Neuroprotective Pentapeptide CN-105 Improves Functional and Histological Outcomes in a Murine Model of Intracerebral Hemorrhage.
Lei B, James ML, Liu J, Zhou G, Venkatraman TN, Lascola CD, Acheson SK, Dubois LG, Laskowitz DT, Wang H.
Presently, no pharmacological treatments have been demonstrated to improve long-term functional outcomes following intracerebralhemorrhage (ICH). Clinical evidence associates apolipoprotein E (apoE) genotype with ICH incidence and outcome. While apoE modifies neuroinflammatory responses through its adaptive role in glial downregulation, intact apoE holoprotein is too large to cross the blood-brain barrier (BBB). Therefore, we developed a 5-amino acid peptide – CN-105 – that mimics the polar face of the apoE helical domain involved in receptor interactions. In the current study, we investigated the therapeutic potential of CN-105 in a mouse model of ICH. Three doses of CN-105 (0.05 mg/kg) was administered by tail vein injection within 24 hours after ICH induction. Functional assessment showed durable improvement in vestibulomotor performance after CN-105 treatment, as quantified by increased Rotarod latencies on Days 1-5 post-ICH, and long-term improvement in neurocognitive performance, as quantified by reduced Morris water maze latencies on Days 29-32 post-ICH. Further, brain water content was significantly reduced, neuroinflammation was decreased and hippocampal CA3 neuronal survival was increased, although hemorrhage volume was not affected by CN-105. We concluded, therefore, that pentapeptide CN-105 improved short- and long-term neurobehavioral outcomes in a murine model of ICH, suggesting therapeutic potential for patients with acute ICH.
Journal of Cardiothoracic and Vascular Anesthesia
Mitral Regurgitation After Orthotopic Lung Transplantation: Natural History and Impact on Outcomes.
McCartney SL, Cooter M, Samad Z, Sivak J, Castleberry A, Gregory S, Haney J, Hartwig M, Swaminathan M.
OBJECTIVE: Progression of mitral regurgitation (MR) after orthotopic lung transplantation (OLT) may be an underrecognized phenomenon due to the overlapping symptomatology of pulmonary and valvular disease. Literature evaluating the progression of MR after OLT currently is limited to case reports. Therefore, the hypothesis that MR progresses after OLT was tested and the association of preprocedure MR with postoperative mortality was assessed.
DESIGN: A retrospective cohort.
SETTING: A tertiary-care hospital.
PARTICIPANTS: Patients who underwent OLT between January 1, 2003 and February 4, 2012.
INTERVENTIONS: After receiving institutional review board approval, a preprocedure transesophageal echocardiogram was compared with a postoperative transthoracic echocardiogram (TTE) to determine the progression of MR. Univariate and multivariate association between preprocedure MR grade and 1- and 5-year mortality was assessed. A p value of<0.05 was considered statistically significant.
MEASUREMENTS AND MAIN RESULTS: From 715 patients who underwent OLT, 352 had a postoperative TTE and were included in the evaluation of progression of MR. Five patients had progression of MR postoperatively, and the mean change in MR score of -0.04 was found to be nonsignificant (p = 0.25). Mortality data were available for 634 of the 715 patients. After covariate adjustment, there was no significant association between MR grade and 1-year mortality (p = 0.20) or 5-year mortality (p = 0.46).
CONCLUSIONS: This study rejected the hypothesis that primary and secondary MR progresses after OLT and found that preprocedure MR was not associated with increased postoperative mortality. Despite the findings that MR does not progress in all patients, there is a subset of patients for whom MR progression is clinically significant.