Evaluation of the JT and corrected JT intervals as a new ECG method for monitoring doxorubicin cardiotoxicity in the dog.
A comparison was made of the sensitivity of ECG, ultrastructural heart pathology, and plasma enzymes CK-MB and alpha-HBDH as methods to assess doxorubicin cardiotoxicity in adult beagle dogs given doxorubicin 30 mg/m2 i.v. once a week for three times. A progressive increase in JT and QT intervals, in corrected JT (JTc) and QT (QTc) intervals as well as a reduction in both T wave amplitude and RR duration, were observed in doxorubicin-treated dogs; the electrocardiogram (ECG) abnormalities were associated with doxorubicin-induced ultrastructural changes in cardiac tissue, consisting of dilation of the sarcoplasmic reticulum, multiform, flasklike invaginations of T-tubules containing electrondense material, and interruption of the junctional sarcoplasmic reticulum, which became more severe as the observation period progressed. On the contrary, doxorubicin treatment was associated with transient changes in plasma CK-MB and alpha-HBDH, which were unrelated to the severity of chronic cardiotoxicity. Overall results suggest that the monitoring of the ECG parameters related to the repolarization of the cardiac muscle, and particularly JT and JTc, might be regarded as a noninvasive method for the study of doxorubicin cardiotoxocity in the dog.
Institute of Medical Pharmacology, University of Pisa, Italy.
R
R
Danesi
M
M
Del Tacca
N
N
Bernardini
G
G
Cardini
O
O
Bellini
D000818:Animals; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D003402:Creatine Kinase / Q000097:blood; D004285:Dogs; D004317:Doxorubicin / Q000633:toxicity*; D004562:Electrocardiography; D006321:Heart / Q000503:physiopathology; D008297:Male; D008854:Microscopy, Electron; D009206:Myocardium / Q000648:ultrastructure*
D004317:Doxorubicin; D003402:Creatine Kinase