Selective left ventricular adriamycin-induced cardiomyopathy in the pig.
OBJECTIVE
The aim of this study was the development of an experimental cardiomyopathy induced with Adriamycin (Pharmacia & Upjohn, Erlangen, Germany) with selective toxic damage of the left ventricular myocardium that avoided an ischemic component.


METHODS
An intracoronary catheter was implanted directly into the left main stem in pigs and connected to a percutaneous access port that was used for repetitive Adriamycin administration (3-5 x 25 mg weekly over a 1-hour period). Hemodynamic and echocardiographic variables were measured before Adriamycin administration, 1 week after, and at 4 weeks. Thereafter, all hearts were autopsied for detailed histologic examination. Statistical analysis was done by an analysis of variance for multiple parameters.


RESULTS
All pigs had normal baseline cardiac function. Measurements after Adriamycin administration and 4 weeks later demonstrated a continued increase of the central venous pressure, pulmonary artery pressure, pulmonary wedge pressure, and pulmonary vascular resistance, whereas cardiac output, stroke volume index, and left ventricular stroke work index decreased. These results were supported by the echocardiographic data depicting an increase of left ventricular diameters and volumes, accompanied by a decrease of intraventricular and left ventricular posterior wall thickness as well as left ventricular ejection fraction. Right ventricular volumes and function did not change during the trial. The histologic examination of the hearts revealed a selective toxic damage of the left ventricular myocardium with multifocal necroses and advanced tissue reorganization.


CONCLUSIONS
This animal model creates a selective left ventricular damage that avoids ischemic damage of the myocardium. Both aspects can improve research on Adriamycin-induced cardiomyopathy, especially preventive or therapeutic strategies.
Christiansen
Stefan
S
Department of Cardiothoracic Surgery, University of Aachen, Aachen, Germany. schristiansen@ukaachen.de
Perez-Bouza
Alberto
A
Schälte
Gereon
G
Hilgers
Ralf-Dieter
RD
Autschbach
Rüdiger
R
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000633:toxicity*; D003331:Coronary Vessels; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage / Q000633:toxicity*; D004452:Echocardiography; D005500:Follow-Up Studies; D006352:Heart Ventricles / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D007269:Injections, Intra-Arterial; D011669:Pulmonary Wedge Pressure / Q000502:physiology; D012720:Severity of Illness Index; D013318:Stroke Volume / Q000187:drug effects; D013552:Swine; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000503:physiopathology
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin