il\VOLVEMENT OF RETII\OIC ACID II{ - MSpace at the University of ...

MATERIALS AND METHODS
l.In Vivo studíes
I.a. Animal Treatment
Male Sprague-Dawley rats (250t10 g) were divided into four gloups: control
(CONT), adriamycin treated (ADR), probucol+adriamycin treated (PROB+ADR) and
probucol treated (PROB). Adriamycin (doxorubicin hydrochloride) was administered to
ADR and PROB+ADR animals using a previously established protocol (Siveski-Iliskovic
et al. 1994). The drug was administered intraperitoneally in 6 equal injections (2.5 mgkg
each injection) over a period of 2 weeks until a cumulative dose of 15 mg/kg of body
weight was reached. PROB+ADR treated animals were also injected with probucol
(cumulative dose 120 mglkg) in twelve equal doses, 2 weeks before and 2 weeks
concomitantly with adriamycin treatment. PROB group animals were injected with
probucol alone using the same regime. CONT group animals were injected with vehicle
(saline) using the same regime as adriamycin.
I.b.Hemodvnamic Assessment
Animals were anesthetizedwith sodium pentobarbital (5Omglkg intraperitoneally)
and weighed. Left ventricular systolic, end diastolic pressure, aortic peak systolic and
diastolic pressures were recorded by the introduction of a miniature pressure transducer
(Mitlar-Micro-Tip) through the right carotid artery into the aorta and left ventricle (Hill
and Singal lggT). The data was recorded for an on-line analysis using the Axotape
acquisition data program. The development of congestive heart failure was assessed
clinically as well as by using the two dimensional Doppler echocardiography. Ejection
fraction, cardiac output and left ventricular mass were recorded.
69