The aging human myocardium:: Tolerance to ischema 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 atria] 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). Conclusion: 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.