[Algorithm for flexible decision-making in the intra-hospital management of patients with the changing requirements of the SARS-CoV-2 pandemic]. / Flexibler Entscheidungsalgorithmus zum innerklinischen stationären Patient*innen-Management unter wechselnden Anforderungen der SARS-CoV-2-Pandemie.

After the initial fulminant outbreak, the SARS-CoV­2 pandemic has now taken a more protracted course which, nevertheless, challenges hospitals in returning to a "normal" mode and in preparing for a worst-case scenario of a second wave. Not only the organization of the first contact with the patient and the admission in the emergency department but also the admission as an in-patient and the subsequent management requires both flexibility and clear directions of action for the medical personnel involved. The aim of the algorithm was to develop a structured, easy to implement and easy to follow guideline while simultaneously preserving resources. The algorithm covers some key points of decision making such as clinical signs, first contact, admission for in-patient treatment, consequences of swab and computed tomography (CT) results, and allocation and isolation measures within the hospital. The algorithm is not intended to guide diagnostics, decisions and treatment in the narrower medical sense but to provide more general instructions for the management of in-patients considering specific aspects of SARS-CoV­2.

Simultaneous quantitative susceptibility mapping and Flutemetamol-PET suggests local correlation of iron and ß-amyloid as an indicator of cognitive performance at high age.

The accumulation of ß-amyloid plaques is a hallmark of Alzheimer's disease (AD), and recently published data suggest that increased brain iron burden may reflect pathologies that synergistically contribute to the development of cognitive dysfunction. While preclinical disease stages are considered most promising for therapeutic intervention, the link between emerging AD-pathology and earliest clinical symptoms remains largely unclear. In the current study we therefore investigated local correlations between iron and ß-amyloid plaques, and their possible association with cognitive performance in healthy older adults. 116 older adults (mean age 75 ±â€¯7.4 years) received neuropsychological testing to calculate a composite cognitive score of performance in episodic memory, executive functioning, attention, language and communication. All participants were scanned on a combined PET-MRI instrument and were administered T1-sequences for anatomical mapping, quantitative susceptibility mapping (QSM) for assessing iron, and 18F-Flutemetamol-PET for estimating ß-amyloid plaque load. Biological parametric mapping (BPM) was used to generate masks indicating voxels with significant (p < 0.05) correlation between susceptibility and 18F-Flutemetamol-SUVR. We found a bilateral pattern of clusters characterized by a statistical relationship between magnetic susceptibility and 18F-Flutemetamol-SUVR, indicating local correlations between iron and ß-amyloid plaque deposition. For two bilateral clusters, located in the frontal and temporal cortex, significant relationships (p<0.05) between local ß-amyloid and the composite cognitive performance score could be observed. No relationship between whole-cortex ß-amyloid plaque load and cognitive performance was observable. Our data suggest that the local correlation of ß-amyloid plaque load and iron deposition may provide relevant information regarding cognitive performance of healthy older adults. Further studies are needed to clarify pathological correlates of the local interaction of ß-amyloid, iron and other causes of altered magnetic susceptibility.

Benefit of 18F-fluorocholine PET imaging in parathyroid surgery.

OBJECTIVES: To assess the additional diagnostic value of 18F-fluorocholine PET imaging in preoperative localization of pathologic parathyroid glands in clinically manifest hyperparathyroidism in case of negative or conflicting ultrasound and scintigraphy results. METHODS: A retrospective, single-institution study of 26 patients diagnosed with hyperparathyroidism. In cases where ultrasound and scintigraphy failed to detect the location of an adenoma in order to allow a focused surgical approach, an additional 18F-fluorocholine PET scan was performed and its results were compared with the intraoperative findings. RESULTS: A total of 26 patients underwent 18F-fluorocholine PET/CT (n = 11) or PET/MRI (n = 15). Adenomas were detected in 25 patients (96.2%). All patients underwent surgery, and the location predicted by PET hybrid imaging was confirmed intraoperatively by frozen section and adequate parathyroid hormone drop after removal. None of the patients needed revision surgery during follow-up. CONCLUSIONS: These results demonstrate that 18F-fluorocholine PET imaging is a highly accurate method to detect parathyroid adenomas even in case of previous localization failure by other imaging examinations. KEY POINTS: • With 18 F-fluorocholine PET imaging, parathyroid adenomas could be detected in 96.2%. • 18 F-fluorocholine imaging is a highly accurate method to detect parathyroid adenomas. • We encourage its use, where ultrasound fails to detect an adenoma.

Partitioning taxonomic diversity of aquatic insect assemblages and functional feeding groups in neotropical savanna headwater streams.

Biological diversity can be divided into: alpha (α, local), beta (ß, difference in assemblage composition among locals), and gamma (γ, total diversity). We assessed the partitioning of taxonomic diversity of Ephemeroptera, Plecoptera and Trichoptera (EPT) and of functional feeding groups (FFG) in neotropical savanna (southeastern Brazilian cerrado) streams. To do so, we considered three diversity components: stream site (α), among stream sites (ß1), and among hydrologic units (ß2). We also evaluated the association of EPT genera composition with heterogeneity in land use, instream physical habitat structure, and instream water quality variables. The percentage of EPT taxonomic α diversity (20.7%) was smaller than the ß1 and ß2 diversity percentages (53.1% and 26.2%, respectively). The percentage of EPT FFG collector-gatherer α diversity (26.5%) was smaller than that of ß1 diversity (55.8%) and higher than the ß2 (17.7%) diversity. The collector-gatherer FFG was predominant and had the greatest ß diversity percentage among stream sites (ß1, 55.8%). Our findings support the need for implementing regional scale conservation strategies in the cerrado biome, which has been degraded by anthropogenic activities.

Cardiac SPECT/CCTA hybrid imaging : One answer to two questions?

Noninvasive cardiac imaging has witnessed tremendous advances in the recent past, particularly with regard to coronary computed tomography angiography (CCTA) where substantial improvements in image quality have been achieved while at the same time patients' radiation dose exposure has been reduced to the sub-millisievert range. Similarly, for single-photon emission computed tomography (SPECT) the introduction of novel cadmium-zinc-telluride-based semiconductor detectors has significantly improved system sensitivity and image quality, enabling fast image acquisition within less than 2-3 min or reduction of radiation dose exposure to less than 5 mSv. However, neither imaging modality alone is able to fully cover the two aspects of coronary artery disease (CAD), that is, morphology and function. Both modalities have distinct advantages and shortcomings: While CCTA may prove a superb modality for excluding CAD through its excellent negative predictive value, it does not allow for assessment of hemodynamic relevance if obstructive coronary lesions are detected. Conversely, SPECT myocardial perfusion imaging cannot provide any information on the presence or absence of subclinical coronary atherosclerosis. This article aims to highlight the great potential of cardiac hybrid imaging that allows for a comprehensive evaluation of CAD through combination of both morphological and functional information by fusing SPECT with CCTA.

Dust-climate couplings over the past 800,000 years from the EPICA Dome C ice core.

Dust can affect the radiative balance of the atmosphere by absorbing or reflecting incoming solar radiation; it can also be a source of micronutrients, such as iron, to the ocean. It has been suggested that production, transport and deposition of dust is influenced by climatic changes on glacial-interglacial timescales. Here we present a high-resolution record of aeolian dust from the EPICA Dome C ice core in East Antarctica, which provides an undisturbed climate sequence over the past eight climatic cycles. We find that there is a significant correlation between dust flux and temperature records during glacial periods that is absent during interglacial periods. Our data suggest that dust flux is increasingly correlated with Antarctic temperature as the climate becomes colder. We interpret this as progressive coupling of the climates of Antarctic and lower latitudes. Limited changes in glacial-interglacial atmospheric transport time suggest that the sources and lifetime of dust are the main factors controlling the high glacial dust input. We propose that the observed approximately 25-fold increase in glacial dust flux over all eight glacial periods can be attributed to a strengthening of South American dust sources, together with a longer lifetime for atmospheric dust particles in the upper troposphere resulting from a reduced hydrological cycle during the ice ages.

Southern Ocean sea-ice extent, productivity and iron flux over the past eight glacial cycles.

Sea ice and dust flux increased greatly in the Southern Ocean during the last glacial period. Palaeorecords provide contradictory evidence about marine productivity in this region, but beyond one glacial cycle, data were sparse. Here we present continuous chemical proxy data spanning the last eight glacial cycles (740,000 years) from the Dome C Antarctic ice core. These data constrain winter sea-ice extent in the Indian Ocean, Southern Ocean biogenic productivity and Patagonian climatic conditions. We found that maximum sea-ice extent is closely tied to Antarctic temperature on multi-millennial timescales, but less so on shorter timescales. Biological dimethylsulphide emissions south of the polar front seem to have changed little with climate, suggesting that sulphur compounds were not active in climate regulation. We observe large glacial-interglacial contrasts in iron deposition, which we infer reflects strongly changing Patagonian conditions. During glacial terminations, changes in Patagonia apparently preceded sea-ice reduction, indicating that multiple mechanisms may be responsible for different phases of CO2 increase during glacial terminations. We observe no changes in internal climatic feedbacks that could have caused the change in amplitude of Antarctic temperature variations observed 440,000 years ago.

Effects of the Large June 1975 Meteoroid Storm on Earth's Ionosphere.

The June 1975 meteoroid storm detected on the moon by the Apollo seismometers was the largest ever observed. Reexamination of radio data taken at that time showed that the storm also produced pronounced disturbances on Earth, which were recorded as unique phase anomalies on very low frequency (VLF) radio propagation paths in the low terrestrial ionosphere. Persistent effects were observed for the major storm period (20 to 30 June 1975), including reductions in the diurnal phase variation, advances in the nighttime and daytime phase levels, and reductions in the sunset phase delay rate. Large nighttime phase advances, lasting a few hours, were detected on some days at all VLF transmissions, and for the shorter propagation path they were comparable to solar Lyman alpha daytime ionization. Ion production rates attributable to the meteor storm were estimated to be about 0.6 to 3.0 ions per centimeter cubed per second at the E and D regions, respectively. The storm was a sporadic one with a radiant (that is, the point of apparent origin in the sky) located in the Southern Hemisphere, with a right ascension 1 to 2 hours larger than the sun's right ascension.

Cytokeratin antibodies as differential markers of trophoblast and fetomaternal syncytial plaques in the sheep placentome.

The sheep placenta is an often used model in placental research. Uterine epithelium and trophoblast of this synepitheliochorial placenta form a complex, intensely interdigitating epithelial barrier separating maternal and fetal organisms. The close topographical relation and additionally the presence of hybrid syncytia formed by focal fusion of both epithelia hamper identification of the various cellular constituents. Therefore we aimed to find a specific immunohistochemical marker differentiating between the fetomaternal syncytial plaques and trophoblast. A monoclonal antibody directed against type II cytokeratins strongly stained unicellular trophoblast. The syncytial plaques were only weakly stained while binucleate trophoblast remained unstained. This antibody proved to be a useful tool for easy histological orientation in the sheep placenta. In combination with other antibodies in double immunohistochemistry it facilitates exact localization of antigens.

Caviomorph placentation as a model for trophoblast invasion.

The guinea pig and its relatives are promising candidates as animal models for studying trophoblast invasion. The origin, migration routes and kinetics of invasive trophoblast cells were examined in two caviomorph species. Histology and immunohistochemistry were done on placentas from 38 guinea pigs of days 20-47 and 13 degus of days 25-51 of gestation. BrdU was used as an in vivo marker for proliferation and for tracing of migration routes in the placenta; it was injected 24h to 15 days before collecting the material. In both species extravillous-like trophoblast cells are derived from proliferating stem cell aggregations in the subplacenta, which are comparable to the cell columns in humans. Migration routes and kinetics under in vivo conditions revealed a mean invasive depth of 300-350 microm/day and a mean life span of the extravillous-like trophoblast of 30 days. The patterns of trophoblast invasion in caviomorphs are analogous to the situation in humans, suggesting that these rodents are appropriate animal models for the study of the dynamics of trophoblast invasion.

Distribution of human endogenous retrovirus type W receptor in normal human villous placenta.

BACKGROUND: The fusion of trophoblast cells into the villous syncytiotrophoblast is crucial for appropriate placental function and fetal development. Fusion occurs following the interaction of syncytin-1, an envelope protein of the endogenous retrovirus HERV-W, and the RD114/mammalian type D retrovirus receptor (RDR/ASCT2) on adjacent cell membranes. This process must be tightly regulated in order to maintain the proliferative pool of cytotrophoblast cells as well as the function of the syncytia. AIM: We sought to investigate whether syncytial fusion of placental cytotrophoblast cells may be regulated via modulation of RDR/ASCT2 expression. METHODS: Expression of RDR/ASCT2 in term and first trimester villous placenta was assessed along with a number of molecular markers using immunofluorescent staining. In a complementary approach, Western blotting was used to investigate RDR/ASCT2 expression in a panel of choriocarcinoma cell lines before and after stimulation of fusion. RESULTS: Villous placental RDR/ASCT2 expression was found to be restricted to the cytotrophoblast compartment, being largely absent in the syncytiotrophoblast. Local variations in RDR/ASCT2 expression were not associated with the proliferative status of cytotrophoblast cells. RDR/ASCT2 expression was also shown to be down-regulated in BeWo choriocarcinoma cells after stimulation of syncytial fusion. CONCLUSION: This first report of the localisation and distribution of RDR/ASCT2 in human placental villi suggests that the fusion of placental trophoblast cells is not regulated by local or temporal variations of RDR/ASCT2 expression in villous cytotrophoblast cells.

The regulatory background of nuclear cardiology in Europe: a survey by the European Council of Nuclear Cardiology.

PURPOSE: Nuclear cardiology is a well-validated, non-invasive imaging modality that is highly cost-effective as a diagnostic and prognostic tool in the evaluation of patients with known or suspected coronary artery disease. However, the number of procedures in Europe is very far from that which would be expected on the basis of epidemiological data, particularly when comparison is made with the USA. As a preliminary step for future action aimed at improving and increasing nuclear cardiology practice in Europe, the European Council of Nuclear Cardiology performed a survey to identify the regulatory issues and the training components pertaining to the practice of nuclear cardiology. METHODS: a questionnaire was sent to 31 national nuclear medicine societies and to 40 national cardiology societies. The main areas covered by the survey were: (1) the license requirements, (2) the theoretical and practical aspects of training and (3) supervision of the stress test during a nuclear cardiology study. RESULTS: The results show that, in a setting of wide heterogeneity of national regulations, education and professional practice, nuclear medicine is a restricted and closely regulated specialty. This situation guarantees the quality and safe use of radionuclides; at the same time, however, it limits integration of nuclear medicine into the clinical arena. CONCLUSION: Cardiologists should become more involved in nuclear cardiology, to further stimulate the use of this powerful diagnostic and prognostic imaging modality.

[Influence of body mass index on coronary artery opacification in 64-slice CT angiography]. / Einfluss des Bodymass-Index auf den Kontrast in den Koronararterien mit der 64-Schicht-CT.

PURPOSE: To evaluate the influence of the body mass index (BMI) on coronary artery opacification in 64-slice CT. MATERIAL AND METHODS: Sixty-two patients retrospectively underwent ECG-gated 64-slice CT coronary angiography (tube potential 120 kV, tube current time product 650 mAs) after intravenous injection of 80 ml of iodinated contrast agent (320 mg/ml, 5 ml/s). Attenuation values (HU) were measured and contrast-to-noise ratios (CNR) were calculated in the right coronary artery (RCA) and left main artery (LMA). The CNR was defined as the difference between the mean attenuation in the vessel and the mean attenuation in the perivascular fat tissue divided by the image noise in the ascending aorta. The height and weight of the patients at the time of the CT scan were recorded and the BMI was calculated. RESULTS: The mean BMI was 26.2 +/- 3.2 kg/m (2) (range 19.7 - 32.2 kg/m (2)), the mean attenuation in the LMA was 330 +/- 64 HU, and the mean attenuation in the RCA was 309 +/- 68 HU. The CNR in the LMA was 16.7 +/- 3.8, and the CNR in the RCA was 15.9 +/- 3.6. The image noise in the ascending aorta significantly correlated with the BMI (r = 0.36, p < 0.01). A weak negative correlation was found between the BMI and LMA attenuation (r = - 0.28, p < 0.05), whereas no significant correlation was found for the RCA (r = - 0.21, p = 0.12). A significant negative correlation was found between the BMI and the CNR in the RCA (r = - 0.41, p < 0.05) and the LMA (r = - 0.47, p < 0.001). CONCLUSION: With constant scan parameters and a constant contrast medium amount, the CNR in both coronary arteries decreases while the BMI increases. This implies a modification of previously standardized and fixed examinations with respect to individually adapted protocols with variable parameters for CT coronary angiography.

Hyperbaric oxygenation in the treatment of life-threatening isobutyl nitrite-induced methemoglobinemia--a case report.

Methemoglobinemia usually results from exposure to oxidizing substances such as nitrates or nitrites. Iron within hemoglobin is oxidized from the ferrous (Fe2+) state to the ferric (Fe3+) state, resulting in the inability to transport oxygen and carbon dioxide. Clinically, this condition causes functional cyanosis. As methemoglobin levels increase, patients show evidence of cellular hypoxia in all tissues. Death usually occurs when methemoglobin fractions approach 70% of total hemoglobin. We describe the case of a 35-year-old female patient with severe life-threatening isobutyl nitrite-induced methemoglobinemia of 75% of total hemoglobin. Toluidine-blue was administered as first-line antidotal therapy immediately, followed by hyperbaric oxygenation. The patient recovered uneventfully and could be discharged 3 days later.

Effect of NO donors on LV diastolic function in patients with severe pressure-overload hypertrophy.

BACKGROUND: Previous experimental studies have shown that nitric oxide (NO) modulates cardiac function by an abbreviation of systolic contraction and an enhancement of diastolic relaxation. However, the response to NO donors of patients with severe pressure-overload hypertrophy and diastolic dysfunction is unknown. METHODS AND RESULTS: Intracoronary NO donors were given to 17 patients with severe aortic stenosis. A dose-response curve was obtained with nitroglycerin (30, 90, and 150 microg) in 11 patients and sodium nitroprusside (1, 2, and 4 microg/min) in 6. Left ventricular (LV) high-fidelity pressure measurements with simultaneous LV angiograms were performed at baseline and after the maximal dose of NO. The dose-response curve for intracoronary NO donors showed a marked fall in LV end-diastolic pressure, from 23 to 14 mm Hg (-39%; P<0.0001), whereas LV peak systolic pressure fell only slightly, from 206 to 196 mm Hg (-4%; P<0.01). End-diastolic chamber stiffness decreased from 0.12 to 0.07 mm Hg/mL (P<0.0001) and end-systolic stiffness from 1.6 to 1.3 mm Hg/mL (P<0.01). Heart rate, right atrial pressure, LV ejection fraction, the time constant of isovolumic pressure decay (tau), and LV filling rates remained unchanged. CONCLUSIONS: In patients with severe pressure-overload hypertrophy, intracoronary NO donors exert a marked decrease in LV end-diastolic pressure without affecting LV systolic pump function. Thus, the hypertrophied myocardium appears to be particularly susceptible to NO donors, with a marked improvement in diastolic function.

Coronary heart disease in smokers: vitamin C restores coronary microcirculatory function.

BACKGROUND: Coronary endothelial function and vasomotion are impaired in smokers without coronary disease, and this is thought to be due to increased oxidative stress. METHODS AND RESULTS: We used positron emission tomography to measure the coronary flow reserve, an integrated measure of coronary flow, through both the large epicardial coronary arteries and the microcirculation in 11 smokers and 8 control subjects before and after administration of the antioxidant vitamin C. At baseline, coronary flow reserve was reduced by 21% in smokers compared with control subjects (P:<0.05) but was normalized after vitamin C, whereas the drug had no effect in control subjects. CONCLUSIONS: The present study is the first to demonstrate that the noxious prooxidant effects of smoking extend beyond the epicardial arteries to the coronary microcirculation and affect the regulation of myocardial blood flow. Vitamin C restores coronary microcirculatory responsiveness and impaired coronary flow reserve in smokers, which provides evidence that the damaging effect of smoking is at least in part accounted for by an increased oxidative stress.

Syncytial fusion of human trophoblast depends on caspase 8.

Differentiation of human placental villous trophoblast includes syncytial fusion of cytotrophoblast forming syncytiotrophoblast. Early stages of the apoptosis cascade were described to be involved in this differentiation process. We investigated the role of the initiator caspase 8 in syncytial fusion in vitro, cultivating placental villous explants with or without caspase 8 antisense oligonucleotides or peptide inhibitors for up to 120 h. Trophoblast fusion and differentiation were assessed by confocal microscopy, immunohistochemistry and Western blot analysis. Culture with caspase 8 antisense oligonucleotides or peptide inhibitors reduced the fusion of cytotrophoblast with the syncytiotrophoblast, and resulted in multilayered cytotrophoblast. Caspase 8 expression was suppressed by antisense oligonucleotides and caspase 8 activities were reduced by peptide inhibitors. The organic anion-transporter hOAT-4 normally expressed in the cytotrophoblast and transferred into the syncytiotrophoblast by syncytial fusion was retained in the cytotrophoblast due to lack of fusion. We conclude that expression and activity of caspase 8 is a prerequisite for differentiation and syncytial fusion of cytotrophoblast cells.

Coronary vasomotion during dynamic exercise: influence of intravenous and intracoronary nicardipine.

OBJECTIVES: Our aim was to evaluate the influence of a calcium channel blocking agent of the dihydropyridine group (nicardipine) on coronary vasomotion during dynamic exercise. BACKGROUND: Coronary vasomotion plays an important role in the pathophysiology of myocardial ischemia. METHODS: Twenty-nine patients with coronary artery disease were studied at rest and during bicycle exercise with the use of biplane quantitative coronary angiography. Twelve patients without pretreatment (group 1) served as control subjects. Seventeen patients (group 2) received nicardipine, either 0.2 mg by intracoronary injection (n = 9) or 2.5 mg intravenously (n = 8) before exercise. RESULTS: In the control group there was exercise-induced vasoconstriction (-29%, p < 0.001) of the stenotic segment but coronary vasodilation (+22%, p < 0.05) of the normal vessel segment. In group 2, nicardipine induced coronary vasodilation of both the normal (+16%, p < 0.001) and the stenotic vessel segment (+35%). During subsequent exercise there was some additional vasodilation of normal (+4%, p = NS) and stenotic arteries (+5%, p = NS). There was no difference between either intracoronary or intravenous nicardipine with regard to vasodilation. Application of sublingual nitroglycerin was associated with significant vasodilation of the normal vessel segment in groups 1 (+18%, p < 0.05) and 2 (+15%, p < 0.001). The stenotic vessels showed a significant increase in percent cross-sectional area after nitroglycerin in groups 1 (+12%, p = NS) and 2 (+51%, p < 0.001). Exertional angina pectoris occurred less frequently in group 2 (18%) than in group 1 (67% [p < 0.005 vs. group 2]); group 2 also had a smaller increase in mean pulmonary artery pressure (+14 vs. +21 mm Hg, p < 0.05). CONCLUSIONS: Exercise induces vasoconstriction of stenotic, but vasodilation of normal, coronary vessel segments. Intravenous and intracoronary nicardipine prevent vasoconstriction of stenotic coronary arteries during exercise and exert a significant anti-ischemic effect. The combination of two anti-ischemic drugs, nitroglycerin and nicardipine, has an additive effect on coronary vasomotion that is seen only in the stenotic vessel segment. Thus, the anti-ischemic action of nicardipine is mainly due to a primary effect on coronary vasomotor response rather than to secondary effects such as changes in loading conditions.

Coronary artery dimensions in primary and secondary left ventricular hypertrophy.

BACKGROUND: Coronary artery enlargement has been previously described in left ventricular hypertrophy. OBJECTIVES: We sought to assess coronary artery dimensions and their relation to left ventricular muscle mass in primary and secondary hypertrophy. METHODS: Cross-sectional area of the left and right coronary arteries was determined by quantitative coronary angiography in 52 patients: 12 control subjects and 40 patients (13 with hypertrophic cardiomyopathy, 12 with dilated cardiomyopathy and 15 with aortic valve disease). As a measure of left ventricular hypertrophy, angiographic left ventricular mass and equatorial cross-sectional muscle area were determined. RESULTS: Cross-sectional area of both the left and right coronary arteries is increased in left ventricular hypertrophy (p < 0.05 vs. values in control subjects). There is a curvilinear relation between left coronary artery size and left ventricular muscle mass (r = 0.76) or cross-sectional muscle area (r = 0.75). However, normalization of coronary cross-sectional area for left ventricular muscle mass or muscle area shows insufficient enlargement of the coronary arteries in both primary and secondary hypertrophy. CONCLUSIONS: 1) Coronary artery size increases as left ventricular mass increases in both primary and secondary hypertrophy. 2) The enlargement of left coronary cross-sectional area is independent of the cause of the increase in left ventricular mass. 3) The size of the coronary arteries is inappropriate with regard to left ventricular hypertrophy. Thus, the stimulus for growth of the coronary arteries is not influenced by the underlying disease but appears to depend on the degree of left ventricular hypertrophy.

Low density lipoprotein cholesterol and coronary microvascular dysfunction in hypercholesterolemia.

OBJECTIVES: The present study evaluates the impact of total cholesterol (TC) and its subfractions on coronary flow reserve (CFR), an index of the integrated function of the coronary circulation, in asymptomatic subjects. BACKGROUND: Endothelial dysfunction of the coronary microcirculation has been reported in asymptomatic subjects with hypercholesterolemia. METHODS: Using oxygen-15-labeled water and positron emission tomography, myocardial blood flow (MBF, in ml/min per g) was measured at rest and during intravenous adenosine (140 microg/kg body weight per min) in 80 asymptomatic nonsmoking men: group 1 (n = 61; age 45 +/- 7 years) had normal TC (< or =6.5 mmol/liter or < or =250 mg/dl) and group 2 (n = 19; age 48 +/- 10 years) had elevated TC. RESULTS: Total cholesterol were 5.1 +/- 0.8 and 7.2 +/- 0.7 mmol/liter in groups 1 and 2 (p < 0.0005), respectively; low density lipoprotein (LDL) cholesterol levels were 3.2 +/- 0.8 and 4.9 +/- 0.7 mmol/liter (p < 0.0005); high density lipoprotein (HDL) cholesterol levels were 1.1 +/- 0.3 and 1.0 +/- 0.4 mmol/liter (p = NS); and triglyceride levels were 1.8 +/- 1.3 and 3.0 +/- 1.8 mmol/liter (p < 0.005). Groups 1 and 2 did not differ with regard to MBF at rest (0.87 +/- 0.14 vs. 0.84 +/- 0.14), MBF during adenosine (3.63 +/- 1.02 vs. 3.30 +/- 0.86) or CFR (4.23 +/-1.29 vs. 3.95 +/- 0.93). A significant but weak correlation was found between CFR and HDL in group 1 (r = 0.29, p < 0.05), but not in group 2. In contrast, a significant inverse correlation between LDL and CFR was found in group 2 (r = -0.61, p < 0.05), but not in group 1. CONCLUSIONS: Low density lipoprotein cholesterol but not TC correlated inversely with CFR in hypercholesterolemic subjects. Thus, LDL-induced coronary microvascular dysfunction could play an important role in the pathogenesis of coronary artery disease and its complications.