Abstract 1788: HO-1 Activation Can Attenuates Cardiomyocytic Apoptosis via Inhibition of NFκB Translocation Following Cardiac Global Ischemia and Reperfusion
Introduction: Recent studies indicated that NFκB played an important role in regulation of inflammatory signals transduction which led to cardiomyocytic injury following cardiopulmonary bypass (CPB) and global cardiac ischemia/reperfusion (I/R) injury. Heme oxygenase-1 (HO-1) had been reproted to block these inflammatory responses and ameliorate I/R injury.
Hypothesis: In this study, experiments were designed to determine whether HO-1 activation could decrease the myocardial I/R injury via NFκB transcription and attenuate the appearance of apoptosis of cardiomyocytes with cardioplegia during CPB .
Methods: Rabbits (10 in each group) were randomized to receive normal saline (Gr 1), hemin (30 mg/kg; HO-1 inducer; Gr 2),or SnPP (7 mg/kg; HO-1 inhibitor; Gr 3), or hemin+SnPP (Gr 4) intravenous injection two days before CPB. Total CPB was initiated and cold (4°C) antegrade intermittent crystalloid cardioplegia was delivered every 20 minutes for a total of 60 minutes of cardiac arrest. Rabbits were weaned from CPB and reperfused for 4 hours. Blood was sampled at various time points. The reperfused hearts were harvested for western blotting and TUNEL experiments.
Results: The post-operative elevation of serum levels of IL-8 (0.5x, 3.9x, 2.9x over Gr 1 in Gr 2, 3, 4, respectively, p<0.05), IL-10 (0.1x, 16.0x, 14.9x over Gr 1 in Gr 2, 3, 4, respectively, p<0.05) and TNF-α (0.4x, 3.1x, 3.9x over Gr 1 in Gr 2, 3, 4, respectively, p<0.05) significantly decreased in Gr 2, which was abolished with HO-1 inhibitor (Gr 3 and 4). The appearance of apoptotic cardiomyocytes was significantly decreased in the Gr 2 (3.6±0.6, 1.7±0.2, 4.4±0.2, 4.6±0.3/hpf, in Gr 1, 2, 3, respectively, p<0.05). Western blot analysis revealed a more significant decrease (p<0.05) in the apoptosis related activated fragments of Caspase-3 and poly-ADP-ribose polymerase in group 2 than that of the other three groups. Using ELISA analysis, NFκB translocation and activation in nuclear extract revealed the same pattern as western blot analyses results.
Conclusions: In this study, we found that HO-1 activation, could ameliorate the surge of proinflammatory cytokines during CPB and decrease the occurrence of cardiomyocytic apoptosis, via inhibition of NFκB translocation, after global cardiac I/R injury.