Document Detail


Adriamycin-induced cardiomyopathy in the dog--an appropriate model for research on partial left ventriculectomy?
MedLine Citation:
PMID:  12100904     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To evaluate the adriamycin-induced cardiomyopathy in the dog for research on partial left ventriculectomy (PLV). METHODS: An intracoronary catheter was introduced into the left main stem via the first diagonal branch in a retrograde fashion in 6 adult FBI (Foxhound Boehringer Ingelheim) dogs weighing 30 to 35 kg. The catheter was connected to a percutaneous access port that was used for weekly adriamycin administration (10 mg over a 1-hour period for 5 times). Follow-up examinations (transthoracic echocardiography, hemodynamic parameters, cardiopulmonary status, and neurohormones) were done before, 1 week after the last adriamycin administration, and 6 weeks later. After the last measurements, all dogs were euthanized with saturated potassium chloride under general anesthesia and the hearts were excised for histologic examinations. All data were calculated as mean values and standard error of the mean. Differences were calculated by the Wilcoxon signed rank test for paired and unpaired data. p values less than 0.05 were considered significant. RESULTS: Central venous pressure (2.2 +/- 0.8 vs 5.2 +/- 0.4 mm Hg, p = 0.03), mean pulmonary artery pressure (8.6 +/- 1.1 vs 12.4 +/- 0.5 mm Hg, p = 0.03), pulmonary wedge pressure (2.6 +/- 0.9 vs 7.0 +/- 0 mm Hg, p = 0.03), left ventricular endsystolic diameter (2.5 +/- 0.2 vs 3.1 +/- 0.4 cm, p = 0.03), and enddiastolic (4.5 +/- 0.2 vs 4.9 +/- 0.2 cm, p = 0.03) diameter increased significantly after adriamycin administration, whereas cardiac output (4.0 +/- 0.3 vs 3.3 +/- 0.1 liter/min, p = 0.03), stroke volume index (66.0 +/- 7.4 vs 54.0 +/- 3.9 ml/beat/m(2), p = 0.03), and ejection fraction (61.1 +/- 5.1 vs 37.7 +/- 5.7%, p = 0.03) decreased markedly. These changes were accompanied by a significant decline of oxygen delivery (1130 +/- 170 vs 790 +/- 65 ml/min, p = 0.03), which led to an enhanced oxygen extraction (0.12 +/- 0.01 vs 0.24 +/- 0.01, p = 0.03). Consequently, venous oxygen saturation (82.7 +/- 4.1 vs 71.3 +/- 2.5%, p = 0.03) decreased. Troponin I (0.02 +/- 0.025 vs 1.7 +/- 0.6 ng/ml, p = 0.03) and the anti-diuretic hormone (1.9 +/- 0.9 vs 20.0 +/- 1.9 pg/ml, p = 0.03) increased significantly after adriamycin administration. Deterioration of cardiac function continued after termination of adriamycin administration, albeit slower than during adriamycin administration. All hearts had severe histologic alterations, which were characteristic of adriamycin-induced toxicity: cytoplasmic vacuolation, myocyte degeneration, and increased fibrosis. CONCLUSIONS: The adriamycin-induced cardiomyopathy in the dog is similar to the dilated cardiomyopathy in humans and may be an appropriate model for PLV.
Authors:
Stefan Christiansen; Klaus Redmann; Hans H Scheld; Uli R Jahn; Jörg Stypmann; Manfred Fobker; Achim D Gruber; Dieter Hammel
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation     Volume:  21     ISSN:  1053-2498     ISO Abbreviation:  J. Heart Lung Transplant.     Publication Date:  2002 Jul 
Date Detail:
Created Date:  2002-07-08     Completed Date:  2002-09-13     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9102703     Medline TA:  J Heart Lung Transplant     Country:  United States    
Other Details:
Languages:  eng     Pagination:  783-90     Citation Subset:  IM    
Affiliation:
Klinik und Poliklinik für Thorax-, Herz- und Gefässchirurgie, Universitätsklinikum-Rheinisch-Westfälische Technische Hochschule Aachen, Aachen, Germany. SChristiansen@UKaachen.de
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MeSH Terms
Descriptor/Qualifier:
Animals
Cardiomyopathy, Dilated* / chemically induced,  pathology,  physiopathology
Disease Models, Animal*
Dogs*
Doxorubicin / adverse effects*
Hemodynamics
Myocardium / pathology
Chemical
Reg. No./Substance:
23214-92-8/Doxorubicin

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