Prevention of doxorubicin (adriamycin)-induced cardiomyopathy by simultaneous administration of angiotensin-converting enzyme inhibitor assessed by acoustic densitometry.
The purpose of our study has to determine the myocardial protective effects of the angiotensin-converting enzyme (ACE) inhibitor temocapril (TEM, 7 mg/kg/day) simultaneously administered with doxorubicin (Adriamycin). Twenty male Sprague-Dawley rats were intraperitoneally administered a cumulative dose of 15 mg/kg of doxorubicin (each dose of 1.0 mg/kg x 15) for 3 weeks, and divided into TEM-untreated and -treated rats. Seven control rats were injected with saline intraperitoneally. Body weight, hemodynamics, and echocardiographic measurements including quantitative analysis of ultrasonic integrated backscatter (IB) were obtained for 12 weeks after treatment. Finally, rats were killed for histopathologic study. At 6 weeks, end-diastolic left ventricular diameter (LVD) and percentage fractional shortening (%FS) were similar in TEM-treated and TEM-untreated rats, but cyclic variation of IB (dB) significantly decreased in TEM-untreated rats (7.3 +/- 1.2; control rats, 9.7 +/- 0.9; p < 0.01). At 12 weeks, %FS decreased in TEM-untreated rats (26.1 +/- 6.1%: TEM-treated rats, 34.2 +/- 6.2; p < 0.05), and calibrated IB (dB) in TEM-untreated rats (15.5 +/- 0.5) increased as compared with that in TEM-treated rats (12.1 +/- 0.7; p < 0.01). Interstitial collagen accumulation increased in TEM-untreated rats and was inhibited in treated rats. Simultaneous administration of TEM with doxorubicin was beneficial in preventing doxorubicin-induced myocardial damage, and myocardial tissue characterization was useful for the early detection of myocardial damage and the assessment of therapy.
Tokudome
T
T
Second Department of Internal Medicine, Kagawa Medical University, Kita, Japan.
Mizushige
K
K
Noma
T
T
Manabe
K
K
Murakami
K
K
Tsuji
T
T
Nozaki
S
S
Tomohiro
A
A
Matsuo
H
H
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D009202:Cardiomyopathies / Q000139:chemically induced / Q000517:prevention & control*; D003094:Collagen / Q000378:metabolism; D003720:Densitometry; D004317:Doxorubicin / Q000633:toxicity*; D004452:Echocardiography; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013841:Thiazepines / Q000627:therapeutic use*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000903:Antibiotics, Antineoplastic; D013841:Thiazepines; D004317:Doxorubicin; C055603:temocapril hydrochloride; D003094:Collagen