title: The effects of ageing on the response to cardiac surgery: protective strategies for the ageing myocardium.
abstract: With ageing of the general population, increasing numbers of elderly patients are presenting for interventional cardiac treatment such as cardiac surgery, angioplasty and thrombolysis. However, the results of these interventions in the elderly are inferior to those in the young. A likely contributing factor is an age-related reduction in cellular energy production in the myocardium during interventions that induce aerobic or ischaemic stress. Coenzyme Q10 (CoQ10) has the potential to improve the efficiency of energy production in mitochondria by bypassing defective components in the respiratory chain as well as reducing the effects of oxidative stress. We hypothesised that CoQ10 pretreatment prior to stress could improve the post-stress recovery of the myocardium. We investigated this hypothesis in three studies. In Study 1, isolated hearts taken from senescent or mature rats, pre-treated with CoQ10 were subjected to rapid electrical pacing and the recovery of work after pacing as a percentage of pre-pacing level was measured. In Study 2, human atrial tissue obtained at the time of open heart surgery was subjected to simulated ischaemia in the organ bath after incubation with CoQ10 or vehicle and recovery measured. Study 3 was a clinical trial of oral CoQ10 therapy for 2 weeks pre-operatively in patients undergoing elective cardiac surgery. Study 1. CoQ10 treatment in senescent rat hearts improved recovery of work after rapid pacing (48.1+/-4.1 vs 16.8+/-4.3%; P < 0.0001) and MVO2 (82.1+/-2.8 vs 61.3+/-4.0%; P < 0.01) in treated versus untreated hearts respectively. Study 2. Post-ischaemic human trabeculae from the > or =70 years old group displayed less contractile recovery compared to the <70 years old group, but this difference was abolished by CoQ10 pre-incubation. Study 3: respiration by mitochondria isolated from trabeculae was more efficient after CoQ10 pretreatment than placebo. Compared to placebo, CoQ10 patients had a lower release of Troponin I, improved cardiac pump function and a shorter length of stay in hospital.
  
  
  CONCLUSIONS
  1) Senescent hearts have reduced baseline function and reduced tolerance to aerobic stress compared to young hearts. 2) Pre-treatment with oral CoQ10 improves baseline function of the senescent myocardium and its tolerance to aerobic stress. 3) CoQ10 pre-treatment in vitro overcomes the reduced capacity of aged human heart muscle to recover contractile function after ischaemia compared to younger muscle. 4) Oral CoQ10 therapy before cardiac surgery improves efficiency of mitochondrial energy production, improves post-operative heart function, reduces intra-operative myocardial damage and shortens hospital stay.
authors.affiliation: Cardiac Surgical Research Unit, Alfred Hospital, Baker Institute, Melbourne, Australia. f.rosenfeldt@alfred.org.au
authors.forename: Franklin L
authors.initials: FL
authors.lastname: Rosenfeldt
authors.forename: Salvatore
authors.initials: S
authors.lastname: Pepe
authors.forename: Anthony
authors.initials: A
authors.lastname: Linnane
authors.forename: Phillip
authors.initials: P
authors.lastname: Nagley
authors.forename: Michael
authors.initials: M
authors.lastname: Rowland
authors.forename: Ruchong
authors.initials: R
authors.lastname: Ou
authors.forename: Silvana
authors.initials: S
authors.lastname: Marasco
authors.forename: William
authors.initials: W
authors.lastname: Lyon
mesh_terms: D000368:Aged; D000375:Aging / Q000502:physiology*; D000818:Animals; D003067:Coenzymes; D006321:Heart / Q000502:physiology*; D006801:Humans; D051381:Rats; D019616:Thoracic Surgical Procedures; D014451:Ubiquinone / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D003067:Coenzymes; D014451:Ubiquinone; C024989:coenzyme Q10