RELATIONSHIP BETWEEN ATP RESYNTHESIS AND CALCIUM ACCUMULATION IN THE REPERFUSED RAT HEART

1. The postulate that the composition of solutions used to reperfuse ischaemic hearts may modulate their ability to synthesize high‐energy compounds was tested in isolated rat hearts subjected to 30 min normothermic ischaemia and then reperfused with either Krebs'‐Henseleit buffer (K‐H) for 20 min (control reperfusion, CR), or a ‘myocardial protective solution’ (MPS) for 5 min, followed by 15 min K‐H (modified reperfusion, MR). The ‘myocardial protective solution’ was designed to protect against damage caused by sodium and calcium accumulation and by free radicals. Metabolic precursors were also included to promote and support adenosine triphosphate (ATP) resynthesis during reperfusion under both aerobic and hypoxic conditions. 2. ³¹P nuclear magnetic resonance (NMR) was used to measure tissue ATP and creatine phosphate (CP), and atomic absorption spectrometry was used to measure Ca⁺⁺. Early during CR, ATP recovered to 28% of the pre‐ischaemic value, but fell to 5.5% with continued perfusion. Similarly, CP recovered to 45.5% of the pre‐ischaemic level during early CR but fell to 25.5% with continued perfusion. 3. Better maintenance of ATP was seen during MR with oxygenated MPS (O₂‐MR), the final ATP remaining at 16.9% of the pre‐ischaemic level. During O₂‐MR, CP recovered to 43.55 of the pre‐ischaemic level but was not maintained and fell to a final level of 29.5%. 4. During MR with O₂‐free MPS (non‐O₂‐MR), there was no reperfusion‐associated fall in ATP or CP, with the levels maintained at 26.6% and 34.55, respectively. 5. During 5 min CR, tissue Ca⁺⁺ was elevated but this did not happen during 5 min reperfusion with O₂‐MR or non‐O₂‐MR. After 20 min reperfusion there was no significant difference in Ca²⁺between the groups (CR 16.56±1.33; O₂‐MR 13.48±1.2; non‐O₂‐MR 15.97±2.4 μmol/g dry weight). When reperfused with O₂‐free histidine‐containing MPS, tissue Ca¹⁺ increased substantially without any change in ATP (26.2 ± 1.65% at 20 min). 6. Thus reperfusion injury, assessed by a secondary reduction in ATP, can be limited by the initial use of appropriately designed reperfusion ‘cocktails', and Ca⁺⁺ overload is not the primary factor limiting ATP regeneration.