Myocardial Glycogen Depletion Cannot Explain the Cardioprotective Effects of Ischemic Preconditioning in the Rat Heart

Abstract

The mechanism of ischemic preconditioning remains unknown. The role of glycogen depletion prior to prolonged ischemia was examined as a potential mechanism of ischemic preconditioning. The glycogen content of the rat heart varies in a 24-h rhythm. In a retrospective study, the relationships between the time of day the animals were sacrificed, pre-ischemic myocardial glycogen content, and post-ischemic functional recovery were assessed in non-conditioned and ischemically preconditioned hearts. The analyses were performed on previously published data (Asimakis et al., 1992, 1993). After an equilibration perfusion, isolated rat hearts were given 40 min of global ischemia followed by 30 min of reperfusion. Preconditioned hearts received 5 min of ischemia followed by a 5-min recovery period prior to the 40-min ischemic period. Some of the hearts were freeze-clamped immediately prior to the 40-min ischemic period to determine pre-ischemic glycogen content. Pre-ischemic glycogen was higher in the morning than afternoon. The time of day correlated significantly with the pre-ischemic glycogen content of non-conditioned ( r=0.67; P<0.005) and preconditioned ( r=0.79; P<0.001) hearts. However, time of day did not correlate significantly with post-ischemic recovery of heart rate×developed pressure (HR×DP) or end-diastolic pressure (EDP) in either the non-conditioned or preconditioned hearts. The relationships were also assessed by subdividing the groups into either morning (a.m.) or afternoon (p.m.) hearts. The pre-ischemic glycogen content was lower in the non-conditioned-p.m. ( n=5) hearts compared to the non-conditioned-a.m. ( n=10) hearts (67.6±9.0 v128.1±13.3 nmol glucose/mg protein, P<0.005). However, there were no significant differences between p.m. ( n=13) and a.m. ( n=9) non-conditioned hearts with respect to post-ischemic recovery of HR×DP (20.6±4 v12.0±4% of baseline, respectively, P= n.s.). In contrast, preconditioned-p.m. ( n=6) and -a.m. ( n=7) had pre-ischemic glycogen contents of 49.6±6 and 76.6±5.0 nmol glucose/mg protein, respectively. These glycogen values were not significantly different from the non-conditioned-p.m. hearts (67.6 nmol/mg protein). However, post-ischemic recovery of HR×DP in the preconditioned-p.m. ( n=5) and -a.m. ( n=6) hearts were 54.6±5 and 51.4±8% of baseline, respectively (these values were significantly higher ( P<0.05) than the recovery for the non-conditioned-p.m. and -a.m. hearts). The results imply that the cardioprotection of ischemic preconditioning cannot be explained solely by myocardial glycogen depletion.