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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 27, No 5, September/October 2016
300
AFRICA
higher than in patients with both valvular and congenital heart
disease.
7
Namiki
et al
.
8
reported that endothelin-1 concentrations
in the pericardial fluid were more elevated in patients with
ischaemic heart disease than in those with non-ischaemic
heart disease. In addition, Ege
et al
.
9
reported that levels
of IL-2R, IL-6, IL-8 and TNF-
α
in pericardial fluid were
significantly higher than in the serum in patients with MI. The
pericardial fluid is partially formed from cardiac interstitial fluid,
which migrates through the epicardium,
10
therefore vasoactive
substances released into the myocardial interstitium may appear
in the pericardial fluid.
6
Although levels of pro-inflammatory cytokines are well
documented in both MI and heart failure, the relationship
between cytokine levels, LV function and location of MI has not
been fully clarified. The purpose of this study was to examine the
relationship between LV function, cytokine levels and site of MI
in patients undergoing coronary artery bypass grafting (CABG).
For this purpose, the patients undergoing CABG were divided
into three groups according to the history of site of MI: anterior
MI, posterior/inferior MI and no previous MI. LV function
was analysed by transthoracic echocardiography and the levels
of adrenomedullin, TNF-
α
, IL-1
β
, IL-6 and angiotensin-II in
both the plasma and pericardial fluid were measured in these
subgroups of patients.
Methods
From September 2006 to September 2007, 60 patients who
underwent primary CABG surgery were enrolled in this
prospective study. There were 54 (90%) males and the mean age
of the patients was 60.89
±
9.39 years.
Coronary angiography and 12-lead electrocardiograms (ECG)
were performed on each patient. All patients had documented
coronary artery disease, defined as more than 75% stenosis in
one or more of the principal coronary arteries, determined by
coronary angiography.
Patients who had a recent MI in the last three weeks,
emergent operation, coronary artery re-operation, cardiogenic
shock, complications of acute MI (LV aneurysm, post-infarction
ventricular septal defect or free wall rupture), haemodynamically
significant valvular disease (severe regurgitation of more than
two degrees or severe stenosis requiring surgical intervention),
atrial fibrillation, active infectious disease, malignancies, chronic
inflammatory disease or renal dysfunction were excluded from
the study.
The baseline characteristics of the patients are shown in Table
1. Ongoing drug treatment included beta-blockers, angiotensin
converting enzyme inhibitors, nitrates, calcium channel blockers
and diuretics. All drugs were withheld on the day of the study.
According to the ECG and cardiac catheterisation findings,
patients were divided into three groups.
1
The group with no
previous MI (
n
=
20) included patients with no documented
history of transmural MI. The anterior MI group (
n
=
20)
included patients who had a total occlusion in the left anterior
descending (LAD) coronary artery or q-waves in at least two
anterior ECG leads. The posterior/inferior MI group (
n
=
20)
included patients who had a total occlusion in the right coronary
artery (RCA) or left circumflex coronary artery (LCx), or
q-waves in the posterior–inferior ECG leads.
This study was conducted in accordance with guidelines
approved by the ethics committee at our institution. Informed
consent was obtained from each participant prior to inclusion
in the study.
Standard anaesthesia and anaesthetic techniques were used
in all patients by the same anaesthesiology team. Following a
median sternotomy, the ascending aorta was cannulated for
arterial inflow and the right atrial appendage was cannulated
with a two-stage cannula for venous uptake. A cardioplegic
tack was introduced into the aortic root, proximal to the aortic
cannulation site for antegrade cardioplegic delivery. Heparin
was given at a dose of 3 mg/kg for systemic anticoagulation, and
cardiopulmonary bypass was established.
Myocardial protection was maintained initially using cold
(0–4°C) crystalloid cardioplegia solution, followed by cold blood
(10ºC) cardioplegia, and finally warm blood (37°C) cardioplegia.
Mild systemic hypothermia (32°C) was applied.
We used the left and right internal thoracic arteries and the
radial artery as arterial grafts, and the saphenous vein as venous
graft during CABG. If the left internal thoracic artery was in
optimal condition and had pulsatile flow, it was preferentially
anastomosed to the left anterior descending coronary artery.
After a median sternotomy, the mediastinal adipose tissue
and thymus were displaced from the pericardium, which was
opened and pericardial fluid was collected. Contact between the
pericardial fluid and blood was meticulously avoided.
Arterial blood samples were simultaneously withdrawn
from an intra-arterial cannula. The samples were immediately
transferred into glass tubes and centrifuged at 3 500 rpm for four
minutes. The samples were kept at –80°C for subsequent assays.
Levels of adrenomedullin, IL-6, TNF-
α
, IL-1
β
and
angiotensin-II in the plasma and pericardial fluid were measured.
Adrenomedullin levels were measured with a commercial kit
(Phoenix Pharmaceuticals Inc, CA, USA) using the enzyme
immunoassay (EIA) method. IL-6, TNF-
α
and IL-1
β
levels
were measured with commercial kits (Biosource Diagnostics,
Nivelles, Belgium) using the EIA method. Angiotensin-II levels
were measured with a commercial kit (Biosource Diagnostics,
Nivelles, Belgium) and radioimmunoassay (RIA) method.
LVfunctionwas analysed indetail inall patientspre-operatively
by transthoracic echocardiography (Vingmed System 5
Performance™, General Electric, USA). Measured indices of
LV function were LV end-diastolic diameter (LVEDD), LV
end-diastolic volume (LVEDV), LV end-diastolic volume index
(LVEDVI), LV end-systolic diameter (LVESD), LV end-systolic
volume (LVESV), LV end-systolic volume index (LVESVI),
fractional shortening (FS) and LV ejection fraction (LVEF). A
two-dimensional echocardiogram from the apical view was used
for determination of LVEF by single-plane planimetry of the left
ventricle (modified Simpson method).
Statistical analysis
For continuous variables, results are presented as mean
±
standard deviation (SD). As the values obtained were not
normally distributed, non-parametric methods were used for
tests of significance. The Kruskall–Wallis test was used to
compare the means between the three groups (no previous MI,
anterior MI and posterior/inferior MI). If this test indicated a
significant difference between the groups, the Mann–Whitney
U
-test was used to compare differences between the groups.