Intermittent pacing therapy favorably modulates infarct remodeling

textabstractDespite early revascularization, remodeling and dysfunction of the left ventricle (LV) after acute myocardial infarction (AMI) remain important therapeutic targets. Intermittent pacing therapy (IPT) of the LV can limit infarct size, when applied during early reperfusion. However, the effects of IPT on post-AMI LV remodeling and infarct healing are unknown. We therefore investigated the effects of IPT on global LV remodeling and infarct geometry in swine with a 3-day old AMI. For this purpose, fifteen pigs underwent 2 h ligation of the left circumflex coronary artery followed by reperfusion. An epicardial pacing lead was implanted in the peri-infarct zone. After three days, global LV remodeling and infarct geometry were assessed using magnetic resonance imaging (MRI). Animals were stratified into MI control and IPT groups. Thirty-five days post-AMI, follow-up MRI was obtained and myofibroblast content, markers of extracellular matrix (ECM) turnover and Wnt/frizzled signaling in infarct and non-infarct control tissue were studied. Results showed that IPT had no significant effect on global LV remodeling, function or infarct mass, but modulated infarct healing. In MI control pigs, infarct mass reduction was principally due to a 26.2 ± 4.4% reduction in infarct thickness (P ≤ 0.05), whereas in IPT pigs it was mainly due to a 35.7 ± 4.5% decrease in the number of infarct segments (P ≤ 0.05), with no significant change in infarct thickness. Myofibroblast content of the infarct zone was higher in IPT (10.9 ± 2.1%) compared to MI control (5.4 ± 1.6%; P ≤ 0.05). Higher myofibroblast presence did not coincide with alterations in expression of genes involved in ECM turnover or Wnt/frizzled signaling at 5 weeks follow-up. Taken together, IPT limited infarct expansion and altered infarct composition, showing that IPT influences remodeling of the infarct zone, likely by increasing regional myofibroblast content

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

Serial measurement of hFABP and high-sensitivity troponin I post-PCI in STEMI: how fast and accurate can myocardial infarct size and no-reflow be predicted?

The objective of this study was to compare heart-specific fatty acid binding protein (hFABP) and high-sensitivity troponin I (hsTnI) via serial measurements to identify early time points to accurately quantify infarct size and no-reflow in a preclinical swine model of ST-elevated myocardial infarction (STEMI). Myocardial necrosis, usually confirmed by hsTnI or TnT, takes several hours of ischemia before plasma levels rise in the absence of reperfusion. We evaluated the fast marker hFABP compared with hsTnI to estimate infarct size and no-reflow upon reperfused (2 h occlusion) and nonreperfused (8 h occlusion) STEMI in swine. In STEMI (n = 4) and STEMI + reperfusion (n = 8) induced in swine, serial blood samples were taken for hFABP and hsTnI and compared with triphenyl tetrazolium chloride and thioflavin-S staining for infarct size and no-reflow at the time of euthanasia. hFABP increased faster than hsTnI upon occlusion (82 +/- 29 vs. 180 +/- 73 min, P < 0.05) and increased immediately upon reperfusion while hsTnI release was delayed 16 +/- 3 min (P < 0.05). Peak hFABP and hsTnI reperfusion values were reached at 30 +/- 5 and 139 +/- 21 min, respectively (P < 0.05). Infarct size (containing 84 +/- 0.6% no-reflow) correlated well with area under the curve for hFABP (r(2) = 0.92) but less for hsTnI (r(2) = 0.53). At 50 and 60 min reperfusion, hFABP correlated best with infarct size (r(2) = 0.94 and 0.93) and no-reflow (r(2) = 0.96 and 0.94) and showed high sensitivity for myocardial necrosis (2.3 +/- 0.6 and 0.4 +/- 0.6 g). hFABP rises faster and correlates better with infarct size and no-reflow than hsTnI in STEMI + reperfusion when measured early after reperfusion. The highest sensitivity detecting myocardial necrosis, 0.4 +/- 0.6 g at 60 min postreperfusion, provides an accurate and early measurement of infarct size and no-reflow

Evolution of reperfusion post-infarction ventricular remodeling: New MRI insights

Background: Our current understanding is that left ventricular (LV) remodeling after acute myocardial infarction (AMI) is caused by expansion of the infarcted myocardium with thinning of the wall and eccentric hypertrophy of the remote myocardium. To study the geometric changes in the remodeling process after reperfused AMI we used cardiac magnetic resonance imaging (CMR). Methods: Nine juvenile swine underwent a 120-min occlusion of the left circumflex coronary artery followed by reperfusion. CMR was performed at 3 and 36 days post-infarction. Global and regional LV remodeling was assessed including geometric changes of infarcted and remote myocardium; infarct longitudinal length (mm), mean circumferential length (mm), total infarct surface (mm(2)), end-diastolic wall thickness (EDWT) (mm) and transmural extent of infarction (TEI). Results: From 3 days to 36 days post-infarction end-diastolic volume increased by 43% (p < 0.01). Infarct mass decreased by 36% (p < 0.01), mainly by reduction of EDWT with 26%, while mean infarct circumferential length and longitudinal infarct length did not change. Remote myocardial mass increased by 23%, which was the result of an increase in its circumferential length from 95 +/- 10 mm to 113 +/- 11 mm (p < 0.01), with no change in its EDWT. In contrast, EDWT in the infarct, peri-infarct and Conclusions: Contrary to the widely held view the present, using CMR measurements, shows that post-infarction remodeling was not associated with expansion of the infarcted myocardium. These findings suggest that eccentric hypertrophy of the remote myocardium, but not expansion of the infarct region, is responsible for left ventricular dilatation after AMI. (C) 2013 Elsevier Ireland Ltd. All rights reserved

Evolution of reperfusion post-infarction ventricular remodeling: New MRI insights.

Abstract BACKGROUND: Our current understanding is that left ventricular (LV) remodeling after acute myocardial infarction (AMI) is caused by expansion of the infarcted myocardium with thinning of the wall and eccentric hypertrophy of the remote myocardium. To study the geometric changes in the remodeling process after reperfused AMI we used cardiac magnetic resonance imaging (CMR). METHODS: Nine juvenile swine underwent a 120-min occlusion of the left circumflex coronary artery followed by reperfusion. CMR was performed at 3 and 36 days post-infarction. Global and regional LV remodeling was assessed including geometric changes of infarcted and remote myocardium; infarct longitudinal length (mm), mean circumferential length (mm), total infarct surface (mm(2)), end-diastolic wall thickness (EDWT) (mm) and transmural extent of infarction (TEI). RESULTS: From 3 days to 36 days post-infarction end-diastolic volume increased by 43% (p<0.01). Infarct mass decreased by 36% (p<0.01), mainly by reduction of EDWT with 26%, while mean infarct circumferential length and longitudinal infarct length did not change. Remote myocardial mass increased by 23%, which was the result of an increase in its circumferential length from 95 \ub1 10 mm to 113 \ub1 11 mm (p<0.01), with no change in its EDWT. In contrast, EDWT in the infarct, peri-infarct and border zone decreased. CONCLUSIONS: Contrary to the widely held view the present, using CMR measurements, shows that post-infarction remodeling was not associated with expansion of the infarcted myocardium. These findings suggest that eccentric hypertrophy of the remote myocardium, but not expansion of the infarct region, is responsible for left ventricular dilatation after AMI

Serial measurement of hFABP and high-sensitivity troponin I post-PCI in STEMI: How fast and accurate can myocardial infarct size and no-reflow be predicted?

The objective of this study was to compare heart-specific fatty acid binding protein (hFABP) and highsensitivity troponin I (hsTnI) via serial measurements to identify early time points to accurately quantify infarct size and no-reflow in a preclinical swine model of ST-elevated myocardial infarction (STEMI). Myocardial necrosis, usually confirmed by hsTnI or TnT, takes several hours of ischemia before plasma levels rise in the absence of reperfusion. We evaluated the fast marker hFABP compared with hsTnI to estimate infarct size and no-reflow upon reperfused (2 h occlusion) and nonreperfused (8 h occlusion) STEMI in swine. In STEMI (n = 4) and STEMI + reperfusion (n = 8) induced in swine, serial blood samples were taken for hFABP and hsTnI and compared with triphenyl tetrazolium chloride and thioflavin-S staining for infarct size and no-reflow at the time of euthanasia. hFABP increased faster than hsTnI upon occlusion (82 ± 29 vs. 180 ± 73 min, P < 0.05) and increased immediately upon reperfusion while hsTnI release was delayed 16 ± 3 min (P < 0.05). Peak hFABP

金融包摂における投資商品 : 低所得世帯の投資スキル

報告番号: ; 学位授与年月日: 2016-09-16 ; 学位の種別: 修士 ; 学位の種類: 修士(国際協力学) ; 学位記番号: 修創域第6139号 ; 研究科・専攻: 新領域創成科学研究科環境学研究系国際協力学専

Studies on intracoronary cell retention for cardiac cell therapy.

<p>Studies on intracoronary cell retention for cardiac cell therapy.</p