Expression of the MDR-1 Gene-encoded P-glycoprotein in Cardiomyocytes of Conscious Sheep Undergoing Acute Myocardial Ischemia Followed by Reperfusion

Rubén P. Laguens ¹, Alberto J. Lazarowski ¹, Luis A. Cuniberti ¹, Gustavo L. Vera Janavel ¹, Patricia M. Cabeza Meckert ¹, Gustavo G. Yannarelli ¹, Héctor F. del Valle ¹, Elena C. Lascano ¹, Jorge A. Negroni ¹ and Alberto J. Crottogini ^1*

¹ Department of Pathology (RPL,LAC,PMCM,GGY) and Department of Physiology (GLVJ,HFV,ECL,JAN,AJC), Favaloro University, Buenos Aires, Argentina; Department of Clinical Biochemistry, Faculty of Pharmacy and Biochemistry, Buenos Aires University, Buenos Aires, Argentina (AJL); and Scientific Investigation Commission of Buenos Aires Province, La Plata, Argentina (PMCM)

^* To whom correspondence should be addressed. E-mail: crottogini{at}favaloro.edu.ar.

Submitted on June 2, 2006
Accepted on 17 October 2006

	Abstract

We have recently reported that in chronic myocardial ischemia, adult mammalian cardiomyocytes express P-glycoprotein. We now investigate if the P-glycoprotein is also expressed in acute regional ischemia followed by reperfusion. Adult conscious sheep underwent 12 minutes occlusion of the mid left anterior descending artery (inflatable cuff). Successful ischemia-reperfusion was confirmed by monitoring percent systolic left ventricular anterior wall thickening (sonomicrometry) during the whole ischemic period and every 10 minutes over 2 hours following cuff deflation. At 3, 24 and 48 hours after reperfusion, P-glycoprotein expression was investigated by immunohistochemistry and Western blot, and MDR-1 mRNA by RT-PCR. The cardiomyocytes in the occluded artery territory (but not those in remote areas) consistently expressed P-glycoprotein at their sarcolemma. While at 3 and 24 hours P-glycoprotein was mainly observed in the T tubules, at 48 hours it predominated in intercalated discs and gap junctions. RT-PCR and Western blot revealed higher expression in ischemic than in control myocardium. We conclude that in adult sheep with acute myocardial ischemia, the MDR-1 gene-encoded P-glycoprotein is expressed at the sarcolemma of the cardiomyocytes from 3 up to at least 48 hours after reperfusion.

Key Words: P-glycoprotein, MDR-1, cardiomyocytes, stunning, acute myocardial ischemia, ischemia-reperfusion injury, sheep

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