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Abstract: Prospective epidemiologic studies have shown that dyslipidemia and hyperglycemia are major risk factors for atherosclerotic cardiovascular diseases. Undesirable metabolic conditions are observed to coexist in patients with metabolic syndrome, which is an important risk factor for cardiovascular disease. To prevent cardiovascular disease, a pleiotropic agent is needed to improve the metabolic disorder in patients with metabolic syndrome. Bile acid binding resins increase the fecal excretion of bile acids. The decrease in bile acids returned to the liver leads to an up-regulation of hepatic low-density lipoprotein (LDL) receptor activity, which decreases LDL cholesterol (LDL-C) in the circulation and increases high-density lipoprotein cholesterol. On the other hand, bile acids can also regulate the transcription of genes involved in LDL-C synthesis and cholesterol homeostasis via nuclear hormone receptors. Consequently, these receptors may represent novel therapeutic targets for dyslipidemia and provide insight into the role of the bile acid pathway in other metabolic processes. This review focuses on the recent findings on bile acid binding resins and cardiovascular disease risk factors. Moreover, known and proposed mechanisms of how bile acid binding resins may improve glucose and energy metabolism are discussed; these effects may help to explain the mechanisms by which bile acid binding resins may reduce cardiovascular disease.

Abstract: BACKGROUND: Alpha-melanocyte-stimulating hormone (alpha-MSH), a pro-opiomelanocortin (POMC) derivative, is a neuropeptide with potent anti-inflammatory properties that inhibits tissue injury in a wide array of inflammation models. OBJECTIVE: To determine if alpha-MSH is involved in the development of congestive heart failure (CHF) with the specific aim of examining its peripheral source and one of the mechanisms. METHODS: The circulating levels of alpha-MSH were measured in 115 patients with CHF using a double-antibody radioimmunoassay. To determine one of the sources of circulating alpha-MSH, human peripheral blood mononuclear cells (PBMC) were stimulated with lipopolysaccharide (LPS) or tumor necrosis factor (TNF)-alpha. Furthermore, to clarify one of the functions of alpha-MSH, PBMC were cultured in the presence or absence of alpha-MSH. RESULTS: Plasma levels of alpha-MSH were significantly higher in NYHA class II patients with CHF than in control subjects (p<0.0001). A significant correlation was found between the levels of alpha-MSH and high-sensitive testing for C-reactive protein in patients with CHF (r=0.41, p<0.0005). PBMC stimulated with LPS or TNF-alpha released alpha-MSH in a concentration-dependent manner. alpha-MSH inhibited LPS-induced TNF-alpha production, and alpha-MSH simultaneously augmented production of interleukin (IL)-10 by PBMC. CONCLUSIONS: Circulating alpha-MSH was increased in patients with CHF. Inflammatory response induced alpha-MSH production in cultured human PBMC. Treatment of alpha-MSH could modify the immunobalance between inflammatory and anti-inflammatory responses in cultured PBMC. These findings suggest that alpha-MSH may play an important role in the pathophysiology of CHF.

Abstract: OBJECTIVE: Vascular endothelial growth factor (VEGF) induces angiogenesis by stimulating reactive oxygen species (ROS) production primarily through the VEGF receptor-2 (VEGFR2). One of the initial responses in established vessels to stimulate angiogenesis is loss of vascular endothelial (VE)-cadherin-based cell-cell adhesions; however, little is known about the underlying mechanisms. IQGAP1 is a novel VEGFR2 binding protein, and it interacts directly with actin, cadherin, and beta-catenin, thereby regulating cell motility and morphogenesis. METHODS AND RESULTS: Confocal microscopy analysis shows that IQGAP1 colocalizes with VE-cadherin at cell-cell contacts in unstimulated human endothelial cells (ECs). VEGF stimulation reduces staining of IQGAP1 and VE-cadherin at the adherens junction without affecting interaction of these proteins. Knockdown of IQGAP1 using siRNA inhibits localization of VE-cadherin at cell-cell contacts, VEGF-stimulated recruitment of VEGFR2 to the VE-cadherin/beta-catenin complex, ROS-dependent tyrosine phosphorylation of VE-cadherin, which is required for loss of cell-cell contacts and capillary tube formation. IQGAP1 expression is increased in a mouse hindlimb ischemia model of angiogenesis. CONCLUSIONS: IQGAP1 is required for establishment of cell-cell contacts in quiescent ECs. To induce angiogenesis, it may function to link VEGFR2 to the VE-cadherin containing adherens junctions, thereby promoting VEGF-stimulated, ROS-dependent tyrosine phosphorylation of VE-cadherin and loss of cell-cell contacts.

Abstract: OBJECTIVE: Endothelial cell (EC) migration is a key event for repair process after vascular injury and angiogenesis. EC migration is regulated by reorganization of the actin cytoskeleton at the leading edge and localized production of reactive oxygen species (ROS) at the site of injury. However, underlying mechanisms are unclear. We reported that IQGAP1, an actin binding scaffold protein, mediates VEGF-induced activation of gp91phox (Nox2)-dependent NAD(P)H oxidase and EC migration. We thus hypothesized that Nox2 and IQGAP1 may play important roles in ROS-dependent EC migration in response to injury. METHODS AND RESULTS: Using a monolayer scratch assay with confluent ECs, we show that ROS production is increased at the margin of scratch area and Nox2 translocates to the leading edge, where it colocalizes and associates with both actin and IQGAP1 in migrating ECs. Knockdown of IQGAP1 using siRNA and inhibition of the actin cytoskeleton blocked scratch injury-induced H2O2 production, Nox2 translocation and its interaction with actin, and EC migration toward the injured site. CONCLUSIONS: These suggest that IQGAP1 may function to link Nox2 to actin at the leading edge, thereby facilitating ROS production at the site of injury, which may contribute to EC migration.

Abstract: BACKGROUND: Neovascularization is potentially important for the treatment of ischemic heart and limb disease. We reported that reactive oxygen species (ROS) derived from gp91phox (Nox2)-containing NAD(P)H oxidase are involved in angiogenesis in mouse sponge models as well as in vascular endothelial growth factor (VEGF) signaling in cultured endothelial cells. The role of gp91phox-derived ROS in neovascularization in response to tissue ischemia is unknown, however. METHODS AND RESULTS: Here, we show that neovascularization in the ischemic hindlimb is significantly impaired in gp91phox-/- mice as compared with wild-type (WT) mice as evaluated by laser Doppler flow, capillary density, and microsphere measurements. In WT mice, inflammatory cell infiltration in the ischemic hindlimb was maximal at 3 days, whereas capillary formation was prominent at 7 days when inflammatory cells were no longer detectable. Increased O2*- production and gp91phox expression were present at both time points. The dihydroethidium staining of ischemic tissues indicates that O2*- is mainly produced from inflammatory cells at 3 days and from neovasculature at 7 days after operation. Relative to WT mice, ischemia-induced ROS production in gp91phox-/- mice at both 3 and 7 days was diminished, whereas VEGF expression was enhanced and the inflammatory response was unchanged. Infusion of the antioxidant ebselen into WT mice also significantly blocked the increase in blood flow recovery and capillary density after ischemia. CONCLUSIONS: gp91phox-derived ROS play an important role in mediating neovascularization in response to tissue ischemia. NAD(P)H oxidases and their products are potential therapeutic targets for regulating angiogenesis in vivo.

Abstract: BACKGROUND: The adaptation of patients with acute myocardial infarction (AMI) to a phase I rehabilitation program has not been widely assessed. METHODS AND RESULTS: Forty-two male patients (62+/-8 years) with AMI were classified as exercise tolerant (group A, n=25) or excessive response (systolic blood pressure (SBP) increase >30 mmHg during exercise; group B, n=17). Hemodynamic parameters during exercise using a cycle-ergometer were monitored for the first 3 days. The power of low- and high-frequency components (LF: 0.05-0.2 Hz; HF: 0.2-1 Hz) was analyzed by heart rate variability. Anxiety status was assessed using the Spielberger's State-Trait Anxiety Inventory. Patients in group B were significantly older, had lower cardiac function and a longer hospitalization than group A (p<0.05, respectively). The excessive elevation of SBP on Day 1 decreased and became <30 mmHg on Day 3 in group B. The decreases in HF during exercise on Days 1 and 3 were significantly smaller in group B than in group A (p<0.05 and p<0.05, respectively). The LF/HF ratio on Day 1 was significantly higher in group B than in group A (p<0.05). In group B, the anxiety score before exercise was significantly higher than that at the time of discharge (p<0.05), whereas there was no change in group A. CONCLUSION: Factors influencing a significant elevation of blood pressure during phase I rehabilitation are age, physical deconditioning, imbalance of autonomic nervous activity and anxiety.

Abstract: Endothelial cell (EC) proliferation and migration are important for reendothelialization and angiogenesis. We have demonstrated that reactive oxygen species (ROS) derived from the small GTPase Rac1-dependent NAD(P)H oxidase are involved in vascular endothelial growth factor (VEGF)-mediated endothelial responses mainly through the VEGF type2 receptor (VEGFR2). Little is known about the underlying molecular mechanisms. IQGAP1 is a scaffolding protein that controls cellular motility and morphogenesis by interacting directly with cytoskeletal, cell adhesion, and small G proteins, including Rac1. In this study, we show that IQGAP1 is robustly expressed in ECs and binds to the VEGFR2. A pulldown assay using purified proteins demonstrates that IQGAP1 directly interacts with active VEGFR2. In cultured ECs, VEGF stimulation rapidly promotes recruitment of Rac1 to IQGAP1, which inducibly binds to VEGFR2 and which, in turn, is associated with tyrosine phosphorylation of IQGAP1. Endogenous IQGAP1 knockdown by siRNA shows that IQGAP1 is involved in VEGF-stimulated ROS production, Akt phosphorylation, endothelial migration, and proliferation. Wound assays reveal that IQGAP1 and phosphorylated VEGFR2 accumulate and colocalize at the leading edge in actively migrating ECs. Moreover, we found that IQGAP1 expression is dramatically increased in the VEGFR2-positive regenerating EC layer in balloon-injured rat carotid artery. These results suggest that IQGAP1 functions as a VEGFR2-associated scaffold protein to organize ROS-dependent VEGF signaling, thereby promoting EC migration and proliferation, which may contribute to repair and maintenance of the functional integrity of established blood vessels.

Abstract: The circulating interleukin (IL)-18 level is a strong predictor of death from cardiovascular causes in patients with coronary artery disease. However, the mechanisms of IL-18 in orchestrating the cytokine cascade and the accelerator of IL-18 production in atherosclerosis are still unknown. In the present study, we measured the serum concentration of IL-18 and other markers of inflammation in 35 patients with acute coronary syndrome. To determine the mechanism of accelerating IL-18 production, we examined the release of IL-18 in human endothelial cells using human recombinant (hr) C-reactive protein (CRP) as a stimulator of IL-18. Furthermore, we investigated the inhibitory effects of hr IL-10 on IL-18 production by hr CRP in human endothelial cells. Circulating levels of IL-18 were significantly higher in patients with acute myocardial infarction than in patients with unstable angina. Incubation with hr CRP, which was equivalent to the serum concentration in patients with acute coronary syndrome, induced IL-18 release. Treatment with hr IL-10 inhibited IL-18 release in the cells stimulated with hr CRP. The serum level of IL-18 was identified as a marker of severity in acute coronary syndrome. Our findings reveal the possibility that circulating CRP by itself could cause a deterioration of the inflammatory cascade in endothelial cells associated with the upregulation of IL-18. This suggests that CRP may contribute to the mechanism of coronary artery disease in addition to being an incidental product of various types of systemic inflammation.

Abstract: BACKGROUND: To maintain the integrity of tissues, endothelial cells play critical roles. Fas ligand (FasL) is well known to deliver a death signal through its receptor, Fas. The Fas/FasL system may concomitantly induce expressions of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) besides triggering apoptosis in endothelial cells. We also investigated whether an inhibitor of caspase-8 (Z-IETD-FMK) does modulate IL-8 and MCP-1 secretion. METHODS AND RESULTS: After treatment with interferon-gamma (IFN-gamma), human recombinant FasL (hr FasL) or Fas agonistic antibody (CH-11) was added to cultured human endothelial cells. IFN-gamma up-regulated Fas mRNA levels. Fas ligation promoted apoptosis assessed by fluorescent-activated cell sorter (FACS) analysis in a dose-dependent manner and induced prominent DNA fragmentation. Simultaneously, IL-8 and MCP-1 were secreted from the endothelial cells in response to hr FasL or CH-11 in a dose-dependent manner (P < 0.01). Fas-neutralizing agent (Fas-Fc) suppressed the Fas-mediated secretions of IL-8 and MCP-1 (P < 0.01) both as well as the Fas-mediated apoptosis. On the other hand, whereas Z-IETD-FMK suppressed apoptosis, the inhibitor enhanced the Fas-mediated secretions of both IL-8 and MCP-1 beyond the value of the Fas stimulation alone (P < 0.01), suggesting an enhanced signalling for the chemokine expression. CONCLUSION: In human endothelial cells, the Fas/FasL system induces both IL-8 and MCP-1 secretions probably via a caspase-8 independent pathway. The Fas/FasL system may amplify the inflammatory cascade in the vascular injury and atherogenesis by recruiting leukocytes at the region of apoptotic endothelial damage.

Abstract: BACKGROUND: Proinflammatory cytokines such as tumor necrosis factor alpha play an important role in the pathophysiology of CHF. However, the mechanisms of immune activation in CHF remain unknown. Interleukin (IL)-18, a newly discovered cytokine with pleiotropic activities, is known to induce proinflammatory cytokines, chemokines, nitric oxide, and prostaglandins. METHODS AND RESULTS: We studied 86 patients with New York Heart Association functional class II-IV heart failure. Mean age was 62 years, 20 were women, and mean left ventricular ejection fraction was 34.8%. Circulating levels of IL-18 and IL-10, high-sensitivity testing for C-reactive protein, and brain natriuretic peptide levels were determined. Serum IL-18 concentrations were significantly higher in patients with NYHA class IV than in patients with classes II and III (P <.001). The serum level of IL-18 and the ratio of IL-18 to IL-10 were greater in patients with ischemic cardiomyopathy than in those with dilated cardiomyopathy. CONCLUSIONS: Th1/Th2 cytokine imbalance exists in patients with advanced CHF according to various etiologies of CHF. The findings suggest an important role for IL-18 in the pathophysiology of CHF and provide a direction for more specific immunomodulating therapy.

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Abstract: Fas/Fas ligand (FasL) is well known for its role in delivering apoptotic signals; however, it is unclear whether FasL can mediate apoptosis in cardiomyocytes. We hypothesized that apoptosis via Fas/FasL system may be augmented in damaged cardiomyocytes. To determine whether FasL mediates cardiomyocyte apoptosis, recombinant FasL (rFasL) was added to the culture of neonatal rat ventricular myocytes pretreated with and without doxorubicin. Without doxorubicin, high dose of rFasL caused an increase in TUNEL-positive cardiomyocytes and a mild decrease in MTT activities. When cardiomyocytes were pretreated with doxorubicin (0.5 microM), rFasL dramatically augmented TUNEL-positive cardiomyocytes in a concentration-dependent manner, which was accompanied with nuclear fragmentations. The rFasL also caused a concentration-dependent reduction in MTT activities in cardiomyocytes. The rFasL-induced caspase-8 activity was greatly facilitated by pretreatment of doxorubicin. TUNEL-positive nuclei with rFasL was inhibited by Fas-Fc, neutralizing agent of rFasL, and Z-IETD-FMK, caspase-8 inhibitor. Fas mRNA transcript by RT-PCR was up-regulated in cardiomyocytes with doxorubicin. We conclude that FasL can induce cardiomyocyte apoptosis particularly when cardiomyocyte becomes susceptible for Fas-mediated apoptosis.

Abstract: The biological actions of tumor necrosis factor-alpha (TNF-alpha) are mediated by 2 distinct receptors, TNF-RI (p55) and TNF-RII (p75). The extracellular domains of both receptors are shed in soluble form (sTNF-RI and sTNF-RII). The soluble receptors are involved in regulating TNF-alpha activities and may have therapeutic potential as TNF-neutralizing agents. However, it remains unclear as to what kind of physiological molecule can regulate TNF receptors. Nitric oxide (NO) mediates a variety of biological and pathophysiological functions. We hypothesized that NO may modulate the expression and shedding of TNF-RI. An NO donor, diethylamine/NO complex (NOC 5), increased sTNF-RI in the supernatants of ECV304, a human umbilical vein cell line, in a dose-dependent manner. TNF-RI mRNA in these cells was upregulated by NOC 5. 8-Br-cGMP and peroxynitrate had no effect on sTNF-RI release. Genistein and herbimycin A, inhibitors of tyrosine kinase, inhibited sTNF-RI release. Herbimycin A inhibited the levels of TNF-RI mRNA enhanced by NOC 5, which downregulated the surface expression of TNF-RI, indicating that NO is also involved in the shedding process of TNF-RI. The shedding of TNF-RI was abolished by a synthetic inhibitor of matrix metalloproteinase, KB-R8301. In conclusion, NO enhanced the release of sTNF-RI from endothelial cells by a cGMP-independent mechanism. Dual pathways suggested for NO-induced sTNF-RI release include (1) enhanced expression of TNF-RI, at least partially, by a tyrosine kinase-dependent mechanism and (2) increased shedding of TNF-RI by a type of metalloproteinase.

Abstract: 123I-15-(p-iodophenyl)-9-R,S-methylpentadecanoic acid (9-MPA) has recently been developed as a tracer for myocardial fatty acid uptake. The aim of this study, which was performed as part of a phase III clinical trial of 9-MPA, was to test the usefulness of 9-MPA for the assessment of myocardial viability in patients with acute coronary syndrome (ACS). METHODS: Fifteen patients with ACS who had undergone direct percutaneous transluminal coronary angioplasty were examined. Myocardial SPECT with 9-MPA and 99mTc-sestamibi and low-dose dobutamine echocardiography were performed within 2 wk after onset. The 9-MPA images were obtained 10 and 60 min after tracer administration, and sestamibi imaging was begun 60 min after the injection. The left ventricle was divided into 9 segments, and 9-MPA and sestamibi uptake were scored from 0 (normal) to 3 (no activity) in each segment. Lower uptake of 9-MPA than of sestamibi was defined as a mismatch. Myocardial segments showing improvement in wall motion during low-dose dobutamine infusion (5-10 microg/kg/ min) were considered viable. RESULTS: The 9-MPA images were of high quality for all patients. Myocardial uptake of 9-MPA was lower in ischemic myocardium than in nonischemic myocardium (58.2%+/-14.2% versus 91.9%+/-6.5%, P<0.0001). Clearance of 9-MPA from ischemic myocardium was slower than that from nonischemic myocardium (10.2%+/-11.7% versus 19.1%+/-5.9%, P<0.01). A mismatch was seen in 10 of 15 patients, and 18 of 20 (90%) mismatched segments were defined as viable by dobutamine echocardiography. Conversely, 18 of 20 (90%) matched segments did not show any improvement in function during dobutamine stimulation (P<0.0001). Uptake of 9-MPA in nonviable segments was lower than that in dysfunctional but viable segments (P<0.05), and 9-MPA clearance from nonviable segments was slower than that from viable segments (P<0.05). CONCLUSION: The imaging characteristics of 9-MPA for SPECT are excellent, allowing noninvasive assessment of myocardial fatty acid uptake. Myocardial imaging with 9-MPA may reveal impaired fatty acid uptake in dysfunctional but viable myocardium and thus provide useful information for clinical decision making in ACS.

Abstract: The circulating levels of soluble Fas ligand was increased in patients with advanced congestive heart failure. This study also indicates that the failing heart may contribute to the increased concentration of soluble Fas ligand in patients with congestive heart failure.

Abstract: Proinflammatory cytokines, i.e., tumor necrosis factor-alpha (TNFalpha), participate in the development and the progression of congestive heart failure (CHF). On the other hand, an anti-inflammatory cytokine may neutralize the proinflammatory cytokines of CHF. Interleukin-10 (IL-10) is known to suppress the synthesis of proinflammatory cytokines. IL-10 and the IL-10 receptor system was investigated in comparison with the behavior of TNFalpha in 68 patients with various causes of CHF (mean age: 61 years) and in 31 normal subjects (61 years). The circulating IL-10 level was higher in CHF patients than in normal subjects (p<0.05). The TNFalpha level was higher in CHF patients than in control subjects (p<0.005). The ratio of IL-10 to TNFalpha tended to be higher in control subjects than in patients with CHF (p = 0.09). With lipopolysaccharide treatment, the release of IL-10 was more enhanced from mononuclear leukocyte of patients with CHF than from control subjects (p<0.05). The expression of the IL-10 receptor estimated by flow cytometry of mononuclear leukocytes was higher in the CHF patients than in the normal subjects. The IL-10/IL-10 receptor system was activated, at least partly, to downregulate an excess of TNFalpha in patients with advanced CHF. IL-10 may be an important inherent component of the cytokine network of CHF.

Abstract: TNFalpha exerts its functions by engaging two receptors (TNF-RI and TNF-RII). The extracellular parts of the receptors are proteolytically shed to the soluble forms by a matrix metalloproteinase-like enzyme (sTNF-RI and sTNF-RII). The soluble TNF receptors can neutralize TNFalpha activities. Circulating levels of both sTNF-RI and sTNF-RII are elevated in patients with congestive heart failure (CHF). It remains unclear how a large amount of sTNF-RI and sTNF-RII is mobilized into the circulation. Mononuclear leukocytes were obtained from 14 controls and 21 patients with CHF. TNF-RII of the cells from CHF patients was upregulated in the cell-surface expression and mRNA transcripts. Besides enhanced shedding of TNF-RII on the cells from CHF patients with phorbol myristate acetate (PMA), sera from CHF induced shedding of TNF-RII on the cells from normal volunteers. Thus, the enhancement of both expression and shedding of TNF-RII may be related to increased circulating levels of the soluble TNF receptor in patients with CHF. The presence of CHF may affect the regulation of TNF receptors, which may modulate the responsiveness to TNFalpha in the tissues of patients with CHF.

Abstract: A 47-year-old man presented with acute renal failure following oxalate ingestion. Nausea and hematoemesis appeared four hours after attempted suicide and acute oliguric renal failure ensued the following day. The patient underwent four sessions of hemodialysis and then reverted to normal state. Histopathologic examination of renal biopsy specimen revealed the degeneration of the renal tubular epithelial cells associated with intracellular calcium oxalate crystal deposition. Most of the renal tubules were patent despite the intraluminar crystal deposition. These findings suggest that dysfunction of the renal tubular epithelial cell plays a more important role than tubular obstruction in developing acute renal failure.

Abstract: BACKGROUND: It has been known that Tc 99m sestamibi/iodine 123 betamethyliodophenylpentadecanoic (123I-BMIPP) (sestamibi/BMIPP) mismatch is an indicator of viable myocardium in acute myocardial infarction (AMI). We have reported that reverse redistribution of sestamibi in AMI indicates the patency of infarct-related artery and a preserved left ventricular function in the chronic stage. In this study we investigated the relationship between reverse redistribution of sestamibi and sestamibi/BMIPP mismatch in patients with AMI. METHODS: Twenty-three patients with AMI who received direct percutaneous transluminal coronary angioplasty underwent both BMIPP and sestamibi SPECT within 2 weeks after onset. Sestamibi images were obtained 1 hour (early) and 3 hours (delayed) after injection of sestamibi. BMIPP imaging was carried out 30 minutes after injection. The left ventricle was divided into 17 segments, and regional myocardial uptakes of the tracers in each segment were scored from 0 (normal) to 3 (no activity). A reverse redistribution pattern was defined as an increase of > or =1 in the regional score at the delayed images. More reduced BMIPP uptake than sestamibi uptake in each segment was determined as sestamibi/BMIPP mismatch. Contrast left ventriculography was performed soon after revascularization and repeated 1 month later. RESULTS: Of 15 patients with sestamibi reverse redistribution, sestamibi/BMIPP mismatch was observed in 14 patients (93%), whereas mismatch was seen in only one of seven patients (14%) without reverse redistribution (p < 0.01). In patients with sestamibi reverse redistribution, regional scores of BMIPP agreed with those of early and delayed images of sestamibi in 51 segments (46%) and in 92 segments (83%), respectively. In the chronic stage, both regional wall motion and left ventricular ejection fraction improved in patients with sestamibi reverse redistribution (wall motion score: 6.7 +/- 2.4 vs 2.7 +/- 2.1, p < 0.01; ejection fraction: 56% +/- 7% vs 64% +/- 8%, p < 0.01), but not in those without reverse redistribution. CONCLUSION: Both reverse redistribution of sestamibi and sestamibi/BMIPP mismatch reflect the recovery of left ventricular function and thus imply myocardial viability in AMI. Because the presence of reverse redistribution of sestamibi agreed with that of sestamibi/BMIPP mismatch, additional BMIPP images can be replaced by the delayed images after a single injection of sestamibi.

Abstract: Compared with soluble Fas molecule (sFas, an inhibitor of Fas-mediated apoptosis) in normal volunteers, the serum level of sFas significantly increased by 41% in New York Heart Association (NYHA) class III (p <0.05) and by 97% in NYHA class IV patients with congestive heart failure (p <0.001). Furthermore, sFas showed correlations with soluble forms of TNF receptor-p55 (RI) and -p75 (RII) (r = 0.68 and r = 0.56) which inhibit activities of TNF alpha.