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

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

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)

Correspondence to: Alberto Crottogini, Favaloro University, Solís 453, 1078 Buenos Aires, Argentina. E-mail: crottogini{at}favaloro.edu.ar

We have recently reported that in chronic myocardial ischemia, adult mammalian cardiomyocytes express P-glycoprotein (P-gp). We now investigate if P-gp is also expressed in acute regional ischemia followed by reperfusion. Adult conscious sheep underwent 12-min 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 min over 2 hr following cuff deflation. At 3, 24, and 48 hr after reperfusion, P-gp expression was investigated by immunohistochemistry and Western blot and MDR-1 mRNA by RT-PCR. Cardiomyocytes in the occluded artery territory (but not those in remote areas) consistently expressed P-gp at their sarcolemma. Whereas at 3 and 24 hr P-gp was mainly observed in the T tubules, at 48 hr 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-gp is expressed at the sarcolemma of the cardiomyocytes from 3 hr up to at least 48 hr after reperfusion. (J Histochem Cytochem 55:191–197, 2007)

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

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