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Biomedical subjects

G Notohamiprodjo

Publications and source records attributed to G Notohamiprodjo.

At least 19 recordsLinked to original sources
PubMed1999

Improvement in coronary flow reserve determined by positron emission tomography after 6 months of cholesterol-lowering therapy in patients with early stages of coronary atherosclerosis.

BACKGROUND: Early stages of coronary atherosclerosis are characterized by a mainly functional impairment of coronary vasodilator capacity under the impact of such risk factors as hypercholesterolemia. The goal of this study was to determine whether 6-month cholesterol-lowering therapy improves coronary flow reserve in patients with angina, reduced flow reserve despite minimally diseased coronary vessels or even normal angiogram, and mild to moderately elevated LDL levels on average. METHODS AND RESULTS: We noninvasively investigated 23 consecutive patients (18 men, 5 women; mean age, 56+/-7.6 years) with a mean LDL level of 165+/-34 mg/dL at baseline by PET for myocardial blood flow measurement with [13N]ammonia at rest and under dipyridamole stress (0.56 mg/kg) before and after lipid-lowering therapy with simvastatin for 6 months. Between baseline and the 6-month follow-up, total cholesterol concentration fell from 241+/-44 to 168+/-34 mg/dL, and the LDL level decreased from 165+/-34 to 95+/-26 mg/dL (P<0.001). Overall, coronary flow reserve increased from 2.2+/-0.6 to 2.64+/-0.6 (P<0.01). Maximal coronary flow increased significantly from 182+/-36 to 238+/-58 mL/minx100 g (P<0.001) at follow-up. Minimum coronary resistance declined significantly from 0. 51+/-0.12 to 0.40+/-0.14 mm Hg. mL-1. minx100 g (P<0.001). Concomitantly, a regression of anginal symptoms was observed in most patients. CONCLUSIONS: Our results suggest that cholesterol-lowering therapy with simvastatin may improve overall coronary vasodilator capacity assessed noninvasively by PET in patients with mild to moderate hypercholesterolemia. Consequently, intensive lipid-lowering therapy is considered a vasoprotective treatment for selected patients in very early stages of coronary atherosclerosis with the potential of preventing further disease progression.

Adult↗
PubMed1998

[Improved coronary vasodilator capacity by drug lipid lowering therapy in patients in the early stage of coronary atherosclerosis with reduced coronary reserves and moderate LDL hypercholesteremia].

BACKGROUND: An abnormal coronary flow reserve represents an early marker of impaired blood flow regulation in the natural history of coronary atherosclerosis under the impact of risk factors such as hypercholesterolemia. Our clinical investigation was aimed at assessing noninvasively the integrative coronary flow response to dipyridamole stress in 18 consecutive patients with microvascular angina, only moderately elevated LDL-cholesterol levels (168 +/- 33 mg/dl), and reduced vasodilator capacity despite normal (n = 9) or slightly abnormal (n = 9) coronary arteriograms (minimal disease with luminal irregularities and/or diameter reduction < or = 30%) before and after 6-month lipid-lowering therapy (simvastatin). METHODS: Regional and averaged myocardial blood flow were measured at rest and after dipyridamole induced vasodilation (0.56 mg/kg) using dynamic positron emission tomography (PET) and N-13 ammonia as flow tracer related to a 3-compartment kinetic model. Baseline data (mean +/- SD): 13 males, 5 females; mean age: 56 +/- 8 years; basal coronary flow: 90 +/- 22 ml/min x 100 g; after lipid intervention: 93 +/- 18 ml/min x 100 g (n.s.). Total cholesterol: 246 +/- 45 mg/dl. RESULTS AFTER 6-MONTH LIPID INTERVENTION: Total cholesterol decreased to 170 +/- 36 mg/dl (p < 0.001); mean LDL level: 97 +/- 26 mg/dl (p < 0.001). Coronary dilator capacity increased, assessed in terms of minimal coronary resistance: 0.38 +/- 0.08 vs 0.49 +/- 0.09 units at baseline (p < 0.01), myocardial blood flow under dipyridamole: 232 +/- 43 vs 186 +/- 37 ml/min x 100 g at baseline (p < 0.01), and instantaneous flow ratio: 2.6 +/- 0.7 vs 2.2 +/- 0.6 (p = 0.06). Concomitantly, a considerable regression of angina was noticed in the majority of patients. CONCLUSIONS: An improvement of the non-invasively determined integrative dipyridamole induced coronary vasodilator capacity may be achieved after 6 months by intensive lipid lowering at a very early stage of coronary atherosclerosis. Consequently, aggressive cholesterol-lowering therapy represents an antiischemic and antianginal approach suggesting, at least in part, functional reversal and probably prevention of further disease progression.

Adult↗
PubMed1998

Improvement of coronary vasodilatation capacity through single LDL apheresis.

A concomitant phenomenon of hypercholesterolemia is reduced coronary vasodilatation capacity due to disturbed endothelial function. Endothelial function can be partially or completely normalized by reducing cholesterol levels through drug therapy, but it is still unclear how rapidly this desired effect is achieved. An interval of between weeks and months has been presumed. LDL apheresis (LDL-A) is capable of achieving a high-degree LDL cholesterol reduction within hours. With positron emission tomography (PET), carried out immediately before and after LDL-A, changes in coronary reserve due to this abrupt LDL cholesterol reduction could be measured both quantitatively and non-invasively. In nine patients (six women, three men) with documented coronary artery disease and hypercholesterolemia, PET was carried out immediately before and 18-20 h after LDL-A. A reduction in LDL cholesterol (from 194 +/- 38 to 81 +/- 20 mg/dl), facilitated significant improvement in myocardial blood flow (MBF) (173 +/- 63 versus 226 +/- 79 ml/min per 100 g) after pharmacologic recruitment of coronary flow capacity (dipyridamole stress), coronary flow reserve (CFR) (1.91 +/- 0.68 versus 2.48 +/- 0.68) and minimum coronary resistance (MCR) (0.61 +/- 0.18 versus 0.43 +/- 0.16 mmHg/100 g per min per ml) within 24 h. Plasma viscosity was reduced slightly, by 6.6%. Probably for the first time, a 30% improvement in coronary vasodilatation capacity could be demonstrated quantitatively and non-invasively by PET after a single LDL-A within 24 h.

Adult↗
PubMed1998

Microanalysis and distribution of cardiac troponin I phospho species in heart areas.

Sequential phosphorylation and dephosphorylation of cTnI by the cAMP dependent protein kinase and by protein phosphatase 2A, respectively, produce the non-, mono- and bisphosphorylated species (Jaquet et al., 1995, Eur. J. Biochem. 231, 486-490). The aim of this study was to determine these forms even in small tissue samples, e.g. in biopsy probes of approximately 30 mg which would allow to define the phosphorylation state of cTnI in heart areas. In order to do so a micro isolation procedure for cTnI had to be established. cTnI is extracted from small bovine, rabbit and human heart tissue samples (30-100 mg) under special conditions avoiding dephosphorylation and is isolated by affinity chromatography on cTnC Sepharose. All three species, the bis-, mono- and dephospho cTnI, are precipitated quantitatively by acetone, then they are separated by non-equilibrium isoelectric focusing and quantified by scanning densitometry. The method presented here allows to quantify the three cTnI species reproducibly. No other phosphorylated species are detected. Truncated cTnI forms of each phospho species are found in human biopsy samples due to removal of a approximately 36 amino acid peptide from the C-terminus. In bovine, human and rabbit heart the pattern of the three cTnI phospho species is characteristic for left and right atrium, left and right ventricle and septum.

Animals↗
PubMed1998

Vascular hamartoma of the left ventricle.

Primary tumors of the heart are very rare. We report a case of a 28-year old female patient in whom a tumor of the left ventricle was first diagnosed by transthoracic echocardiography. Angiography, nuclear magnetic resonance imaging and fasting positron emission tomography with 18-fluorodesoxyglucose suggested the diagnosis of a well vascularized tumor. The tumor was subtotally excised during heart surgery under total cardiopulmonary bypass and histological examination identified a predominantly vascular hamartoma.

Adult↗
PubMed1997

Validation of the limulus amebocyte lysate (LAL) test for routine PET radiopharmaceuticals.

The kinetic turbidimetric limulus amebocyte lysate test was validated as method for detecting endotoxins in short-lived radiopharmaceutical samples. Using this method, radiopharmaceuticals can be released for administration to humans after the test, without extensive loss of radioactivity. Inhibition or enhancement on the LAL results by the product samples were examined in more detail and eliminated.

Ammonia↗
PubMed1994

Effects of temperature and sodium on myocardial and hepatocellular fatty acid uptake.

Fatty acid influx into human myocardium was studied in 15 patients during the cooling phase of cardiopulmonary bypass at myocardial temperatures of 37 degrees to 25 degrees C. The fitting of the data to a functional relation, developed in this study, revealed fatty acid influx to be a temperature-dependent saturable process corresponding to a Michaelis-Menten constant (Km) at 37 degrees C of 0.26 +/- 0.084 mumol/g, a maximal fatty acid influx velocity (Vmax) at 37 degrees C of 0.28 +/- 0.045 mumol/g per minute, activation energy for fatty acid binding to the putative carrier (E) of 23.8 +/- 5.6 kcal/mol, and a free energy for conformational change of the carrier (U) of 10.9 +/- 8.0 kcal/mol. In short-term cultured hepatocytes, Km increased in the absence of Na+ from 171 +/- 48 to 301 +/- 71 nmol/L, and Vmax of [3H]oleate decreased from 1063 +/- 69 to 847 +/- 68 pmol/min per milligram protein. The fitting of these data to a functional relation revealed a transmembrane potential-dependent component of parameters E and U to be -0.479 and -0.374 kcal/mol, respectively. It is proposed that for fatty acid influx a protonated fatty acid form is preferred that consists of a Na+ complex with the mesomeric form of nondissociated fatty acid from which Na+ and H+ are released during collision with the carrier.

Animals↗
PubMed1993

Beta-oxidation of 1-[14C]-17-[131I]-iodo-heptadecanoic acid following intracoronary injection in humans results in similar release of both tracers.

Radioiodine labelled 17-iodo-heptadecanoic acid (IHA) is used for non-invasive study of myocardial metabolism in coronary heart disease and cardiomyopathy. Yet in the interpretation of in vivo myocardial tracer kinetics, it is controversial whether the intracellular degradation of IHA or the removal of iodide across cellular membranes is the rate-limiting step in iodide release from the myocardium. In five patients undergoing coronary sinus catheterization, a mixture of about 40 kBq of [123I] NaI was injected into the left coronary artery. During the following 15-min period, frequent blood samples were taken from the aorta and the coronary sinus. In the aqueous phase of the venous blood, 14CO2 and inorganic 131I appeared nearly in parallel, with a peak time of 4-5 min. Moreover, as shown by the AV difference, there was no significant back diffusion of IHA and no significant non-specific deiodination detectable over the period of observation. There was myocardial retention of inorganic iodide (123I) injected into the left coronary artery. The data strongly support the premise that lipid turnover through beta-oxidation is the rate-limiting step in the externally measured release of iodide after IHA injection, provided that recirculating inorganic radioactive iodide is corrected for. In addition, 15 volunteers were studied using [11C]palmitic acid and [123I]IHA using PET and dynamic planar camera scintigraphy with iodide correction. There was no significant difference between the mean values of the elimination half-times, and also no significant correlation between half-times of both fatty acids for single individuals.

Carbon Radioisotopes↗
PubMed1991

Fatty acid uptake in normal human myocardium.

Fatty acid binding protein has been found in rat aortic endothelial cell membrane. It has been identified to be a 40-kDa protein that corresponds to a 40-kDa fatty acid binding protein with high affinity for a variety of long chain fatty acids isolated from rat heart myocytes. It is proposed that this endothelial membrane fatty acid binding protein might mediate the myocardial uptake of fatty acids. For evaluation of this hypothesis in vivo, influx kinetics of tracer-labeled fatty acids was examined in 15 normal subjects by scintigraphic techniques. Variation of the plasma fatty acid concentration and plasma perfusion rate has been achieved by modulation of nutrition state and exercise conditions. The clinical results suggest that the myocardial fatty acid influx rate is saturable by increasing fatty acid plasma concentration as well as by increasing plasma flow. For analysis of these data, functional relations describing fatty acid transport from plasma into myocardial tissue in the presence and absence of an "unstirred layer" were developed. The fitting of these relations to experimental data indicate that the free fatty acid influx into myocardial tissue reveals the criteria of a reaction on a capillary surface in the vicinity of flowing plasma but not of a reaction in extravascular space or in an unstirred layer and that the fatty acid influx into normal myocardium is a saturable process that is characterized by the quantity corresponding to the Michaelis-Menten constant, Km, and the maximal velocity, Vmax, 0.24 +/- 0.024 mumol/g and 0.37 +/- 0.013 mumol/g(g.min), respectively. These data are compatible with a nondiffusional uptake process mediated by the initial interaction of fatty acids with the 40-kDa membrane fatty acid binding protein of cardiac endothelial cells.

Animals↗
PubMed1991

[Results of myocardial scintigraphy in patients with left bundle-branch block using Tl-201 and Tc-99m-MIBI].

Tl-201 myocardial scintigrams in patients with left bundle-branch block (LBBB) are frequently non-diagnostic with respect to presence or absence of coronary artery disease (CAD). The new myocardial perfusion tracer Tc-99m-MIBI requires a different protocol due to its insignificant redistribution. Therefore, scintigraphic patterns in LBBB cannot be deduced from experiences with Tl-201. In a total of 132 patients with LBBB, 81 studies were carried out with Tl-201, another 81 studies with Tc-99m-MIBI. In 30 patients both radiopharmaceuticals were employed. 72% of the Tl-201 scintigraphies in constant LBBB resulted in a reversible septal deficit and 9% in a constant septal deficit. In contrast, 70% of the Tc-99m-MIBI scintigraphies resulted in a constant septal deficit and only 19% in a reversible septal deficit. Similar "discrepancies" were found in LBBB patients in whom CAD has been angiographically excluded (N = 17). All patients, however, with LAD or RCA stenoses and constant LBBB showed reversible septal deficits with either tracer, Tl-201 (N = 12) or Tc-99m-MIBI (N = 10). It is concluded: 1) that the majority of patients with LBBB has reduced septal perfusion, 2) that this reduction is typically stress-independent in absence of CAD, and 3) that this stress-independent perfusion deficit is, in general, only differentiated from stress-induced ischemia (in case of CAD) with using the Tc-99m-MIBI protocol.

Adult↗
PubMed1991

[Multivessel PTCA as an alternative to bypass operation: effect of complete revascularization on long-term follow-up].

In this study we examine the influence of the initial grade of revascularisation on clinical follow-up in patients with multivessel PTCA instead of CABG. Between I/85 and VII/89 multivessel PTCA was performed in 231 patients (202 m, 29 w; age 57 +/- 9 years). 71% of the patients had 2-vessel disease (VD), 14% 3-VD. 15% had angioplasty of one major and at least one important side branch. Clinical follow-up was achieved by a questionnaire 19.8 +/- 10.1 months after PTCA. 473 of 508 (93.1%) treated stenoses were successfully (residual stenosis less than 50%). 198 patients (86%) had successful angioplasty of all treated lesions. 31 patients (13%) had failed PTCA of one stenosis, 1 patient of both treated lesions. 1 patient underwent emergency CABG. A complete revascularisation (group A) - no residual stenosis greater than 50% in any coronary artery - was achieved in 164 patients (71%). 65 patients (28%) had incomplete revascularisation [group B]. 206 patients (89.1%) had clinical follow-up by questionnaire, 144 patients in group A (87.8%) and 60 patients in group B (92.3%) [n.s.]. 3 patients had died by noncardiac reasons (two in group A and one in group B), 1 patient of group A by cardiac reason. 70% in group A and 68% in group B had continuous clinical improvement (n.s.). Total amount of cardiac events (PTCA, CABG, cardiac death, MI) showed no significance between both groups - 35 (24%) vs 23 (38%). Patients in group B had more CABG (12% vs 3%) and angioplasty of further lesions (7% vs 1%) [p less than 0.05] during follow-up. We conclude multivessel PTCA shows good primary results with low risk.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1990

[Risk factors in patients with recurrent coronary heart disease].

Progression of the coronary heart disease (CHD) and early occlusion of the coronary artery bypass grafts (CABG) represent significant problems for patients after myocardial revascularisation. Between November 1984 and August 1988 121 patients underwent surgery for a second and 3 patients for a third myocardial revascularisation. The mean age at the time of the second and third operation was 59 and 62 years, respectively. The mean interval between the first and second operation was 5.4 years, between the second and third 4.0 years. The indications for reoperation were graft stenosis or occlusion (graft dysfunction) in 43 patients (35%), progression of CHD in 25 patients (25%) and graft dysfunction as well as progression of CHD in 56 patients (45%). During the reoperation 109 patients received new venous CABG, whereas 15 patients were given an IMA-bypass graft, either solely or in addition to venous CABG. The IMA-grafts implanted during the first operation were patent in all 6 patients. They did, however, in some cases cause considerable preparatory difficulties during the reoperation. Perioperative complications were: low-output-syndrome in 9 patients (4 x lethal), myocardial infarction in 5 patients (1 x lethal), malignant ventricular cardiac dysrhythmia in 5 patients (2 x lethal), postoperative bleeding in 3 patients and cerebrovascular insufficiency in 2 patients. The perioperative lethality amounted to 5.7% (n = 5). The results of our retrospective study indicate that one third of the patients had to undergo a reoperation primarily as a result of graft dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

[Changes in fatty acid metabolism in dilated cardiomyopathy and hypertrophic cardiomyopathy in childhood].

The aetiology and the pathomechanisms in both types of cardiomyopathy (CM) are still unknown. In vivo measurements of myocardial metabolism in CM may be useful, but there is hardly any information on this subject. Free fatty acids (FFA) are the main source of energy for the normal myocardium. A method for external measurement of the FFA extraction rate (FFA-ER) in different myocardial regions by the simultaneous use of two isotopes has been developed. 201 TI indicates the myocardial perfusion and 15-(p-123 I-phenyl)-pentadecanoid acid (IPPA) represents the FFA uptake. The relation of IPPA/TI reflects the FFA-ER. 8 patients with hypertrophic CM (HCM), age 0.2-20 years, and 8 patients with dilated CM (DCM), age 0.2-18 years were investigated. 12 healthy adults and 4 infants after an arterial switch operation were used as a control group. All patients with HCM showed normal myocardial perfusion but the FFA uptake was strongly diminished, resulting in a reduction in FFA-ER to 42 +/- 12% of the normal value. The maximal influx rate (IR) of FFA was diminished too. In patients with DCM both the myocardial perfusion and the FFA uptake were globally reduced, resulting in a virtually normal FFA-ER. The IR was slightly increased. In HCM and DCM FFA utilisation was disturbed. The alterations were significantly different in both types of CM and different pathomechanisms can be assumed.

Adolescent↗
PubMed1988

Regional myocardial free fatty acid extraction in normal and ischemic myocardium.

The rate constant for free fatty acid influx (k1) was studied in normal and ischemic myocardium. In 15 normal subjects and 30 patients with coronary artery disease, 201Tl and 15-(p-123I-iodophenyl)-pentadecanoic acid (IPPA) were administered during exercise under fasting conditions and at rest. In 10 patients, the study was repeated after percutaneous transluminal coronary angioplasty; in three patients, the study was repeated after infarction. The initial accumulation of IPPA, related to that of 201Tl (both background and crossover corrected), was used for determinations of the regional rate constant of IPPA influx into myocardial tissue (k1*). In normal subjects, no significant differences in k1* between major myocardial segments were found; the average value of k1* was 0.57 +/- 0.13/min (mean +/- SD) at rest and 0.42 +/- 0.06/min at exercise (average workload, 123 +/- 47 W). With increasing free fatty acid plasma concentration and perfusion, free fatty acid influx increased in a saturable fashion. The Michaelis-Menten constant (KM*) and the maximal velocity (Vmax*) for IPPA influx into myocardial tissue were estimated to be 470 nmol/g and 430 nmol/g.min, respectively. In ischemic areas, k1* was reduced to 57 +/- 18% of k1* value in nonaffected segments. The areas were larger than those showing reduced 201Tl uptake. Preinfarction and postinfarction studies showed that the size of 201Tl defects in postinfarction images corresponded with the size of the area with reduced k1* observed in preinfarction scintigrams. Revascularization led to an increase of 201Tl uptake and to normalization of k1*.

Coronary Disease↗
PubMed1988

Double-nuclide study of the myocardium using 201Tl and 123I-labeled fatty acids in non-ischemic myocardial diseases.

Metabolic impairment and perfusion abnormalities are known to occur in hypertensive heart disease (HHD) and in cardiomyopathies. Free fatty acid (FFA) extraction is severely inhibited in a number of pathobiochemical reactions. This parameter was assessed using the radiolabeled FFA analogue 123I-(p-iodo-phenyl-)-pentadecanoic acid (IPPA) and 201Tl as perfusion marker, both of them injected at maximal physical workload. The regional extraction fraction of IPPA (IPPA-EF) was estimated by relating the regional IPPA and 201Tl uptake to each other. In HHD (normal coronary arteries) with posterior wall thickness less than or equal to 12 mm IPPA-EF was 77 +/- 18% (SD) in septum and 92 +/- 17% in the posterolateral wall (N = 13), with thickness of greater than 12 mm 60 +/- 23% in septum and 61 +/- 20% in the posterolateral wall (N = 8) when compared with IPPA-EF in normal subjects (= 100%, N = 9). In hypertrophic cardiomyopathy (HCM) IPPA-EF averaged 51 +/- 20% in septum and 87 +/- 10% in the posterolateral wall (N = 11). In these patient groups no systematic regional changes in 201TI uptake were observed. In dilated cardiomyopathy (DCM) both IPPA-EF and 201Tl uptake showed distinct regional variations and a great interindividual variability with a mean IPPA-EF reduction of 12% (N = 9). Thus, IPPA uptake in primarily non-ischemic myocardial disease may already be compromised when 201Tl uptake is unchanged. The double-nuclide method for IPPA-EF determination allows to eliminate the influence of flow in FFA imaging and enhances the potential of scintigraphy in the differential diagnosis of HHD versus coronary artery disease.

Cardiomyopathies↗
PubMed1987

Absolute quantification of pharmacokinetic distribution of RES colloids in individuals with normal liver function.

Estimates of the radiation dose resulting from liver-spleen scintigraphy 99Tcm-labelled colloids are based on pharmacokinetic data mainly determined in animals. The aim of this study was to check the pharmacokinetic data by direct, absolute in vivo quantification in man. For this purpose appropriate methods of measurement were developed, or procedures taken over from literature were modified. Liver and spleen activities were directly measured using a double-energy window technique. Activities in other organs were quantified by conjugate whole-body scans. All measurement procedures were checked using the whole-body Alderson phantom. Pharmacokinetic data for sulphur colloid, tin colloid, human serum albumin (HSA) millimicrospheres, and phytate were obtained in 13 to 20 normal subjects for each type of colloid. Depending on the colloid type liver uptake was between 54 and 75% of the total administered dose (TAD) and spleen uptake was 3.5 to 21% TAD. Activity measured in blood, urine, lung and thyroid proved to be far from negligible. The results of this work suggest a correction of the animal-based data of colloid distribution and radiation dose on the basis of the direct measurement of absolute uptake in man.

Adult↗
PubMed1986

Sequential sampling: a new acquisition technique for fatty acid kinetics from quasi-simultaneous multiple projections.

Studies of myocardial metabolism by rapidly catabolized fatty acids like omega-I-123-heptadecanoic acid (IHA) are usually limited to one planar view of require sophisticated equipment, such as bidirectional slant-hole collimators or seven-pinhole collimators for multiplane or tomographic views. To solve this problem a normal SPECT camera was utilized to acquire sequentially sampled dynamic studies from up to six different views. This was done by a periodically repeated sequence of acquisitions in different projections, which followed one another clockwise. This procedure overcomes the single-plane limitations of the usual IHA dynamic studies. It reveals regional myocardial patterns of tracer uptake and elimination not obtainable from any single viewing angle. In this way one methodological disadvantage relative to thallium perfusion studies is removed. Furthermore, the non-invasive diagnosis of cardiomyopathies, for which no other radioisotope procedure is appropriate, should be improved using this new method.

Cardiomyopathies↗