title: High inborn aerobic capacity does not protect the heart following myocardial infarction.
abstract: Maximal oxygen uptake (Vo2max) is a strong prognostic marker for morbidity and mortality, but the cardio-protective effect of high inborn Vo2max remains unresolved. We aimed to investigate whether rats with high inborn Vo2max yield cardio-protection after myocardial infarction (MI) compared with rats with low inborn Vo2max. Rats breed for high capacity of running (HCR) or low capacity of running (LCR) were randomized into HCR-SH (sham), HCR-MI, LCR-SH, and LCR-MI. Vo2max was lower in HCR-MI and LCR-MI compared with respective sham (P < 0.01), supported by a loss in global cardiac function, assessed by echocardiography. Fura 2-AM loaded cardiomyocyte experiments revealed that HCR-MI and LCR-MI decreased cardiomyocyte shortening (39%, and 34% reduction, respectively, both P < 0.01), lowered Ca(2+) transient amplitude (37%, P < 0.01, and 20% reduction, respectively), and reduced sarcoplasmic reticulum (SR) Ca(2+) content (both; 20%, P < 0.01) compared with respective sham. Diastolic Ca(2+) cycling was impaired in HCR-MI and LCR-MI evidenced by prolonged time to 50% Ca(2+) decay that was partly explained by the 47% (P < 0.01) and 44% (P < 0.05) decrease in SR Ca(2+)-ATPase Ca(2+) removal, respectively. SR Ca(2+) leak increased by 177% in HCR-MI (P < 0.01) and 67% in LCR-MI (P < 0.01), which was abolished by inhibition of Ca(2+)/calmodulin-dependent protein kinase II. This study demonstrates that the effect of MI in HCR rats was similar or even more pronounced on cardiac- and cardiomyocyte contractile function, as well as on Ca(2+) handling properties compared with observations in LCR. Thus our data do not support a cardio-protective effect of higher inborn aerobic capacity.
authors.affiliation: K.G. Jebsen Center of Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway;
authors.forename: M A
authors.initials: MA
authors.lastname: Høydal
authors.forename: G
authors.initials: G
authors.lastname: Kaurstad
authors.forename: N P
authors.initials: NP
authors.lastname: Rolim
authors.forename: A B
authors.initials: AB
authors.lastname: Johnsen
authors.forename: M
authors.initials: M
authors.lastname: Alves
authors.forename: L G
authors.initials: LG
authors.lastname: Koch
authors.forename: S L
authors.initials: SL
authors.lastname: Britton
authors.forename: T O
authors.initials: TO
authors.lastname: Stølen
authors.forename: G L
authors.initials: GL
authors.lastname: Smith
authors.forename: U
authors.initials: U
authors.lastname: Wisløff
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D003971:Diastole / Q000502:physiology; D017079:Exercise Tolerance / Q000502:physiology*; D005260:Female; D006321:Heart / Q000503:physiopathology*; D009200:Myocardial Contraction / Q000502:physiology; D009203:Myocardial Infarction / Q000378:metabolism / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology; D010101:Oxygen Consumption / Q000502:physiology; D010805:Physical Conditioning, Animal / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D012420:Running / Q000502:physiology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism / Q000502:physiology
chemical_list: D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D000251:Adenosine Triphosphatases; D002118:Calcium
keywords: calcium cycling/excitation-contraction coupling; cardio-protection; inborn aerobic capacity; myocardial infarction