Quantification of Myocardial Perfusion Defect Size in Rats: Comparison between Quantitative Perfusion SPECT and Autoradiography

Purpose

Ultra-high resolution single-photon emission computed tomography (SPECT) system, using multiple pinhole collimators, has been applied to the imaging of small rodents. We aimed to compare the myocardial infarction (MI) area on quantitative perfusion single-photon emission computed tomography (QPS; Cedars-Sinai Medical Center, USA) with that on high-resolution autoradiography in rat model to determine the accuracy of perfusion defect measurement by QPS.

Procedures

After thoracotomy, rats (n?=?9) had their left coronary arteries occluded and reperfused before injection with 185 MBq [^99mTc] methoxyisobutylisonitrile ([^99mTc]MIBI) for SPECT and autoradiography. Healthy rats (n?=?28) were similarly scanned to create a normal database on which to base QPS. The MI area on SPECT images was analysed automatically by QPS software. For the autoradiography images, regions of interest for MI were set at 1 mm intervals.

Results

In normal rats, [^99mTc]MIBI accumulated throughout the left ventricles, and a polar map of ventricular perfusion showed the lowest and highest uptakes in the inferior (68 %?±?4 %) and anterior (92 %?±?5 %) walls, respectively. In the rat MI model, the percentage of polar map with reduced [^99mTc]MIBI uptake correlated strongly with the percentage of left ventricle with MI on autoradiography (r²?=?0.90).

Conclusions

QPS can quantitatively evaluate MI severity on myocardial perfusion images in rats, with comparable results to autoradiography. This widely available software could promote the development of new techniques for analysing cardiac images in small animals.

     

Complete Resolution of a Case of TAFRO Syndrome Accompanied by Mediastinal Panniculitis,Adrenal Lesion,and Liver Damage with Hyperbilirubinemia

TAFRO syndrome is a systemic inflammatory, lymphoproliferative disorder, but the pathophysiology of the disease is unknown. It is typically characterized by thrombocytopenia, anasarca, a fever, reticulin fibrosis, renal dysfunction, and organomegaly. However, other manifestations have been also reported. We encountered a 43-year-old man with TAFRO syndrome who showed mediastinal panniculitis, liver damage, and adrenal lesions in addition to the core signs. He achieved complete remission with combination therapy of corticosteroids, tocilizumab, and cyclosporin, and remission was maintained even after drug discontinuation at 15 months. Atypical manifestations and complete remission of TAFRO syndrome were remarkable features of our case.     

Nationwide survey for patients with acute-on-chronic liver failure occurring between 2017 and 2019 and diagnosed according to proposed Japanese criteria

Journal of Gastroenterology - The significance of the 2018 Japanese diagnostic criteria for acute-on-chronic liver failure (ACLF) has not yet been evaluated. A nationwide survey was performed for...     

Accelerated myocardial metabolic and functional recovery with terminal nicorandil-Mg cardioplegia in heart transplantation

Cardiac reperfusion injury after heart transplantation or cardiopulmonary bypass has been difficult to control due to the variable degree of myocardial damage with respect to the length of ischemia and the complexity of the surgical procedure. Here, we evaluated the myocardial metabolic and functional recovery of hearts infused with a nicorandil vasodilator-magnesium (Mg) solution just prior to reperfusion (terminal cardioplegia). Donor hearts (20 dogs) were removed and immersed in a 4 degrees C water bath containing 20 mEq/l KCL-5% glucose for 6 hours, and then were transplanted to recipient dogs. Orthotopically transplanted dog hearts were either reperfused without any further treatment or received a terminal cardioplegic solution containing 8 mg/l nicorandil, 30 mEq/l Mg, and 50 g/l glucose, which was infused at a pressure of 75 cm H2O for 2 minutes. During the reperfusion period, myocardial tissue PCO2 (t-PCO2) and calcium ion (t-Ca) were continuously monitored by an ISFET (ion-sensitive field effect transistor) sensor. Myocardial oxygen consumption and lactate flux were calculated/monitored at 5, 10, 20 and 40 minutes of reperfusion. Thereafter, myocardial function was evaluated at 45 minutes of reperfusion using LVSWI. Just after reperfusion, the treatment group (group B, n = 10) had a significantly greater coronary flow than the control group (Group A, n = 10, 35.0 +/- 10.1; group B, 47.4 +/- 8.5 ml/100 g/min, p less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)     

Gastric Mucosal Injury Induced by Local Ischemia-Reperfusion in Rats (Role of Endogenous Endothelin-1 and Free Radical)

We investigated the role of an endogenousvasoconstrictor peptide endothelin-1 (ET-1) and freeradicals in local gastric ischemia-reperfusion injury inrats. Local gastric ischemia was induced by clamping the left gastric artery for 15 min andreperfusion was done for 10-30 min in the presence of150 mM exogenous HCl intragastrically. Local gastricischemia and reperfusion resulted in significantmacroscopic and microscopic gastric mucosal damage togetherwith elevation of gastric tissue ET-1 concentration.Gastric tissue ET-1 was found to increase after 15 minof ischemia alone and also with 30 min of reperfusion. A novel nonpeptide endothelin receptorantagonist, bosentan, or a combination of radicalscavengers (superoxide dismutase, catalase, anddeferoxamine) both attenuated gastric mucosal injury.However, the greater protection observed with bosentan thanwith radical scavengers might reflect a preferentialrole of endothelin-1 in this type of injury.     

Attenuated Apoptosis in H. pylori-Colonized Gastric Mucosa of Mongolian Gerbils in Comparison with Mice

Although gastric cancer formation with H. pylori in Mongolian gerbils was recently reported, the same inoculation procedure did not result in cancer formation in other animals such as mice. Disturbed regulation of apoptosis and cell proliferation are known to link the multistep process of carcinogenesis. The present study is designed to examine the level of gastric epithelial cell apoptosis in Mongolian gerbils colonized with the H. pylori (Sydney strain: SS1) in comparison with that in mice. Mice (C57BL/6) and Mongolian gerbils were orally inoculated with SS1 and the stomachs were examined 9 and 18 months later. MPO activity increased persistently in gerbils, but increased transiently in mice. While the levels of DNA fragmentation, caspase-3 activity, and the number of TUNEL-positive cells increased significantly in mice, such parameters were attenuated in gerbils. On the other hand, the number of PCNA-positive cells increased after SS1 inoculation only in Mongolian gerbils, suggesting the enhancement of cell turnover in H. pylori-colonized gerbils. In conclusion, the SS1-induced increase in gastric mucosal apoptosis observed in mice was attenuated significantly in Mongolian gerbils, suggesting the causative role for the higher incidence of gastric carcinogenesis in this animal.     

Anti-eosinophil peroxidase antibodies detected in patients with primary biliary cirrhosis.

OBJECTIVE:: The possible involvement of eosinophils in primary biliary cirrhosis (PBC) has been suggested for many years. Activated eosinophils release basic granule proteins and are thought to be involved in the tissue damage of PBC. Eosinophil peroxidase (EPO) is one of the eosinophilic granule proteins and is toxic to epithelial cells. In this study, we examined whether autoantibodies to EPO are present in sera of patients with PBC and we evaluated the relationship between the presence of anti-EPO antibodies and the clinical features of PBC. METHODS:: Sera obtained from 61 patients with PBC, 31 patients with autoimmune hepatitis (AIH), 87 patients with chronic viral hepatitis (CVH), 27 patients with bronchial asthma, and 20 healthy controls were examined. Enzyme-linked immunosorbent assay (ELISA) and Western blot methods were used for detection of anti-EPO antibodies. RESULTS:: The mean OD value of anti-EPO antibodies, as determined by ELISA, was significantly (p<0.01) higher in patients with PBC (0.197+/-0.121) than in patients with AIH (0.124+/-0.077), CVH (0.090+/-0.038) or bronchial asthma (0.073+/-0.025) and in healthy controls (0.072+/-0.029). The results of ELISA showed that 32 (52.5%) of the 61 patients with PBC, 9 (29.0%) of the 31 patients with AIH, 7 (8.0%) of the 87 patients with CVH, and 1 (3.7%) of the 27 patients with bronchial asthma were positive for anti-EPO antibodies. In addition, PBC patients who were positive for anti-EPO antibodies had a significantly smaller number of peripheral eosinophils than did patients who were negative for anti-EPO antibodies (99.2+/-54.4cells/mul versus 176.9+/-117.5cells/mul, p<0.01). However, there was no correlation between the titers of anti-EPO antibodies and those of AMA or AMA-M2, ANA or serum levels of IgM. CONCLUSIONS:: This is the first report of the detection of anti-EPO antibodies in patients with PBC. Further study is needed to clarify the role of anti-EPO antibodies in the pathogenesis of PBC.     

Induction of Mutant Sik3Sleepy Allele in Neurons in Late Infancy Increases Sleep Need

Sleep is regulated in a homeostatic manner. Sleep deprivation increases sleep need, which is compensated mainly by increased EEG δ power during non-rapid eye movement sleep (NREMS) and, to a lesser extent, by increased sleep amount. Although genetic factors determine the constitutive level of sleep need and sleep amount in mice and humans, the molecular entity behind sleep need remains unknown. Recently, we found that a gain-of-function Sleepy (Slp) mutation in the salt-inducible kinase 3 (Sik3) gene, which produces the mutant SIK3(SLP) protein, leads to an increase in NREMS EEG δ power and sleep amount. Since Sik3^Slp mice express SIK3(SLP) in various types of cells in the brain as well as multiple peripheral tissues from the embryonic stage, the cell type and developmental stage responsible for the sleep phenotype in Sik3^Slp mice remain to be elucidated. Here, we generated two mouse lines, synapsin1^CreERT2 and Sik3^ex13flox mice, which enable inducible Cre-mediated, conditional expression of SIK3(SLP) in neurons on tamoxifen administration. Administration of tamoxifen to synapsin1^CreERT2 mice during late infancy resulted in higher recombination efficiency than administration during adolescence. SIK3(SLP) expression after late infancy increased NREMS and NREMS δ power in male synapsin1^CreERT2; Sik3^ex13flox/+ mice. The expression of SIK3(SLP) after adolescence led to a higher NREMS δ power without a significant change in NREMS amounts. Thus, neuron-specific expression of SIK3(SLP) after late infancy is sufficient to increase sleep.SIGNIFICANCE STATEMENT The propensity to accumulate sleep need during wakefulness and to dissipate it during sleep underlies the homeostatic regulation of sleep. However, little is known about the developmental stage and cell types involved in determining the homeostatic regulation of sleep. Here, we show that Sik3^Slp allele induction in mature neurons in late infancy is sufficient to increase non-rapid eye movement sleep amount and non-rapid eye movement sleep δ power. SIK3 signaling in neurons constitutes an intracellular mechanism to increase sleep.     

Clinical and neuroendocrinological characteristics of delayed orthostatic hypotension in Parkinson’s disease

Clinical Autonomic Research - Delayed orthostatic hypotension (DOH), a fall in blood pressure after a 3-min cutoff, is clinically meaningful. The aim of this study was to elucidate the clinical and...