Cyclooxygenase-2 inhibitor treatment improves left ventricular function and mortality in a murine model of doxorubicin-induced heart failure.

Autor:	Delgado RM 3rd; Department of Adult Cardiology, Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, Tex 77030, USA. rdelgado@pol.net, Nawar MA, Zewail AM, Kar B, Vaughn WK, Wu KK, Aleksic N, Sivasubramanian N, McKay K, Mann DL, Willerson JT
Jazyk:	angličtina
Zdroj:	Circulation [Circulation] 2004 Mar 23; Vol. 109 (11), pp. 1428-33. Date of Electronic Publication: 2004 Mar 15.
DOI:	10.1161/01.CIR.0000121354.34067.48
Abstrakt:	Background: Progression of heart failure after initial myocardial injury is mediated in part by various redundant inflammatory mediators, including the widely expressed cyclooxygenase-2 (COX-2). Because COX-2 inhibitors are useful in treating many inflammation-mediated diseases, we asked whether COX-2 inhibition can attenuate heart failure progression. Methods and Results: Heart failure was experimentally induced in 100 mice by administration of doxorubicin (4 mg. kg(-1). wk(-1) for 6 weeks). Beginning at day 42, mice were fed daily with either COX-2 inhibitor-containing mice chow (n=50) or plain mice chow (controls; n=50). Left ventricular ejection fraction was evaluated as a measure of heart failure by a novel method of transthoracic echocardiography (with intravascular ultrasound catheters) at baseline and on days 42, 56, and 70. From baseline to study termination, left ventricular ejection fraction in COX-2 inhibitor-treated mice decreased significantly less than in control mice (9% versus 29%, P<0.01). Mortality was significantly lower for COX-2 inhibitor-treated mice than for control mice (18% versus 38%, P<0.01). These results were confirmed in a revalidation study in COX-2 inhibitor-treated mice (n=25) and controls (n=25). That study revealed that the hearts from control mice weighed roughly the same as hearts from COX-2 inhibitor-treated mice but showed more extensive signs of cardiomyopathy (as determined by pathological analysis by an independent, blinded observer) and higher levels of COX-2 proteins (as determined by immunoblotting [6442+/-1635 versus 4300+/-2408 arbitrary units, P<0.022]). Conclusions: COX-2 inhibitors can attenuate the progression of heart failure in a murine model of doxorubicin-induced heart failure.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu