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1.
EuroIntervention ; 9(9): 1050-6, 2014 Jan 22.
Article in English | MEDLINE | ID: mdl-24457276

ABSTRACT

AIMS: Nicorandil, an ATP sensitive potassium channel opener, may reduce the incidence of microvascular dysfunction after percutaneous coronary intervention (PCI) by dilating coronary resistance vessels. The aim of the study was evaluation of the impact of the administration of intravenous nicorandil on measuring the index of microcirculatory resistance (IMR) in PCI to patients with stable angina pectoris (SAP). METHODS AND RESULTS: Intravascular ultrasound (IVUS), fractional flow reserve (FFR), IMR and blood examination (CK-MB), cardiac troponin I (cTnI) immediately post-PCI (and 24 hours later) were performed in 62 consecutive patients with SAP undergoing PCI. FFR and IMR were measured simultaneously with a single coronary pressure wire. IMR was defined as Pd/coronary flow (or Pd* mean transit time) at peak hyperaemia. Patients were randomised to the control (n=29), or nicorandil group (n=33). In the nicorandil group, nicorandil was intravenously administered as a 6 mg bolus injection just before PCI and as a constant infusion at 6 mg/hour for 24 hours thereafter. All volumetric IVUS parameters and FFR were similar between the two groups both pre- and post-PCI. However, IMR immediately post-PCI and cTnI 24 hours post-PCI were significantly higher in the control group compared to the nicorandil group (IMR: 25.4±12.1 vs. 17.9±9.1 units, and cTnI: 0.21±0.13 vs. 0.12±0.08 ng/mL, for control vs. nicorandil). The incidence for cTnI elevation more than fivefold the normal range (>0.20 ng/mL) was significantly larger in the control group than in the nicorandil group (41% vs. 12%, p<0.01). Additionally, the control group showed a closer correlation between plaque volume reduction during stenting as assessed by volumetric IVUS, and cTnI elevation than the nicorandil group (r=0.55 vs. 0.42, p<0.001 for control vs. nicorandil). CONCLUSIONS: In patients undergoing successful coronary stenting for stable angina, administration of nicorandil is associated with reduced microvascular dysfunction induced by PCI.


Subject(s)
Angina, Stable/surgery , Antihypertensive Agents/therapeutic use , Coronary Circulation/drug effects , Microcirculation/drug effects , Nicorandil/therapeutic use , Percutaneous Coronary Intervention , Vascular Resistance/drug effects , Aged , Aged, 80 and over , Angina Pectoris/complications , Angina Pectoris/drug therapy , Antihypertensive Agents/administration & dosage , Coronary Vessels/drug effects , Coronary Vessels/surgery , Female , Humans , Male , Microcirculation/physiology , Middle Aged , Nicorandil/administration & dosage , Percutaneous Coronary Intervention/methods , Stents , Treatment Outcome
2.
Int J Cardiovasc Imaging ; 26(3): 285-92, 2010 Mar.
Article in English | MEDLINE | ID: mdl-19960263

ABSTRACT

The purpose of this study was to examine the usefulness of (11)C-acetate positron emission tomography (PET) for assessing the efficacy of cardiac resynchronization therapy (CRT). Enrolled in this study were 20 patients with severe heart failure. All patients underwent 11C-acetate PET within 1 week after CRT. The oxygen consumption was measured by the monoexponential clearance rate of 11C-acetate (K(mono)) for both CRT-off and -on. Cardiac efficiency (CE) was determined using the concept of the work metabolic index (WMI). WMI was calculated as WMI = (stroke volume index) x (systolic blood pressure) x (heart rate)/K(mono). The patients were divided into two groups: 14 patients with improved CE (from 5.27 +/- 0.91 to 6.77 +/- 1.12) and 6 patients with deteriorated CE (from 5.35 +/- 0.92 to 4.86 +/- 0.84) by CRT-on. K(mono) decreased from 0.053 +/- 0.006 to 0.046 +/- 0.003 by CRT-on in the improved CE group (p = 0.028), but increased from 0.049 +/- 0.006 to 0.050 +/- 0.006 in the deteriorated-CE group (p = 0.036). Stroke volume index, systolic blood pressure, and heart rate did not change by CRT-on for either group. At the one-year follow-up, there were significantly higher rates of major cardiac adverse events in the deteriorated-CE group than in the improved-CE group (p = 0.032). Therefore, the improvement of CE, as assessed by 11C-acetate PET in the early period after CRT, is produced by the decrease in oxygen consumption in patients showing good responses to CRT. The decrease in oxygen consumption in the early period after CRT is thus a useful marker for predicting a good clinical outcome after CRT.


Subject(s)
Acetates , Carbon , Cardiac Pacing, Artificial , Heart Failure/diagnostic imaging , Heart Failure/therapy , Myocardium/metabolism , Oxygen Consumption , Positron-Emission Tomography , Radiopharmaceuticals , Aged , Aged, 80 and over , Blood Pressure , Cardiac Pacing, Artificial/adverse effects , Chi-Square Distribution , Disease-Free Survival , Echocardiography, Doppler , Energy Metabolism , Female , Heart Failure/metabolism , Heart Failure/physiopathology , Heart Rate , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Predictive Value of Tests , Recovery of Function , Severity of Illness Index , Stroke Volume , Time Factors , Treatment Outcome
3.
Hypertens Res ; 31(7): 1307-13, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18957800

ABSTRACT

The purposes of this study were to examine the effects of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) on myocardial flow reserve in patients with acute myocardial infarction (AMI) in the subacute phase using oxygen-15 positron emission tomography (PET) and to elucidate the relationship between the myocardial flow reserve and remodeling in the chronic phase. Sixty patients who had been treated with coronary angioplasty within 12 h after the onset of AMI were enrolled. Patients were divided into an enalapril (ACEI) group and a candesartan (ARB) group. The myocardial flow reserve was measured by oxygen-15 water PET in the subacute phase from the 20th to the 30th day after the onset of AMI. Left ventriculography was performed to measure the left ventricular ejection fraction in the chronic phase about 6 months after the onset. Ten patients (33%) in the enalapril group and 4 patients (13%) in the candesartan group stopped taking their respective medications within a few days of starting, because of side effects such as cough or hypotension. Thus, the prevalence of medication intolerance was higher in the enalapril group. The myocardial flow reserve in the subacute phase and the left ventricular ejection fraction in the chronic phase were lower in the enalapril group (2.08 +/- 0.30 and 42 +/- 6%) than in the candesartan group (2.25 +/- 0.20 and 49 +/- 5%) (p < 0.05). The myocardial flow reserve significantly correlated with the left ventricular ejection fraction in all patients (r = 0.45, p < 0.01). The myocardial flow reserve assessed by PET in the subacute phase after AMI was found to be related to left ventricular remodeling in the chronic phase.


Subject(s)
Coronary Circulation , Myocardial Infarction/physiopathology , Oxygen Radioisotopes , Positron-Emission Tomography/methods , Ventricular Remodeling , Adult , Aged , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Female , Humans , Male , Middle Aged , Myocardial Infarction/drug therapy , Stroke Volume , Ventricular Function, Left
4.
Circ J ; 72(11): 1900-3, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18787291

ABSTRACT

A 65-year-old man with a history of coronary artery bypass grafting was admitted because of severe heart failure. Echocardiography showed diffuse severe hypokinesis of the left ventricle (ejection fraction 25%) and severe mitral regurgitation caused by tethering of the leaflet secondary to left ventricular (LV) dilation. He underwent mitral valve annuloplasty and LV papillary muscle imbrication, but postoperative sustained ventricular tachycardia developed and echocardiography showed ventricular dyssynchrony with a long septal-to-posterior wall motion delay (>130 ms). Cardiac resynchronization therapy (CRT) was performed using a biventricular pacing system with an implantable cardioverter defibrillator, but biventricular pacing prolonged the QRS duration from 130 to 160 ms, so (11)C-acetate positron emission tomography was performed to evaluate the CRT. During biventricular pacing, myocardial oxidative consumption decreased by 15% and cardiac efficiency increased by 33%. The plasma brain natriuretic peptide level, which was 9,500 pg/ml preoperatively, decreased to 173 pg/ml just before discharge from hospital.


Subject(s)
Electric Countershock , Heart Failure/metabolism , Mitral Valve Insufficiency/metabolism , Myocardium/metabolism , Oxygen Consumption , Positron-Emission Tomography , Ventricular Remodeling , Aged , Echocardiography , Heart Failure/diagnostic imaging , Humans , Male , Mitral Valve/diagnostic imaging , Mitral Valve/metabolism , Mitral Valve Insufficiency/diagnostic imaging , Natriuretic Peptide, Brain/blood , Oxidation-Reduction , Radiography
6.
J Nucl Med ; 47(10): 1571-6, 2006 Oct.
Article in English | MEDLINE | ID: mdl-17015889

ABSTRACT

UNLABELLED: 67Ga scintigraphy has been used for years in sarcoidosis for diagnosis and the extent of the disease. However, little information is available on the comparison of 18F-FDG PET and 67Ga scintigraphy in the assessment of sarcoidosis. The purpose of this study was to compare the uptake of 18F-FDG and 67Ga in the evaluation of pulmonary and extrapulmonary involvement in patients with sarcoidosis. METHODS: Eighteen patients with sarcoidosis were examined. 18F-FDG PET was performed at 1 h after injection of 185-200 MBq 18F-FDG. 67Ga whole-body planar and thoracic SPECT images were acquired 72 h after injection of 111 MBq 67Ga. We evaluated 18F-FDG and 67Ga uptake visually and semiquantitatively using standardized uptake values (SUVs) and the ratio of lesion to normal lumbar spine (L/N ratio), respectively. The presence of pulmonary and extrapulmonary lesions was evaluated histopathologically or by the radiologic findings. RESULTS: Five patients had only pulmonary lesions, 12 patients had both pulmonary and extrapulmonary lesions, and 1 patient had only an extrapulmonary lesion. Both 67Ga planar and SPECT images detected 17 of 21 (81%) clinically observed pulmonary sites. The mean +/- SD of the L/N ratio was 1.97 +/- 1.09. 67Ga planar images detected 15 of 31 (48%) clinically observed extrapulmonary sites. The mean +/- SD of the L/N ratio was 1.17 +/- 0.33. 18F-FDG PET detected all 21 (100%) clinically observed pulmonary sites. The mean +/- SD of the SUV was 7.40 +/- 2.48. 18F-FDG PET detected 28 of 31 (90%) clinically observed extrapulmonary sites. The mean +/- SD of the SUV was 5.90 +/- 2.75. CONCLUSION: The results of this clinical study suggest that 18F-FDG PET can detect pulmonary lesions to a similar degree as 67Ga scintigraphy. However, 18F-FDG PET appears to be more accurate and contributes to a better evaluation of extrapulmonary involvement in sarcoidosis patients.


Subject(s)
Fluorodeoxyglucose F18 , Radiopharmaceuticals , Sarcoidosis/pathology , Adult , Aged , Aged, 80 and over , Female , Gallium Radioisotopes , Humans , Lung/diagnostic imaging , Lung/pathology , Lung Diseases/diagnostic imaging , Lung Diseases/pathology , Male , Middle Aged , Positron-Emission Tomography , Sarcoidosis/diagnostic imaging , Tomography, Emission-Computed
7.
Biochem Biophys Res Commun ; 327(1): 124-9, 2005 Feb 04.
Article in English | MEDLINE | ID: mdl-15629439

ABSTRACT

Hypophosphatasia (HOPS) is a clinically heterogeneous heritable disorder characterized by defective skeletal mineralization, deficiency of tissue-nonspecific alkaline phosphatase (TNSALP) activity, and premature loss of deciduous teeth. To date, various mutations in the TNSALP gene have been identified. Especially, A115V located in exon 5 has been detected in a Japanese patient with severe periodontitis and adult-type HOPS. In this study, we have characterized the protein translated from the mutant A115V gene. Wild-type and A115V mutant-type TNSALP cDNA expression vector pcDNA3 have been constructed and transfected to COS-1 cells by lipofectin technique. After 48-h transfection, the cells were subjected to assay ALP activity. In order to identify possible dominant effect of the mutation, we performed co-transfections of wild-type and mutated cDNA, and evaluated the residual activities of each mutation. Detection of TNSALP synthesized by COS-1 cells transfected with the wild- or the mutated-type was also performed by using an immunofluorescent method. ALP activity of cell transfected with the mutant cDNA (A115V) plasmid after 48-h transfection exhibited 0.399+/-0.021 U/mg. As the enzymatic activity of the wild type was taken as 100%, the value of the mutant was estimated as 16.9%. When co-transfected this mutant showed no inhibition of the wild-type enzyme. TNSALP in COS-1 cells with transfected with the mutant exhibited strong fluorescence at the surface of cells as wild-type. This study indicated that the mutant (A115V) TNSALP gene produced the defective ALP enzyme and it could be recessively transmitted and be a disease-causing mutation of the adult-type hypophosphatasia.


Subject(s)
Alanine/genetics , Alkaline Phosphatase/genetics , Alkaline Phosphatase/metabolism , Hypophosphatasia/enzymology , Hypophosphatasia/genetics , Mutation/genetics , Alanine/metabolism , Animals , COS Cells , Chlorocebus aethiops , DNA, Complementary/genetics , Female , Gene Expression Regulation, Enzymologic , Humans , Hypophosphatasia/pathology , Immunohistochemistry , Middle Aged , RNA, Messenger/genetics , RNA, Messenger/metabolism , Transfection
8.
J Med Dent Sci ; 51(1): 67-74, 2004 Mar.
Article in English | MEDLINE | ID: mdl-15137467

ABSTRACT

Hypophosphatasia (HOPS) is a heritable disorder characterized by defective skeletal mineralization, deficiency of tissue-nonspecific alkaline phosphatase (TNSALP) activity and premature loss of deciduous teeth. In a previous study, we detected missense mutations in the TNSALP gene of a patient who inherited the F310L and the V365I mutation with severe periodontitis and childhood HOPS. Expression of the mutant V365I TNSALP gene using COS-1 cells demonstrated that the protein translated from the mutant had undetectable ALP activity. In the present study, we characterized another ALP enzyme translated from the mutant F310L and compared it with the ALP in the patient's serum. The COS-1 cells transfected with the F310L and co-transfected with F310L and V365I (F310L/V365I) exhibited levels of 67% and 31%, respectively, with the enzymatic activity of the wild-type taken as 100%. In the thermostability test, TNSALPs in the COS-1 cells transfected with the mutant F310L or F310L/V365I were significantly more heat labile compared with that of the wild-type. Moreover, ALP from the patient's serum was also more heat labile than normal ALP. These results suggest that the protein translated from the mutant F310L, in addition to the mutant V365I, may be responsible for the expression of symptoms of the childhood-type HOPS.


Subject(s)
Alkaline Phosphatase/genetics , Hypophosphatasia/enzymology , Mutation/genetics , Adult , Alkaline Phosphatase/blood , Animals , COS Cells , Chlorocebus aethiops , Genes, Recessive/genetics , Hot Temperature , Humans , Hypophosphatasia/genetics , Male , Mutagenesis, Site-Directed/genetics , Periodontitis/genetics , Protein Biosynthesis , Reverse Transcriptase Polymerase Chain Reaction , Transfection
9.
J Bone Miner Res ; 17(11): 1945-8, 2002 Nov.
Article in English | MEDLINE | ID: mdl-12412800

ABSTRACT

Hypophosphatasia (HOPS) is a clinically heterogeneous heritable disorder characterized by defective skeletal mineralization, deficiency of tissue-nonspecific alkaline phosphatase (TNSALP) activity, and premature loss of deciduous teeth. The gene for TNSALP is located on chromosome 1p34-36.1 and consists of 12 exons and 11 introns. In our previous study, we found the novel point mutations (G1144A and T979C) from the genomic TNSALP gene of a patient with childhood HOPS. In this study, we have characterized the protein translated from the mutant G1144A gene. Wild-type and G1144A mutant-type TNSALP cDNA expression vector pcDNA3 have been constructed and transfected to COS-1 cells by lipofectin technique. After 48-h or 72-h transfection, cells were collected and homogenized using polytron homogenizer. After centrifugation at 10,000 g for 10 minutes, the supernatant was assayed. ALP activity was determined with 10 mM of p-nitrophenylphosphate as a substrate in 100 mM of 2-amino-2-methyl-1,3-propanediol-HCl buffer containing 5 mM of MgCl2. ALP activity of cells transfected with the mutant cDNA (G1144A) plasmid after 48-h or 72-h transfection exhibited 0.063 +/- 0.012 U/mg and 0.054 +/- 0.012 U/mg, respectively. As the enzymatic activity of the wild type was taken as 100%, the value of the mutant was estimated as 2.7% and 1.7%, respectively. These values were not significantly different from those found with mock-transfected cells, that is, 2.5% and 1.5%, respectively. This study indicated that the mutation (G1144A) produced the inactive ALP enzyme and would be a disease-causing mutation of the childhood-type HOPS.


Subject(s)
Alkaline Phosphatase/genetics , Alkaline Phosphatase/metabolism , Hypophosphatasia/enzymology , Hypophosphatasia/genetics , Adult , Animals , Buffers , COS Cells , DNA, Complementary , Enzyme Activation/genetics , Genetic Vectors , Humans , Magnesium Chloride/chemistry , Male , Nitrophenols/metabolism , Organ Specificity , Organophosphorus Compounds/metabolism , Point Mutation , Transfection
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