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.

Level thesis:degree_level

thesis.doctoral

Grantor dc:publisher

Ludwig-Maximilians-Universität

Year

2004

Author dc:creator

• Nimz, Christina

Repository record source_url

https://edoc.ub.uni-muenchen.de/1840/

OAI identifier oai:identifier

oai:edoc.ub.uni-muenchen.de:1840