Myocardial dysfunction in donor hearts - A possible etiology

Background-Potential cardiac donors show various degrees of myocardial dysf unction, and the most severely affected hearts are unsuitable for transplan tation. The cause of this acute heart failure is poorly understood. We inve stigated whether alterations in calcium-handling proteins, beta-adrenocepto r density, or the inhibitory G protein G(i alpha) could account for this ph enomenon in unused donor hearts (n=4 to 8). We compared these with end-stag e failing hearts (n=14 to 16) and nonfailing hearts (n=3 to 12). Methods and Results-Myocardial samples were obtained from unused donor hear ts displaying ejection fractions <30%. Both trabeculae and isolated myocyte s responded as poorly as those from the group of failing hearts to increasi ng stimulation frequency with regard to inotropic function in vitro. Immuno detectable abundance of sarcoplasmic reticulum calcium-ATPase and sodium ca lcium exchanger were greater (177%; P<0.01) and smaller (29%; P<0.01), resp ectively, in the unused donor hearts relative to the failing group, which s uggests that alterations of these proteins are not a common cause of contra ctile dysfunction in the 2 groups. Myocytes from the unused donor group wer e desensitized to isoprenaline to a similar degree as those from the failin g heart group. However, beta-adrenoceptor density was reduced in the failin g (P<0.001) but not in the unused donor heart group (P=0.37) relative to th e nonfailing heart group (n=5), G(i alpha) activity was increased in sample s from unused donor and failing hearts relative to nonfailing hearts (P<0.0 5). Conclusions-Increased activity of the inhibitory G protein G(i alpha) is a significant contributory factor for impaired contractility in these acutely failing donor hearts.