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R Nagai

Publications and source records attributed to R Nagai.

At least 343 records · Page 19Linked to original sources
PubMed1997

Hydroxyl radical mediates N epsilon-(carboxymethyl)lysine formation from Amadori product.

Recent studies demonstrated N epsilon-(carboxymethyl)lysine (CML) in several tissue proteins. Incubation of proteins with glucose leads through a Schiff base to Amadori products. Oxidative cleavage of Amadori products is considered as a major route to CML formation in vivo, whereas it is not known which reactive oxygen species (ROS) is involved. The present study is undertaken to identify such a ROS. We prepared heavily glycated human serum albumin (HSA) which contained a high level of Amadori products, but an undetectable level of CML. Incubation of glycated HSA with FeCl2, but not with H2O2, led to CML formation which was enhanced by H2O2, but inhibited by catalase or mannitol, whereas superoxide dismutase had no effect. Similar data were obtained by experiments using Boc-fructose-lysine as a model Amadori compound. These data indicate that hydroxyl radical generated by the reaction of Fe2+ with H2O2 mediates CML formation from Amadori compounds.

Catalase↗
PubMed1997

Four novel KVLQT1 and four novel HERG mutations in familial long-QT syndrome.

BACKGROUND: Familial long-QT syndrome (LQTS) is characterized by prolonged ventricular repolarization. Clinical symptoms include recurrent syncopal attacks, and sudden death may occur due to ventricular tachyarrhythmias. Three genes responsible for this syndrome (KVLQT1, HERG, and SCN5A) have been identified so far. We investigated mutations of these genes in LQTS families. METHODS AND RESULTS: Thirty-two Japanese families with LQTS were brought together for screening for mutations. Genomic DNA from each proband was examined by the polymerase chain reaction-single-strand conformation polymorphism technique followed by direct DNA sequencing. In four of the families, comprising 16 patients, mutations were identified in KVLQT1; five other families (9 patients) segregated mutant alleles of HERG. All 25 of these patients carried the specific mutations present in their respective families, and none of 80 normal individuals carried these alleles. Mutations were confirmed by endonuclease digestion or hybridization of mutant allele-specific oligonucleotides. No mutation in SCN5A was found in any family. CONCLUSIONS: We identified nine different mutations among 32 families with LQTS. Eight of these were novel and account for 25% of all types of mutations reported to date. Such a variety of mutations makes it difficult to screen high-risk groups using simple methods such as endonuclease digestion or mutant allele-specific amplification.

Alleles↗
PubMed1997

Co-elevation of brain natriuretic peptide and proprotein-processing endoprotease furin after myocardial infarction in rats.

We investigated the expression of the yeast Kex2 family endoproteases furin and PACE4, and brain natriuretic peptide (BNP) in the atrium and ventricle after infarction as well as the conversion of the BNP precursor gammaBNP to BNP-45. In a rat heart failure model, plasma BNP rose in two phases--first at day 3, and again at day 14. BNP mRNA, as measured by Northern blot analysis, increased strongly at day 3, then at days 14 and 28 less strongly in the atrium, and in the ventricle it increased weakly at day 3, then strongly at days 14 and 28. Furin mRNA showed the same pattern of expression as that of BNP message, whereas PACE4 message stayed unchanged after the infarction. Both furin and BNP were immunostained in the myocardium adjacent to the infarcted tissue. We suggest that after myocardial infarction, furin is co-expressed with BNP in both the atrium and ventricle, and that furin may be responsible for the conversion of gammaBNP to BNP-45.

Animals↗
PubMed1997

The relationship between accumulation of advanced glycation end products and expression of vascular endothelial growth factor in human diabetic retinas.

Both advanced glycation end products and vascular endothelial growth factor are believed to play a role in the pathogenesis of diabetic retinopathy. It is known that vascular endothelial growth factor causes retinal neovascularization and a breakdown of the blood-retinal barrier; how advanced glycation end products affect the retina, however, remains largely unclear. The substance-Ne-(carboxymethyl)lysine is a major immunologic epitope, i.e. a dominant advanced glycation end products antigen. We generated an anti-Ne-(carboxymethyl)lysine antibody to investigate the relationship between the localization of advanced glycation end products and that of vascular endothelial growth factor in 27 human diabetic retinas by immunohistochemistry. Nine control retinas were also examined. In all 27 diabetic retinas, Ne-(carboxymethyl)lysine was located in the thickened vascular wall. In 19 of the 27 retinas, strand-shaped Ne-(carboxymethyl)lysine immunoreactivity was also observed around the vessels. In all 27 diabetic retinas, vascular endothelial growth factor revealed a distribution pattern similar to that of Ne-(carboxymethyl)lysine. Vascular endothelial growth factor was also located in the vascular wall and in the perivascular area. Neither Ne-(carboxymethyl)lysine nor vascular endothelial growth factor immunoreactivity was detected in the 9 control retinas. Vessels with positive immunoreactivity for Ne-(carboxymethyl)lysine and/or vascular endothelial growth factor were counted. A general association was noted between accumulation of Ne-(carboxymethyl)lysine and expression of vascular endothelial growth factor in the eyes with non-proliferative diabetic retinopathy (p < 0.01) and proliferative diabetic retinopathy (p < 0.05).

Aged↗
PubMed1997

Ventilation/perfusion ratios and simultaneous dual-radionuclide single-photon emission tomography with krypton-81m and technetium-99m macroaggregated albumin.

To date, there has been neither a good method to clarify the three-dimensional distribution of pulmonary ventilation/perfusion (V. A/Q.) ratios, nor a convenient way to assess V.A/Q. inequality. The purpose of this study was to develop a functional image of pulmonary V.A/Q. ratios based on data acquired with simultaneous dual-radionuclide single-photon emission tomography (SPET) and to assess V.A/Q. unevenness through the V.A/Q. histogram in patients with various pulmonary diseases. Dual-radionuclide SPET was performed with technetium-99m macroaggregated albumin (MAA) and krypton-81m, with the patient in the supine position. After correction for linear cross-talk, the total acquisition counts of both radionuclides were equalized. The V.A/Q. ratio, which was calculated in each pixel by dividing the 81mKr count by the 99mTc-MAA count, was expressed as a V.A/Q. image. A histogram of the pixel number plotted against the V.A/Q. ratios was then produced and its centre of weight (CW) and standard deviation (SD) determined. Ten healthy volunteers and 46 patients [seven with pulmonary vascular disease (PVD), nine with pulmonary emphysema (PE), 18 with bronchogenic carcinoma and 12 with miscellaneous diseases] participated in this study. In normal volunteers, V.A/Q. ratios were generally even, but were slightly lower in dorsal regions. Patients with PVD had lobar and/or segmental areas with a high V.A/Q. ratio. Low V.A/Q. areas extended widely in patients with PE. Bronchogenic carcinoma exceeding 3 cm in diameter was detected as a very low V. A/Q. area. The SD of V.A/Q. ratios had a significant positive correlation both with A-aDO2 (r=0.64, P<0.001) and with cigarette smoking history (r=0.72, P<0.001). It is concluded that the V.A/Q. ratio image produced with simultaneous dual-radionuclide SPET using 99mTc-MAA and 81mKr is a unique and simple method for demonstrating the three-dimensional distribution of V.A/Q. ratios. The unevenness of V.A/Q. distribution can be assessed through the SD of the V.A/Q. histogram.

Adult↗
PubMed1997

[Increased serum concentration of myosin heavy chain in aortic dissection: discussion of 2 cases].

Despite the availability of diagnostic modalities such as transesophageal echocardiography, computed tomography or magnetic resonance imaging up to 30% of patients with acute aortic dissection remain undiagnosed before death. A novel immunoassay of serum smooth muscle myosin heavy chain was recently developed as a potential diagnostic tool for the detection of aortic dissection. The immunoassay was applied in two patients with an acute chest pain syndrome but no initial clinical suspicion of aortic disease. In both patients myocardial ischemia was ruled out by laboratory, electrocardiographic and echocardiographic examinations. In the first patient both dilation of the aorta and long-standing arterial hypertension were known; however, it was not before 48 h until dissection was suspected and a spiral-CT was performed demonstrating a localized ascending aortic dissection. At this time (48 h after onset of symptoms) the smooth muscle myosin heavy chain concentration in the serum was close to normal. In the other patient there was neither a suggestive history nor any clinical sign of aortic dissection. Widening of the abdominal aortic wall on an ultrasound examination was the key to the incidental diagnosis of a clinically unsuspected type B dissection. The serum test 12 h after onset of pain revealed elevated (diagnostic) serum levels of smooth muscle myosin heavy chains. Both cases exemplify important gaps in the diagnostic strategy for the detection of acute aortic dissection. A novel immunoassay for smooth muscle myosin heavy chains provides rapid and reliable diagnostic information especially in patients without clinically suspected aortic dissection and may avoid limitations in the diagnostic work-up of patients with acute aortic disease, if used early in the evaluation of patients with chest pain syndromes.

Aged↗
PubMed1997

Renal tubular acidosis and osteopetrosis with carbonic anhydrase II deficiency: pathogenesis of impaired acidification.

Renal tubular acidosis with osteopetrosis is an autosomal recessive disorder due to deficiency of carbonic anhydrase II (CAII). A 3.5-year-old Egyptian boy with osteopetrosis and cerebral calcification has a persistent normal anion gap type of metabolic acidosis (plasma pH 7.26) and a mild degree of hypokalemia. A baseline urine pH was 7.0; ammonium (NH4+) excretion was low at 11 mumol/min per 1.73 m2; fractional excretion of bicarbonate HCO3 (FEHCO3) was high at 9% when plasma HCO3 was 20 mmol/l; citrate excretion rate was high for the degree of acidosis at 0.35 mmol/mmol creatinine. Intravenous administration of sodium bicarbonate led to a urine pH of 7.6, a FEHCO3 of 14%, a urine-blood PCO2 difference of 7 mmHg, NH4+ excretion fell to close to nil, and citrate excretion remained at 0.38 mmol/mmol creatinine. Intravenous administration of arginine hydrochloride caused the urine pH to fall to 5.8, the FEHCO3 to fall to 0, the NH4+ excretion rate to rise to 43 mumol/min per 1.73 m2, and citrate excretion to fall to < 0.01 mmol/mmol creatinine. These results show that our patient had a low rate of NH4+ excretion, a low urine minus blood PCO2 difference in alkaline urine, and a low urinary citrate excretion, but only when he was severely acidotic. He failed to achieve a maximally low urine pH. These findings indicate that his renal acidification mechanisms were impaired in both the proximal and distal tubule, the result of his CAII deficiency.

Acidosis, Renal Tubular↗
PubMed1997

Pulmonary expression of vascular endothelial growth factor and myosin isoforms in rats with congenital diaphragmatic hernia.

Abnormalities of the pulmonary vasculature are well documented in cases of congenital diaphragmatic hernia (CDH). Vascular endothelial growth factor (VEGF), an angiogenic factor, is a recently described endothelial cell-specific growth factor. Myosin heavy chain (MHC) isoforms such as SMemb, SM1 and SM2 are important molecular markers used to study vascular smooth muscle cell differentiation. SMemb is predominantly expressed in immature smooth muscle cells (SMC), and SM2 is expressed in mature SMCs. The authors investigated the expression of VEGF and SMC differentiation in pulmonary vessels in CDH rat lungs and in controls. The lungs of nitrofen-induced CDH rat fetuses (n = 16, gestational age 16, 18, 20, and 22 days) were stained immunohistochemically using antibodies against VEGF, SMemb and SM2, while alpha-actin was used as a general marker of vascular smooth muscle cells. In the CDH group VEGF expression was negative in pulmonary vessels before birth, and in the control group VEGF was positive in smooth muscle cells in vessel walls from 20 days both in vessels at the hilum and in pulmonary parenchyma. In both control and CDH groups, SMemb expression was positive from 16 days' gestation. SM2 expression was negative in vessel walls during the prenatal period in both groups. Alpha-actin was localized in both lungs obtained from control and CDH groups in the lung hilum from 16 days and around peripheral vessels from 18 days. Differences in vascular smooth muscle cell differentiation were not observed between control and CDH lung. These findings suggest that differences in pulmonary vascular development exist between control and CDH rats for VEGF expression, and maturational differences in smooth muscle cell differentiation are not present. This role of altered endothelial cell growth might be related to the different pulmonary vascular reactivity present in CDH lungs.

Animals↗
PubMed1997

Proliferation of smooth muscle cells in acute allograft vascular rejection.

OBJECTIVES: To determine whether immune injury during acute cardiac rejection induces phenotypic modulation of arterial smooth muscle cells and lesion formation, we studied the expression of embryonic myosin heavy-chain isoform and degrees of intimal proliferation in aortas and coronary arteries of allografted rabbit hearts. Modulation of phenotype in arterial smooth muscle cells during acute vascular injury is a widely reported phenomenon, and proliferation and migration of medial smooth muscle cells contribute to development of intimal hyperplasia of arteries in response to immune injury. METHODS: Rabbit hearts were heterotopically transplanted to the neck without immunosuppression. Hearts were harvested at 2, 5, 7, and 10 days after transplantation. Proliferation of smooth muscle cells was assessed by bromodeoxyuridine labeling. Staining for immunohistochemical indicators was done with use of monoclonal antibodies that recognize T lymphocytes and all types of smooth muscle cells (SM1), adult type of smooth muscle cells (SM2), and embryonic myosin heavy-chain isoform. Intimal thickening and luminal narrowing were assessed with a computer-assisted video image analysis system. RESULTS: Intimal thickening and luminal narrowing in aortas and coronary arteries gradually increased in a time-dependent manner. The neointima thus formed consisted of proliferating smooth muscle cells positive for both SM1 and embryonic myosin heavy-chain isoform and massive T lymphocyte accumulation. Intimal proliferation was more prominent in aortas and large epicardial coronary arteries than in the intramyocardial small coronary arteries. CONCLUSIONS: These findings suggest that allogeneic immune injury facilitates phenotypic modulation of smooth muscle cells, which may contribute to subsequent transplantation-associated atherosclerosis.

Animals↗
PubMed1997

Decrease in myocardial polyamine concentration in rats with myocardial infarction.

Cardiac polyamines are thought to protect the myocardium against harmful stimuli and to be regulated by sympathetic nerve activation. In the present study, polyamines concentrations in non-infarcted myocardium were investigated. Myocardial polyamines contents decreased significantly in the non-infarcted regions by day 3 in rats with myocardial infarction compared with sham-operated rats and with the untreated control rats. The cardiac catecholamine concentration decreased by day 1 after myocardial infarction. Myocardial ornithine decarboxylase activity also decreased in the non-infarcted regions; suggesting that the decrease in cardiac polyamines contents relate to an insufficiency of the ornithine decarboxylase activity in rats with myocardial infarction. These results suggest that the decrease in polyamines concentrations after myocardial infarction is associated with functional sympathetic nerve denervation and that the vulnerability of the heart after myocardial infarction may be due to a decrease in polyamine concentrations in the non-infarcted region.

Animals↗
PubMed1997

Idiopathic membranous nephropathy in the elderly: a comparative study.

This is a retrospective study of 74 elderly patients (60 years of age or older) with idiopathic membranous nephropathy. They represented 23% of the total of 323 cases of idiopathic membranous nephropathy who presented during the 19-year review period. The mean age of these patients was 67 years versus 41 in the younger-onset group. The median presenting serum creatinine in the elderly group was higher (1.3 mg/dL v 1.0 mg/dL, P < 0.001), and the median creatinine clearance calculated by Cockcroft-Gault to correct for age, gender, and weight was lower (55 mL/min v 95 mL/min, P < 0.0001). The incidence of chronic renal insufficiency, defined as a creatinine clearance of less than 50 mL/min, was significantly worse in the elderly after a mean observation period of 47 months (59% v 25%, P < 0.0001) although end-stage renal failure (ESRF) was not (18% v 12%). The rate of change of renal function, however, as measured by the time to doubling of baseline creatinine, was similar in both groups, as was the complete remission rate. Forty-six percent of patients (33 of 74) in the elderly group received treatment: steroids alone (76%), immunosuppression drugs alone (9%), or a combination (15%). There was no benefit noted in terms of complete remission rate or incidence of chronic renal insufficiency. In summary, more elderly patients with membranous nephropathy develop chronic renal insufficiency, but this appears to be related to their age and decreased functional reserve, because the rate of decline in renal function after initiation of the disease is no different than in the younger age-group. The data also indicate that an accurate assessment of renal function in this older age-group requires an estimated or calculated creatinine clearance, given the inaccuracy when only serum creatinine is used. There was no evidence of improved outcome with prednisone therapy, and in view of the increased incidence of complications associated with this drug in the elderly as well as the decreased reserve at presentation, we suggest that routine steroid treatment of these patients should not be undertaken.

Adolescent↗
PubMed1997

Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM), the most common cause of sudden death in the young, is an autosomal dominant disease characterized by ventricular hypertrophy accompanied by myofibrillar disarrays. Linkage studies and candidate-gene approaches have demonstrated that about half of the patients have mutations in one of six disease genes: cardiac beta-myosin heavy chain (c beta MHC), cardiac troponin T (cTnT), alpha-tropomyosin (alpha TM), cardiac myosin binding protein C (cMBPC), ventricular myosin essential light chain (vMLC1) and ventricular myosin regulatory light chain (vMLC2) genes. Other disease genes remain unknown. Because all the known disease genes encode major contractile elements in cardiac muscle, we have systematically characterized the cardiac sarcomere genes, including cardiac troponin I (cTnI), cardiac actin (cACT) and cardiac troponin C (cTnC) in 184 unrelated patients with HCM and found mutations in the cTnI gene in several patients. Family studies showed that an Arg145Gly mutation was linked to HCM and a Lys206Gln mutation had occurred de novo, thus strongly suggesting that cTnI is the seventh HCM gene.

Actins↗
PubMed1997

Change of plasma 1,5-anhydro-D-glucitol levels after the onset of diabetes in spontaneous diabetes prone BB/Wor/(/)Tky rats.

Plasma 1,5-anhydro-D-glucitol (AG) is a marker of the diabetic state and also reflects the glycosuria induced by hyperglycemia but not by renal pathology. To investigate the benefits of the AG determination in order to diagnose diabetes in BB/Wor/(/)Tky rats, AG was measured in non-diabetic (n = 104) and diabetic (n = 113) BB/Wor/(/)Tky rats. AG was significantly higher in non-diabetic rats than in diabetic rats (25.2 +/- 9.3 vs 4.1 +/- 7.4 micrograms/ ml, mean +/- SD, p < 0.001). The best cut-off level for AG (8.5 micrograms/ml) was highly specific (100%) for ruling out diabetes and fairly sensitive (82.3%) to detect diabetes. Based on the AG cut-off levels, 90% of false-negative diabetic rats (18/20) were observed within 4 days after the onset of diabetes, which corresponded to 38.3% in diabetic rats (18/47) at that time. The false-negative diabetic rats and positive rats could be effectively distinguished based on the cumulative points given according to the urinary glucose after the onset of diabetes. 1 point for each cross [+] indicating glycosuria using the Testape, i.e. 2 or less points false negative and 4 or more points for diabetic rats in the first 4 days. In conclusion, there is a close inverse relation between the level of plasma AG and the amount of glycosuria detected just after the onset of overt diabetes in BB/Wor/(/)Tky rats.

Animals↗
PubMed1997

Extracellular components implicated in the stationary organization of the actin cytoskeleton in mesophyll cells of Vallisneria.

In mesophyll cells of Vallisneria gigantea Graebner, an aquatic angiosperm, the association of the plasma membrane with the cell wall at the end wall has been reported to be indispensable for the mechanism that maintains the stationary organization of the bundles of microfilaments (MFs) [Masuda et al. (1991) Protoplasma 162: 151]. To identify putative extracellular components that might play a crucial role in this mechanism, we examined the effects of two exogenously applied synthetic hexapeptides, GRGDSP and ARYDEI, which include an RGD and an RYD motif, respectively. The RGD motif is known as a recognition site in molecules required for adhesion to the substratum at sites of focal contacts. Within 24 h, both peptides (at concentrations of 1-15 mM) induced extremely abnormal patterns of cytoplasmic streaming, as well as the striking disruption of the arrangement of bundles of MFs. GRGESP and ARYEEI peptides, used as controls, had no detectable effects. Immunofluorescence microscopy revealed that polyclonal antibodies against the ARYDEI peptide bound to the cell walls of mesophyll cells while a preimmune serum did not. Western blotting analysis demonstrated that the antibodies recognized polypeptides of 54 kDa and 27 kDa in an extract of total proteins from the leaves of Vallisneria. The results suggest that some extracellular proteins(s), with a conserved RGD or RYD motif in its amino acid sequence, might be involved in the maintenance of the stationary organization of the bundles of MFs.

Actin Cytoskeleton↗
PubMed1997

Chronic blockade of nitric oxide synthesis increases urinary endothelin-1 excretion.

OBJECTIVES: Our objective was to determine the effect of nitric oxide (NO) inhibition on renal synthesis of endothelin-1 (ET-1) in vivo. DESIGN AND METHODS: Rats were administered 500 mg/l NG-nitro-L-arginine methyl ester (L-NAME) in their drinking water or its vehicle for 2 weeks (2W-L-NAME, n = 10; 2W-CONT, n = 10) or for 6 weeks (6W-L-NAME, n = 13; 6W-CONT, n = 11). We measured the levels of albumin, NO metabolites and ET-1 both in their blood and in 24 h urine samples, and determined the expression of preproET-1 messenger RNA in the renal cortex and the inner medulla. We also examined renal histology. RESULTS: L-NAME administration for 6 weeks reduced NO metabolites both in serum (21.5 versus 3.66 nmol/ml in 6W-CONT) and in urine (5.72 versus 22.53 nmol/24 h in 6W-CONT), raised the systolic blood pressure (228 versus 162 mmHg in 6W-CONT), and the increased urinary excretion of albumin (24.29 +/- 11.66 versus 0.60 +/- 0.08 mg/day in 6W-CONT) and of ET-1 (112.0 +/- 38.3 versus 35.8 +/- 4.4 pg/day in 6W-CONT). There were no significant differences between the plasma levels of ET-1 in the control and L-NAME groups. Expression of preproET-1 messenger RNA increased in the renal cortex but not in the inner medulla in the 6W-L-NAME group. Bleeding and marked arteriolar narrowing were observed in the renal cortex of the 6W-L-NAME group. CONCLUSIONS: Prolonged inhibition of NO synthesis increases urinary excretion of ET-1 and albumin without having any effect on plasma ET-1 levels. These results do not support the hypothesis that NO plays an inhibitory role in the regulation of ET-1 in the systemic circulation, although it is possible that such a role could exist in renal tissue. However, in view of the albuminuria, a more likely explanation is that increased urinary ET-1 is secondary to L-NAME-induced renal hyperfiltration injury.

Albuminuria↗
PubMed1997

Inflammatory cytokines cause coronary arteriosclerosis-like changes and alterations in the smooth-muscle phenotypes in pigs.

We recently developed a porcine model in which chronic, local treatment with interleukin-1 beta (IL-1 beta) causes coronary arteriosclerosis-like changes and hyperconstrictive responses. This study was designed to examine whether or not other major inflammatory cytokines [tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 alpha (IL-1 alpha) might also cause similar coronary responses and whether those responses are associated with alterations in the smooth-muscle phenotypes. A segment of the porcine coronary artery was aseptically wrapped with cotton mesh, absorbing IL-1 beta, TNF-alpha, and IL-1 alpha. Two weeks after the operation, coronary arteriography showed the development of mild stenotic lesions at the cytokine-treated sites, where hyperconstrictive responses were repeatedly induced by intracoronary serotonin or histamine. Histologically mild intimal thickening was noted at those cytokine-treated sites. Immunostaining and immunoblotting demonstrated that all three myosin heavy chain isoforms, SM1, SM2 (smooth-muscle type), and SMemb (nonmuscle type), were noted in the normal coronary segments, whereas in the segments treated with inflammatory cytokines, SM1 and SM2 were markedly reduced, and only SMemb was noted. These results indicate that inflammatory cytokines all have a similar ability to induce coronary arteriosclerosis-like changes and hyperconstrictive responses, which are associated with alterations in smooth-muscle phenotypes toward dedifferentiation.

Animals↗
PubMed1997

Depressed contractile response to exercise in diabetic patients in the absence of cardiovascular disease: relationship to adrenergic cardiac dysinnervation.

We investigated the presence of subclinical left ventricular dysfunction by determining left ventricular diastolic filling at rest and the left ventricular ejection fraction (LVEF) response to exercise with radionuclide angiography. The subjects were 40 patients with non-insulin-dependent diabetes who showed no evidence of cardiovascular disease based on clinical findings, electrocardiography and 201T1 perfusion scintigraphy. We also used 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy to investigate whether subclinical left ventricular abnormalities were related to adrenergic cardiac dysinnervation. The change on LVEF in response to exercise (delta LVEF) was < 5% in 1 of 20 normal controls and in 22 of 40 diabetic patients (P < 0.01). The peak filling rate was within normal limits in all controls but was abnormal (< 2.3 EDV s-1) in 5 of 40 patients (P = N.S.). Of the clinical and scintigraphic variables that correlated significantly with delta LVEF, the heart-to-mediastinum 123I-MIBG uptake ratio on the late planar images was the most important and independent predictor. Nearly half of the patients with non-insulin-dependent diabetes without apparent cardiovascular disease exhibited a depressed LVEF response to exercise. This subnormal response was significantly associated with diminished myocardial 123I-MIBG uptake, suggesting a causal relationship.

3-Iodobenzylguanidine↗