The aging human myocardium: tolerance to ischemia and responsiveness to ischemic preconditioning.
BACKGROUND
Increasing age has been recognized as a cause for adverse prognosis in the setting of myocardial infarction, coronary angioplasty, and cardiac surgery. This is attributed to a greater susceptibility of the senescent heart to ischemic injury and to a lower response to protective interventions. This study investigated the effect of aging on the tolerance to ischemia of the human myocardium and its response to ischemic preconditioning.


METHODS
Right atrial specimens from 128 patients undergoing elective heart surgery were collected, sliced, and equilibrated for 30 minutes before being randomized into 3 study protocols: (1) 210 minutes of aerobic incubation (time-matched control), (2) 90 minutes of simulated ischemia and 120 minutes of reoxygenation, and (3) ischemic preconditioning with 5 minutes of ischemia and 5 minutes of reoxygenation before 90 minutes of ischemia and 120 minutes of reoxygenation. Patients were subdivided into 3 age groups: 30 to 49 years, 50 to 69 years, and 70 to 90 years. At the end of each protocol, tissue injury and viability were assessed by the leakage of creatine kinase and the reduction of 3-(4,5 dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide to insoluble formazan dye.


RESULTS
There were no differences among the 3 groups of patients in their comorbid conditions or their cardiac medications. Ischemic injury was similar in all 3 groups (creatine kinase = 4.1 +/- 0.7, 3.6 +/- 1.0, and 4.3 +/- 1.1 U/g wet weight, respectively; 3-(4,5 dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide = 64.7 +/- 31.3, 96.3 +/- 32.0, and 61.0 +/- 30.4 mM/g wet weight, respectively, P = not significant in all cases), and ischemic preconditioning equally protected against ischemia at all ages (creatine kinase = 1.9 +/- 0.5, 1.8 +/- 0.4, and 2.1 +/- 0.6 U/g wet weight, respectively; 3-(4,5 dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide = 157.9 +/- 31.5, 170.7 +/- 35.3, and 138.4 +/- 43.8 mM/g wet weight, respectively; P <.05 in all cases vs ischemia alone).


CONCLUSIONS
Age does not influence the tolerance of the human myocardium to ischemia or the protective effect of ischemic preconditioning. These results indicate the need for a reevaluation of the importance of age in risk scoring in cardiac surgery.
Loubani
Mahmoud
M
Department of Integrative Human Cardiovascular Physiology and Cardiac Surgery, University of Leicester, Glenfield Hospital, United Kingdom.
Ghosh
Sudip
S
Galiñanes
Manuel
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D015415:Biomarkers / Q000097:blood; D003402:Creatine Kinase / Q000378:metabolism; D005260:Female; D006321:Heart / Q000502:physiology*; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000378:metabolism / Q000628:therapy; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D006113:United Kingdom
D015415:Biomarkers; D013778:Tetrazolium Salts; D013844:Thiazoles; D003402:Creatine Kinase; C022616:thiazolyl blue