stay; AF: atrial fibrillation; AKI: acute kidney
injury, postoperative rise in s-crea > 2.2 mg/dl. 1Of pts with preoperative SR, Group 1 n =136, Group 2 n = 94;
2Of pts with preopera tive s-crea < 2.25 mg/dl, Group 1 n = 13 3 Group 2, n = 94.
Single Dose Inamrinone in Terminal Warm Cardioplegia in On-Pump Coronary Artery Bypass Patients
SVR decreased in both Groups after CPB, significantly
in Group, 28.40% 1, p < 0.0001 but not significantly in
Group 2 9.02%, p = 0.05. See Table 4.
PDE III inhibitors were discovered in the 70’s and their
hemodynamic effects soon evaluated [10] which led to
widespread use in cardiac surgery and used instead or
together with cathecholamines for pts who developed
low output after CPB [11-13]. Several different dosing
regimens have been used usually with a loading dose and
iv-infusion for several hours post surgery. Single dosage
use has been tried sp ecifically with Inocor [4,6 ,7 ] with its
longer half life. The drugs ar e usually given into the CPB
or intravenously with no obvious hemodynamic differ-
ences but both leaves the heart for second or third p ass of
the drug. Also the timing of introducing the drug has
many modifications, they have been given prior to CPB,
at the end of CPB or after CPB but all regimens seem to
have good hemodynamic effects.
The heart is the primary target for PDI but there are no
clinical reports available where the drug have been given
into coronary circulation (i.e. via cardioplegia) at the end
or CPB. There is one recent experimental study from Ko
and coworkers from 2009 [5] where high dose of Inocor
was given in the terminal warm blood cardioplegia before
releasing the crossclamp. They observed much improved
cardiac function with Inocor vs no Inocor specifically
increased myocardial cAMP. Coronary perfusion was
also higher with Inocor as reported for humans also [14].
They concluded that (one dose) Inocor promote a rapid
and sustained cardiac functional recovery with various
cellular protective effects [15,16] after open heart surgery
Our idea was to deliver Inocor directly into the heart in
order to have the first pass of the drug in the heart/myo-
cardium and possibly have less effect of the vasodilatory
properties with less use of medications to boost low blood
pressure commonly seen with intravenous infusions.
Our results parallel the results of Ko [5] although we
do not have any biochemical data. Comparing the groups
there is a definite improvement in cardiac performance in
Group 1 specially comparing pre- and post CPB CI and
less use of cathecolamine suppor t.
SVR and MAP also decreased statistically more in Group
1 but there were no instances where the blood pressure
needed to be medically improved. This is in contrast to
giving PDI as a loading dose and continue with intrave-
nous infusion and it has been recommended to give si-
multaneous norepinephrine with this dosing. Intracardiac
route decreases or eliminates the inappropriate fall of blood
pressure but is highly effective in promoting better hemo-
dynamics and stability in the early postoperative hours.
There are no statistical differences in early outcomes
as reported by others [17,18] although there is a tendency
of longer IC U and LOS in Grou p 2 pts.
The reason for postoperative AF is multifactorial but
theoretically good myocardial recovery together with good
myocardial protection should result in lesser amount of
postoperative AF but it was not evid ent in this stud y. In a
recent report Fleming and coworkers [19] found increased
amount of postoperative AF when PDI was used after
separation from CPB but the pts who had AF had lower
EF, were older, had longer CPB times and already had
cathecholamine support which all resu lt in an increase in
postope ra t ive AF.
No adverse effects of Inocor were observed.
7. Drawbacks
There are several shortcomings in this study. It is an ob-
servational retrospective single unit study with rather low
numbers of patient s .
The goal of this study was to analyze hemodynamic
effects and safety of a not earlier reported way of deliv-
ering preemptive PDI during on-pump CABG surgery.
8. Conclusions
Preemptive intracardiac/intracoronary PDI at the end of
CPB is safe and reliable way to improve hemodynamics
and myocardial recovery after cardiac surgery.
Table 4. Changes in cardiac index, mean arterial pressure and systemic vascular re sistanc e post CPB.
Variable Group 1
m ± SD/n (%) Group 2
m ± SD/n (%) p
Pre CPB CI 2.61 ± 0.66 2.68 ± 0.56 0.35
Post CPB CI 3.03 ± 0.74 2.64 ± 0.58 <0.0001
Pre CPB MAP 83.60 ± 8.17 83.64 ± 8.17 0.97
Post CPB MAP 77.36 ± 5.12 79.61 ± 5.87 0.002
Pre CPB SVR 1277.16 ± 421.5 4 1277.50 ± 390.55 0.99
POST CPB SVR 914.48 ± 278.50 1162.214 ± 413. 64 <0.0001
CPB: cardiopulmonary bypass; CI: cardiac index, l/min/m2; MAP: mean arterial pressure, mmHg; SVR: systemic
vascular resistance, dyne*sec/cm5.
Copyright © 2012 SciRes. OJTS
Single Dose Inamrinone in Terminal Warm Cardioplegia in On-Pump Coronary Artery Bypass Patients 9
When given directly into the heart with terminal warm
cardioplegia the expected improvements in hemodynamics
are prominent but the strong vasodilatation seen with
intravenous use is decreased.
The study was funded by Elma Larsson Foundation
and Los Angeles Thoracic and Cardiovascular Foundation.
Los Angeles, USA.
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