Abstract 27: Paclitaxel Protects Heart from Cold Ischemia Through Inhibition of Mitochondrial Permeability Transition Pore (MPTP) Opening and Reduction of Myocardial Necrosis
Introduction. The objective of this study was to evaluate whether Taxol (paclitaxel), a microtubule stabilizing-agent, could be protective against long period of myocardial cold ischemia.
Methods. Wistar rat hearts were harvested and preserved 8 hours of in vitro cold ischemia at 4°C in Celsior cardioplegic solution supplemented with either vehicle (control group), Taxol (250 nM), Cyclosporine A (Ciclo, a MPTP inhibitor, 250 nM), or Taxol + Ciclo A. Cold ischemia was followed by a 60 min reperfusion for functional assessment. Necrosis was evaluated by TTC staining method and by measuring CK and LDH leakage in the coronary effluents. Hearts were also reperfused 10 min and mitochondria were isolated to assess Ca2+ resistance capacity of the MPTP.
Results. All functional parameters were significantly improved in Taxol, Cyclo, and Taxol + Ciclo groups vs controls (Panel-A). Likewise, LDH and CK releases and infarct size (Panel-B), were reduced in Taxol, Ciclo and Taxol + Ciclo groups vs control hearts (p < 0.01 and p < 0.001). Surprisingly, Taxol slightly increased MPTP opening on isolated mitochondria. However, the combination Taxol + Ciclo abolished this deleterious effect.
Conclusion. During myocardial cold ischemia, taxol showed a dual effect: it was both protective against functional recovery and necrosis and slightly deleterious by increasing MPTP opening. The combination with Cyclosporine A efficiently abolished this last effect and further improved heart protection.