Closed-chest animal model of chronic coronary artery stenosis. Assessment with magnetic resonance...

ORIGINAL PAPER

Closed-chest animal model of chronic coronary arterystenosis. Assessment with magnetic resonance imaging

Ming Wu • Jan Bogaert • Jan D’hooge •

Karin Sipido • Frederik Maes • Steven Dymarkowski •

Frank E. Rademakers • Piet Claus

Received: 8 October 2009 / Accepted: 30 November 2009 / Published online: 10 December 2009

� Springer Science+Business Media, B.V. 2009

Abstract To evaluate the consequences of chronic

non-occlusive coronary artery (CA) stenosis on myo-

cardial function, perfusion and viability, we developed

a closed-chest, closed-pericardium pig model, using

magnetic resonance imaging (MRI) as quantitative

imaging tool. Pigs underwent a percutaneous copper-

coated stent implantation in the left circumflex CA

(n = 19) or sham operation (n = 5). To evaluate the

occurrence of myocardial infarction, cardiac troponin I

(cTnI) levels were repetitively measured. At week 6,

CA stenosis severity was quantified with angiography

and cine, first-pass and contrast-enhanced MRI were

performed to evaluate cardiac function, perfusion and

viability. In the stenting group, cTnI values signifi-

cantly increased at day 3 and day 5 (P = 0.01), and

normalized at day 12. At angiography, 13/19 stented

pigs had a stenosis [75%. Mean degree of CA stenosis

was 91 ± 4%, range 83–98%. At contrast-enhanced

MRI, mean infarct size was 7 ± 6%, range 0.7–18.4%.

Five of the 6 pigs with stenosis \75% had no

infarction. Stented pigs showed significantly higher

Left-ventricular volumes and normalized mass

(P \ 0.05), and lower ejection fraction (P = 0.03)

than the sham pigs. Both wall thickening and myocar-

dial perfusion were significantly lower in animals with

at least one segment [50% infarct (23 ± 8%;

0.05 ± 0.01 a.u./s) and animals with only \50%

infarct segments (29% ± 12%; 0.07 ± 0.02 a.u./s),

than sham pigs (52 ± 6%; 0.10 ± 0.03 a.u./s)

(P \ 0.001; P \ 0.05). This minimally-invasive ani-

mal model of chronic, non-occlusive CA stenosis,

presenting a mixture of perfusion and functional

impairment and a variable degree of myocardial

necrosis, can be used as substitute to study chronic

myocardial hypoperfusion.

Keywords Coronary artery stenosis � Ischemia �Myocardial infarction �Magnetic resonance imaging �Animal model

The authors Ming Wu and Jan Bogaert contributed equally to

this work.

M. Wu � J. D’hooge � F. E. Rademakers � P. Claus

Cardiovascular Imaging and Dynamics, Department of

Cardiovascular Diseases, Catholic University Leuven,

Leuven, Belgium

J. Bogaert � S. Dymarkowski

Department of Radiology, Catholic University Leuven,

Leuven, Belgium

K. Sipido

Experimental Cardiology, Department of Cardiovascular

Diseases, Catholic University Leuven, Leuven, Belgium

F. Maes

Department of Electrical Engineering (ESAT/PSI),

Catholic University Leuven, Leuven, Belgium

P. Claus (&)

Medical Imaging Research Center, University Hospitals

Leuven, Campus Gasthuisberg, Herestraat 49, 3000

Leuven, Belgium

e-mail: [email protected]

123

Int J Cardiovasc Imaging (2010) 26:299–308

DOI 10.1007/s10554-009-9551-1

Background

Animal research has provided a large body of

knowledge regarding pathophysiology, possible

treatment strategies, and relevant pharmacological

interventions in myocardial ischemia, myocardial

infarction (MI) and heart failure [1, 2]. The better

these animal models reflect the true clinical

situation, the more appropriate they will be in

understanding the complex interaction between

coronary artery (CA) narrowing, occurrence of

myocardial ischemia and infarction, and the ven-

tricular response to the locally altered loading

conditions [3, 4]. Several approaches to study

chronic ischemia are currently available. From

an angiographic point of view they can be divided

in 3 groups: models with CA occlusion, with

CA patent and with CA stenosis. The first

group includes CA ligation or ameroid constrictor

implantation [5] using an open-chest preparation,

or the implantation of coiling/gelfoam [6], or open-

cell sponges [7]. In the second group, the models

consist of intracoronary microembolization [8],

gelatine sponge embolization [9]. In the last group,

hydraulic occluders [10, 11], or ameroid constric-

tors [12, 13] are generally used to create a CA

stenosis. A major drawback is that often these

models require a surgical thoracotomy. We there-

fore developed, a minimally-invasive approach

using percutaneous implantation of a copper-coated

stent leading to a gradually growing, non-occlusive

CA stenosis due to induction of intima prolifera-

tion [14, 15].

In the past, usually a combination of techniques

has been used to study the impact on regional

myocardial function (e.g., ultrasonic crystals, echo-

cardiography) [5, 12], myocardial perfusion (e.g.,

microspheres, nuclear imaging) [6, 10], and myocar-

dial viability (e.g., triphenyltetrazolium chloride

(TTC) staining [16], microscopy [7]). Nowadays,

magnetic resonance imaging (MRI) offers the oppor-

tunity to obtain all the above information in an

accurate, reproducible and non-invasive way within a

single examination session [17]. The purpose of the

current study was therefore to quantify the impact of

a percutaneous copper-coated stent implantation on

the myocardial function, perfusion and infarct size

using MRI.

Materials and methods

Instrumentation

This study was conformed to the Guide for the Care

and Use of Laboratory Animals published by the US

National Institutes of Health (NIH Publication No.

85-23, revised 1996) and was approved by a local

ethical committee (Ethische Commissie Dierproeven,

K.U. Leuven, Leuven, Belgium).

A bare-metal stent (Freedom Force coronary stent,

Gobal Therapeutics, Inc. Broomfield, CO, USA) was

eroded in hydrochloric acid for 2 min and coated

with copper by electroplating. Before implantation

the copper-coated stent was immersed in heparin in

an attempt to prevent acute in-stent thrombosis.

Twenty-four crossbred domestic pigs of either

gender (weight 20–30 kg, Animalium K.U. Leuven,

Leuven, Belgium) were loaded with 300 mg aspirin

(ASA) (Dispril, Reckitt Benckiser, Brussels, Belgium)

and 300 mg clopidogrel (Plavix, Sanofi, Paris, France)

1 day before the intervention. After intramuscular

premedication with tiletamine (4 mg kg-1) and zo-

lazepam (4 mg kg-1) (Zoletil100, Virbac Animal

Health, Carros, France) and xylazine (2.5 mg kg-1)

(Vexylan, CEVA Sante Animale, Brussels, Belgium),

an endotracheal tube was intubated. Anaesthesia was

induced with intraveneous propofol (3 mg kg-1)

(Diprivan, AstraZeneca, Brussels, Belgium) and main-

tained with a continuous intravenous infusion of

propofol (10 mg kg-1 h-1). Mechanical ventilation

with a mixture of air and oxygen (1:1) at a tidal volume

of 8–10 ml kg-1 was adjusted to maintain normocap-

nia and normoxia, as controlled with arterial blood gas

values, measured at regular time intervals during the

study. A continuous 3-lead electrocardiogram moni-

tored heart rate (HR) and rhythm. A lateral cut-down

was performed in the cervical region. An 8F sheath

was placed in the right carotid artery. A bolus of ASA

(500 mg) (Aspegic, Sanofi, Brussels, Belgium) and

heparin (10,000 IU) (Heparine Leo, Leo pharma,

Wilrijk, Belgium) were administrated through the

sheath to prevent thromboembolism. The left main CA

was catheterised under X-ray fluoroscopic guidance

with an 8F Judkins left catheter. In 19 of the 24

animals, assigned to the stented group, a copper-

coated stent was placed in the proximal segment of the

circumflex CA (LCx) through an angioplasty balloon

300 Int J Cardiovasc Imaging (2010) 26:299–308

123

(2.5 mm to 3.0 mm) by standard catheterisation

techniques. This procedure is known to induce coro-

nary stenosis by reactive intima hyperplasia. The

incision was sutured. In the other 5 pigs, a sham

operation was performed. To prevent infection of the

wound enrofloxacin (2.5 mg kg-1) (Baytril, Bayer,

Brussels, Belgium) was administered intramuscular.

ASA (300 mg) and clopidogrel (75 mg) were admin-

istrated orally daily for 6 weeks.

Experimental protocol

In the 6th week after the intervention (stent placement

or sham operation), an angiographic examination and

a cardiac MRI were performed. In all animals, HR and

rhythm were monitored during the entire protocol.

Premedication, anaesthesia and ventilation followed

the same protocol as described above. After the study

animals were euthanized with an overdose of satu-

rated potassium chloride under deep anaesthesia.

Cardiac troponin I (cTnI) measurement

To evaluate the occurrence of myocardial infarction,

a subgroup of 7 pigs in the stented group and 5 sham

animals were studied. Blood samples (2.5 ml) were

collected for the measurement of plasma concentra-

tion of cTnI at the following instances in both groups:

before intervention (BL), day 3, 5, 12, 19, 26 and

33 days after.

Coronary angiography

Coronary angiography was performed with a 6F

Judkins left coronary catheter. Contrast medium

(Visipaque 320, Amersham Health, Wemmel, Bel-

gium) was injected selectively in the left and right

CA. Images were saved and written on CDs for

review and quantification.

Magnetic resonance imaging protocol

All animals were scanned in supine position in a 1.5

Tesla MRI scanner (Magnetom, Sontana, Siemens

Medical Solutions, Erlangen, Germany) with a phased

array body coil wrapped over the heart to enhance the

signal to noise ratio. Images were acquired with ECG

gating and during suspended respiration.

Function imaging

Cine images at rest were acquired in vertical long

axis (VLA), horizontal long axis (HLA), and short

axis (SA) using true fast imaging with steady-state

precession (True-FISP) sequences with the following

imaging parameters: repetition time 3 ms, echo time

1.51 ms, 65� flip angle, field of view 370 mm, voxel

size 2.2 9 1.4 9 6.0 mm, 35 cardiac phases and

bandwidth 977 Hz/Px. In SA, a set of contiguous

slices was obtained covering the entire left ventricle

along its long axis from base to apex.

Perfusion imaging

For the assessment of myocardial perfusion, first-pass

perfusion imaging was performed with a bolus of

0.05 mmol kg-1. Gadolinium diethylenetriaminepen-

taacetic acid bis(methylamide) (GdDTPA-BMA)

(Omniscan, GE Healthcare, Diegem, Belgium) intra-

venous delivery. Three slice locations (basal, mid,

and apical) were acquired every R-R interval with a

trufi (steady-state free precession)-sr (saturation-

recovery) gradient-echo echo planar sequence for a

period lasting 100 heartbeats. Typical imaging

parameters included repetition time 2.3 ms, echo

time 0.96 ms, inversion time 110 ms, 50� flip angle,

field of view 350 mm, voxel size 3.6 9 2.7 9

8.0 mm, acquisition window 764 ms and bandwidth

1400 Hz/Px.

Late enhancement imaging (LE)

About 15 min after total injection of 0.2 mmol kg-1

GdDTPA-BMA, delayed contrast enhanced images

were obtained using a 3D inversion-recovery Turbo-

FLASH sequence: repetition time 3.84 ms, echo time

1.35 ms, 10� flip angle, field of view 300 mm, voxel

size 2.2 9 1.6 9 5.0 mm. The inversion time (TI)

was modified iteratively to obtain maximal nulling of

remote normal left-ventricular (LV) myocardium.

Typical inversion times ranged from 280 to 350 ms.

Images were obtained 15 min after contrast injection.

Data analysis

cTnI plasma levels were determined by a 1-step

sandwich enzyme-linked immunosorbent assay tech-

nique and analyzed on a Dimension clinical chemistry

Int J Cardiovasc Imaging (2010) 26:299–308 301

123

analyzer (Dade Behring Inc, Brussels, Belgium). The

commercial anti-human antibody has been shown to

completely cross react with the swine polypeptide [18].

Coronary angiography was assessed quantitatively

using dedicated software (ACOM, Siemens Medical

Solutions, Erlangen, Germany) and relative luminal

diameter reduction (in %) was measured by compar-

ing the minimal lumen diameter to the diameter of a

reference segment of the left coronary artery prox-

imal to the stenosis. Animals with a stenosis larger

than 75% were considered as suitable models for

chronic hypoperfusion.

All MRI data sets were analysed with in house

developed software (CardioViewer, K.U. Leuven,

Leuven, Belgium). The American Heart association

(AHA) 17 segment model [19] was applied for

regional myocardial analysis. The 3 level correspond-

ing myocardial perfusion slices were divided into 6

equiangular segments at basal and mid slices and 4 at

apical slice. To standardize the segmentation, the

anterior junction of the right ventricle on the left

ventricle was taken as reference. For the SA cine and

LE image stacks, apical and basal LV slices were

visually identified. For the cine images, end diastolic

and end systolic phases were determined, and the

endo- and epicardial boundaries were manually

delineated to extract LV myocardial mass, LV

end-systolic volume (LVESV), LV end-diastolic

volume (LVEDV) and ejection fraction (EF). Volu-

metric parameters were indexed to body weight.

Systolic wall thickening was defined as: (end-systolic

wall thickness—end-diastolic wall thickness)/

end-diastolic wall thickness. On the LE images,

endo- and epicardial borders and the region of late

enhanced regions were manually contoured. Myocar-

dial infarct size was calculated as total LE volume

normalized to LV myocardial volume. The first-pass

perfusion images were analysed by manually tracing

epi- and endocardial borders on the first image, and

propagating contours to subsequent phases, manual

adjusting contours where necessary to compensate for

breathing artefacts. Time-signal intensity curves of

the LV cavity and the myocardial segments were

generated. Baseline frames were used to adjust the

zero level of the signal intensity curves. The first-pass

of contrast was manually determined as the time

period between the initial onset of contrast in the

cavity and myocardium and the onset of the recircu-

lation of contrast. A gamma-variate function was

fitted to the signal intensities during this first pass.

The peak upslope of the resulting time-signal inten-

sity curves was determined in the myocardial and LV

curves. The results of the myocardial segments were

corrected for differences of the speed and compact-

ness of the contrast agent bolus by division of the

myocardial upslope through the LV upslope. The

stented group was divided into MI?? (at least one

segment with [50% of the segmental area shows LE)

and MI? (all segments show LE B50% of the

segmental area). Segments belonging to the ventric-

ular septum were defined as remote regions.

Statistical methods

Data were analyzed with Statistica (Statistica 8.0,

Statsoft Inc, Tulsa, OK, USA). T-test was performed

for global and regional parameters between two

different groups. Simple regression analysis was used

to compare two parameters. One way analysis of

variance (ANOVA) was used to test the levels of

significance between the MI?, MI?? and the

inferolateral region from the sham group. If signif-

icance was indicated, a Duncan test correction was

used as a post-hoc test for multiple comparisons. Data

are expressed as mean ± SD. Statistical significance

was inferred for a value of P \ 0.05.

Results

The 19 stented animals were studied based on the

combination of the resulting CA stenosis and infarct

size (Fig. 1).

At coronary angiography performed at week 6, 13

out of 19 stented animals (68%) had a significant CA

stenosis [75% and were considered as appropriate

models. The 6 animals with a CA stenosis \75%

were excluded from further analysis. Noteworthy,

one animal with a stenosis of 70% presented with an

infarct size of 8.5%, while the other 5 had no LE

(Fig. 1).

All sham pigs showed a normal coronary angiog-

raphy. In the 13 animals with a significant CA

stenosis, a mean CA stenosis of 91 ± 4% (range 83

to 98%) was found. Twelve out of 13 animals with

significant CA stenosis presented with LE. In these

animals mean infarct size was 7.0 ± 6.0% of LV


123

mass, ranging from 1 to 18%. The number of

segments presenting LE per pig was 6 ± 3, ranging

from 2 to 11. Mean infarct-transmurality per segment

was 20 ± 1.4%, range 0 to 90%. From these

appropriate models, 5 animals were classified as

MI??, while 8 animals as MI?, including the

animal without LE. Representative examples are

given in Figs. 2 and 3 for MI? and MI??,

respectively.

cTnI values were obtained in a subgroup of 7

stented animals and the 5 sham animals. Regarding

baseline cTnI values, no differences were found

between the stenting group and the sham group, i.e.,

0.41 ± 0.40 and 0.54 ± 0.49 lg/l, respectively,

P = 0.65. Stented pigs showed a significant increase

in cTnI values at day 3 and day 5 (P = 0.01) in 6/7

pigs, which all normalized at day 12 (Fig. 4). In the

sham pigs no changes in cTnI values were found. In

the stented animals, there was a positive correlation

between the maximal cTnI values and infarct size

(IS) (cTnI = 1.66*IS ? 6.56; r2 = .65; P = 0.029).

Taking into account only pigs with severe CA

stenosis (i.e. [75%) (n = 13), LV EDV, ESV, as

well as normalized LV EDV, ESV, and LV mass

values were significantly higher in stented pigs

compared to sham pigs (P \ 0.05)(Table 1). LV EF

was slightly but significantly lower in the stenting

group compared to the sham group (P = 0.03). LV

EF (P = 0.0002) was negatively correlated with

infarct size (LV EF = -1.24*IS ? 57; r2 = .74;

P = 0.0002). Wall thickening in the remote myocar-

dium was comparable between sham and stented pigs

(46 ± 6% versus 43 ± 8%; P = 0.48). Wall thick-

ening was significantly lower in both MI?

(29 ± 12%) and MI?? (23 ± 8%) groups compared

to sham pigs (52 ± 6%) (MI?: P = 0.001, MI??:

P = 0.0003) (Fig. 5).

No differences were found in regional perfusion in

the remote region between sham and stented pigs

(0.09 ± 0.03 a.u./s versus 0.09 ± 0.03 a.u./s;

P = 0.86). In contrast, the upslope was significantly

lower in the stented pigs showing LE and significant

CA stenosis, i.e., MI?: 0.07 ± 0.02 a.u./s; MI??:

0.05 ± 0.01 a.u./s versus sham pigs (0.10 ± 0.03

a.u./s) (MI?: P = 0.04; MI??: P = 0.001) (Fig. 6).

Discussion

In the current study, we presented a pig model of

chronic CA stenosis, using percutaneous implantation

of a copper-coated stent and MRI as quantitative

imaging tool to assess myocardial morphology,

function, perfusion and viability.

At 6 weeks post implantation, the majority of pigs

(68%) showed a significant CA stenosis ([75% at

coronary angiography) but no CA occlusion. In the

perfusion territory distally to the CA stent, a mild but

variable amount of myocardial necrosis in terms of

size and transmurality was found at contrast-

enhanced MRI. Moreover stent implantation induced

resting perfusion defects, regional functional impair-

ment and adverse LV remodelling, using sham pigs

as reference. This combined minimally-invasive

approach using trans-catheter implantation in combi-

nation with MRI provides a reliable model to

accurately study chronic CA stenosis, useful to

investigate the issue of chronic regional ischemia in

a controlled setting.

Repetitive measurement of cardiac enzymes (cTnI

levels) in a subgroup of stented animals suggested an

onset of myocardial necrosis in the first (i.e. 3–5) days

post stent implantation, i.e. early after stent implan-

tation. Yarbrough et al. [18] recorded a peak concen-

tration as soon as 90 min after the coronary occlusion

in the pig. Leonardi et al. [20] demonstrated that cTnI

levels began to increase at day 1 to 3 after coronary

ligation and after myoblast implantation and gradually

Fig. 1 Overview of the infarct size and coronary stenosis at

6 weeks in the stented group. The six animals (5 without

infarct and 1 (the point in a circle) with 8.5% infarct size) with

coronary artery stenosis \75% were excluded from further

study. At LE, 5 animals had at least one segment with [50%

segmental area showing LE (MI??) and 8 had all segments

showing B50% LE of the segmental area (MI?)


123

recovered to physiological levels in the next 14 days

in a sheep model. Serum cTnI levels are proportional

to the extension of myocardial injury measured with

contrast-enhanced MRI in humans [21] and in a dog

model [22]. This relation was confirmed in the

present study. Taking into account the angiographic

findings at 6 weeks after implantation showing

absence of CA occlusion in all stented pigs, this

suggests that myocardial necrosis is more likely due

to early in-stent thrombosis with spontaneous reper-

fusion, while the chronic CA stenosis results from

gradual intima proliferation in the copper coated

stent. In this respect, one animal excluded from the

model (Fig. 4) showed interesting characteristics:

cTnI 35.96 lg/l at day 5, 8.5% infarct size and

70% stenosis. This is further indicating that intima

proliferation did not result in myocardial necrosis in

this model.

Since copper is highly immunogenic and causes

inflammatory reactions in porcine CAs [23], it pro-

vides a mean to reliably create CA narrowing ranging

from non-occlusive stenosis to complete obstruction

[24]. Thus, depending on the copper stent design, and

the time of follow-up, different experimental models

can be developed. Ameroid constrictors are frequently

used in studying therapies for chronic ischemia such as

angiogenesis. They cause different degrees of CA

stenosis to CA occlusion within a month, and produce

chronic ischemia with mild infarction similar to

copper-coated stents, but need a thoracotomy [13].

Moreover, due to the rapid and maximal development

of collateral vessels in the pig in the presence of total or

Fig. 2 Correlative imaging data of an animal in the

MI? group. A A coronary stenosis (CS) is visible within the

stent. B In this animal a small non-transmural infarct was

induced. C A perfusion defect was clearly visible in the lateral

wall extending between the two papillary muscles. D No

considerable thinning of the at-risk wall (lat) was observed as

compared to the anterior wall (ant)


123

near complete obstruction, myocardial blood flow and

function can frequently restore to normal levels at rest

[12]. So the application of this ameroid model was

sometimes limited.

MRI data obtained at 6 weeks, suggested signif-

icant LV remodelling with increased LV EDV and

ESV, resulting in a slight but significant decrease in

LVEF. Moreover, LVEF was negatively correlated to

infarct size. Thus even relatively small infarcts had a

negative impact on global LV volumes and function,

findings that are concordant with the previous work

from our group [25].

The interaction between myocardial injury and

compensatory changes in LV mass is less clear, with

no relation between neither LV mass and LV

volumes, nor LV mass and infarct mass. Thus,

besides total infarct size, most likely the CA patency

and thus severity of myocardial ischemia should be

taking into account too.

In the myocardial perfusion territory distally to the

CA stent, both the resting myocardial perfusion as

systolic wall thickening significantly decreased com-

pared to similar regions in sham pigs. For both

myocardial perfusion and systolic wall thickening no

differences were found between MI?? and MI?

pigs. These findings are in line with previous studies

using echocardiography [15]. Moreover, in the one

excluded animal who had 70% stenosis, the rest

perfusion (0.085 a.u./s) from the MI?? area did not

decrease as much as the mean MI?? upslope value

Fig. 3 Correlative imaging data of an animal in the

MI?? group. A A coronary stenosis (CS) similar to Fig. 1 is

visible within the stent. B A large transmural infarct is detected

by late contrast enhancement in the lateral wall extending from

the anterior to the posterior papillary muscle. C In the same

region a concomitant perfusion defect is visible together with a

thin lateral wall (lat) as compared to the anterior wall (ant) (D)


123

(0.05 a.u./s). These findings suggest that the stenotic

lesion is the main cause for the reduced perfusion.

Limitations

For the regional analysis we used the 17-segment

model established by the AHA [19], which was

designed for patient studies, and has not been

validated in pigs. As the CA anatomy is similar

between humans and pigs, use of this model is

defendable, though ideally true CA perfusion territo-

ries should be used [3]. To better establish myocar-

dial flow patterns in the presence of CA stenosis flow

studies should be performed under stress conditions

using vasodilatory agents.

Clinical implications

Since this animal model of chronic, non-occlusive

CA stenosis mimics a patient population presenting

non-occlusive CA stenosis at coronary angiography,

often with a variable degree of myocardial infarction,

regional dysfunction, and LV remodelling, this model

can serve to study the relationship between coronary

and myocardial abnormalities, and ventricular

response in a controlled setting.

Fig. 4 Individual profiles cTnI evolution in a subgroup (n = 7)

of the stented animals. The infarct occurs at day 3–5. IS: infarct

size

Table 1 The characteristics and hemodynamic parameters

(mean ± SD) for sham and stented animals with severe coro-

nary artery stenosis [75%

Group Sham Stented

Weight (kg) 60 ± 12 55 ± 7

Stenosis (%) – 91 ± 4

Infarct size (%) – 7 ± 6

LVESV (ml) 45 ± 9 76 ± 24*

LVESV index (ml/kg) 0.76 ± 0.07 1.40 ± 0.49*

LVEDV (ml) 112 ± 28 145 ± 25*

LVEDV index (ml/kg) 1.85 ± 0.11 2.66 ± 0.53*

LV mass (g) 81 ± 14 91 ± 13

LV mass index (g/kg) 1.37 ± 0.13 1.66 ± 0.20*

EF (%) 59 ± 5 49 ± 9*

* P \ 0.05 vs. sham; LVEDV: left ventricular end diastolic

volume; LVESV: left ventricular end systolic volume; EF:

ejection fraction; index: normalized for body weight

Fig. 5 MRI regional function measurements (wall thickening)

in the sham and the stenting group. * P \ 0.005 vs.

inferolateral wall region in sham

Fig. 6 MRI regional perfusion measurements (relative ups-

lope) in the sham and the stenting group. * P \ 0.05 vs.

inferolateral wall region in sham


123

Conclusion

We presented an minimally invasive approach to

create in a pig model a chronic, non-occlusive CA

stenosis presenting a mixture of myocardial infarc-

tion, perfusion and function abnormalities, and com-

pensatory LV remodeling, using MRI as quantitative

imaging tool. This combined approach may contrib-

ute to better investigate the pathophysiological

mechanisms of chronic myocardial ischemia and

ultimately lead to improved patient treatment.

Acknowledgments This work was supported by the Gecon-

certeerde OnderzoeksActie (GOA) project (K.U. Leuven,

Leuven, Belgium) and two research grants (G.0438.06 and

G.0613.09) from the Flanders Research Foundation (FWO-

Vlaanderen, Belgium). We thank Mr. Pascal Hamaekers for

technical assistance.

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Closed-chest animal model of chronic coronary artery stenosis. Assessment with magnetic resonance...

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