Abstract 25: Transition From Reversible to Irreversible Injury Following Prolonged Cold Myocardial Ischemia. Implication of Mitochondrial Permeability Transition Pore (MPTP) Opening
Introduction. The aim of this study was to evaluate the ischemic functional recovery related with mitochondrial dysfunction during different time of hypothermic heart preservation.
Methods. Rat hearts (n=65) were perfused according to Langendorff technique, arrested and preserved with Saint-Thomas’ Hospital solution during 4, 8, 12, 16 or 24 hours at 4C°. 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. Data showed that a transition from reversible to irreversible ischemia occured between 8 and 12 hours cold preservation. Hearts preserved 4 and 8 hours showed better functionnal recovery with RPP averaging at the end of the reperfusion 17664±1941and 14278.4±2176. On the contrary, hearts preserved 12, 16 and 24 hours were irreversibly damaged (with RPP averaging respectively 2683±895, 2711.5±378 and 1776±98 mmHg/min, p<0.001 vs 4 and 8 hours preservation). Enzymes releases (CK and LDH) and TTC staining showed an absence of necrosis prior to 8 hours preservation (Panel A). Identically, mean calcium load inducing MPTP opening after 8 hours of preservation was significantly less in comparison with hearts preserved 12 hours or more (p<0.001, Panel-B).
Conclusion. This study is the first to show a transition from reversible to irreversible cold ischemia between 8 and 12 hours. Irreversible cold ischemia would involve higher sensitivity of MPTP.