Tolerance to ischemia and hypoxia is reduced in aged human myocardium

Background: Recovery of cardiac function after cardiac surgery and other in terventional cardiac procedures in elderly patients is inferior to that in younger patients, suggesting that the aged myocardium is more sensitive to ischemia and other stresses, Although convincing data from animal studies o f senescence now exist, there is a dearth of controlled in vitro studies th at examine the specific response of aged human myocardium to the stress of hypoxia or ischemia. Objective: We sought to determine the effect of age on the capacity of huma n atrial trabeculae to recover contractile function after in vitro hypoxic or ischemic stress. Methods: Atrial pectinate trabeculae were dissected from the tip of 58 righ t atrial appendages harvested during an operation in patients aged between 34 and 89 years and electrically stimulated at 1 Hz in oxygenated Ringer's solution at 37 degrees C. Tissues experienced 30 minutes of either hypoxia (N-2 and perfusate) or simulated ischemia (humidified N-2 without perfusate ) and were returned to normoxia for recovery of function for 30 minutes. De veloped force and other contractile variables were determined during each p eriod. Results: Under normoxic conditions, no significant age difference was obser ved for any contractile function variable. However, after hypoxia, the old (70-89 years) and intermediate age groups (60-69 years) showed reduced reco very of developed force (48.5% +/- 22.2% [n = 11] and 44.9% +/- 19% [n = 12 ], respectively) compared with that found (66.4% +/- 19.7% [n = 15]) in the younger (34-59 years) group (mean +/- SD, P =.02). Similarly, after simula ted ischemia, the groups of 70- to 89-year-old and 60- to 69-year-old subje cts showed reduced recovery of developed force (35.7% +/- 17% [n = 5] and 5 1.1% +/- 11.8% [n = 9], respectively) compared with that found (68.2% +/- 1 0.4% [n = 6]) in the group of 34- to 59-year-old subjects (P =.01). Multiva riable analysis, comparing 20 factors of surgical patient characteristics a nd recovery of developed force, found that only age (P =.01) and hypertensi on (P =.01) were predictors of reduced recovery of developed force after ei ther hypoxia or simulated ischemia. Conclusions: In aged human atrial myocardium, the capacity to recover contr actile function after in vitro hypoxia or simulated ischemia is reduced com pared with the younger myocardium of mature adults. These findings suggest that enhanced myocardial protective strategies may be indicated for elderly patients undergoing cardiac surgery.