Previously we have reported in vitro evidence suggesting that that H2O2 may support wound healing by inducing VEGF expression in human keratinocytes (C. K. Sen et al., 2002, J. Biol. Chem.277, 33284-33290). Here, we test the significance of H2O2 in regulating wound healing in vivo. Using the Hunt-Schilling cylinder approach we present the first evidence that the wound site contains micromolar concentrations of H2O2. At the wound site, low concentrations of H2O2 supported the healing process, especially in p47(phox)- and MCP-1-deficient mice in which endogenous H2O2 generation is impaired. Higher doses of H2O2 adversely influenced healing. At low concentrations, H2O2 facilitated wound angiogenesis in vivo. H2O2 induced FAK phosphorylation both in wound-edge tissue in vivo and in human dermal microvascular endothelial cells. H2O2 induced site-specific (Tyr-925 and Tyr-861) phosphorylation of FAK. Other sites, including the Tyr-397 autophosphorylation site, were insensitive to H2O2. Adenoviral gene delivery of catalase impaired wound angiogenesis and closure. Catalase overexpression slowed tissue remodeling as evidenced by a more incomplete narrowing of the hyperproliferative epithelium region and incomplete eschar formation. Taken together, this work presents the first in vivo evidence indicating that strategies to influence the redox environment of the wound site may have a bearing on healing outcomes.
Stent thrombosis (ST) is a rare but devastating complication after percutaneous coronary intervention. Newer generation drug-eluting stents (DES) and newer antiplatelet therapies have been shown to decrease the incidence of ST, but we continue to observe ST-segment elevation myocardial infarction (STEMI) due to ST in contemporary practice. A retrospective analysis of 527 patients who presented with STEMI was performed; 57 patients (11%) with angiographically confirmed ST were compared with the patients with STEMI due to de novo lesion. The type of previous stent, the timing of ST, and the use of antiplatelet therapy were reviewed in patients with ST. Patients with ST had higher prevalence of comorbid conditions, such as hypertension, diabetes mellitus, and coronary artery disease, and had lower left ventricular ejection fraction (37???5 vs. 44???16%, p?=?0.0011). There was no difference in in-hospital mortality (2 vs. 4%, p?=?0.7082). ST was seen most commonly as ?very late? (56%), and with previous second-generation DES (40%). Eighty-two percent of patients among early ST, compared with 22% of patients with very late ST were on dual antiplatelet therapy (DAPT). In 12% of patients, ST happened after DAPT was stopped by physician for procedures. ST is seen in a variety of clinical settings with the most common presentation being very late ST and in second-generation DES, which most likely represent the growing population with previous second-generation stents.
This is a case of a 77-year-old woman who underwent a multiple-gated acquisition (MUGA) scan to evaluate her cardiac function after initially presenting with chest pain and shortness of breath. The scan revealed the presence of an apicoaortic conduit (AAC) and incidentally found a left ventricular pseudoaneurysm. After aneurysmectomy, the MUGA scan was repeated.
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