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Right Ventricular Cardiomyocyte Apoptosis in Patients With Acute Myocardial Infarction of the Left Ventricular Wall

      Cardiac remodeling after acute myocardial infarction (AMI) is characterized by molecular and cellular mechanisms involving both the left (LV) and right ventricular (RV) walls. Cardiomyoycte apoptosis in the peri-infarct and remote LV myocardium has a central role in cardiac remodeling. Whether apoptosis also occurs in the right ventricle of patients with ischemic heart disease has not been investigated. The aim of the present study was to investigate the presence of cardiomyocyte apoptosis in the right ventricle in patients with AMI. We assessed the number of apoptotic cardiomyocytes using multiple samplings in the LV and RV walls of 12 patients selected at autopsy who died 4 to 42 days after AMI. Five patients without cardiac disease were also selected at autopsy as controls. Apoptotic rates were calculated from the number of cardiomyocytes showing double positive staining for in situ end-labeling of DNA fragmentation (TUNEL) and for activated caspase-3. Potentially false-positive results (DNA synthesis and RNA splicing) were excluded from cell counts. The apoptotic rate in the right ventricle in patients with AMI was significantly higher than in control hearts (median 0.8%, interquartile range 0.3 to 1.0 vs median 0.01%, interquartile range 0.01 to 0.03, p <0.001). RV apoptosis significantly correlated with such parameters of global adverse remodeling as cardiac diameter to LV free wall thickness (R = +0.57, p = 0.050). RV apoptosis was significantly higher in five cases (42%) with infarct involving the ventricular septum and an adjacent small area of the RV walls (median 1.0%, interquartile range 0.8 to 2.2 vs median 0.5%, interquartile range 0.2 to 1.0, p = 0.048, p <0.001 vs controls). The association between apoptotic rate in the right ventricle and cardiac remodeling was apparent even after exclusion of cases with RV AMI involvement (R = +0.82, p = 0.023 for diameter to LV wall thickness ratio and R = −0.91, p = 0.002 for RV free wall thickness). In conclusion, patients with cardiac remodeling after AMI had a significant increase in RV apoptosis even when ischemic involvement of the RV wall was not apparent.
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      References

        • Patten R.D.
        • Aronovitz M.J.
        • Deras-Meja L.
        • Pandian N.G.
        • Hanak G.G.
        • Smith H.J.
        • Mendelsohn M.E.
        • Konstam M.A.
        Ventricular remodeling in a mouse model of myocardial infarction.
        Am J Physiol. 1998; 274: H1812-H1820
        • Brower G.L.
        • Janicki J.S.
        Contribution of ventricular remodeling to pathogenesis of heart failure in rats.
        Am J Physiol. 2001; 280: H674-H683
        • Hirose K.
        • Shu N.H.
        • Reed J.E.
        • Rumberger J.A.
        Right ventricular dilatation and remodeling the first year after an initial transmural wall left ventricular myocardial infarction.
        Am J Cardiol. 1993; 72: 1126-1130
        • Oakley C.
        Importance of right ventricular function in congestive heart failure.
        Am J Cardiol. 1988; 62: 14A-19A
        • Di Salvo T.G.
        • Mathier M.
        • Semigran M.J.
        • Dec G.W.
        Preserved right ventricular ejection fraction predicts exercise capacity and survival in advanced heart failure.
        J Am Coll Cardiol. 1995; 25: 1143-1153
        • Pfeffer M.A.
        • Braunwald E.
        Ventricular remodeling after myocardial infarction—experimental observations and clinical implications.
        Circulation. 1990; 81: 1161-1172
        • Anversa P.
        • Olivetti G.
        • Capasso J.M.
        Cellular basis of ventricular remodeling after myocardial infarction.
        Am J Cardiol. 1991; 68: 7D-16D
        • Krijnen P.A.J.
        • Nijmeijer R.
        • Meijer C.J.L.M.
        • Visser C.A.
        • Hack C.E.
        • Niessen H.W.M.
        Apoptosis in myocardial ischaemia and infarction.
        J Clin Pathol. 2002; 55: 801-811
        • Abbate A.
        • Biondi-Zoccai G.G.L.
        • Baldi A.
        Pathophysiologic role of myocardial apoptosis in post-infarction left ventricular remodeling.
        J Cell Physiol. 2002; 193: 145-153
        • Baldi A.
        • Abbate A.
        • Bussani R.
        • Patti G.
        • Melfi R.
        • Angelini A.
        • Dobrina A.
        • Rossiello R.
        • Silvestri F.
        • Baldi F.
        • Di Sciascio G.
        Apoptosis and post-infarction left ventricular remodeling.
        J Mol Cell Cardiol. 2002; 34: 165-174
        • Abbate A.
        • Biondi-Zoccai G.G.L.
        • Bussani R.
        • Dobrina A.
        • Camilot D.
        • Feroce F.
        • Rossiello R.
        • Baldi F.
        • Silvestri F.
        • Biasucci L.M.
        • Baldi A.
        Increased myocardial apoptosis in patients with unfavorable left ventricular remodeling and early symptomatic post-infarction heart failure.
        J Am Coll Cardiol. 2003; 41: 753-760
        • Bussani R.
        • Abbate A.
        • Biondi-Zoccai G.G.
        • Dobrina A.
        • Leone A.M.
        • Camilot D.
        • Di Marino M.P.
        • Baldi F.
        • Silvestri F.
        • Biasucci L.M.
        • Baldi A.
        Right ventricular dilatation after left ventricular acute myocardial infarction is predictive of extremely high peri-infarctual apoptosis at postmortem examination in humans.
        J Clin Pathol. 2003; 56: 672-678
        • Biondi-Zoccai G.G.
        • Abbate A.
        • Vasaturo F.
        • Scarpa S.
        • Santini D.
        • Leone A.M.
        • Parisi Q.
        • De Giorgio F.
        • Bussani R.
        • Silvestri F.
        • et al.
        Increased apoptosis in remote non-infarcted myocardium in multivessel coronary disease.
        Int J Cardiol. 2004; 94: 105-110
        • Sinagra G.
        • Bussani R.
        • Abbate A.
        • Piro M.
        • Biondi-Zoccai G.G.
        • Kontos M.C.
        • Sabbadini G.
        • Barresi E.
        • Crea F.
        • Biasucci L.M.
        • et al.
        Left ventricular diastolic filling pattern at Doppler echocardiography and apoptotic rate in fatal acute myocardial infarction.
        Am J Cardiol. 2007; 99: 307-309
        • Hunt S.A.
        • Baker D.W.
        • Chin Mh
        • Cinquegrani M.P.
        • Feldman A.M.
        • Francis G.S.
        • Ganiats T.G.
        • Goldstein S.
        • Gregoratos G.
        • Jessup M.L.
        • et al.
        American College of Cardiology/American Heart Association ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines.
        J Am Coll Cardiol. 2001; 38: 2101-2113
        • Voelkel N.F.
        • Quaife R.A.
        • Leinwand L.A.
        • Barst R.J.
        • McGoon M.D.
        • Meldrum D.R.
        • Dupuis J.
        • Long C.S.
        • Rubin L.J.
        • Smart F.W.
        • et al.
        • National Heart, Lung, and Blood Institute Working Group on Cellular and Molecular Mechanisms of Right Heart Failure
        Right ventricular function and failure: report of a National Heart, Lung, and Blood Institute Working Group on Cellular and Molecular Mechanisms of Right Heart Failure.
        Circulation. 2006; 114: 1883-1891
        • Sabbah H.N.
        • Stein P.D.
        • Kono T.
        • Gheorghiade M.
        • Levine T.B.
        • Jafri S.
        • Hawkins E.T.
        • Goldstein S.
        A canine model of chronic heart failure produced by multiple sequential coronary microembolization.
        Am J Physiol. 1991; 260: H1379-H1384
        • Ferlinz J.
        Right ventricular function in adult cardiovascular disease.
        Prog Cardiovasc Dis. 1982; 25: 225-267
        • Gibson C.M.
        • Ryan K.A.
        • Murphy S.A.
        • Mesley R.
        • Marble S.J.
        • Giugliano R.P.
        • Cannon C.P.
        • Antman E.M.
        • Braunwald E.
        Impaired coronary blood flow in nonculprit arteries in the setting of acute myocardial infarction.
        J Am Coll Cardiol. 1999; 34: 974-982
        • Araujo L.I.
        • Camici P.
        • Spinks T.J.
        • Jones T.
        • Maseri A.
        Abnormalities in myocardial metabolism in patients with unstable angina as assessed by positron emission tomography.
        Cardiovasc Drugs Ther. 1988; 2: 41-46