• Korean Journal of Radiology
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• 제21권6호
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• pp.647-659
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• 2020

Objective: The occurrence of intramyocardial hemorrhage (IMH) and microvascular obstruction (MVO) in myocardial infarction (MI), known as severe ischemia/reperfusion injury (IRI), has been associated with adverse remodeling. APT102, a soluble human recombinant ecto-nucleoside triphosphate diphosphohydrolase-1, can hydrolyze extracellular nucleotides to attenuate their prothrombotic and proinflammatory effects. The purpose of this study was to temporally evaluate the therapeutic effect of APT102 on IRI in rats and to elucidate the evolution of IRI in the acute stage using cardiovascular magnetic resonance imaging (CMRI). Materials and Methods: Fifty-four rats with MI, induced by ligation of the origin of the left anterior descending coronary artery for 60 minutes, were randomly divided into the APT102 (n = 27) or control (n = 27) group. Intravenous infusion of APT102 (0.3 mg/kg) or placebo was administered 15 minutes before reperfusion, and then 24 hours, 48 hours, 72 hours, and on day 4 after reperfusion. CMRI was performed at 24 hours, 48 hours, 72 hours, and on day 5 post-reperfusion using a 7T system and the hearts were collected for histopathological examination. Cardiac function was quantified using cine imaging and IMH/edema using T2 mapping, and infarct/MVO using late gadolinium enhancement. Results: The extent of infarction (p < 0.001), edema (p < 0.001), IMH (p = 0.013), and MVO (p = 0.049) was less severe in the APT102 group than in the control group. IMH size at 48 hours was significantly greater than that at 24 hours, 72 hours, and 5 days after reperfusion (all p < 0.001). The left ventricular ejection fraction (LVEF) was significantly greater in the APT102 group than in the control group (p = 0.006). There was a negative correlation between LVEF and IMH (r = -0.294, p = 0.010) and a positive correlation between IMH and MVO (r = 0.392, p < 0.001). Conclusion: APT102 can significantly alleviate damage to the ischemic myocardium and microvasculature. IMH size peaked at 48 hours post reperfusion and IMH is a downstream consequence of MVO. IMH may be a potential therapeutic target to prevent adverse remodeling in MI.

• Journal of Korean Neurosurgical Society
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• 제54권6호
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• pp.467-476
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• 2013

Objective : This study aimed to evaluate the hypotheses that administration routes [intra-arterial (IA) vs. intravenous (IV)] affect the early stage migration of transplanted human bone marrow-derived mesenchymal stem cells (hBM-MSCs) in acute brain infarction. Methods : Male Sprague-Dawley rats (n=40) were subjected to photothrombotic infarction. Three days after photothrombotic infarction, rats were randomly allocated to one of four experimental groups [IA group : n=12, IV group : n=12, superparamagnetic iron oxide (SPIO) group : n=8, control group : n=8]. All groups were subdivided into 1, 6, 24, and 48 hours groups according to time point of sacrifice. Magnetic resonance imaging (MRI) consisting of T2 weighted image (T2WI), $T2^*$ weighted image ($T2^*WI$), susceptibility weighted image (SWI), and diffusion weighted image of rat brain were obtained prior to and at 1, 6, 24, and 48 hours post-implantation. After final MRI, rats were sacrificed and grafted cells were analyzed in brain and lung specimen using Prussian blue and immunohistochemical staining. Results : Grafted cells appeared as dark signal intensity regions at the peri-lesional zone. In IA group, dark signals in peri-lesional zone were more prominent compared with IV group. SWI showed largest dark signal followed by $T2^*WI$ and T2WI in both IA and IV groups. On Prussian blue staining, IA administration showed substantially increased migration and a large number of transplanted hBM-MSCs in the target brain than IV administration. The Prussian blue-positive cells were not detected in SPIO and control groups. Conclusion : In a rat photothrombotic model of ischemic stroke, selective IA administration of human mesenchymal stem cells is more effective than IV administration. MRI and histological analyses revealed the time course of cell migration, and the numbers and distribution of hBM-MSCs delivered into the brain.

• Journal of Dental Anesthesia and Pain Medicine
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• 제17권4호
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• pp.265-270
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• 2017

Background: Endotracheal intubation during anesthesia induction may increase airway resistance ($R_{aw}$) and decrease dynamic lung compliance ($C_{dyn}$). We hypothesized that prophylactic treatment with a transdermal ${\beta}2$-agonist tulobuterol patch (TP) would help to reduce the risk of bronchospasm after placement of the endotracheal tube. Methods: Eighty-two American Society of Anesthesiologists (ASA) category I or II adult patients showing obstructive patterns were divided randomly into a control and a TP group (n = 41 each). The night before surgery, a 2-mg TP was applied to patients in the TP group. Standard monitors were recorded, and target controlled infusion (TCI) with propofol and remifentanil was used for anesthesia induction and maintenance. Simultaneously, end-tidal carbon dioxide, $R_{aw}$, and $C_{dyn}$ were determined at 5, 10, and 15 min intervals after endotracheal intubation. Results: There was no significant difference in demographic data between the two groups. The TP group was associated with a lower $R_{aw}$ and a higher $C_{dyn}$, as compared to the control group. $R_{aw}$ was significantly lower at 10 min (P < 0.05) and 15 min (P < 0.01), and $C_{dyn}$ was significantly higher at 5 min (P < 0.05) and 15 min (P < 0.01) in the TP group. A trend towards a lower $R_{aw}$ was observed showing a statistically significant difference 5 min after endotracheal intubation (P < 0.01) in each group. Conclusions: Prophylactic treatment with TP showed a bronchodilatory effect through suppressing an increase in $R_{aw}$ and a decrease in $C_{dyn}$ after anesthesia induction without severe adverse effects.