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 d ose of 15 mg/kg of doxorubicin (each dose of 1.0 mg/kg x 15) for 3 weeks, a nd divided into TEM-untreated and -treated rats. Seven control rats were in jected with saline intraperitoneally. Body weight, hemodynamics, and echoca rdiographic measurements including quantitative analysis of ultrasonic inte grated backscatter (IB) were obtained for 12 weeks after treatment. Finally , rats were killed for histopathologic study. At 6 weeks, end-diastolic lef t ventricular diameter (LVD) and percentage fractional shortening (%FS) wer e similar in TEM-treated and TEM-untreated rats; but cyfclic variation of I B (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 r ats (26.1 +/- 6.1%; TEM-treated rats, 34.2 +/- 6.2; p < 0.05), and calibrat ed 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 ac cumulation increased in TEM-untreated rats and was inhibited in treated rat s. Simultaneous administration of TEM with doxorubicin was beneficial in pr eventing doxorubicin-induced myocardial damage, and myocardial tissue chara cterization was useful for the early detection of myocardial damage and the assessment of therapy.