Publications

BACKGROUND

We investigated the hypothesis that postconditioning by FTY720 (FTY) in isolated perfused mouse hearts is independent of the sphingosine 1-phosphate (S1P) pathway.

MATERIAL AND METHODS

Ex vivo hearts were exposed to postconditioning (POST) by either ischemia or FTY720. Protection against ischemia/reperfusion (IR) injury was measured by recovery of left ventricular developed pressure (LVDP) and infarct size.

RESULTS

FTY effectively postconditioned (POST) ex vivo hearts against ischemia/reperfusion (IR) injury as measured by recovery of LVDP and a low infarct size. FTY protection, unlike S1P but like sphingosine (Sph), was insensitive to inhibition of S1P G-Protein Coupled Receptors (GPCRs) or inhibition of PI3 kinase. Protection by FTY and Sph was however blocked by inhibitors of PKA and PKG. Thus, FTY follows the same cardioprotective pathway as Sph. This was further supported by studies of FTY POST in knockout (KO) mice lacking the SphK2 form of Sph kinase that is needed for phosphorylation of FTY to an S1P analog. In the absence of SphK2, FTY (and Sph) POST was still cardioprotective. This differed from the effect of SphK2 KO on protection by ischemic POST (IPOST). IPOST was not effective in KO hearts. To see if the GPCR signaling pathway to protection is normal in KO hearts, we looked at POST by GPCR agonists S1P and adenosine. Both provided effective protection even in KO hearts suggesting that the problem with IPOST in KO hearts is a low level of S1P available for release during IPOST. Thus, pharmacologic POST with FTY or Sph, like adenosine and S1P, is unaffected in the KO.

CONCLUSIONS

FTY720 administered in vivo might behave in a dual manner showing both S1P-like effects and sphingosine-like effects. It appears that the latter may have been overlooked and may be the more important in aging hearts.

Readmissions to the hospital are common and costly, often resulting from poor care coordination. Despite increased attention given to improving the quality and safety of care transitions, little is known about patient and provider perspectives of the transitional care needs of rehospitalized Veterans. As part of a larger quality improvement initiative to reduce hospital readmissions, the authors conducted semi-structured interviews with 25 patients and 14 of their interdisciplinary health care providers to better understand their perspectives of the transitional care needs and challenges faced by rehospitalized Veterans. Patients identified 3 common themes that led to rehospitalization: (1) knowledge gaps and deferred power; (2) difficulties navigating the health care system; and (3) complex psychiatric and social needs. Providers identified different themes that led to rehospitalization: (1) substance abuse and mental illness; (2) lack of social or financial support and homelessness; (3) premature discharge and poor communication; and (4) nonadherence with follow-up. Results underscore that rehospitalized Veterans have a complex overlapping profile of real and perceived physical, mental, and social needs. A paradigm of disempowerment and deferred responsibility appears to exist between patients and providers that contributes to ineffective care transitions, resulting in readmissions. These results highlight the cultural constraints on systems of care and suggest that process improvements should focus on increasing the sense of partnership between patients and providers, while simultaneously creating a culture of empowerment, ownership, and engagement, to achieve success in reducing hospital readmissions.