Congestive heart failure in rabbits after a single intrapleural administration of a low dose of doxorubicin or epirubicin.
Seventeen healthy rabbits were given doxorubicin, 0.1-1.6 mg kg-1, or epirubicin, 0.4-1.6 mg kg-1, through a catheter into the right pleural space. Sacrifice and autopsy one week later showed a local inflammatory reaction with, in some animals, sparse adhesion forming between parietal and visceral pleura. There was a clearly dose-dependent production of thin, straw-coloured exudate. Nineteen healthy rabbits were given intrapleural doxorubicin or epirubicin, 0.2, 0.4 or 0.8 mg kg-1. Autopsy on spontaneously dead (n = 3) or sacrificed animals after six weeks gave clear indications of congestive heart failure after the two higher doses. There were also fibrous adhesions and/or tissue necrosis engaging the pleura, diaphragm and lung. It was concluded that doxorubicin and epirubicin are 40 to 100-fold more cardiotoxic in rabbits when given by the intrapleural route than when given by the intravenous route. The implications are two-fold: 1. doxorubicin or epirubicin should not be given intrapleurally to patients, 2. a new model for drug-induced congestive heart failure has been created, which has the advantage of requiring very small quantities of drug.
Elisson
L O
LO
Department of Lung Medicine, University of Lund, Sweden.
Björkman
S
S
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000633:toxicity*; D015251:Epirubicin; D005260:Female; D006333:Heart Failure / Q000139:chemically induced* / Q000473:pathology; D007267:Injections; D008297:Male; D010994:Pleura; D011817:Rabbits
D015251:Epirubicin; D004317:Doxorubicin