Abstract 8: Influence of Receiving Hospital Characteristics on Survival after Cardiac Arrest

Hospital management of out-of-hospital cardiac arrest (OHCA) patients after return of spontaneous circulation (ROSC) can influence patient survival via interventions such as hypothermia and cardiac catheterization (CATH). This study tested the hypothesis that survival differed between different types of hospitals for subjects with ROSC after OHCA. Methods: Adult (≥ 18 years) subjects with paramedic-documented ROSC or who lived &gt;1 day after OHCA were identified with their receiving hospital in a prospective database from 9 regions in the US and Canada. Hospitals were characterized using the American Hospital Directory or the Guide to Canadian Healthcare Facilities. Hospitals were categorized by bed number (large &gt;400; medium 250 – 400; small &lt;250) and CATH capability. Associations between clinical variables, hospital categories, survival time, and survival to hospital discharge were determined using Cox regression and analysis of variance. Results: Between December 2005 and July 2007, 3644 OHCA subjects were treated in 254 hospitals, with similar numbers in large (1026), medium (1094) and small (1276) hospitals. CATH hospitals treated 2123 (58%) subjects, and patient features (63% male, 42% VF/VT, 67% witnessed collapse, and mean call-arrival interval of 5.7 (SD 2.8) minutes) did not differ between hospital categories. CATH hospitals had higher survival than non-CATH hospitals in large (35.1% vs. 27.7%), medium (34.4% vs. 30.7%) and small (38.6% vs. 26.5%) categories (F=19.55; p&lt;0.001). VF/VT (p &lt; 0.001), age (p &lt; 0.001) and witnessed collapse (p &lt; 0.001) were associated with survival time. When adjusted for initial rhythm, call-arrival interval, witnessed collapse, age, sex, region, teaching institution, and trauma center level, there was no significant effect of CATH. However, the interaction of large hospital and CATH was associated with lower hazard of death (0.71, 95% CI [0.54, 0.93]). Conclusions: Transport to a CATH hospital is associated with increased probability of survival to discharge after OHCA. These data cannot determine whether cardiac catheterization was performed or if CATH hospital is a surrogate for more comprehensive cardiac care. Therefore, further work should examine what aspects of in-hospital care affected outcome.</jats:p

HSP70-binding motifs function as protein quality control degrons

Protein quality control (PQC) degrons are short protein segments that target misfolded proteins for proteasomal degradation, and thus protect cells against the accumulation of potentially toxic non-native proteins. Studies have shown that PQC degrons are hydrophobic and rarely contain negatively charged residues, features which are shared with chaperone-binding regions. Here we explore the notion that chaperone-binding regions may function as PQC degrons. When directly tested, we found that a canonical Hsp70-binding motif (the APPY peptide) functioned as a dose-dependent PQC degron both in yeast and in human cells. In yeast, Hsp70, Hsp110, Fes1, and the E3 Ubr1 target the APPY degron. Screening revealed that the sequence space within the chaperone-binding region of APPY that is compatible with degron function is vast. We find that the number of exposed Hsp70-binding sites in the yeast proteome correlates with a reduced protein abundance and half-life. Our results suggest that when protein folding fails, chaperone-binding sites may operate as PQC degrons, and that the sequence properties leading to PQC-linked degradation therefore overlap with those of chaperone binding. </p