Hyperpolarized MRI - An Update and Future Perspectives.

In recent years, hyperpolarized 13C magnetic resonance spectroscopic (MRS) imaging has emerged as a complementary metabolic imaging approach. Hyperpolarization via dissolution dynamic nuclear polarization is a technique that enhances the MR signal of 13C-enriched molecules by a factor of > 104, enabling detection downstream metabolites in a variety of intracellular metabolic pathways. The aim of the present review is to provide the reader with an update on hyperpolarized 13C MRS imaging and to assess the future clinical potential of the technology. Several carbon-based probes have been used in hyperpolarized studies. However, the first and most widely used 13C-probe in clinical studies is [1-13C]pyruvate. In this probe, the enrichment of 13C is performed at the first carbon position as the only modification. Hyperpolarized [1-13C]pyruvate MRS imaging can detect intracellular production of [1-13C]lactate and 13C-bicarbonate non-invasively and in real time without the use of ionizing radiation. Thus, by probing the balance between oxidative and glycolytic metabolism, hyperpolarized [1-13C]pyruvate MRS imaging can image the Warburg effect in malignant tumors and detect the hallmarks of ischemia or viability in the myocardium. An increasing number of clinical studies have demonstrated that clinical hyperpolarized 13C MRS imaging is not only possible, but also it provides metabolic information that was previously inaccessible by non-invasive techniques. Although the technology is still in its infancy and several technical improvements are warranted, it is of paramount importance that nuclear medicine physicians gain knowledge of the possibilities and pitfalls of the technique. Hyperpolarized 13C MRS imaging may become an integrated feature in combined metabolic imaging of the future.

SpraySyn-A standardized burner configuration for nanoparticle synthesis in spray flames.

In many scientific communities, the definition of standardized experiments has enabled major progress in process understanding. The investigation of the spray-flame synthesis of nanoparticles at a well-defined standard burner by experiment and simulation makes it possible to produce a comprehensive data set with various established and novel measuring methods. In this work, we introduce the design of the SpraySyn burner as a new standard for a free-jet type burner that offers well-defined and simulation-friendly boundary conditions and geometries as well as accessibility for optical diagnostics. A combustible precursor solution is fed through a centrally located capillary and aerosolized with an oxygen dispersion gas flow. The spray flame is stabilized by a premixed flat methane/oxygen pilot flame fed via a porous bronze matrix surrounded by a stabilizing nitrogen coflow emanating through the same porous matrix, providing easy-to-calculate boundary conditions for simulations. This burner design enables the use of a wide choice of solvents, precursors, and precursor combinations. Best-practice operating instructions and parameters are given, and large-eddy simulations are performed demonstrating the suitability of the SpraySyn burner for computational fluid dynamics simulations. For ensuring reproducible operation across labs, we define a consumer-camera-based flame characterization scheme for the quantitative assessment of the flame geometry such as flame length, diameter, tilt angle, and photometric distribution of visible chemiluminescence along the center axis. These parameters can be used for benchmarking the pilot and spray flame by each user of the SpraySyn burner with the reference flames.

Exchange-coupled donor dimers in nanocrystal quantum dots.

Doping of semiconductor nanocrystals (NCs) is expected to enable the control of key NC properties, yet its practical exploitation requires an understanding of exchange interactions when multiple dopants are incorporated in a single NC. Here, we experimentally probe the exchange of donor dimers in NCs via a deviation of their triplet-state magnetic resonance from Curie paramagnetism. We show that the exchange coupling of the closely spaced donors can be well described by effective mass theory, which allows the consideration of statistical effects crucial in NC ensembles. While a dimer induces discrete states in a NC, their energy splitting differs by up to 3 orders of magnitude for randomly placed dimers in a NC ensemble, due to an enormous dependence of the exchange energy on the dimer configuration.

Metabolic effects of short-term GLP-1 treatment in insulin resistant heart failure patients.

We studied the metabolic effects of 48-h GLP-1 treatment in insulin resistant heart failure patients.In a randomized placebo-controlled double-blinded cross-over study, 11 non-diabetic HF patients with IHD received 48-h GLP-1 and placebo-infusion. We applied OGTT, hyperinsulinemic clamp, indirect calorimetry, forearm, and tracer methods.7 insulin resistant HF (EF 28%±2) patients completed the protocol. GLP-1 decreased plasma glucose levels (p=0.048) and improved glucose tolerance. 4 patients had hypoglycemic events during GLP-1 vs. none during placebo. GLP-1 treatment tended to increase whole body protein turnover (p=0.08) but did not cause muscle wasting. No significant changes in circulating levels of insulin, glucagon, free fatty acids or insulin sensitivity were detected.GLP-1 treatment decreased glucose levels and increased glucose tolerance in insulin resistant HF patients with IHD. Hypoglycemia was common and may limit the use of GLP-1 in these patients. Insulin sensitivity, lipid-, and protein metabolism remained unchanged.Data were collected at the examinational laboratories of Department of Endocrinology and Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.

From nanoparticles to nanocrystalline bulk: percolation effects in field assisted sintering of silicon nanoparticles.

Nanocrystalline bulk materials are desirable for many applications as they combine mechanical strength and specific electronic transport properties. Our bottom-up approach starts with tailored nanoparticles. Compaction and thermal treatment are crucial, but usually the final stage sintering is accompanied by rapid grain growth which spoils nanocrystallinity. For electrically conducting nanoparticles, field activated sintering techniques overcome this problem. Small grain sizes have been maintained in spite of consolidation. Nevertheless, the underlying principles, which are of high practical importance, have not been fully elucidated yet. In this combined experimental and theoretical work, we show how the developing microstructure during sintering correlates with the percolation paths of the current through the powder using highly doped silicon nanoparticles as a model system. It is possible to achieve a nanocrystalline bulk material and a homogeneous microstructure. For this, not only the generation of current paths due to compaction, but also the disintegration due to Joule heating is required. The observed density fluctuations on the micrometer scale are attributed to the heat profile of the simulated powder networks.

Integration of Ligand- and Target-Based Virtual Screening for the Discovery of Cruzain Inhibitors.

A myriad of methods are available for virtual screening of small organic compound databases. In this study we have successfully applied a quantitative model of consensus measurements, using a combination of 3D similarity searches (ROCS and EON), Hologram Quantitative Structure Activity Relationships (HQSAR) and docking (FRED, FlexX, Glide and AutoDock Vina), to retrieve cruzain inhibitors from collected databases. All methods were assessed individually and then combined in a Ligand-Based Virtual Screening (LBVS) and Target-Based Virtual Screening (TBVS) consensus scoring, using Receiving Operating Characteristic (ROC) curves to evaluate their performance. Three consensus strategies were used: scaled-rank-by-number, rank-by-rank and rank-by-vote, with the most thriving the scaled-rank-by-number strategy, considering that the stiff ROC curve appeared to be satisfactory in every way to indicate a higher enrichment power at early retrieval of active compounds from the database. The ligand-based method provided access to a robust and predictive HQSAR model that was developed to show superior discrimination between active and inactive compounds, which was also better than ROCS and EON procedures. Overall, the integration of fast computational techniques based on ligand and target structures resulted in a more efficient retrieval of cruzain inhibitors with desired pharmacological profiles that may be useful to advance the discovery of new trypanocidal agents.

Electronic transport in phosphorus-doped silicon nanocrystal networks.

We have investigated the role of doping and paramagnetic states on the electronic transport of networks assembled from freestanding Si nanocrystals (Si-NCs). Electrically detected magnetic resonance (EDMR) studies on Si-NCs films, which show a strong increase of conductivity with doping of individual Si-NCs, reveal that P donors and Si dangling bonds contribute to dark conductivity via spin-dependent hopping, whereas in photoconductivity, these states act as spin-dependent recombination centers of photogenerated electrons and holes. Comparison between EDMR and conventional electron paramagnetic resonance shows that different subsets of P-doped nanocrystals contribute to the different transport processes.

Effects of organic solvents on the enzyme activity of Trypanosoma cruzi glyceraldehyde-3-phosphate dehydrogenase in calorimetric assays.

In drug discovery programs, dimethyl sulfoxide (DMSO) is a standard solvent widely used in biochemical assays. Despite the extensive use and study of enzymes in the presence of organic solvents, for some enzymes the effect of organic solvent is unknown. Macromolecular targets may be affected by the presence of different solvents in such a way that conformational changes perturb their active site structure accompanied by dramatic variations in activity when performing biochemical screenings. To address this issue, in this work we studied the effects of two organic solvents, DMSO and methanol (MeOH), in the isothermal titration calorimetry (ITC) kinetic assays for the catalyzed reaction of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from Trypanosoma cruzi. The solvent effects on T. cruzi GAPDH had not yet been studied. This enzyme was shown here to be affected by the organic solvents content up to 5.0% for MeOH and up to 7.5% for DMSO. The results show that when GAPDH is assayed in the presence of DMSO (5%, v/v) using the ITC experiment, the enzyme exhibits approximately twofold higher activity than that of GAPDH with no cosolvent added. When MeOH (5%, v/v) is the cosolvent, the GAPDH activity is sixfold higher. The favorable effects of the organic solvents on the Michaelis-Menten enzyme-substrate complex formation ensure the consistency of the biological assays, structural integrity of the protein, and reproducibility over the measurement time. The reaction was also kinetically monitored by standard spectrophotometric assays to establish a behavioral performance of T. cruzi GAPDH when used for screening of potential inhibitors.

Abnormalities of whole body protein turnover, muscle metabolism and levels of metabolic hormones in patients with chronic heart failure.

OBJECTIVE: It is well known that chronic heart failure (CHF) is associated with insulin resistance and cachexia, but little is known about the underlying substrate metabolism. The present study was undertaken to identify disturbances of basal glucose, lipid and protein metabolism. DESIGN: We studied eight nondiabetic patients with CHF (ejection fraction 30 +/- 4%) and eight healthy controls. Protein metabolism (whole body and regional muscle fluxes) and total glucose turnover were isotopically assayed. Substrate oxidation were obtained by indirect calorimetry. The metabolic response to exercise was studied by bicycle ergometry exercise. RESULTS: Our data confirm that CHF patients have a decreased lean body mass. CHF patients are characterised by (i) decreased glucose oxidation [glucose oxidation (mg kg(-1) min(-1)): 1.25 +/- 0.09 (patients) vs. 1.55 +/- 0.09 (controls), P < 0.01] and muscle glucose uptake [a - v diff(glucose) (micromol L(-1)): -10 +/- 25 (patients) vs. 70 +/- 22 (controls), P < 0.01], (ii) elevated levels of free fatty acids (FFA) [FFA (mmol L(-1)): 0.72 +/- 0.05 (patients) vs. 0.48 +/- 0.03 (controls), P < 0.01] and 3-hydroxybutyrate and signs of elevated fat oxidation and muscle fat utilization [a - v diff(FFA) (mmol L(-1)): 0.12 +/- 0.02 (patients) vs. 0.05 +/- 0.01 (controls), P < 0.05] and (iii) elevated protein turnover and protein breakdown [phenylalanine flux (micromol kg(-1) h(-1)): 36.4 +/- 1.5 (patients) vs. 29.6 +/- 1.3 (controls), P < 0.01]. Patients had high circulating levels of noradrenaline, glucagon, and adiponectin, and low levels of ghrelin. We failed to observe any differences in metabolic responses between controls and patients during short-term exercise. CONCLUSIONS: In the basal fasting state patients with CHF are characterized by several metabolic abnormalities which may contribute to CHF pathophysiology and may provide a basis for targeted intervention.

Prediction of reversible myocardial dysfunction by positron emission tomography, low-dose dobutamine echocardiography, resting ECG, and exercise testing.

We studied different algorithms to identify patients with heart failure who could potentially benefit from revascularization. Thirty-five coronary artery bypass (graft) patients with an ejection fraction of 35 +/- 7% underwent preoperative 18F-fluoro-2-deoxyglucose positron emission tomography (PET), low-dose dobutamine echocardiography (LDDE), and exercise testing. Follow-up by echocardiography and coronary angiography was performed 6 months after coronary artery bypass grafting. The sensitivity for prediction of reversible myocardial dysfunction was highest for PET and for ST depression or angina pectoris during exercise testing (100 and 93%, p = NS), 71% for LDDE (p < 0.05 vs. PET), and 50% for resting ECG (p < 0.02 vs. PET and exercise test). The specificity did not differ between LDDE (81%), PET (67%), and resting ECG (71%), but was lowest for exercise testing (33%; p < 0.02 vs. PET, LDDE, and resting ECG). Accuracies were: PET 80%, LDDE 77%, exercise testing 62%, and resting ECG 58% (p < 0.05 vs. PET). In patients with a negative exercise test, recovery was unlikely, and further viability testing may not be needed. In patients with a positive test, recovery may occur, and additional PET or LDDE should be performed. In these cases, PET with an 18F-fluoro-deoxyglucose uptake of > or =70% as the criterion for viability yields optimum diagnostic characteristics. This strategy awaits further evaluation in larger patient populations with heart failure.

Electromechanical mapping for detection of myocardial viability in patients with ischemic cardiomyopathy.

BACKGROUND: We evaluated the ability of electromechanical mapping of the left ventricle to distinguish between nonviable and viable myocardium in patients with ischemic cardiomyopathy. METHODS AND RESULTS: Unipolar voltage amplitudes and local endocardial shortening were measured in 31 patients (mean+/-SD age, 62+/-8 years) with ischemic cardiomyopathy (ejection fraction, 30+/-9%). Dysfunctional regions, identified by 3D echocardiography, were characterized as nonviable when PET revealed matched reduction of perfusion and metabolism and as viable when perfusion was reduced or normal and metabolism was preserved. Mean unipolar voltage amplitudes and local shortening differed among normal, nonviable, and viable dysfunctional segments. Coefficient of variation for local shortening exceeded differences between groups and did not allow distinction between normal and dysfunctional myocardium. Optimum nominal discriminatory unipolar voltage amplitude between nonviable and viable dysfunctional myocardium was 6.5 mV, but we observed a great overlap between groups. Individual cutoff levels calculated as a percentage of electrical activity in normal segments were more accurate in the detection of viable dysfunctional myocardium than a general nominal cutoff level. The optimum normalized discriminatory value was 68%. Sensitivity and specificity were 78% for the normalized discriminatory value compared with 69% for the nominal value (P:<0.02). CONCLUSIONS: Endocardial ECG amplitudes in patients with ischemic cardiomyopathy display a wide scatter, complicating the establishment of exact nominal values that allow distinction between viable and nonviable areas. Individual normalization of unipolar voltage amplitudes improves diagnostic accuracy. Electroanatomic mapping may enable identification of myocardial viability.

Energy stores and metabolites in chronic reversibly and irreversibly dysfunctional myocardium in humans.

OBJECTIVES: Our goal was to study metabolic energy stores and lactate content in chronic reversibly and irreversibly dysfunctional myocardium. BACKGROUND: It is unknown whether metabolism is deranged in chronic reversibly and irreversibly dysfunctional myocardium in humans. Semiquantitative histological examinations have shown altered mitochondrial morphology and glycogen accumulation in dysfunctional regions. METHODS: We studied 25 patients with a mean ejection fraction of 38 +/- 9% scheduled for coronary artery bypass surgery. Regional perfusion and metabolism were assessed by positron emission tomography, and regional function was assessed by echocardiography. Perioperative myocardial biopsies were obtained from a control region and from a dysfunctional region. We analyzed biopsies for contents of noncollagen protein (NCP), ATP, ADP, AMP, glycogen and lactate. Six months after surgery we assessed wall motion by echocardiography to group patients in those with (n = 11) and without (n = 14) functional improvement. RESULTS: Reversibly dysfunctional myocardium had reduced perfusion (0.59 +/- 0.16 vs. 0.69 +/- 0.20 ml/g/min, p < 0.05), similar glucose-tracer uptake (92 +/- 12 and 95 +/- 14%), ATP/ADP ratio (2.4 +/- 1.1 and 2.4 +/- 0.7), glycogen content (631 +/- 174 and 632 +/- 148 nmol/microg NCP) and lactate levels (59 +/- 27 and 52 +/- 29 nmol/microg NCP) compared with control regions. Irreversibly dysfunctional regions (n = 14) had severely reduced perfusion (0.48 +/- 0.15 vs. 0.72 +/- 0.12 ml/g/min, p < 0.001) and glucose-tracer uptake (52 +/- 16 vs. 94 +/- 15%, p < 0.001), reduced ATP/ADP ratio (1.5 +/- 0.9 vs. 2.3 +/- 0.9, p < 0.05), similar glycogen content (579 +/- 265 vs. 593 +/- 127 nmol/microg NCP) and increased lactate levels (114 +/- 52 vs. 89 +/- 24 nmol/microg NCP, p < 0.01) compared with control regions. CONCLUSIONS: Contents of metabolic energy stores and lactate in chronic reversibly dysfunctional myocardium were preserved. In contrast, energy stores were depleted in myocardium without functional recovery after revascularization.

Formation and in situ sizing of gamma-Fe2O3 nanoparticles in a microwave flow reactor.

Nanocrystalline gamma-Fe2O3 particles were produced in a microwave flow reactor. The reaction of iron pentacarbonyl [Fe(CO)5] with the plasma gases Ar/O2 to form nanosized particles was followed by in situ particle mass spectrometry. The particle mass spectrometer combines a nonintrusive sampling technique with a calibration-free mass determination. The influence of process parameters like microwave power, precursor concentration, and pressure on the particle size was studied. The results reveal a mean particle diameter in the range of 4-5 nm with a slight dependence on the process parameter. The geometric standard deviation of the measured size distribution was always between 1.1 and 1.2.

Positron emission tomography and low-dose dobutamine echocardiography in the prediction of postrevascularization improvement in left ventricular function and exercise parameters.

BACKGROUND: We studied the value of low-dose dobutamine echocardiography (LDDE) and positron emission tomography (PET) in predicting improvement of left ventricular function and exercise parameters after revascularization. METHODS: Forty-six consecutive patients with ischemic heart disease and an ejection fraction (EF) of 35% +/- 7% were included. Before revascularization, the patients underwent exercise testing and myocardial viability testing by LDDE and fluoride 18-fluoro-2-deoxyglucose PET. Six months after revascularization they underwent coronary angiography to study graft patency, and echocardiographic examination and the exercise test were repeated. RESULTS: In the prediction of the presence or absence of improved postrevascularization function in left ventricular regions with patent grafts, PET was more sensitive than LDDE (42/52 regions [81%] vs 27/52 regions [51%], P <.01), whereas LDDE was more specific than PET (187/209 regions [89%] vs 118/209 regions [56%], P <.001). Improvement of regional myocardial dysfunction was found in 19 patients, but their global left ventricular function did not improve significantly (EF 34% +/- 6% and 36% +/- 7%). In the remaining 27 patients with irreversible dysfunction, EF decreased (EF 36% +/- 7% vs 32% +/- 8%, P <.05). Among patients with reversible myocardial dysfunction, the rate pressure product (RPP) increased after revascularization (19,522 +/- 5474 vs 26,190 +/- 5610 mm Hg/min, P <.01), whereas the RPP did not change in patients with irreversible myocardial dysfunction (21,546 +/- 5450 and 22,774 +/- 8249 mm Hg/min). The number of PET viable segments was a predictor of the postoperative increase in the RPP in univariate (P <.04) and multivariate analyses (P <.001). In contrast, LDDE did not bear any prognostic information about improvement in the RPP. CONCLUSIONS: This study confirms earlier findings of higher sensitivity and lower specificity of PET compared with LDDE in predicting improvement of regional left ventricular function after revascularization. However, the feasibility of predicting postrevascularization improvement of exercise parameters seems unique for PET. The potential prognostic value of this finding needs further investigation.

Short-term effects of growth hormone on myocardial glucose uptake in healthy humans.

Cardiac muscle is characterized by insulin resistance in specific heart diseases such as coronary artery disease and congestive heart failure, but not in generalized disorders like diabetes mellitus and essential hypertension when cardiac manifestations are absent. To examine whether the insulin antagonistic effect of growth hormone (GH) acts upon the heart, we compared insulin-stimulated whole body and myocardial glucose uptake with and without GH administration during a 3.5-h euglycemic-hyperinsulinemic clamp in eight healthy males. Myocardial 2-deoxy-2-[(18)F]fluoro-D-glucose uptake was measured with positron emission tomography. The data were converted to myocardial glucose uptake by tracer kinetic analysis. GH did not change the rate-pressure product. GH decreased whole body insulin-stimulated glucose disposal by 26% (48.0 +/- 12.1 vs. control 62.8 +/- 6.1 micromol. kg(-1). min(-1), P < 0.02). Free fatty acids were suppressed to a similar extent with and without GH during the insulin clamp. Insulin-stimulated myocardial glucose uptake was similar in the presence and in the absence of GH (0.34 +/- 0.05 and 0.31 +/- 0.03 micromol. g(-1). min(-1), P = 0.18). In conclusion, GH does not impair insulin-stimulated myocardial glucose uptake despite a considerable whole body insulin antagonistic effect. Myocardial insulin resistance is not an inherent consequence of whole body insulin resistance.

Measurement of myocardial glucose uptake in patients with ischemic cardiomyopathy: application of a new quantitative method using regional tracer kinetic information.

UNLABELLED: Quantification of myocardial glucose uptake (MGU) by 18F-fluoro-2-deoxyglucose (FDG) using PET may be inaccurate, because the correction factor that relates myocardial FDG uptake to MGU, the lumped constant (LC), is not a true constant. Recent studies have shown that analysis of FDG time-activity curves allows determination of individual LCs and that variable LCs yield accurate determination of MGU. We compared the magnitude of the LC in different regions of the heart in patients with ischemic cardiomyopathy. METHODS: Twenty patients with ischemic cardiomyopathy and an average ejection fraction of 33% underwent dynamic 13N-ammonia and FDG PET. We determined myocardial perfusion and MGU in 177 regions classified as control (71 regions), mismatch (50 regions) and match (56 regions), according to findings on PET and echocardiography. Regional MGU was calculated with both regional LCs and a fixed LC of 0.67. RESULTS: All results were expressed as mean +/- SD. Myocardial perfusion was highest in control regions (0.52+/-0.18 mL/g/min), reduced in mismatch regions (0.43+/-0.19 mL/g/min; P < 0.05 versus control) and severely reduced in match regions (0.28+/-0.17 mL/g/min; P < 0.001 versus control and mismatch). Regional LCs ranged from 0.45 to 1.30 and differed between patients (P < 0.001). Regional LCs were similar in regions diagnosed as control (0.78+/-0.23), mismatch (0.80+/-0.24) and match (0.72+/-0.21). MGU (micromol/g/min) calculated by regional LCs was similar in control (0.52+/-0.16) and mismatch (0.49+/-0.19) regions and decreased in match regions (0.31+/-0.12, P < 0.001). The agreement between MGU calculated with variable and fixed LCs was poor. CONCLUSION: The LC used in the calculation of MGU was not affected by regional differences in the metabolic state of the myocardium. However, the LC varied substantially between patients in control, mismatch and match regions. These findings indicate that quantitative measurements of MGU using a fixed LC must be interpreted with caution.

Increased amounts of collagenase and gelatinase in porcine myocardium following ischemia and reperfusion.

We studied the presence of collagen degrading enzymes (matrix metalloproteinases, MMPs) in porcine myocardium following ischemia and late reperfusion. In nine pigs, left anterior descending coronary artery was occluded for 6 h followed by reperfusion for 3 h. Six pigs without coronary occlusion served as controls. After the reperfusion period, transmural biopsies from the anterior (ischemic zone) and posterior wall (non-ischemic myocardium) in the left ventricle were obtained and extracted. Heparin-Sepharose isolated components in extracts were analysed for collagenase (triple-helical collagen degradation) and gelatinase activity (zymography). Immunohistochemistry using anti-human (MMP-1, MMP-2, MMP-9, and fibronectin) antibodies was performed on additional biopsies. Collagenase (MMP-1) and gelatinases (MMP-2, MMP-9) could be demonstrated in the extracts of non-ischemic myocardium from ischemic/reperfused as well as control pigs and MMP-1 and MMP-9 activity was found to be increased in ischemic/reperfused myocardium compared with non-ischemic myocardium. In ischemic/reperfused myocardium from live pigs investigated, myocyte necrosis could be confirmed by fibronectin immunoreaction in myocytes and MMP-1 and MMP-9 immunoreactions were increased. MMP-9 was present in cells likely to be infiltrating leukocytes in a patchy distribution throughout the ischemic myocardium. Quite coincident with MMP-9 positive cells, MMP-1 immunoreaction appeared in necrotic myocytes, in addition to reactions observed in vessel walls, endo- and epicardium, and extracellular matrix in non-ischemic myocardium. Thus, the results showed increased amounts of collagenase (MMP-1) and gelatinase (MMP-9) in ischemic/ reperfused myocardium, indicating the appearance of increased amounts of collagen degrading enzymes very early following ischemia and late reperfusion.

Ischemia and reperfusion of the porcine myocardium: effect on collagen.

We studied the effect of acute myocardial infarction and late reperfusion on myocardial collagen in a closed chest porcine model, to investigate if any collagen degradation could be detected in blood samples and myocardium. Sixteen 60-80 kg pigs were used with six animals serving as controls and 10 submitted to ischemia-reperfusion. In the ischemia-reperfusion group the left anterior descending coronary artery was occluded for 6 h by inflation of a percutaneous transluminal coronary angioplasty balloon followed by reperfusion for 3 h. Blood samples were taken from the aorta and the coronary sinus and analyzed for creatine kinase and collagen degradation products, i.e. the N-terminal propeptide of procollagen type III (PIIINP) and C-terminal pyridinoline cross-linked telopeptide of collagen type I (ICTP). Myocardial tissue samples were analyzed for content of hydroxyproline, collagen volume fraction and amount of extractable PIIINP/dry weight. Transmission electron microscopy of biopsies was performed to evaluate myocytes and collagen structure outside and within the infarct zone. Creatine kinase showed a statistically significant increase during ischemia and reperfusion but we found no evidence of release of collagen degradation products either during ischemia or reperfusion compared with control. Myocardial content of hydroxyproline, collagen volume fraction and extractable PIIINP/dry weight did not differ between groups. Transmission electron microscopy of biopsies from the infarct zone showed myocyte damage but no visible evidence of collagen degradation when photos were evaluated blindly. In this porcine model of acute myocardial infarction and late reperfusion no release of collagen degradation products from the myocardium or any decrease in or damage to myocardial collagen was detected.

Chronic total occlusions of coronary arteries--medical versus surgical treatment.

Coronary artery bypass grafting (CABG) is an established treatment of patients with angina pectoris and chronic total coronary occlusion of major coronary arteries. However, in patients with mild or absent angina and chronic total coronary occlusion, optimal treatment is unsettled. We compared the prognosis of patients with chronic total coronary occlusion treated medically because of mild or absent angina with a matched group of patients undergoing CABG. In a retrospective design we evaluated all coronary angiographies performed in our department over a 5-year period. We identified 77 patients with chronic total occlusion of major coronary arteries eligible for CABG but treated medically because of mild or absent angina. The medically treated patients were matched on age, sex and ejection fraction with 77 patients with occluded major coronary arteries and angina pectoris who were treated surgically. The main outcome measures were death, acute myocardial infarction (AMI) and CABG. At baseline, CABG patients demonstrated an increased duration and severity of angina pectoris and an increased consumption of anti-anginal drugs. No differences were found with regard to angiographic parameters. The 5-year event rates (medically treated versus CABG) were: death, 14% vs 7% (p = 0.08); death or AMI; 27% vs 16% (p = 0.10); death, AMI or CABG, 34% vs 16% (p = 0.03) (log-rank statistics). In conclusion, our data indicate that patients with chronic total coronary occlusions and mild or absent anginal symptoms may benefit from surgical treatment.

[Parvovirus B19 infection as the cause of hepatitis and neutrophil granulocytosis in a 20-year old woman]. / Parvovirus B19-infektion som årsag til hepatitis og neutrofil granulocytose hos en 20-årig kvinde.

A case of Parvovirus B19 infection (erythema infectiosum) in a 20 year old woman is presented. The patient presented with fever, arthritis in one knee, neutrophil granulocytosis and biochemical evidence of hepatitis. Serological evidence of Parvovirus B19 infection was found as the only explanation of the clinical picture. Hepatitis was due to Parvovirus B19 infection as there was no serological evidence of EBV or CMV reactivation. Neutrophil granulocytosis and thrombocytosis were found and were probably due to an active bone marrow in the recovery phase of bone marrow aplasia.