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Knoedler, Martina Daniela (2005): Die Wirkung des Apoptose-hemmenden Proteins p35 auf die Hämodynamik und die Infarktgröße im Herzinfarktmodell an der Ratte. Dissertation, LMU München: Tierärztliche Fakultät



Effect of apoptosis-inhibition by protein p35 on hemodynamics and infarct size in a rat myocardial infarct model Numerous in vitro studies showed the ability of the baculoviral protein p35 to effectively inhibit apoptosis in cells. Furthermore ex vivo Langendorff-experiments proved a reduction of infarct size by p35-intervention. The aim of the present study is to investigate the p35 dependent inhibition of apoptosis after adenoviral gene transfer into the myocardium with respect to infarct size as well as to cardiac function and hemodynamics. Myocardial infarction is induced by ligation of the left anterior descending artery (LAD) for 30 minutes followed by a 24 h reperfusion period. The following measurements are performed during the examination period: echocardiography (EF), left ventricular pressure measurement (LVPsys, LVPedp, dLVP/dtmax, dLVPdtmin), planimetry (infarct size, AR, I/AR). The evaluated echocardiographical data show a significant improvement of ejection fraction (EF: p35-G 50,35% ± 0,76, GFP-CG 46,54 ± 1,18) in the p35-group (n=18) in comparison to the control group (n=15). Likewise left ventricular pressure parameters showed a significant improvement except for LVPedp which was not significantly different. (LVPsys: p35-G 106,48 mmHg ± 4,48, GFP-CG 91,58 mmHg ± 3,86, LVPedp: p35-G 6 mmHg ± 3, GFP-CG 9,03 mmHg ± 4, dLVP/dtmax: p35-G 5659 mmHg/s ± 584,8, GFP-CG 4634 mmHG/s ± 256,21, dLVP/dtmin: p35-G -3882 mmHg/s ± 256,43, GFP-CG -3193 mmHg/s ± 191,15). No significant differnce was seen for the mean heart weight of the p-35 group measured 1,325 g ± 0,04 compared to the mean heart weight of 1,317 g ± 0,06 in the GFP-control group. In agreement with previous studies infarct size showed a significant reduction in the p35 transfected hearts, in opposition to the control animals with AR remaining constant in both groups. (Absolute infarct size: p35-G 0,11 cm3 ± 0,03, GFP-CG 0,33 cm3 ± 0,06, I/AR %: p35-G 6% ± 0,0 , GFP- CG 17% ± 0,02). The present study demonstrates that inhibition of apoptosis after adenoviral gene transfer of p35 reduces infarct size, and further improves cardiac function in a rat model of myocardial infarction. This confirms that Caspase-inhibition helps to maintain the function of the contractile apparatus in infarcted Cardiomyocytes. Thus, not only securing survival, but maintaining the function of Cardiaomyocytes in myocardial infarction.