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Atorvastatin Worsens Left Ventricular Diastolic Dysfunction and Endothelial Dysfunction of Epicardial Coronary Arteries in Normocholesterolemic Porcine With Left Ventricular Hypertrophy

Forcillo, Jessica MD, MSc*; Maltais, Simon MD, MSc*; Aubin, Marie-Claude PhD; Shi, Yan Fen MD; Carrier, Michel MD*; Tardif, Jean-Claude MD; Perrault, Louis P MD, PhD*

Journal of Cardiovascular Pharmacology: September 2011 - Volume 58 - Issue 3 - p 295-306
doi: 10.1097/FJC.0b013e3182244993
Original Article

Statins have pleiotropic effects that can reverse endothelial dysfunction and prevent the development of left ventricular hypertrophy (LVH). The goal of this study was to assess the effect of treatment with atorvastatin on the endothelial dysfunction of epicardial coronary arteries and the development of LVH in a porcine model. LVH was induced through 2 months of aortic banding (AB) of the ascending aorta. Experimental groups were (1) sham untreated: without AB, (2) LVH untreated: with AB, and (3,4) LVH treated: with AB treated with 40 and 80 mg of atorvastatin, respectively, for 60 days, and (5) sham treated: without AB treated with 80 mg of atorvastatin for 60 days. Vascular reactivity studies were performed in organ chambers experiments. NO bioavailability was assessed using cyclic guanosine monophosphate quantification. Oxidative stress levels were measured by quantifying angiotensin II) and nitrite/nitrate levels. LVH and LV diastolic function were evaluated using echocardiography. Atorvastatin decreased endothelium-dependent relaxations and cyclic guanosine monophosphate levels in all treated animals. Angiotensin II levels were increased, whereas nitrite levels were similar among groups (P > 0.05). LV diastolic dysfunction and LVH were significantly greater in all treated animals (P < 0.01). High-density lipoprotein levels and low-density lipoprotein levels were significantly decreased in animals receiving atorvastatin (P < 0.05). In this swine model of LVH, atorvastatin did not prevent LVH development or coronary endothelial dysfunction and resulted in worsening of the LV diastolic dysfunction.

From the Departments of *Cardiac Surgery; †Pharmacology; ‡Medicine, Montreal Heart Institute and Université de Montréal, Montreal, Quebec, Canada.

Received for publication June 11, 2010; accepted May 12, 2011.

Supported by Montreal Heart Institute Foundation. Grants were from the Fondation de l'Institut de Cardiologie de Montréal (FICM), the Department of Surgery of the Université de Montréal, the Fonds de la Recherche en Santé du Québec (FRSQ), and Pfizer Canada.

J. Forcillo and S. Maltais are students funded by FRSQ, and M.C. Aubin is funded by the Heart and Stroke Foundation of Canada. J.-C. Tardif holds the Université de Montréal, Pfizer Research Chair in Atherosclerosis.

The authors declare no conflicts of interest.

Reprints: Louis P. Perrault, MD, PhD, Department of Surgery, Montreal Heart Institute, 5000 Bélanger St, Montreal, Quebec H1T 1C8, Canada (e-mail: louis.perrault@icm-mhi.org).

© 2011 Lippincott Williams & Wilkins, Inc.