Experimental Studies
Repeated stunning precedes myocardial hibernation in progressive multiple coronary artery obstruction

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Abstract

OBJECTIVE

The aim of this study was to characterize a regional myocardial flow-function relationship in collateral dependent myocardium produced by multiple coronary artery obstruction.

METHODS

Ameroid constrictors were placed around the proximal right (RC) and circumflex (CX) coronary arteries and a silicon tubing cuff around the proximal LAD (left anterior descending artery) (luminal stenosis ±77%) in 18 dogs. Weekly two-dimensional echocardiography was performed for regional function (anterior [A], inferoposterior [IP], wall thickening [WT]), and fractional shortening (FS). Colored microspheres injected at baseline and before sacrifice, before and after dipyridamole (0.5 mg/kg) injection, determined resting flow (RF) and coronary reserve (CR), respectively.

RESULTS

Coronary angiography performed at four weeks after surgery confirmed occlusion of RC and CX with collateralization and a tight stenosis of LAD. Initially, an episodic reduction in A and IP WT was observed which became persistent later (AWT: 16 ± 3%; IPWT: 16 ± 4%, FS: 20 ± 4%, p < 0.005 vs. baseline [BS]). With dobutamine a biphasic response (improvement in A and IP WT between 5–15 and dysfunction between 20–30 μg/kg/min) was observed. Seven dogs were sacrificed at eight weeks and showed normal RF but reduced transmural CR (A: 75 ± 18%; IP: 46 ± 22% of control). Seven dogs underwent PTCA of the LAD at eight weeks and showed gradual improvement in AWT with normalization at 12 weeks (AWT: 30 ± 5%, p < 0.001 vs. eight weeks). At sacrifice RF and CR in the A wall were normal but there was reduced subendocardial RF in the IP region (64% of BS). Further, biopsy samples showed normal histological findings and high energy phosphate content in all dogs. Radioligand binding assays using 125I-iodocyanopindolol showed downregulation of beta-adrenergic receptor density in the dysfunctional regions compared with control.

CONCLUSIONS

In this canine model of viable, collateral dependent and reversibly dysfunctional myocardium, there was early episodic dysfunction followed by persistent dysfunction which was initially associated with normal RF and later with subendocardial hypoperfusion.

Abbreviations

A
anterior
AR
adrenergic receptors
AS
anteroseptum
AW
anterior wall
Bmax
maximum number of binding sites
BS
baseline
CM
colored microspheres
CR
coronary reserve
ECG
electrocardiogram
endo
endocardial
epi
epicardial
FS
fractional shortening
HEPC
high energy phosphate content
HPLC
high performance liquid chromatography
i.m.
intramuscularly
IP
inferoposterior
IV
intravenous
Kd
dissociation constant
IW
inferior wall
LAD
left anterior descending artery
LV
left ventricle
MS
midseptum
PTCA
percutaneous transluminal coronary angioplasty
PW
posterior wall
QCA
quantitative coronary analysis
WT
wall thickening

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This study was supported, in part, by The Michael Ondetti Chair in Cardiology at The University of Leuven held by Dr. Johan Vanhaecke. Part of the study was conducted during the tenure of a scholarship awarded to Dr. Bharati Shivalkar by The European Society of Cardiology.