Biomedical subjects

M Kinoshita

Publications and source records attributed to M Kinoshita.

At least 73 records · Page 4Linked to original sources

PubMed2001

Endothelial cell-binding activity of anti-U1-ribonucleoprotein antibodies in patients with connective tissue diseases.

In order to elucidate the immunological properties of anti-U1-ribonucleoprotein (RNP) antibody, one of the autoantibodies detected in patients with connective tissue diseases (CTDs), we tested the endothelial cell-binding by anti-U1-RNP antibodies and epitopes on human pulmonary artery endothelial cells (HPAECs) to which the autoantibody bound. IgG fractions positive for anti-U1-RNP from patients with CTDs bound to the HPAECs. Furthermore, intact and F(ab')2 IgG anti-U1-RNP purified by affinity chromatography also bound to endothelial cells. The binding activity of IgG fractions positive for anti-U1-RNP to the endothelial cells could be effectively absorbed by U1-RNP-Sepharose. An immunoblotting assay of purified IgG anti-U1-RNP antibodies showed that these antibodies could bind to various membrane proteins of NP40-treated HPAECs such as 68, 48, 43, 38, 33, 29, 28 and 24 kDa. Some bands, 68, 33, 28 and 24 kDa, seemed to correspond to components of U1-RNP, i.e. 68 kDa, A, B' and C peptides, respectively. We confirmed that the anti-U1-RNP antibody from patients with CTDs can directly recognize a variety of antigens on the endothelial surface of the pulmonary artery, including the components of U1-RNP or other unknown polypeptides. These results suggest that binding to pulmonary artery endothelial cells of this autoantibody may be one of the triggers of endothelial cell inflammation in CTDs.

Animals↗

PubMed2001

Two possible mechanisms underlying nitrate tolerance in monkey coronary arteries.

1. Previous studies using isolated arteries have demonstrated cross-tolerance between nitric oxide (NO) donors such as nitroglycerin (NTG) and sodium nitroprusside (SNP). However, it remains unclear whether the vasorelaxing effect of atrial natriuretic peptide (ANP), an activator of particulate guanylate cyclase, is affected by treatment with NO donors. To investigate the cross-tolerance and interactions between NTG and ANP in coronary vasorelaxant responses, we used two models of monkey coronary arterial strips (Macaca fuscata). 2. In one model, which was induced by a 1 h treatment with 4.4 x 10(-4) mol/L NTG followed by washout of the agent for 1 h, the vasorelaxing effects of subsequent NTG were markedly attenuated, whereas those of ANP and NO were not affected. These findings suggest that the development of NTG tolerance is associated with a biotransformation process from NTG to NO. In the other model, which did not include washout after exposure to 3 x 10(-6) mol/L NTG, the vasorelaxant responses to 10(-8) mol/L ANP (31.1+/-5.4 vs 5.1+/-2.1%, respectively; P < 0.001), 10(-6) mol/L NO (61.5+/-2.4 vs 29.5+/-8.5%, respectively; P < 0.001) and 10(-8) mol/L SNP (49.4+/-6.4 vs 8.0+/-2.0%, respectively; P < 0.001) were significantly attenuated. The concentration- response curve for 8-bromo-cGMP (8-Br-cGMP) was shifted to the right, whereas responses to papaverine and forskolin were unchanged. These findings suggest that an intracellular process that occurs after the synthesis of cGMP is responsible for this interaction. 3. As a mechanism of NTG tolerance, two possible processes may be impaired: (i) biotransformation from NTG to NO; and (ii) an intracellular process that occurs after the synthesis of cGMP.

Animals↗

PubMed2001

Breakthrough waves during ventricular fibrillation depend on the degree of rotational anisotropy and the boundary conditions: a simulation study.

INTRODUCTION: The left ventricle (LV) and right ventricle (RV) are characterized by specific fiber orientation known as "rotational anisotropy." However, it remains unclear whether the LV and RV are different with regard to the effect of rotational anisotropy on the dynamics of scroll waves during ventricular fibrillation (VF). To resolve this issue, we used a computation-based model to study scroll wave behavior. METHODS AND RESULTS: We composed an environment of simulated three-dimensional ventricular wall slabs, with optional ratios of fiber rotation to wall thickness (0 degrees, 6 degrees, and 12 degrees/mm thickness; LV 10 mm, RV 5 mm), using Luo-Rudy phase I equations. When rotational anisotropy was not incorporated into the LV wall slab (theta endo to approximately theta epi = 0 degrees), most scroll waves rotated around the filaments perpendicular to the tissue surface, with only a few accompanying breakthrough waves. In a twisted LV model (theta endo to approximately theta epi = 60 degrees and 120 degrees), the scroll waves were demonstrated as multiple wavelets scattered spatiotemporally, frequently accompanied by breakthrough waves that were promoted by rotational anisotropy. In a twisted RV model (theta endo to approximately theta epi = 30 degrees and 60 degrees), single scroll waves and/or figure-of-eight reentrant waves appeared, with comparatively few breakthrough waves, regardless of the degree of fiber twist. CONCLUSION: The proportion of electrical effects of rotational anisotropy and tissue boundaries plays an important role in the genesis of breakthrough waves during VF, and the difference in wave propagating patterns and frequency spectrum of the ventricles may arise, in part, from the number of breakthrough waves promoted by rotational anisotropy.

Anisotropy↗

PubMed2001

Electroporation in a model of cardiac defibrillation.

INTRODUCTION: It is known that high-strength shock disrupts the lipid matrix of the myocardial cell membrane and forms reversible aqueous pores across the membrane. This process is known as "electroporation." However, it remains unclear whether electroporation contributes to the mechanism of ventricular defibrillation. The aim of this computer simulation study was to examine the possible role of electroporation in the success of defibrillation shock. METHODS AND RESULTS: Using a modified Luo-Rudy-1 model, we simulated two-dimensional myocardial tissue with a homogeneous bidomain nature and unequal anisotropy ratios. Spiral waves were induced by the S1-S2 method. Next, monophasic defibrillation shocks were delivered externally via two line electrodes. For nonelectroporating tissue, termination of ongoing fibrillation succeeded; however, new spiral waves were initiated, even with high-strength shock (24 V/cm). For electroporating tissue, high-strength shock (24 V/cm) was sufficient to extinguish ongoing fibrillation and did not initiate any new spiral waves. Weak shock (16 to 20 V/cm) also extinguished ongoing fibrillation; however, in contrast to the high-strength shock, new spiral waves were initiated. Success in defibrillation depended on the occurrence of electroporation-mediated anodal-break excitation from the physical anode and the virtual anode. Some excitation wavefronts following electrical shock used a deexcited area with recovered excitability as a pass-through point; therefore, electroporation-mediated anodal-break excitation is necessary to block out the pass-through point, resulting in successful defibrillation. CONCLUSION: The electroporation-mediated anodal-break excitation mechanism may play an important role in electrical defibrillation.

Action Potentials↗

PubMed2001

Relationship between plasma levels of cardiac natriuretic peptides and soluble Fas: plasma soluble Fas as a prognostic predictor in patients with congestive heart failure.

BACKGROUND: Cardiac natriuretic peptides may induce apoptosis in myocytes; however, the relationship between plasma levels of cardiac natriuretic peptides and those of soluble Fas (sFas) and tumor necrosis factor (TNF)-alpha remains unknown in patients with congestive heart failure (CHF). METHODS AND RESULTS: We measured plasma levels of sFas and TNF-alpha and those of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), norepinephrine, and endothelin 1 in 96 patients with CHF (ejection fraction < 45%). The patients were monitored for 3 years. Plasma levels of sFas and TNF-alpha increased with the severity of CHF. There was no significant correlation between sFas plasma levels and those of ANP and BNP. Cox proportional hazard analysis showed that high levels of sFas (P = .009) and BNP (P < .0001) and a low ejection fraction (P = .019) were independent significant prognostic predictors. CONCLUSIONS: There is no significant correlation between cardiac natriuretic peptide and sFas levels in plasma. Plasma sFas is a useful prognostic marker independent of neurohumoral factors, suggesting that immune activation and/or apoptosis play a significant role in the pathogenesis of CHF.

Age Factors↗

PubMed2001

The diagnostic pathway in amyotrophic lateral sclerosis.

INTRODUCTION: We present the findings of a survey of the diagnostic pathways and treatment of 50 patients with amyotrophic lateral sclerosis (ALS). RESULTS: The mean time between first symptoms and first consultation with a physician was 5.7 months; mean time between first symptoms and first consultation with a neurologist was 9.7 months; mean time from symptom onset to confirmation of diagnosis was 11.6 months. Patients with bulbar onset appeared to be diagnosed earlier than those with limb onset, but the difference was not statistically significant. The first physician seen was an orthopedist in 30%, a general practitioner (GP) in 28%, and a neurologist in 28% of cases. The mean diagnostic intervals were 9.4 months when the neurologist was the first physician seen, and 9.8 months when the neurologist saw a patient referred from a GP. Otherwise, when a neurologist saw patients referred from an orthopedist, the mean diagnostic interval was 14.9 months. Differences between the values of mean diagnostic interval were not statistically significant. EMG and MRI were performed in all patients, cerebrospinal fluid examination and muscle biopsy in most. Treatment was by vitamins in 38% of cases, thyrotropin-releasing hormone in 24%, physical therapy in 22%, and anticholinesterase agent in 12%. CONCLUSION: The number of patients in our study is limited, and a further prospective nation-wide survey is necessary.

Adult↗

PubMed2001

Chronic cerebral hypoperfusion induces MMP-2 but not MMP-9 expression in the microglia and vascular endothelium of white matter.

White matter lesions are closely associated with cognitive impairment and motor dysfunction in the aged. To explore the pathophysiology of these lesions, the authors examined the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9 in the white matter in a rat model of chronic cerebral hypoperfusion. After bilateral clipping of the common carotid arteries, myelin staining revealed demyelinating changes in the optic tract and the corpus callosum on day 7. Zymographic analyses indicated an increase in the level of MMP-2, but not MMP-9, after the hypoperfusion. Immunohistochemical analyses revealed the presence (most abundantly on day 3) of MMP-2-expressing activated microglia in the optic tract and corpus callosum. In contrast, the capillary endothelial cells expressed MMP-2 later. IgM-immunoreactive glial cells were absent in the sham-operated animals, but were present in the hypoperfused animals by day 3, reflecting the disrupted blood-brain barrier. These findings suggest that the main sources of the elevated MMP-2 were the microglia and the endothelium, and that these cells may contribute to the remodeling of the white matter myelin and microvascular beds in chronic cerebral hypoperfusion.

Animals↗

PubMed2001

Association analyses between genetic polymorphisms of endothelial nitric oxide synthase gene and hypertension in Japanese: The Suita Study.

OBJECTIVES: Endothelium-derived nitric oxide plays a key role in the regulation of vascular tone. Recently, endothelial nitric oxide synthase (eNOS) gene polymorphisms were reported to be associated with hypertension or coronary spasm. We investigated the association between the eNOS gene polymorphisms and hypertension in a large population-based sample of 4055 Japanese. DESIGN AND METHODS: We investigated two polymorphisms of the eNOS gene, Glu298Asp polymorphism of exon 7 and T(-786)C polymorphism of the promoter region. The genotype distribution in hypertensive subjects was compared to that in the other subjects. The influence of the genotype on blood pressure values was analyzed in the subjects not taking hypertensive medication. The promoter activities of the eNOS gene with the (-786)T or (-786)C allele were measured by a luciferase reporter gene assay. RESULTS: There was significant linkage disequilibrium between the two polymorphisms (P < 0.0001). The genotype distribution of the Glu298Asp or T(-786)C polymorphism did not differ between the hypertensive and the other subjects. No significant differences in the blood pressure of subjects not taking hypertensive medication were observed among the three genotypes of Glu298Asp or T(-786)C polymorphisms. No significant differences in the promoter activity were observed between bovine endothelial cells transfected with the (-786)T and (-786)C alleles. CONCLUSIONS: Our data suggested that these polymorphisms of the eNOS gene are unlikely to be major factors in the susceptibility to hypertension in the Japanese population studied.

Adult↗

PubMed2001

Comparison of neurohumoral effects of short-acting and long-acting loop diuretics in patients with chronic congestive heart failure.

We evaluated the comparative effects of furosemide, a short-acting loop diuretic, and azosemide, a long-acting loop diuretic, on neurohumoral factors and quality of life (QOL) in patients with congestive heart failure (CHF). Twenty-five stable patients with mild chronic CHF who had been administered furosemide (n = 14) or azosemide (n = 11) orally for more than 3 months were studied. We changed furosemide to azosemide or azosemide to furosemide and followed for 3 months. Echocardiography was performed, and we also measured neurohumoral factors and assessed QOL by questionnaire. Blood pressure, body weight, renal function and echocardiographic findings were the same during the furosemide and azosemide treatments. Plasma levels of atrial natriuretic peptide and brain natriuretic peptide were not different between the two treatments. However, plasma concentrations of active renin and norepinephrine were significantly higher with furosemide treatment than with azosemide treatment. QOL score was significantly lower with azosemide than with furosemide. These findings suggest that long-acting loop diuretics may have fewer adverse effects on the neuroendocrine system and QOL than short-acting loop diuretics in patients with mild CHF.

Administration, Oral↗

PubMed2001

Unsaturated fatty acids in membrane lipids protect the photosynthetic machinery against salt-induced damage in Synechococcus.

In this study, the tolerance to salt stress of the photosynthetic machinery was examined in relation to the effects of the genetic enhancement of the unsaturation of fatty acids in membrane lipids in wild-type and desA+ cells of Synechococcus sp. PCC 7942. Wild-type cells synthesized saturated and mono-unsaturated fatty acids, whereas desA+ cells, which had been transformed with the desA gene for the Delta12 acyl-lipid desaturase of Synechocystis sp. PCC 6803, also synthesized di-unsaturated fatty acids. Incubation of wild-type and desA+ cells with 0.5 M NaCl resulted in the rapid loss of the activities of photosystem I, photosystem II, and the Na+/H+ antiport system both in light and in darkness. However, desA+ cells were more tolerant to salt stress and osmotic stress than the wild-type cells. The extent of the recovery of the various photosynthetic activities from the effects of 0.5 M NaCl was much greater in desA+ cells than in wild-type cells. The photosystem II activity of thylakoid membranes from desA+ cells was more resistant to 0.5 M NaCl than that of membranes from wild-type cells. These results demonstrated that the genetically engineered increase in unsaturation of fatty acids in membrane lipids significantly enhanced the tolerance of the photosynthetic machinery to salt stress. The enhanced tolerance was due both to the increased resistance of the photosynthetic machinery to the salt-induced damage and to the increased ability of desA+ cells to repair the photosynthetic and Na+/H+ antiport systems.

Cyanobacteria↗

PubMed2001

Quantitative analysis of hTERT mRNA expression in colorectal cancer.

OBJECTIVES: Telomerase is highly activated in a variety of malignant neoplasms including colon cancer. Among the major components of telomerase, human telomerase reverse transcriptase (hTERT) is thought to regulate telomerase activity. To assess the importance of telomerase for the diagnosis of colorectal cancer, we measured the expression of hTERT mRNA and telomerase activity in a large series of 140 colorectal cancers, 140 adjacent normal tissues, and 20 adenomas. METHODS: The expression level of hTERT was measured quantitatively by competitive reverse transcriptase-polymerase chain reaction (RT-PCR), and telomerase activity was examined by telomeric repeat amplification protocol (TRAP) assay in the same samples. RESULTS: The median expression level of hTERT mRNA in carcinomas was significantly higher than that in either adenomas or normal tissues. The median level of hTERT in adenomas was significantly higher than that in normal tissues. Telomerase activities in carcinomas were significantly higher than those in either adenomas or normal tissues. Telomerase activities in adenomas were also significantly higher than those in normal tissues. Furthermore, the relative expression levels of hTERT mRNA in adenomas and carcinomas were significantly correlated with the relative telomerase activities; the Spearman rank correlation was 0.53 (p = 0.021) and 0.18 (p = 0.031), respectively. CONCLUSIONS: Our data suggest that determination of hTERT mRNA by competitive RT-PCR is superior in quantitative accuracy and sensitivity and would support the importance of telomerase activity for the diagnosis of colorectal cancer.

Adenoma↗

PubMed2001

Activation of inositol 1,4,5-trisphosphate receptor is essential for the opening of mouse TRP5 channels.

We studied the opening mechanism of Ca(2+)-permeable channels formed with mouse transient receptor potential type 5 (mTRP5) using Xenopus oocytes. After stimulation of coexpressed muscarinic M(1) receptors with acetylcholine (ACh) in a Ca(2+)-free solution, switching to 2 mM Ca(2+)-containing solution evoked a large Cl(-) current, which reflects the opening of endogenous Ca(2+)-dependent Cl(-) channels following Ca(2+) entry through the expressed channels. The ACh-evoked response was not affected by a depletion of Ca(2+) store with thapsigargin but was inhibited by preinjection of antisense oligodeoxynucleotides (ODNs) to G(q), G(11), or both. The mTRP5 channel response was also induced by a direct activation of G proteins with injection of guanosine 5'-3-O-(thio)triphosphate (GTP gamma S). The ACh- and GTP gamma S-evoked responses were inhibited by either pretreatment with a phospholipase C inhibitor, U73122, or an inositol-1,4,5-trisphosphate (IP(3)) receptor inhibitor, xestospongin C (XeC). An activation of IP(3) receptors with injection of adenophostin A (AdA) evoked the mTRP5 channel response in a dose-dependent manner. The AdA-evoked response was not suppressed by preinjection of antisense ODNs to G(q/11) or U73122 but was suppressed by either preinjection of XeC or a peptide mimicking the IP(3) binding domain of Xenopus IP(3) receptor. These findings suggest that the activation of IP(3) receptor is essential for the opening of mTRP5 channels, and that neither G proteins, phosphoinositide metabolism, nor depletion of the Ca(2+) store directly modifies the IP(3) receptor-linked opening of mTRP5 channels.

Acetylcholine↗

PubMed2001

Dynamic localization and function of Bni1p at the sites of directed growth in Saccharomyces cerevisiae.

Formin homology (FH) proteins are implicated in cell polarization and cytokinesis through actin organization. There are two FH proteins in the yeast Saccharomyces cerevisiae, Bni1p and Bnr1p. Bni1p physically interacts with Rho family small G proteins (Rho1p and Cdc42p), actin, two actin-binding proteins (profilin and Bud6p), and a polarity protein (Spa2p). Here we analyzed the in vivo localization of Bni1p by using a time-lapse imaging system and investigated the regulatory mechanisms of Bni1p localization and function in relation to these interacting proteins. Bni1p fused with green fluorescent protein localized to the sites of cell growth throughout the cell cycle. In a small-budded cell, Bni1p moved along the bud cortex. This dynamic localization of Bni1p coincided with the apparent site of bud growth. A bni1-disrupted cell showed a defect in directed growth to the pre-bud site and to the bud tip (apical growth), causing its abnormally spherical cell shape and thick bud neck. Bni1p localization at the bud tips was absolutely dependent on Cdc42p, largely dependent on Spa2p and actin filaments, and partly dependent on Bud6p, but scarcely dependent on polarized cortical actin patches or Rho1p. These results indicate that Bni1p regulates polarized growth within the bud through its unique and dynamic pattern of localization, dependent on multiple factors, including Cdc42p, Spa2p, Bud6p, and the actin cytoskeleton.

Actins↗

PubMed2001

Neural representation of the luminance and brightness of a uniform surface in the macaque primary visual cortex.

The perceived brightness of a surface is determined not only by the luminance of the surface (local information), but also by the luminance of its surround (global information). To better understand the neural representation of surface brightness, we investigated the effects of local and global luminance on the activity of neurons in the primary visual cortex (V1) of awake macaque monkeys. Single- and multiple-unit recordings were made from V1 while the monkeys were performing a visual fixation task. The classical receptive field of each neuron was identified as a region responding to a spot stimulus. Neural responses were assessed using homogeneous surfaces at least three times as large as the receptive field as stimuli. We first examined the sensitivity of neurons to variation in local surface luminance, while the luminance of the surround was held constant. The activity of a large majority of surface-responsive neurons (106/115) varied monotonically with changes in surface luminance; in some the dynamic range was over 3 log units. This monotonic relation between surface luminance and neural activity was more evident later in the stimulus period than early on. The effect of the global luminance on neural activity was then assessed in 81 of the surface-responsive neurons by varying the luminance of the surround while holding the luminance of the surface constant. The activity of one group of neurons (25/81) was unaffected by the luminance of the surround; these neurons appear to encode the physical luminance of a surface covering the receptive field. The responses of the other neurons were affected by the luminance of the surround. The effects of the luminances of the surface and the surround on the activities of 26 of these neurons were in the same direction (either increased or decreased), while the effects on the remaining 25 neurons were in opposite directions. The activities of the latter group of neurons seemed to parallel the perceived brightness of the surface, whereas the former seemed to encode the level of illumination. There were differences across different types of neurons with regard to the layer distribution. These findings indicate that global luminance information significantly modulates the activity of surface-responsive V1 neurons and that not only physical luminance, but also perceived brightness, of a homogeneous surface is represented in V1.

Animals↗

PubMed2001

The protease-activated receptor-2 agonist induces gastric mucus secretion and mucosal cytoprotection.

Protease-activated receptor-2 (PAR-2), a receptor activated by trypsin/tryptase, modulates smooth muscle tone and exocrine secretion in the salivary glands and pancreas. Given that PAR-2 is expressed throughout the gastrointestinal tract, we investigated effects of PAR-2 agonists on mucus secretion and gastric mucosal injury in the rat. PAR-2-activating peptides triggered secretion of mucus in the stomach, but not in the duodenum. This mucus secretion was abolished by pretreatment with capsaicin, which stimulates and ablates specific sensory neurons, but it was resistant to cyclo-oxygenase inhibition. In contrast, capsaicin treatment failed to block PAR-2-mediated secretion from the salivary glands. Intravenous calcitonin gene-related peptide (CGRP) and neurokinin A markedly elicited gastric mucus secretion, as did substance P to a lesser extent. Specific antagonists of the CGRP1 and NK2, but not the NK1, receptors inhibited PAR-2-mediated mucus secretion. Pretreatment with the PAR-2 agonist strongly prevented gastric injury caused by HCl-ethanol or indomethacin. Thus, PAR-2 activation triggers the cytoprotective secretion of gastric mucus by stimulating the release of CGRP and tachykinins from sensory neurons. In contrast, the PAR-2-mediated salivary exocrine secretion appears to be independent of capsaicin-sensitive sensory neurons.

Animals↗

PubMed2001

Surgical treatment for hallux valgus with painful plantar callosities.

We retrospectively reviewed the results of a distal soft-tissue procedure and proximal crescentic osteotomy of the first metatarsal combined with a proximal shortening osteotomy of the second and/or third metatarsal. This was in patients who had hallux valgus with painful plantar callosities. The review covered seven years of procedures (1989-1996) in 12 patients (14 feet) averaging 53 years of age. Average follow-up was 52 months. All patients had pain at the first metatarsophalangeal joint and had metatarsalgia preoperatively. At follow-up, 11 feet had no pain at the first metatarsophalangeal joint, and three had some improvement of pain. Ten feet had no metatarsalgia, two had improvement of metatarsalgia, and two feet had transfer lesions postoperatively and required reoperation. The angle of hallux valgus averaged 40 degrees preoperatively and 13 degrees postoperatively. The intermetatarsal angle averaged 18 degrees preoperatively and 6 degrees postoperatively. Mean decreases in length of the second and third metatarsal after surgery were 5.4 mm and 4.8 mm, respectively. Our results suggested that this combined procedure for hallux valgus with painful plantar callosities may be successful, in carefully selected patients.

Adult↗

PubMed2001

Roles of septins in the mammalian cytokinesis machinery.

Septins comprise a eukaryotic guanine nucleotide binding protein subfamily which form filamentous heteropolymer complexes. Although mechanism of cytokinesis is diverged by species and tissues, loss of septin function results in the multinuclear phenotype in many organisms. Hence septin filaments beneath the cleavage furrow are hypothesized as a structural basis to ensure completion of cytokinesis. However, molecular mechanisms of septin assembly, disassembly and function have been elusive despite the potential importance of this ubiquitous cytoskeletal system. Meanwhile, growing evidence suggests that mammalian septins functionally or physically interact with diverse molecules such as actin, actin-binding proteins, proteins of membrane fusion machinery, Cdc42 adapter proteins, a ubiquitin-protein ligase, and phosphoinositides. Careful integration of these data may provide insights into the mechanism of mammalian septin organization and functions in cytokinesis.

Animals↗

PubMed2001

Relationship between cardiac 123I-metaiodobenzylguanidine imaging and the transcardiac gradient of neurohumoral factors in patients with dilated cardiomyopathy.

Cardiac sympathetic nervous function is altered in congestive heart failure (CHF) and the uptake and washout rate of cardiac 123I-metaiodobenzylguanidine (MIBG) are useful markers for evaluating the severity of it. To assess what parameters predict decreased uptake or increased washout rate of MIBG, the concentrations of neurohumoral factor in both the aorta (Ao) and coronary sinus (CS) were measured, as well as hemodynamic parameters by catheterization, in patients with dilated cardiomyopathy (DCM). MIBG imaging was performed within 1 week of cardiac catheterization. Regarding MIBG parameters, the correlation with the transcardiac gradient of norepinephrine (NE), brain natriuretic peptide (BNP) and hemodynamics was investigated. Stepwise multivariate regression analysis was used to determine which variables closely correlated with cardiac MIBG parameters. There was a significant increase in the NE level between the Ao (446 pg/ml) and the CS (727 pg/ml). According to stepwise multivariate regression analysis, the heart/mediastinum (H/M) ratio independently correlated with the transcardiac gradient of BNP (r=-0.480, p<0.01), and the washout rate independently correlated with the transcardiac gradient of NE (r=0.481, p<0.01). These findings indicate that the H/M ratio may reflect the transcardiac gradient of BNP, which implies the degree of left ventricular dysfunction and/or damage and the washout rate may reflect altered cardiac sympathetic nerve terminal in DCM patients with CHF, suggesting that both the H/M ratio and washout rate provide important information about the failing ventricle.

3-Iodobenzylguanidine↗