Myocardial Dysfunction in Donor Hearts

Background—Potential cardiac donors show various degrees of myocardial dysfunction, and the most severely affected hearts are unsuitable for transplantation. The cause of this acute heart failure is poorly understood. We investigated whether alterations in calcium-handling proteins, b-adrenoceptor density, or the inhibitory G protein Gia could account for this phenomenon in unused donor hearts (n54 to 8). We compared these with end-stage failing hearts (n514 to 16) and nonfailing hearts (n53 to 12). Methods and Results—Myocardial samples were obtained from unused donor hearts displaying ejection fractions ,30%. Both trabeculae and isolated myocytes responded as poorly as those from the group of failing hearts to increasing stimulation frequency with regard to inotropic function in vitro. Immunodetectable abundance of sarcoplasmic reticulum calcium-ATPase and sodium calcium exchanger were greater (177%; P,0.01) and smaller (29%; P,0.01), respectively, in the unused donor hearts relative to the failing group, which suggests that alterations of these proteins are not a common cause of contractile dysfunction in the 2 groups. Myocytes from the unused donor group were desensitized to isoprenaline to a similar degree as those from the failing heart group. However, b-adrenoceptor density was reduced in the failing (P,0.001) but not in the unused donor heart group (P50.37) relative to the nonfailing heart group (n55). Gia activity was increased in samples from unused donor and failing hearts relative to nonfailing hearts (P,0.05). Conclusions—Increased activity of the inhibitory G protein Gia is a significant contributory factor for impaired contractility in these acutely failing donor hearts. (Circulation. 1999;99:2565-2570.)