Novel attenuation correction of SPECT images using scatter photopeak window data for the detection of coronary artery disease.

BACKGROUND: Attenuation correction using segmentation with scatter and photopeak window data (SSPAC) may enable evaluation of the attenuation map in a patient-specific manner without the need for additional radiation exposure and more acquisition time. We examined the feasibility of SSPAC and compared the sensitivity, specificity, and accuracy of this new correction method with that of conventional non-corrected myocardial perfusion single-photon emission computed tomography (SPECT) among patients with suspected or diagnosed coronary artery disease. METHODS AND RESULTS: One hundred sixty-one patients who underwent both (99m)Tc-tetrofosmin stress/rest SPECT examination and invasive coronary angiography were enrolled in the study. Data from the SSPAC-corrected and non-corrected methods were analyzed quantitatively using summed stress scores. Attenuation maps were obtained successfully for 150 (93%) of the patients. The SSPAC-corrected and non-corrected methods accurately predicted coronary artery disease defined as >50% luminal stenosis verified by coronary artery angiography and/or prior myocardial infarction, for 91% and 77% patients, respectively (P < .05). For diagnosis of coronary artery disease, SSPAC improved sensitivity in the left anterior descending artery territory and specificity in the right coronary artery territory. CONCLUSIONS: Attenuation correction with SSPAC may be a feasible method of correction for myocardial perfusion SPECT and in some cases may provide better accuracy for diagnosing coronary artery disease.

Solvent-manipulated guest binding and signaling of a fluorescent resorcin[4]arene cavitand with 1,3,2-benzodiazaboryl D-π-A conjugation flaps.

The conformation of resorcin[4]arene cavitand system 1 was controlled by DMSO through a hydrogen bonding network between benzodiazaborole NHs of the cavitand flaps and DMSO molecules to stabilize the vase form. Subsequently, a guest-binding cavity of 1 was formed to accommodate tetraalkylammonium guest 3, permitting the monitoring of the guest by the unaided eye as a result of a CH-π interaction between the benzodiazaborole π-donor group and the guest.

Familial hypercholesterolemia with multiple large tendinous xanthomas and advanced coronary artery atherosclerosis.

We herein report the case of a 53-year-old man with severe coronary ischemia who underwent successful coronary artery bypass surgery. Of note, he had hypercholesterolemia and presented with multiple large tendinous xanthomas and thickened Achilles tendons that had been present for more than two decades. Together with a family history of dyslipidemia, the patient was diagnosed as having familial hypercholesterolemia. Irrespective of an extensive search for possible mutations in the genes presumably involved in the patient's pathophysiology, including low-density lipoprotein receptor (LDLR), proprotein convertase subtilisin/kexin type 9 (PCSK9), autosomal recessive hypercholesterolemia (ARH) and apolipoprotein B (APOB), we were not able to identify the gene mutations responsible for the phenotype observed in the present case.

Atrial natriuretic peptide exerts protective action against angiotensin II-induced cardiac remodeling by attenuating inflammation via endothelin-1/endothelin receptor A cascade.

We aimed to investigate whether atrial natriuretic peptide (ANP) attenuates angiotensin II (Ang II)-induced myocardial remodeling and to clarify the possible molecular mechanisms involved. Thirty-five 8-week-old male Wistar-Kyoto rats were divided into control, Ang II, Ang II + ANP, and ANP groups. The Ang II and Ang II + ANP rats received 1 µg/kg/min Ang II for 14 days. The Ang II + ANP and ANP rats also received 0.1 µg/kg/min ANP intravenously. The Ang II and Ang II + ANP rats showed comparable blood pressure. Left ventricular fractional shortening and ejection fraction were lower in the Ang II rats than in controls; these indices were higher (P < 0.001) in the Ang II + ANP rats than in the Ang II rats. In the Ang II rats, the peak velocity of mitral early inflow and its ratio to atrial contraction-related peak flow velocity were lower, and the deceleration time of mitral early inflow was significantly prolonged; these changes were decreased by ANP. Percent fibrosis was higher (P < 0.001) and average myocyte diameters greater (P < 0.01) in the Ang II rats than in controls. ANP decreased both myocardial fibrosis (P < 0.01) and myocyte hypertrophy (P < 0.01). Macrophage infiltration, expression of mRNA levels of collagen types I and III, monocyte chemotactic protein-1, and a profibrotic/proinflammatory molecule, tenascin-C (TN-C) were increased in the Ang II rats; ANP significantly decreased these changes. In vitro, Ang II increased expression of TN-C and endothelin-1 (ET-1) in cardiac fibroblasts, which were reduced by ANP. ET-1 upregulated TN-C expression via endothelin type A receptor. These results suggest that ANP may protect the heart from Ang II-induced remodeling by attenuating inflammation, at least partly through endothelin 1/endothelin receptor A cascade.

Enhanced expression of the S100A8/A9 complex in acute myocardial infarction patients.

BACKGROUND: S100A8/A9 complex (S100A8/A9) is expressed in activated human neutrophils and macrophages. Enhanced expression of S100A8/A9 in atherosclerotic plaque of patients with unstable angina pectoris (UAP) has been demonstrated, but its profile in acute myocardial infarction (AMI) has not been clarified. METHODS AND RESULTS: Serum S100A8/A9 levels were serially measured in patients with AMI (n=55) and UAP (n=16) during the acute period. The expression of S100A8/A9 was examined immunohistochemically in the infarcted myocardium of 7 autopsied patients with AMI. Serum S100A8/A9 levels on the 1st day were 1,118+/-115 (SE) ng/ml in AMI patients as compared with 787+/-147 ng/ml in UAP patients. On days 3-5, serum S100A8/A9 levels in AMI patients reached a peak value and were significantly higher than the values in UAP patients (1,690+/-144 ng/ml vs 844+/-100 ng/ml; P<0.0001). In AMI patients, peak S100A8/A9 levels positively correlated with peak white blood cell and neutrophil counts, and peak creatine kinase-MB and peak C-reactive protein levels. Double immunostaining revealed that S100A8/A9 was specifically expressed in neutrophils and macrophages infiltrating the infarcted myocardium. CONCLUSIONS: S100A8/A9 is implicated in the pathophysiology of AMI and may be an additional biomarker of the local inflammatory response following AMI.

Thiamine prevents obesity and obesity-associated metabolic disorders in OLETF rats.

We previously found that thiamine mitigates metabolic disorders in spontaneously hypertensive rats, harboring defects in glucose and fatty acid metabolism. Mutation of thiamine transporter gene SLC19A2 is linked to type 2 diabetes mellitus. The current study extends our hypothesis that thiamine intervention may impact metabolic abnormalities in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, exhibiting obesity and metabolic disorders similar to human metabolic syndrome. Male OLETF rats (4 wk old) were given free access to water containing either 0.2% or 0% of thiamine for 21 and 51 wk. At the end of treatment, blood parameters and cardiac functions were analyzed. After sacrifice, organs weights, histological findings, and hepatic pyruvate dehydrogenase (PDH) activity in the liver were evaluated. Thiamine intervention averted obesity and prevented metabolic disorders in OLETF rats which accompanied mitigation of reduced lipid oxidation and increased hepatic PDH activity. Histological evaluation revealed that thiamine alleviated adipocyte hypertrophy, steatosis in the liver, heart, and skeletal muscle, sinusoidal fibrosis with formation of basement membranes (called pseudocapillarization) which accompanied significantly reduced expression of laminin ß1 and nidogen-1 mRNA, interstitial fibrosis in the heart and kidney, fatty degeneration in the pancreas, thickening of the basement membrane of the vasculature, and glomerulopathy and mononuclear cell infiltration in the kidney. Cardiac and renal functions were preserved in thiamine treatment. Thiamine has a potential to prevent obesity and metabolic disorders in OLETF rats.

High prevalence of chronic myocarditis in dilated cardiomyopathy referred for left ventriculoplasty: expression of tenascin C as a possible marker for inflammation.

The objectives of this study were to analyze the incidence of chronic myocarditis in dilated cardiomyopathy and to evaluate the diagnostic value of tenascin C for assessing inflammatory activity in the resected myocardium. Dilated cardiomyopathy patients with chronic myocarditis have a poor clinical outcome despite recent advances in medical treatments. Therefore, a precise diagnosis of inflammatory activity is critical to ensuring appropriate therapy. Tenascin C is an extracellular matrix glycoprotein that plays an important role in tissue remodeling in various heart diseases. Myocardial samples obtained during left ventriculoplasty from 64 patients (50 +/- 13 years, 56 men and 8 women) with dilated cardiomyopathy were examined by immunostaining for tenascin C. Histologic diagnosis was based on the Dallas criteria modified by the International Society and Federation of Cardiology task force. Nine cases (14%) had active myocarditis, 21 (33%) had borderline myocarditis, and 34 (53%) had no myocarditis. Intense tenascin C expression was observed at the site of active inflammation, with abundant cell accumulation, and in organized granulation tissue during the resolving phase but not in scar tissue during the healing phase. The ratio of tenascin C-positive area to the whole myocardium in the active and borderline myocarditis groups was significantly greater than that in the noninflammatory group. These findings suggest a high prevalence of chronic myocarditis in dilated cardiomyopathy patients and that tenascin C may prove to be a useful marker for distinguishing inflammatory cardiomyopathy from other types of dilated cardiomyopathy.

Suppression of inflammation in rat autoimmune myocarditis by S100A8/A9 through modulation of the proinflammatory cytokine network.

AIMS: S100A8/A9 is expressed in activated monocytes/macrophages and assumed to be heavily involved in the pathogenesis of acute inflammation. Although several studies have asserted that S100A8/A9 has a proinflammatory function, the exact biological function of S100A8/A9 is yet to be described. We examined the anti-inflammatory effects of S100A8/A9 on experimental autoimmune myocarditis (EAM) in rats. METHODS AND RESULTS: Experimental autoimmune myocarditis was induced in Lewis rats by immunization with porcine cardiac myosin. The recombinant (R-) S100A8/A9 was injected intraperitoneally into EAM rats. R-S100A8/A9 attenuated the severity of myocarditis, as evidenced by echocardiographic and histological findings. In addition, we found that not only the mRNA expression of proinflammatory cytokines [interleukin (IL)-1beta, IL-6, and tumour necrosis factor (TNF)-alpha] in the myocardium, but also their serum concentrations were suppressed in EAM rats treated with R-S100A8/A9. Nuclear factor-kappa B expression in inflammatory cells was also suppressed in the treated rats. To elucidate the mechanistic function of S100A8/A9 on proinflammatory cytokines in vivo, we used an ELISA on the supernatant of homogenized heart tissue treated with R-S100A8/A9. The findings revealed high-affinity binding of R-S100A8/A9 with IL-1beta, IL-6, and TNF-alpha in the myocardium, suggesting the trapping of proinflammatory cytokines by R-S100A8/A9. CONCLUSION: S100A8/A9 attenuates EAM through modulation of the proinflammatory cytokine network.

Markedly increased intracellular lipid droplets and disruption of intercellular junctions in biopsied myocardium from a patient with arrhythmogenic right ventricular cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by the progressive replacement of myocardial cells by fat and fibrous tissue. Here we describe the histopathological features of biopsied myocardium from a patient with ARVC. A large amount of adipose tissue was present in the biopsy specimen, and a group of myocardial cells were isolated as an island-like region in the adipose tissue. Electron microscopic examination of cardiomyocytes revealed a large number of intracellular lipid droplets, including some extremely large droplets. Disruptions of the plasma membrane and dissociation of intercellular junctions were associated with discharge of intracellular lipid droplets into the interstitial space. The high accumulation of intracellular lipid droplets may be involved in the pathogenesis of ARVC and may have played an important role in myocardial cell death and progressive replacement of cardiomyocytes by fatty tissue in the current case.

Prevention of incipient diabetic cardiomyopathy by high-dose thiamine.

Diabetic cardiomyopathy can progress toward overt heart failure with increased mortality. The hexosamine biosynthesis pathway has been implicated in signaling for fibrosis by the kidney. Thiamine (vitamin B(1)) is an indispensable coenzyme and required at intracellular glucose metabolism. In this study, we assessed if decrease of flux through the hexosamine biosynthesis pathway induced by high-dose thiamine therapy counteracts diabetes-induced cardiac fibrosis. The diabetes model used was the streptozotocin-induced diabetic rat. Normal control and diabetic rats were studied for 2 weeks with and without thiamine, and followings were analyzed; plasma biochemicals (total cholesterol and triglycerides), morphological changes, mRNA abundance relevant to cardiac failure (brain natriuretic peptide) and fibrosis (transforming growth factor-beta1, thrombospondine, fibronectin, plasminogen activator-I and connective tissue growth factor) as well as and matrix metalloproteinase activity were investigated. Thiamine repletion prevented diabetes-induced cardiac fibrosis without changes in plasma glucose concentration. This was achieved by prevention of thiamine depletion, increased pro-fibrotic mRNA abundance and decreased metalloproteinase activity in the heart of diabetic rats. O-glycosylated protein was significantly higher in the left ventricular of diabetic rats compared to control rats, which was decreased by thiamine administration. Thiamine repletion prevented diabetes-induced cardiac fibrosis in experimental diabetes, probably by suppression of hexosamine biosynthesis pathway.

Enhanced expression of type 1 helper T-cell cytokines in the myocardium of active cardiac sarcoidosis.

BACKGROUND: Various cytokines are involved in the pathogenesis of sarcoidosis, but their expression in the myocardium has not been documented for cardiac sarcoidosis. METHODS AND RESULTS: Myocardial tissue was obtained from 12 patients with cardiac sarcoidosis at the time of left ventriculoplasty, biopsy or autopsy. mRNA expression of various inflammatory cytokines was analyzed using quantitative real-time polymerase chain reaction, as well as by immunohistochemistry. Ten patients with dilated cardiomyopathy (DCM) served as controls. Enhanced expression of interleukin (IL)-1alpha, IL-2, IL-12 p40 and interferon (IFN)-gamma mRNA was limited to the myocardium of cardiac sarcoidosis patients. Expression of IL-1beta, IL-8, IL-10, IL-15 and TNF-alpha occurred in both cardiac sarcoidosis and DCM patients, but IL-4 and IL-5 were not detected in either disease. Immunohistochemistry of the myocardial tissue of sarcoidosis revealed positive staining for IL-12 and IFN-gamma. IL-12 was localized in multinucleated giant cells and macrophages of the sarcoid granulomas, whereas IFN-gamma was detected in lymphocytes and vascular endothelial cells. CONCLUSIONS: Type 1 helper T-cell cytokines may be involved in the pathogenesis of cardiac sarcoidosis.

Cardiac sarcoidosis underlies idiopathic dilated cardiomyopathy: importance of mediastinal lymphadenopathy in differential diagnosis.

BACKGROUND: Cardiac sarcoidosis is frequently overlooked or misdiagnosed as idiopathic dilated cardiomyopathy (DCM), primarily because of difficulties in its diagnosis. This is a crucial issue because appropriate therapy with immunosuppressive agents can be initiated if early diagnosis is achieved. METHODS AND RESULTS: Thoracic computed tomography (CT) was retrospectively analyzed in detail with special reference to lymph node swelling (LNS) in the mediastinum of 8 patients diagnosed with idiopathic DCM who underwent left ventriculoplasty (LVP), and were later proven to have active cardiac sarcoidosis by histological evaluation of the resected myocardium. Twenty age-matched patients with idiopathic DCM who also underwent LVP served as controls. On conventional chest radiographs, none of the cardiac sarcoidosis patients exhibited lymph node involvement, including bilateral hilar lymphadenopathy. However, CT demonstrated significant mediastinal LNS in 7 (88%) of them and in only 1 (5%) of the 20 controls. There was a significant difference in the incidence of LNS in the 2 groups (p=0.00005). CONCLUSION: Evaluation of mediastinal lymphadenopathy by CT is an easy and valuable initial screening method for distinguishing cardiac sarcoidosis from idiopathic DCM.

Enhanced expression of myeloid-related protein complex (MRP8/14) in macrophages and multinucleated giant cells in granulomas of patients with active cardiac sarcoidosis.

BACKGROUND: The myeloid-related protein complex (MRP8/14) is expressed in activated human macrophages and reported to be involved in the inflammatory process. The expression of MRP8/14 in patients with cardiac sarcoidosis and idiopathic dilated cardiomyopathy (DCM) was investigated. METHODS AND RESULTS: Serum MRP8/14 levels were measured in 35 patients with sarcoidosis and 23 patients with DCM. Sera from 30 normal volunteers served as controls. Additionally, the expression profiles of MRP8/14 in the myocardium from 12 patients with active cardiac sarcoidosis and 10 DCM patients were examined immunohistochemically. Serum MRP8/14 levels were significantly higher in patients with sarcoidosis than in normal controls [515+/-549 (SD) ng/ml vs 230+/-115 ng/ml, p=0.0019]. In the sarcoidosis group, serum MRP8/14 levels in patients with definite cardiac involvement (n=10) were significantly higher than in those without (n=25) (974+/-878 ng/ml vs 332+/-204 ng/ml, p=0.0227) and they were also higher than in DCM patients (vs 252+/-108 ng/ml, p=0.0026). Immunohistochemically, MRP8/14 was specifically positive in the cytoplasm of macrophages and multinucleated giant cells in the myocardial granulomas. CONCLUSIONS: MRP8/14 may be involved in the pathogenesis of sarcoid granulomas. The measurement of serum MRP8/14 levels is useful for the diagnosis of sarcoidosis, and their higher levels suggest the cardiac involvement.

Right atrial blood cyst with total occlusion of the right coronary artery.

Cardiac blood cysts are rarely seen in adult patients and in the right atrium. The origin of cardiac blood cysts is not understood, and several hypotheses have been proposed. We present a rare case of right atrial blood cyst with total occlusion of the right coronary artery (RCA). Inflammatory processes may have played an important role in the development of the cyst, because infiltration of inflammatory cells was observed in the cystic wall. Additionally, total obstruction of the proximal RCA indicated that ischemia and/or infarction in the right atrium might be related to formation of the cyst.