Microarray and Proteomic Analysis of the Cardioprotective Effects of Cold Blood Cardioplegia in the Mature and Aged Male and Female

Kendra M. Black, Reanne J. Barnett, Monoj K Bhasin, Christian Daly, Simon T. Dillon, Towia A. Libermann, Sidney Levitsky, James D. McCully


Recently we have shown that the cardioprotection afforded by cardioplegia is modulated by age and gender and is significantly decreased in the aged female. In this report we use microarray and proteomic analyses to identify transcriptomic and proteomic alterations affecting cardioprotection using cold blood cardioplegia in the mature and aged male and female heart. Mature and aged male and female New Zealand White rabbits were used for in-situ blood perfused cardiopulmonary bypass. Control hearts received 30 minutes sham ischemia and 120 minutes sham reperfusion. Global ischemia (GI) hearts received 30 minutes of GI achieved by crossclamping of the aorta. Cardioplegia (CP) hearts received cold blood cardioplegia prior to GI. Following 30 minutes of GI the hearts were reperfused for 120 minutes and then used for RNA and protein isolation. Microarray and proteomic analyses were performed. Functional enrichment analysis showed that mitochondrial dysfunction, oxidative phosphorylation and calcium signaling pathways were significantly enriched in all experimental groups. Glycolysis/gluconeogenesis and the pentose phosphate pathway were significantly changed in the aged male only (P<0.05) while glyoxylate/dicarboxylate metabolism was significant in the aged female only (P<0.05). Our data show that specific pathways associated with the mitochondrion modulate cardioprotection with CP in the aged and specifically in the aged female. The alteration of these pathways significantly contributes to decreased myocardial functional recovery and myonecrosis following ischemia and may be modulated to allow for enhanced cardioprotection in the aged and specifically in the aged female.

  • Heart
  • Ischemia
  • Reperfusion
  • Cardioplegia
  • Mitochondria