Pathologisch-anatomische und immunhistologische Untersuchungen des ischämischen Schweinemyokards

2 SUMMARY Pathologically-anatomical and immunhistochemistric
investigation of ischemic myocardium in the pig Background:
Different degrees of histological alteration have been seen in
hibernating myocardium. Hibernation is associated with structural
myocardial changes, which involve both the cardiomyocytes and the
cardiac interstitium. The purpose of this study is to investigate
the effects of chronic myocardial ischemia on histological patterns
to understand the underlying mechanism of hibernation. Methods: A
model of ischemic injury was produced in 16 pigs (German land
breed) by placement of a modified stent graft in the left anterior
descending artery (LAD), which initially produced 75% stenosis,
followed by a slow complete occlusion. Wall motion abnormalities
were investigated by Magnetic Resonance Imaging (MRI) and
ultrasound images at day 7 after implantation. Metabolism and
perfusion were imaged by Positron Emission Tomography (PET) at day
7 (group 1) and at day 28 (group 2). After PET images the animals
were sacrificed and tissue samples were taken for histology.
Results: Viability in PET is defined by a relative decrease in
perfusion in an area where there is a relative increase in FDG
(fluorodeoxyglucose) concentration. This is often referred to as a
“mismatch” pattern. In the study nearly all pigs showed this
“mismatch” in the LAD area. The following significant results could
be found in the mismatched samples: the accumulation of collagen
(0,12 ± 0,12 %, p < 0,05) in LAD samples compared to those taken
from remote area (0,02 ± 0,02 %) and glycogen rich perinuclear
zones in LAD samples (0,06 ± 0,03 %, p < 0,05). Despite the
difficulties of reproducing a long-term hibernating myocardium in
an animal model, one pig (No.8) demonstrated physiological
alterations that can be compared to those of human beings with
hibernating myocardium. After 28 days the artery of the pig was
completely occluded. A mismatch was determined by PET, and wall
motion abnormalities were present. Furthermore in cells which were
exposed to a repetitive ischemia, a small degree of fibrosis and
glycogen richness were shown. Conclusion: In contrast to various
short-term hibernating myocardium models, no equivalent model
exists for long-term hibernating myocardium over a time period of
weeks or months yet. For this reason, the complete mechanism of
chronic hibernating myocardium is still unclear. The fluent
transition of the different heart failure up to the infarct as seen
in the clinic reflect the dynamic process, the interindividuell
differences and last but not least the reduced compensation
abilities of the heart. Due to this it is difficult to find a
matching in-vivo model that shows the same mechanism as humans.
Therefore every small and large animal model is helpful for
clarification.