Abstract 169: Brief Left Ventricular Pressure Overload Reduces Apoptosis After Myocardial Ischemia and Reperfusion
Introduction: Both apoptosis and necrosis contribute to cell death after myocardial ischemia and reperfusion. We previously reported brief left ventricular pressure overload decreased myocardial infarct (MI) size.
Hypothesis: We investigated whether pressure overload reduces apoptosis and the mechanisms involved.
Methods: MI was induced by 40-minute occlusion of the left anterior descending coronary artery followed by 3-hour reperfusion in anesthetized Sprague-Dawley rats. Brief left ventricular pressure overload was achieved by two episodes of 10-minute partial snaring of the ascending aorta, raising the systolic left ventricular pressure 50% above the baseline value. Ischemic preconditioning was elicited by two 10-minute coronary artery occlusions and 10-mintue reperfusion.
Results: Brief left ventricular pressure overload as well as ischemic preconditioning significantly decreased MI size (p < 0.001). Pressure overload significantly reduced myocardial apoptosis, as evidenced by decrease in the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive nuclei (p < 0.001), little or no DNA laddering, and less caspase-3 activation (p < 0.01). Western blot analysis revealed that pressure overload significantly increased Bcl-2, and decreased Bax and p53 (p < 0.01). Akt phosphorylation was significantly increased by pressure overload, while c-Jun N-terminal kinase (JNK) phosphorylation was significantly decreased (p < 0.001). The hemodynamics, area at risk and mortality were not significantly different among groups.
Conclusions: Thus, brief left ventricular pressure overload significantly reduces apoptosis. The underlying mechanisms might be related to modulation of expression of Bcl-2 and Bax, inhibition of p53, increase of Akt phosphorylation, and suppression of JNK phosphorylation.
Author Disclosures: H. Huang: None. C. Lai: None. S. Chiang: None. S. Chang: None. C. Chang: None. J. Lin: None. C. Huang: None.
- © 2014 by American Heart Association, Inc.