Influence of ageing on functional recovery and guanine nucleotide levels of the heart following cold cardioplegic arrest

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Abstract

Objective:

The effect of age on metabolism and mechanical recovery of the heart after cardioplegic arrest is important, but remains a relatively unexplored subject. In this study, functional recovery and nucleotide levels were compared in the heart at different ages subjected to prolonged hypothermic cardioplegic arrest.

Methods:

Three different age groups of rats: 1 (A); 4 (B); and 16 months (C) were perfused in working mode and subjected to cardioplegic arrest (St. Thomas' No. 1) and ischemia for 4 h at 4°C, followed by reperfusion for 35 min. Cardiac function (cardiac output and aortic pressure) was recorded before and after ischemia. Another series of hearts in all three age groups underwent 5 min of normoxic perfusion to obtain pre-ischemic baseline metabolite concentrations. Hearts were freeze-clamped at the end of each experiment and used for determination of nucleotide and creatine metabolites by HPLC.

Results:

The post-ischemic recovery (% of the pre-ischemic value) of the cardiac power was 48.9±7.8% for group A, which was significantly higher than the functional recovery of group B (24.1±3.5%) or C (21.4±4.7%, P<0.05, respectively). There was no difference in ATP or the total adenine nucleotide or creatine metabolite concentrations between the three age groups. In contrast, both GTP and the total guanine nucleotide concentration was highest in A (P<0.05). Total guanylate pool was 1.52±0.10 1 μmol/g dry wt. in A, as compared to B (1.05±0.04) or C (1.12±0.04). NAD was significantly higher in B (4.1±0.1, P<0.05), when compared to A (3.6±0.1) and C (3.8±0.1).

Conclusion:

Best post-ischemic functional recovery after cardioplegic arrest was observed in the 1-month-old hearts (A) and was associated with highest guanine nucleotide concentration; preservation of guanine nucleotide pool in the youngest hearts may be an important mechanism for improved cardioprotection due to the important role of GTP in signalling pathways.

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