title: Age-related decline in stress responses of human myocardium may not be explained by changes in mtDNA.
abstract: Elderly patients undergoing cardiac surgery are more likely to suffer postoperative heart failure than younger patients. This phenomenon is mirrored by an age-related loss of mitochondrial function and by an in vitro loss of myocardial contractile force following a stress. To examine the possibility that loss of mtDNA integrity may be responsible, we quantified representative age-associated mtDNA mutations (mtDNA(4977) and mtDNA(A3243G)) and mtDNA copy number using quantitative polymerase chain reaction in atrial samples obtained during cardiac surgery. The myocardium underwent organ bath contractility testing before and after either an ischaemic or hypoxic stress. We found that with age, recovery of developed force after either stressor significantly declined (p<0.0001). The abundance of mtDNA(4977) correlated weakly with loss of contractility (R(2)=0.09, p=0.047). However, the abundance level was low (average 0.0075% of total mtDNA) and the correlation disappeared when age was included in a multivariate analysis. Neither the abundance of mtDNA(A3243G) nor mtDNA copy number correlated with reduced recovery of developed force after stress. We conclude that, although mtDNA mutations (as exemplified by mtDNA(4977)) accumulate in the ageing heart, they are unlikely to make a major contribution to loss of contractile function.
authors.affiliation: Cardiac Surgical Research Unit, Alfred Hospital, Dept of Surgery, Monash University, and Baker Heart Research Institute, Commercial Road Prahran, Victoria 3181, Australia. francismiller1066@hotmail.com
authors.forename: Francis
authors.initials: F
authors.lastname: Miller
authors.forename: Phillip
authors.initials: P
authors.lastname: Nagley
authors.forename: Justin A
authors.initials: JA
authors.lastname: Mariani
authors.forename: Ruchong
authors.initials: R
authors.lastname: Ou
authors.forename: Vincent W S
authors.initials: VW
authors.lastname: Liu
authors.forename: Chunfang
authors.initials: C
authors.lastname: Zhang
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Linnane
authors.forename: Salvatore
authors.initials: S
authors.lastname: Pepe
authors.forename: Franklin
authors.initials: F
authors.lastname: Rosenfeldt
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D016275:Atrial Function; D002648:Child; D002675:Child, Preschool; D004272:DNA, Mitochondrial / Q000032:analysis* / Q000235:genetics; D006325:Heart Atria / Q000737:chemistry; D006801:Humans; D000860:Hypoxia; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D009154:Mutation; D009200:Myocardial Contraction / Q000502:physiology*; D017202:Myocardial Ischemia; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000737:chemistry*; D016133:Polymerase Chain Reaction
chemical_list: D004272:DNA, Mitochondrial