Thorac Cardiovasc Surg 2006; 54 - V_102
DOI: 10.1055/s-2006-925766

Apoptosis inhibition improves myocardial protection during cardioplegic arrest

UM Fischer 1, O Klass 2, D Pfriem 1, M Probst 1, M Steinhoff 3, JH Fischer 4, W Bloch 5, U Mehlhorn 1
  • 1Universität zu Köln, Klinik für Herz- und Thoraxchirurgie, Köln, Germany
  • 2Universität zu Ulm, Klinik für Herzchirurgie, Ulm, Germany
  • 3Universität zu Köln, Experimentelle Medizin, Köln, Germany
  • 4Texas A & M University, Experimentelle Medizin, Köln, Germany
  • 5Deutsche Sporthochschule, Institut für Kreislaufforschung und Sportmedizin, Köln, Germany

Objectives: As cardioplegic arrest (CPA) is associated with cardiac apoptosis induction, pharmacological inhibition of CPA-induced apoptosis may represent a new strategy in myocardial protection. Therefore, we studied the effect of apoptosis inhibition on myocardial apoptosis-signal-pathway and left ventricular function in a pig model of cardiopulmonary bypass (CPB) and CPA.

Methods: Eigtheen pigs instrumented with LV sonomicrometry and micromanometry for cardiac performance determination were subjected to 1 hour CPA on CPB. LV biopsies were collected before CPB (Baseline), at 15 and 60min CPA, at 30min reperfusion on CPB, and at 120min post-CPB. In two treatment groups (n=6 each) we administered either the specific caspase-3 inhibitor DEVD or the non-specific apoptosis inhibitor YVAD-cmk. Six additional animals served as controls. LV specimen were immuno-cytochemically stained against activated caspase-3, apoptosis inducing factor (AIF), and TNF-a. Cardiomyocytes were then quantitatively investigated using TV densitometry (gray units: U).

Results: In controls, active caspase-3 significantly increased over time; in YVAD-cmk, caspase-3 was increased at 15 and 60min CPA, but decreased during reperfusion to reach baseline values at 120min post CPB; in DEVD, caspase-3 was not activated. AIF increased significantly over time in controls, but remained unchanged in both DEVD and YVAD-cmk. TNF-a increased over time in controls and in DEVD, but remained unchanged in YVAD-cmk. Post-CPB LV contractility was significantly better preserved in both DEVD and YVAD-cmk as compared to controls.

Conclusions: Apoptosis inhibition improves post-cardioplegia cardiac function and respresents a promising new strategy for myocardial protection in cardiac surgery.