S100A1 in human heart failure: lack of recovery following left ventricular assist device support.

BACKGROUND: We hypothesized that S100A1 is regulated during human hypertrophy and heart failure and that it may be implicated in remodeling after left ventricular assist device. S100A1 is decreased in animal and human heart failure, and restoration produces functional recovery in animal models and in failing human myocytes. With the potential for gene therapy, it is important to carefully explore human cardiac S100A1 regulation and its role in remodeling. METHODS AND RESULTS: We measured S100A1, the sarcoplasmic endoplasmic reticulum Ca(2+)ATPase, phospholamban, and ryanodine receptor proteins, as well as ß-adrenergic receptor density in nonfailing, hypertrophied (left ventricular hypertrophy), failing, and failing left ventricular assist device-supported hearts. We determined functional consequences of protein alterations in isolated contracting muscles from the same hearts. S100A1, sarcoplasmic endoplasmic reticulum Ca(2+)ATPase and phospholamban were normal in left ventricular hypertrophy, but decreased in failing hearts, while ryanodine receptor was unchanged in either group. Baseline muscle contraction was not altered in left ventricular hypertrophy or failing hearts. ß-Adrenergic receptor and inotropic response were decreased in failing hearts. In failing left ventricular assist device-supported hearts, S100A1 and sarcoplasmic endoplasmic reticulum Ca(2+)ATPase showed no recovery, while phospholamban, ß-adrenergic receptor, and the inotropic response fully recovered. CONCLUSIONS: S100A1 and sarcoplasmic endoplasmic reticulum Ca(2+)ATPase, both key Ca(2+)-regulatory proteins, are decreased in human heart failure, and these changes are not reversed after left ventricular assist device. The clinical significance of these findings for cardiac recovery remains to be addressed.

A preliminary study of peritraumatic dissociation, social support, and coping in relation to posttraumatic stress symptoms for a parent's cancer.

This study examined predictors of posttraumatic stress disorder (PTSD) symptoms in adults who, as children, had a parent diagnosed with cancer. Possible predictors of adulthood PTSD examined were peritraumatic dissociation, satisfaction with social support, coping through denial, behavioral disengagement and self-distraction, and whether or not the parent died. Thirty research participants (20 women and 10 men, ages 18-38) were recruited who were 8-17-years old at the time of a parent's cancer diagnosis. Each participant completed measures of their current PTSD symptoms in response to their parent's cancer, peritraumatic dissociative experiences, demographic characteristics, and satisfaction with social support and use of coping strategies at the time of their parent's cancer diagnosis. Seventeen percent met screening criteria for likely PTSD. As hypothesized, PTSD symptoms were strongly and positively correlated with peritraumatic dissociation. Furthermore, PTSD symptoms were greater among females and were related to greater use of denial and behavioral disengagement and to less satisfaction with social support. These results suggest that health care providers need to recognize symptoms of peritraumatic dissociation in the children of parents who are diagnosed with cancer so that steps can be taken to minimize the children's development of PTSD that may extend into their adult lives.