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The protective effect of University of Wisconsin solution (UW) for hypothermic storage of donor hearts has been demonstrated in the laboratory. However, clinical usage is associated with occasional primary graft failures. We postulated that this could be related to adverse effects of UW on the coronary vasculature during cardiac implantation and rewarming. We therefore assessed recovery of contractile function and coronary flow in rat hearts after cardioplegic arrest using UW compared with St. Thomas' solution (ST) at 4 degrees C or 25 degrees C.Cardioplegia was induced in isolated rat hearts using either UW or ST at 4 degrees C. Hearts were then maintained at 4 degrees C or 25 degrees C. In some hearts, UW at 4 degrees C was used for inducing arrest followed by flushing with ST at 4 degrees C and then rewarming to 25 degrees C. After 40 minutes of arrest, recovery of function and coronary flow were measured. Nuclear track emulsion was used to assess microvascular competence.Compared with ST-treated hearts, UW-treated hearts showed significant reduction in recovery of function at 25 degrees C (76.2% +/- 4.0% versus 25.0% +/- 4.1%; p0.01) but not at 4 degrees C (88.0% +/- 1.6% versus 87.1% +/- 2.6%). Recovery of coronary flow in the UW-treated hearts at 25 degrees C was significantly lower than that in the ST-treated hearts at 25 degrees C (71.7% +/- 3.0% versus 94.5% +/- 6.3%; p0.01). At 25 degrees C, microvascular competence was reduced in the UW group compared with the ST group. At 25 degrees C, flushing out UW with ST resulted in greater recovery of function compared with UW throughout (73.4% +/- 7.1% versus 25.0% +/- 4.1%; p0.01).University of Wisconsin solution provides effective donor heart protection under hypothermic conditions but can be deleterious at warmer temperatures.

Ca(2+) overload plays an important role in the pathogenesis of cardioplegic ischemia-reperfusion injury. The standard technique to control Ca(2+) overload has been to reduce Ca(2+) in the cardioplegic solution (CP). Recent reports suggest that Na(+)/H(+) exchange inhibitors can also prevent Ca(2+) overload. We compared 4 crystalloid CPs that might minimize Ca(2+) overload in comparison with standard Mg(2+)-containing CP: (1) low Ca(2+) CP (0.25 mmol/L), (2) citrate CP/normal Mg(2+) (1 mmol/L Mg(2+)), (3) citrate CP/high Mg(2+) (9 mmol/L Mg(2+)), and (4) the addition of the Na(+)/H(+) exchange inhibitor HOE-642 (Cariporide). We also tested the effect of citrate titration in vitro on the level of free Ca(2+) and Mg(2+) in CPs.Isolated working rat heart preparations were perfused with oxygenated Krebs-Henseleit buffer and subjected to 60 minutes of 37 degrees C arrest and reperfusion with CPs with different Ca(2+) concentrations. Cardiac performance, including aortic flow (AF), was measured before and after ischemia. Myocardial high-energy phosphates were measured after reperfusion. The in vitro addition of citrate to CP (2%, 21 mmol/L) produced parallel reductions in Mg(2+) and Ca(2+). Because only Ca(2+) was required to be low, the further addition of Mg(2+) increased free Mg(2+), but the highest level achieved was 9 mmol/L. Citrate CP significantly impaired postischemic function (AF 58.3+/-2. 5% without citrate versus 41.6+/-3% for citrate with normal Mg(2+), P:0.05, versus 22.4+/-6.2% for citrate with high Mg(2+), P:0.05). Low-Ca(2+) CP (0.25 mmol/L Ca(2+)) significantly improved the recovery of postischemic function in comparison with standard CP (1.0 mmol/L Ca(2+)) (AF 47.6+/-1.7% versus 58.3+/-2.5%, P:0.05). The addition of HOE-642 (1 micromol/L) to CP significantly improved postischemia function (47.6+/-1.7% without HOE-642 versus 62.4+/-1. 7% with HOE-642, P:0.05). Postischemia cardiac high-energy phosphate levels were unaffected by Ca(2+) manipulation.(1) A lowered Ca(2+) concentration in CP is beneficial in Mg(2+)-containing cardioplegia. (2) The use of citrate to chelate Ca(2+) is detrimental in the crystalloid-perfused isolated working rat heart, especially with high Mg(2+). (3) The mechanism of citrate action is complex, and its use limits precise simultaneous control of Ca(2+) and Mg(2+). (4) HOE-642 in CP is as efficacious in preservation of the ischemic myocardium as is the direct reduction in Ca(2+).

Background: Recovery of cardiac function after cardiac surgery and other interventional 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 of senescence now exist, there is a dearth of controlled in vitro studies that 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 human atrial trabeculae to recover contractile function after in vitro hypoxic or ischemic stress. Methods: Atrial pectinate trabeculae were dissected from the tip of 58 right 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°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. Developed force and other contractile variables were determined during each period. Results: Under normoxic conditions, no significant age difference was observed for any contractile function variable. However, after hypoxia, the old (70-89 years) and intermediate age groups (60-69 years) showed reduced recovery 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 simulated ischemia, the groups of 70- to 89-year-old and 60- to 69-year-old subjects showed reduced recovery of developed force (35.7% ± 17% [n = 5] and 51.1% ± 11.8% [n = 9], respectively) compared with that found (68.2% ± 10.4% [n = 6]) in the group of 34- to 59-year-old subjects ( P = .01). Multivariable analysis, comparing 20 factors of surgical patient characteristics and recovery of developed force, found that only age ( P = .01) and hypertension ( P = .01) were predictors of reduced recovery of developed force after either hypoxia or simulated ischemia. Conclusions: In aged human atrial myocardium, the capacity to recover contractile function after in vitro hypoxia or simulated ischemia is reduced compared with the younger myocardium of mature adults. These findings suggest that enhanced myocardial protective strategies may be indicated for elderly patients undergoing cardiac surgery. (J Thorac Cardiovasc Surg 2000;120:660-7)