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Apoptosis Inhibition Improves Left Ventricular Function After Prolonged Cold Cardioplegic Arrest
Author(s) -
Fischer Uwe M,
MonzonPosadas Werner Otoniel,
Fischer Jürgen H,
Bloch Wilhelm,
Mehlhorn Uwe,
Wahlers Thorsten
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1462-c
Subject(s) - contractility , apoptosis , medicine , ventricular pressure , cardiology , cold storage , ischemia , cardiac function curve , anesthesia , chemistry , blood pressure , heart failure , biology , biochemistry , horticulture
Cardioplegic arrest (CA) is associated with myocardial apoptosis induction. Apoptosis inhibition during regional myocardial ischemia reduces infarct size and improves regional contractility. We investigated whether inhibition of the apoptosis‐signal‐pathway improves left ventricular (LV) function following prolonged cold CA. Ten adult rat hearts were arrested using ice‐cold cardioplegia (Bretschneider solution, Custodiol®, 10 ml/kg) with and without supplementation of a non‐selective caspase‐inhibitor (z‐VAD‐fmk, 10 mM, n=5 each). Hearts were stored for 4h in cardioplegia (4°C). Subsequently, hearts were reperfused with Krebs‐Henseleit‐Solution (37°C) on a Langendorff‐System. Five additional rats without ischemic storage served as controls. After 4h cold CA, hearts with apoptosis‐inhibition had higher left ventricular pressure throughout the 60min reperfusion as compared to those without apoptosis‐inhibition. Apoptosis‐inhibition even resulted in significantly higher LV pressures as compared to controls at 30, 40 and 50 min reperfusion (58.6±10, 59.2±8.1 and 58.6±8.6 mmHg vs. 42±8.7, 42.8±10.6 and 42.2±8.6 mmHg, respectively; p<0.013). Recovery time on reperfusion defined as duration until heart rate and LV pressure reached steady state was significantly shorter with apoptosis inhibition as compared to non‐inhibition (13.4±11.6 vs 29.6±8.2 min, p=0.017). Apoptosis‐inhibition improves LV‐function after prolonged cold CA and represents a new promising strategy in myocardial protection for cardiac allografts.