Ventrikelteilresektion bei Adriamycin-induzierter Cardiomyopathie am Tiermodell

Background: Partial left ventriculectomy (PLV) was introduced in clinical settings without a detailed scientific basis. Heterogenous clinical studies of different centers resulted in varying outcomes, preventing that the PLV became really established. Therefore, there has been great demand for an appropriate animal model. The purpose of this study was to evaluate modified adriamycin-induced cardiomyopathy in the dog for research on PLV. Methods: An intracoronary catheter was introduced into the left main stem via the first marginal branch in a retrograde fashion in 12 adult foxhound dogs. The catheter was connected to a percutaneous access port that was used for weekly adriamycin administration (10 mg over a 1-hour period on 5 occasions). Follow-up examinations (transthoracic echocardiography, hemodynamic parameters, cardiopulmonal status, neurohormones) were done before, 1 week after the last adriamycin administration, and then 6 weeks later. This protocol was performed in 6 dogs (control group: Group 1). The other 6 dogs underwent PLV 1 week after the last adriamycin administration (Group 2). After the last measurements, all dogs were killed with saturated potassium chloride under general anesthesia and the hearts were excised for histologic examination. All data were calculated as mean and standard error of the mean. Differences were calculated by the Wilcoxon signed-rank test for paired and unpaired data. p < 0,05 was considered statistically significant. Results: One dog from each group died suddenly during adriamycin administration (probably due to ventricular arrhythmia). In addition, 1 dog from Group 2 suffered from a severe systemic inflammatory response syndrome after PLV and died 36 hours after surgery. Thus, 5 dogs from Group 1 and 4 from Group 2 undervent the entire study protocol. Adriamycin administration resulted in a severe dilated cardiomyopathy that was comparable in both groups (significant increase of central venous pressure, mean pulmonary artery pressure, pulmonary wedge pressure, left ventricular end-systolic and end-diastoliy diameters, oxygen extraction, troponin I and anti-diuretic hormone, whereas cardiac output, ejection fraction and venous oxygen saturation decreased significantly). Deterioration of cardiac function continued after termination of adriamycin administration in Group 1 dogs, albeit not as progressively as during adriamycin administration. In contrast, cardiac function improved in group 2 dogs after PLV, but did not reach baseline values. Cardiac index increased and oxygen extraction (p = 0,03) decreased, resulting in an enhanced venous oxygen saturation (p = 0,02). In particular, the distance of the papillary muscles at end diastole (p = 0,02) and at end systole (p = 0,02) at the mid-papillary level decreased significantly after PLV, resulting in reduced left ventricular diameter and volume (statistically significant for left ventricular end-systolic diameter and volume). All hearts had severe histologic alterations characteristic of adriamycin.induced toxicity, including cytoplasmic vacuolation, myocyte degeneration and increased fibrosis. Conclusions: Modified adriamycin-induced cardiomyopathy in the dog may be suitable for reasearch on PLV. Our results confirm, that the cardiac function can be initial improved by PLV in case of adriamycin-induced cardiomyopathy.

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2005

Author dc:creator

• Dornseifer, Ulf

Contributors dc:contributor

• Autschbach, Rüdiger

• info:eu-repo/classification/ddc/610
• Medizin
• Ventrikelteilresektion
• Dilatative Cardiomyopathie
• Tiermodell
• Batista
• ventriculectomy
• dilated cardiomyopathy
• animal model

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

ger

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-121981%22

OAI identifier oai:identifier

oai:publications.rwth-aachen.de:60258