1. In addition to Ca²⁺‐dependent mediation of excitation– contraction coupling during cardiac work and ATP hydrolysis, Ca²⁺ also stimulates the Krebs’ cycle and mitochondrial matrix dehydrogenases to maintain the nicotinamide adenine dinucleotide redox potential and ATP synthesis. Thus, the balance between energy demand and supply is maintained during increases in cardiac work by elevated cytosolic Ca²⁺ that is transmitted to the mitochondrial matrix via regulation of uniporter and antiporter pathways across the inner mitochondrial membrane.

2. Brief ischaemia perturbs Ca²⁺ homeostasis but mitochondrial buffering of Ca²⁺ permits maintained mitochondrial function. However, prolonged ischaemia and reperfusion causes Ca²⁺‘overload’ at supramicromolar levels. The onset of vicious cycles that abrogate contractile function and, ultimately, may cause irreversible cell injury involves: (i) loss of ionic homeostasis, energy production and anti‐oxidant enzyme activity; (ii) activation of phospholipases; and (iii) accumulation of free radicals, membrane lipid peroxidation products and protein adducts.

3. Increased permeability of the inner mitochondrial membrane to solutes occurs causing mitochondrial swelling, ‘proton leak’, reduced efficiency of the respiratory chain and uncoupling of oxidative phosphorylation. The opening of the mitochondrial permeability transition pore is potentiated by high mitochondrial Ca²⁺ and inducers, such as P_i, long‐chain acyl coenzyme (Co)A and oxygen free radicals. Opening of this channel depolarizes the mitochondrion and dissipates the H⁺ electrochemical gradient (ΔμH), preventing oxidative phosphorylation. Together with the release of cytochrome c and subsequent activation of caspase pathways, these events precede cell death.

4. Compared with younger counterparts, the senescent myocardium has a reduced capacity to recover from ischaemia and reperfusion. The consequent events described above are augmented in ageing. Elevated mitochondrial Ca²⁺ and increased dehydrogenase activation are linked to inefficient mitochondrial function and limited postischaemic recovery of contractile function.

5. Notably, a distinct decrease in the ratio of mitochondrial membrane ω‐3 to ω‐6 polyunsaturated fatty acids (PUFA) and a decrease in the mitochondrial phospholipid cardiolipin occurs in aged rat hearts. A diet rich in ω‐3 PUFA directly increases membrane ω‐3:ω‐6 PUFA and cardiolipin content and also facilitates improved tolerance of ischaemia and reperfusion. A major consequence of dietary ω‐3 PUFA may be the effect of altered mitochondrial Ca²⁺ flux and Ca²⁺‐dependent processes.