Preparation and characterization of two phosphopeptide fractions from calf thymus nuclei; similarity to corresponding fractions in the DNA prepared from the nuclei.

In this study two phosphopeptide (PP) fractions from purified, calf thymus nuclei, prepared under protective conditions were characterized. The nuclei were lysed and dialyzed, and the material in the dialysates was fractionated by anion exchange column chromatography. This revealed the presence of two main phosphopeptide (PP) fractions, numbers 1 and 5. Amino acid analysis of the fraction 1, occurring in the greatest amount, showed that, after deionization, it contained the metal ion complexes of phosphoserine, aspartic and glutamic acids in large amounts, and nine other amino acids. In the same way the two main PP fractions, P1 and P5, were obtained during the dialysis of the EDTA-reacted, highly purified DNA (N-DNA) prepared from calf thymus nuclei. Fraction 1 from nuclei had practically the same amino acid composition as fraction P1 from EDTA-reacted N-DNA. In both cases, the second main fraction obtained (fraction 5) had nearly the same amino acid composition as fraction 1, but the total Pser molar ratio, was about twice as high as for fraction 1. In contrast to the low molecular weights of 900-1400 daltons observed for PPs isolated directly from the dialysates in water without exposure to HCOOH, the high molecular weight of 10,260 daltons was obtained for the PP fraction 1, after exposure to HCOOH used in the gradient for the column chromatography.

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.

Characterization of the cardiac troponin I phosphorylation domain by 31P nuclear magnetic resonance spectroscopy.

Cardiac holotroponin can be phosphorylated at serine 23 and/or 24 in the heart-specific region of bovine troponin I. When isolated freshly it is composed of a mixture of non-, two mono-, and bisphosphorylated species. At neutral pH the monophosphorylated form carrying phosphate at serine 24 yields a resonance signal at 4.6 ppm and that carrying phosphate at serine 23 at 4.4 ppm; the two phosphate groups of the bisphosphorylated form yield only one 31P-NMR signal at 4.2 ppm. From the chemical shift dependence on pH, pKa values have been estimated to be 5.3 and 5.6 for the phosphate groups at serine 24 and serine 23, respectively. Both phosphates of the bisphosphorylated form exhibit very similar pKa values of approximately 5.8. Separation of bisphosphotroponin I from the complex results in a downfield shift and the appearance of two 31P-NMR signals at positions comparable to those of the two monophospho forms. Complex formation of cardiac troponin I with C or T does not alter the spectrum obtained with isolated troponin I; however, the original troponin spectrum is restored by reconstitution of the holocomplex from all three components T, I, and C. Two signals are also observed with a bisphosphorylated synthetic peptide [PVRRRS(P)S(P)ANYR] representing the phosphorylation domain. pKa values of about 5.3 and 5.6 have been determined for serine 7 (corresponding to serine 24 of troponin I) and serine 6 of the peptide (corresponding to serine 23 of troponin I).

Role of the carotid sinus in response of integrated venous system to pulsatile and nonpulsatile perfusion.

Effects of pulsatile and nonpulsatile perfusion on capacity system were investigated in 33 open-chest mongrel dogs with extracorporeal circulation. In 28 dogs with intact carotid sinus nerves, after changing from nonpulsatile to pulsatile systemic perfusion the mean arterial pressure decreased by 14 +/- 1.5 mm Hg, peripheral resistance by 423 +/- 15 dyne.cm-5.sec, and venous blood volume by 3.3 +/- 0.4 ml/kg. After changing from pulsatile perfusion to nonpulsatile systemic perfusion the mean arterial pressure increased by 15 +/- 2.2 mm Hg, the peripheral resistance by 431 +/- 15 dyne.cm-5.sec, and venous volume by 3.9 +/- 0.5 ml/kg. The same effects were observed in five dogs with bilateral isolated carotid pulsatile perfusion or nonpulsatile perfusion and systemic nonpulsatile perfusion. These effects were abolished after denervation of pressor receptors and pharmacologic blockade of alpha and beta receptors. It is proposed that with nonpulsatile perfusion carotid sinus-mediated vasoconstriction occurs in the downstream part of the capacitive system, where more pronounced wall musculature with increased number of adrenergic receptors is present. The throttle effect caused by this "resistance" part of venous circulation leads to increase of pressure in the upstream section of the capacitive system, compensates for the constrictive effect of the sympathetic tone, and leads finally to an increased volume of the capacity system. We conclude that venous response to different perfusion modalities is critically dependent on intact carotid sinus nerves and adrenergic receptors in the veins.

The influence of pulsatile and nonpulsatile extracorporeal circulation on fluid retention following coronary artery bypass grafting.

Thirty male patients undergoing coronary artery bypass grafting were divided into two groups, group I receiving pulsatile perfusion, group II nonpulsatile perfusion. A double roller pump system for extracorporeal circulation was employed. Intra- and postoperative fluid balances and bodyweight gains were controlled under clinical conditions. There were no significant differences between the groups with regard to clinical data, operative procedure, perfusion parameters, drug treatment or intensive care treatment. The intra-operative mean fluid balance of group I was 794.0ml (66%) lower than that of group II, while the balance 24 hours postoperatively was 136.7ml (37%) lower in group I. Thus, the total mean fluid balance for the pulsatile group was 931.0ml (59%) lower than the nonpulsatile group, in accordance with the bodyweights, which showed a 954.0g (63%) lower outcome in the pulsatile group. Less supplementary volume and higher urine production were the main factors. It appears that volume saved during pulsatile ECC need not be replaced postoperatively. These findings indicate that pulsatile perfusion leads to diminished fluid overloading, which could be an important advantage, especially for high-risk patients.

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.

The membrane fatty acid-binding protein is not identical to mitochondrial glutamic oxaloacetic transaminase (mGOT).

For evaluation whether the membrane fatty acid-binding protein is related to mGOT, studies on the structure and function of both purified proteins were performed. Physicochemical characterization revealed that both proteins are different: the membrane fatty acid-binding protein has a molecular weight of 40 kD and a pI of 8.5-9.0, whereas rat mGOT has a molecular weight of 44 kD and a pI of 9.5-10.0. According to this distinct differences, they migrated separately on 2-dimensional electrophoresis. Furthermore, monospecific antibodies against the membrane fatty acid binding protein did not react with rat mGOT. In co-chromatography studies only the membrane fatty acid-binding protein showed affinity for long chain fatty acids, but not mGOT. Moreover, membrane binding studies were performed with the monospecific antibody to the membrane fatty acid binding protein. The inhibitory effect of this antibody on plasma membrane binding of oleate was reversed after preabsorption of the antibody with the membrane fatty acid binding protein, but was not affected after preabsorption with mGOT. These results indicate that the membrane fatty acid binding protein and mGOT are structurally and functionally not related. The data also support the significance of this membrane protein in the plasma membrane binding process of long chain fatty acids.

Functional aspect of a phosphopeptide derived from calf thymus nuclei and DNA.

Phosphopeptides (PPs) isolated from highly purified calf thymus DNA (N-DNA) and extracted from calf thymus nuclei were fractionated, and the effect of one PP fraction on DNA replication has been examined. In the absence of inhibitors, the increasing PP concentration caused a linear decrease of 3H-thymidine uptake in L5178Y cells. If PP fraction was mildly hydrolysed with 1NHCl, the decrease in uptake was much steeper. The studies in which the inhibitors were used revealed that by the addition of the unhydrolysed PP fraction the inhibition of 3H-thymidine uptake by alpha-amanitin could be completely overcome, and that the inhibition by puromycin was reduced to 65-77% of the control. With puromycin, there was a gradual decrease of 3H-thymidine uptake with PP concentration above 3 mg/ml. The PPs gave an increase in incorporation of 3H-thymidine even after removal of alpha-amanitin and puromycin; thus, it is suggested that there is no direct interaction of either inhibitor with PP in the cell. Data on the utilization of 3H-cytidine for the synthesise of new DNA suggest that PP fraction might cause an acceleration of DNA replication.

Effects of pulsatile perfusion on plasma catecholamine levels and hemodynamics during and after cardiac operations with cardiopulmonary bypass.

Thirty patients scheduled for elective coronary artery bypass grafting were studied in two groups. Group A had standard cardiopulmonary bypass with nonpulsatile perfusion and group B had pulsatile perfusion. Measurements of plasma epinephrine, norepinephrine, granulocyte elastase, and hemodynamic parameters including mean arterial pressure total peripheral resistance, cardiac index, and pulmonary capillary wedge pressure were made before and after anesthesia induction, after surgical incision, during cardiopulmonary bypass, and 2, 4, and 24 hours after the operation. The venous compliance of the total body venous bed was measured at the end of the operation. In all patients the total net fluid balance was determined during bypass and in the postoperative period. In both groups plasma catecholamine levels increased 5 minutes after institution of bypass (epinephrine 176 +/- 56 to 611 +/- 108 pg/ml and norepinephrine 231 +/- 48 to 518 +/- 100 pg/ml in group A; epinephrine 168 +/- 40 to 444 +/- 100 pg/ml and norepinephrine 162 +/- 44 to 267 +/- 52 pg/ml in group B). The maximum catecholamine level was measured between the end of bypass and 2 hours after the end of bypass (epinephrine 1489 +/- 169 pg/ml and norepinephrine 1542 +/- 108 pg/ml in group A; epinephrine 990 +/- 134 pg/ml and norepinephrine 934 +/- 197 pg/ml in group B). During the same period mean arterial pressure and total peripheral resistance were also significantly higher in group A than in group B mean arterial pressure, 61.4 +/- 3 versus 53.6 +/- 3, p less than 0.06; total peripheral resistance, 1055 +/- 60 versus 899 +/- 45, p less than 0.01). The venous compliance was significantly higher in group A than in group B (2.4 +/- 0.3 versus 1.2 +/- 0.3 ml/mm Hg/kg body weight). The intraoperative and perioperative net fluid balance were significantly higher in group A than in group B (p less than 0.005). The average postoperative tracheal intubation time was also significantly longer in group A than in group B (4.6 +/- 1.2 hours versus 2.7 +/- 0.8 hours, p less than 0.001). No significant difference was detected in either hemoglobin or plasma free hemoglobin content between the two groups postoperatively. The results suggest that pulsatile perfusion, when compared with nonpulsatile perfusion, can attenuate the catecholamine stress response to cardiopulmonary bypass, reduce the fluid overloading of patients, and improve the postoperative recovery period as evaluated by tracheal intubation time.

Management of concomitant occlusive disease of coronary and carotid arteries using cardiopulmonary bypass for both procedures.

The incidence of neurological complications following operative treatment of concomitant occlusive disease of coronary and carotid arteries has been reported to be between 0.7 and 18 per cent by different preoperative screening methods and surgical strategy. From the opening of our institution in November 1984 until March 1988 5443 open-heart procedures were performed. In 116 patients of 3540 consecutive coronary artery bypass grafting (CABG) candidates simultaneous carotid endarterectomy (TEA) was carried out because of hemodynamically relevant stenosis of one or both carotid arteries; 50 patients were neurologically symptomatic with TIA's and amaurosis fugax preoperatively. Sixty of 66 patients with asymptomatic carotid artery stenosis had either a morphologically severe stenosis of the carotid artery or multifocal occlusive disease of the extracranial supraaortic arteries. Prior to carotid-TEA cardiopulmonary bypass was inserted with mild hypothermia maintaining a beating heart for pulsatile body perfusion. An intraluminal shunt was only used in patients with bilateral carotid stenosis. Intraoperative EEG-monitoring was carried out to detect cerebrovascular insufficiency. In 108/116 patients no neurological complications were observed, but 6/116 patients had transient minor neurological symptoms. Two of 116 patients sustained a severe neurological deficit with hemiplegia and one of them died on the 21st postoperative day. Based on these data we conclude that patients requiring carotid TEA and CABG should be operated upon simultaneously using cardiopulmonary bypass for both procedures.

[Changes in fatty acid metabolism in dilated cardiomyopathy and hypertrophic cardiomyopathy in childhood]. / Veränderungen im Fettsäuremetabolismus bei dilatativer und hypertropher Kardiomyopathie im Kindesalter.

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.

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*.

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.

Phosphopeptides in highly purified calf thymus DNA.

Highly purified DNA obtained from calf thymus nuclei was found to cleave after reaction with a chelating agent and subsequent dialysis against 0.01 M phosphate. During the cleavage release of proteineous material into the dialysate was observed. By means of anion exchange resin column chromatography, this material was separated into 9 main fractions. Two of these fractions P1 and P5) were found to contain the amino acids phosphoserine, asp, thr, ser, glu, gly, ala, val, ile, leu, and arg, as well as metal ion complexes of phosphoserine. The complexes were dissociated by Chelex 100 treatment. The proportion of phosphoserine was much greater in P5 than in P1. P1 and P5 contained essentially no nucleotide material. All other fractions (P2, P3, P3a, P4, P5a, P6, P7, P8, P6a, P9) were found to contain ribonucleotides and deoxynucleotides. The deoxynucleotide content was about 10% of total nucleotide content. After a deionizing treatment with Chelex, the amounts of nucleotides were extensively reduced to a level corresponding to about 1 nucleotide of 10 amino acids. In separate experiments, commercial DNA (S-DNA) was ultrasonicated, and digested with pancreatic DNAase, exonuclease III, and S1 nuclease. From DEAE Sephacel chromatography of this material the fraction obtained having the highest proportion of protein aceous material was hydrolyzed with Pronase and again chromatographed on DEAE Sephacel. From this fractionation a single fraction containing deoxynucleotides and amino acids was found. The mixture obtained by hydrolysis of this fraction with snake venom diesterase and was again rechromatographed, which revealed two peaks, one corresponding to deoxynucleotide material and a second one to a mixture of 4 amino acids, phosphoserine, asp, glu, and gly. From this it was concluded that the fraction used for diesterase digestion consisted of deoxynucleotide-amino acids, with covalent diester bonds between their deoxynucleotide and amino acid portions. The results indicate that in purified S-DNA phosphopeptides are linked through covalent bonds to the terminal deoxynucleotide residues.

17-Iodine-123 iodoheptadecanoic acid for metabolic liver studies in humans.

(17-123I)-Iodoheptadecanoic acid ([123I]HA) was used for dynamic planar scintigraphy of the liver in normal individuals (control I), in patients without liver disease but with elevated serum cholesterol and/or triglycerides (control II), and in patient groups with alcohol-induced fatty liver (PG I), fatty liver not due to alcohol (PG II), alcohol-induced liver cirrhosis (PG III), or liver cirrhosis of the posthepatitic type (PG IV). Tracer uptake and elimination time were assayed in different liver regions; mean elimination time was expressed for total liver. In control I, tracer uptake was homogeneous, and mean elimination time was 20.7 +/- 5.3 min without significant local variations. In control II, tracer uptake was reduced but homogeneous and mean elimination time was 59.4 +/- 35.8 min with some local variations. In PG I, uptake was reduced and inhomogeneous and elimination time was the same as in control I, irrespective of cholesterol and triglyceride values. In PG II, uptake was the same as in PG I but mean elimination time was 48 +/- 8.1 min with some local variations. In PG III, uptake was extremely reduced and spotty and elimination time correlated with the severity of disease from 19 to 881 min in different liver regions.

Myocardial fatty acid metabolism after acute ethanol consumption.

This study was undertaken to assess the effect of ethanol ingestion on myocardial fatty acid metabolism in man. Nine individuals with informed consent and with a habitual ethanol consumption of approximately 40 g per day, but without any clinical signs of heart and metabolic disease, were examined after i.v. injection of omega-123I-heptadecanoic acid (IHA). Eight days later, these individuals were similarly examined after 2 h of continuous ingestion of a body weight dependent amount of ethanol, which was calculated to produce a blood level of 100 mg per 100 ml (1%). Then the subjects had been asked to reduce their ethanol consumption rigorously for 15 months. Subsequently after 2 weeks of abstinence a follow-up investigation without ethanol loading was carried out. The investigations were performed with an Anger scintillation camera in LAO-45 degrees projection. The measurement period was 40 min. Tracer accumulation and regional elimination half-times of IHA were analysed. In all patients, acute ethanol loading produced significant changes in pattern of accumulation and/or regional elimination half-times. Ethanol-induced alterations in segmental accumulation did not appear to be predictably correlated with changes in segmental elimination half-times. After rigorous reduction of ethanol consumption followed by 2 weeks of abstinence a normalization of the tracer uptake was observed; the distribution pattern was almost homogeneous. Also the regional elimination half-times became normal. The data demonstrate the significant effects of both chronic ethanol consumption and particularly acute ethanol loading on myocardial fatty acid metabolism and the reversibility of the effects.

A new radiographic method for cardiac output and cardiac shunt determination in vivo.

The present paper describes a new method for the measurement of cardiac output (CO) and cardiac shunt (CS). The CO method is based on the accurate determination of the concentration of the indicator in large vessels. For the measurement of the left to right shunting volumes, a double tracer technique is used by which radioactively labeled transferrin or erythrocytes are applied together with radioactively labelled human-serum-albumin (HSA) microspheres. The results obtained using these methods were compared with the data obtained by invasive methods. High correlation of both sets of data suggests that the proposed methods might provide an excellent extension of noninvasive procedures in the first months of a childs life.

Radioiodinated fatty acids for cardiological diagnosis.

The development of fatty acids labelled with iodine-123 is reviewed. The variety of methods for producing 123I and introducing radioiodine into the molecule is discussed and the important points of the biochemical background are recalled with the aim of finding a broad application for 123I-labelled fatty acids. The results of the pharmacokinetic studies and biochemical analyses are presented as they prove that both 17-123I-heptadecanoic acid (IHA) and 15-(p-123I-phenyl)pentadecanoic acid (IPPA) exhibit analogous behaviour to that of the naturally occurring fatty acids. Clinical applications demonstrated two fields of importance: applications solely for imaging the heart and assessment of myocardial turnover rates of fatty acids for functional diagnosis. Moreover, very recent studies show that the provision of information about prognosis of myocardial diseases and the applied cardiological therapy appear to be possible.

Use of 3-fluoro-deoxyglucose for the assessment of cerebral perfusion and glucose transport. I. Theory.

A new model is described applying dynamic positron emission tomography (dPET) and 3-fluoro-deoxyglucose (3FDG) to the measurement of local cerebral perfusion and glucose transport across the blood-brain-barrier (BBB). The model takes advantage of 3FDG being practically not metabolized in brain and being transported back from tissue into the circulation. Simultaneous registration of tracer concentration in blood and tissue by dPET permits the in vivo determination of the Michaelis-Menten constant (K) and maximal velocity (V) for 3FDG and glucose transport across the BBB as well as the determination of local perfusion rate. Values obtained in normal cortex using this method were K = 6.3 mumol/g and V = 2.46 mumol/g min. Local perfusion rate ranged between 0.8 and 0.98 ml/min g.