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Sven Hermann

Publications and source records attributed to Sven Hermann.

9 recordsLinked to original sources
PubMed2007

Molecular cardiovascular imaging using scintigraphic methods.

Molecular cardiovascular imaging plays an increasingly important role both in basic research and in clinical diagnosis. Scintigraphic methods have long been used to study pathophysiological changes on a cellular and molecular level, and they are likely to remain important molecular imaging modalities in the foreseeable future. This article provides an overview over current developments in cardiovascular molecular imaging using scintigraphic methods. The focus lies on imaging of cardiac innervation, plaque instability, hypoxia and angiogenesis, gene expression and stem and progenitor cell migration and proliferation.

Animals↗
PubMed2006

High-density lipoproteins and their constituent, sphingosine-1-phosphate, directly protect the heart against ischemia/reperfusion injury in vivo via the S1P3 lysophospholipid receptor.

BACKGROUND: All treatments of acute myocardial infarction are aimed at rapid revascularization of the occluded vessel; however, no clinical strategies are currently available to protect the heart from ischemia/reperfusion injury after restitution of blood flow. We hypothesized that some of the cholesterol transport-independent biological properties of high-density lipoprotein (HDL) implied in atheroprotection may also be beneficial in settings of acute myocardial reperfusion injury. METHODS AND RESULTS: In an in vivo mouse model of myocardial ischemia/reperfusion, we observed that HDL and its sphingolipid component, sphingosine-1-phosphate (S1P), dramatically attenuated infarction size by approximately 20% and 40%, respectively. The underlying mechanism was an inhibition of inflammatory neutrophil recruitment and cardiomyocyte apoptosis in the infarcted area. In vitro, HDL and S1P potently suppressed leukocyte adhesion to activated endothelium under flow and protected rat neonatal cardiomyocytes against apoptosis. In vivo, HDL- and S1P-mediated cardioprotection was dependent on nitric oxide (NO) and the S1P3 lysophospholipid receptor, because it was abolished by pharmacological NO synthase inhibition and was completely absent in S1P3-deficient mice. CONCLUSIONS: Our data demonstrate that HDL and its constituent, S1P, acutely protect the heart against ischemia/reperfusion injury in vivo via an S1P3-mediated and NO-dependent pathway. A rapid therapeutic elevation of S1P-containing HDL plasma levels may be beneficial in patients at high risk of acute myocardial ischemia.

Animals↗
PubMed2006

Successful high-resolution animal positron emission tomography of human Ewing tumours and their metastases in a murine xenograft model.

PURPOSE: As primary osseous metastasis is the main adverse prognostic factor in patients with Ewing tumours, a NOD/scid mouse model for human Ewing tumour metastases has been established to examine the mechanisms of metastasis. The aim of this study was to evaluate the feasibility of diagnostic molecular imaging by small animal PET in this mouse model. METHODS: Human Ewing tumour cells were transplanted into immune-deficient NOD/scid mice via s.c injection (n=17) or i.v. injection (n=17). The animals (mean weight 23.2 g) were studied 2-7 weeks after transplantation using a submillimetre resolution animal PET scanner. To assess glucose utilisation and bone metabolism, mice were scanned after intravenous injection of 9.6 MBq (mean) 2-[(18)F]fluoro-2-deoxy-D: -glucose (FDG) or 9.4 MBq (mean) [(18)F]fluoride. Whole-body PET images were analysed visually and semi-quantitatively [%ID/g, tumour to non-tumour ratio (T/NT)]. Foci of pathological uptake were identified with respect to the physiological organ uptake in corresponding regions. RESULTS: Subcutaneously transplanted Ewing tumours demonstrated a moderately increased glucose uptake (median %ID/g 2.5; median T/NT 2.2). After i.v. transplantation, the pattern of metastasis was similar to that in patients with metastases in lung, bone and soft tissue. These metastases showed an increased FDG uptake (median %ID/g 3.6; median T/NT 2.7). Osseous metastases were additionally visible on [(18)F]fluoride PET by virtue of decreased [(18)F]fluoride uptake (osteolysis; median %ID/g 8.4; median T/NT 0.59). Metastases were confirmed immunohistologically. CONCLUSION: Diagnostic molecular imaging of Ewing tumours and their small metastases in an in vivo NOD/scid mouse model is feasible using a submillimetre resolution PET scanner.

Animals↗
PubMed2006

Accurate noninvasive measurement of infarct size in mice with high-resolution PET.

UNLABELLED: Reliable, repeatable, and time-efficient noninvasive measurement of infarct size in mice with PET would benefit studies aimed at the exploration of biochemical and functional changes associated with acute myocardial infarction (MI). PET with the radioactively labeled glucose derivative (18)F-FDG is used in humans to distinguish between viable but dysfunctional and nonviable myocardium. In this study, the feasibility, accuracy, and time efficiency of (18)F-FDG PET for quantification of infarct size in mice using a high-resolution animal PET device was evaluated in comparison with histomorphometry. METHODS: Mice were subjected to surgery with permanent ligation of the left anterior descending artery. PET was performed before and 7 d after surgery. The infarct size was determined from the PET studies using both manual and automated delineation. The second PET scan was followed by histomorphometric analysis. RESULTS: An excellent correlation between PET and histomorphometry was found for both manual (R = 0.98) and automated (R = 0.98) delineation, with linear regression curves close to unity (manual: y = 1.10x - 0.01; automated: y = 1.12x - 0.02). Automated analysis required <1 min per study. CONCLUSION: The measurement of infarct size in mice with (18)F-FDG PET is feasible and highly accurate. This noninvasive methodology permits unique longitudinal studies of biochemical parameters in mice and facilitates studies that aim to assess the effect of surgical and pharmacologic intervention after acute MI.

Algorithms↗
PubMed2005

[Scintigraphic molecular imaging].

Modern medicine is currently focusing its basic and clinical research towards "molecular medicine". This trend, together with the decoding of the human genome and the resulting design and use of transgenic mouse models of human diseases, demands that innovative imaging approaches are developed for man and mice. Non-invasive imaging modalities capable of quantifying molecular processes in vivo (collectively defined as "molecular imaging" techniques) are extremely interesting in this respect. This review focuses on the clinical and experimental scintigraphic molecular-imaging modalities SPECT and PET, and summarizes their actual and future impact in medicine.

Animals↗
PubMed2005

Monitoring left ventricular dilation in mice with PET.

UNLABELLED: Molecular imaging by small-animal PET is an important noninvasive means to phenotype transgenic mouse models in vivo. When investigating pathologies of the left ventricular (LV) myocardium, the serial assessment of LV volumes is important. By this, the presence of LV dilation as a sign of developing heart failure can be detected. Whereas PET is usually used to derive biochemical and molecular information, functional parameters such as ventricular volumes are generally measured using echocardiography or MRI. In this study, a novel method to monitor LV dilation in mice with PET is presented and evaluated using cardiac MRI. METHODS: A semiautomatic 3-dimensional algorithm was used to delineate the LV myocardial wall on static PET images depicting myocardial glucose metabolism ((18)F-FDG PET) for 20 mice: 10 wild-type and 10 genetically modified littermates designed to develop a dilative cardiomyopathy phenotype (cardiomyocyte-specific knockout of survivin). The volume enclosed by the 3-dimensional midmyocardial contour was calculated as a measure for LV volume for each mouse. Data were compared with ventricular volumes measured by MRI in the same animals. RESULTS: LV volumes obtained by PET and MRI correlated well (R = 0.89) for hearts with small and large left ventricles. In accordance with the hypothesis, the LV volumes were increased significantly for transgenic mice examined at an older age compared with those examined at a younger age (MRI: 160.5 +/- 25.7 microL vs. 114.7 +/- 15.2 microL [P = 0.012]; PET: 129.3 +/- 15.3 microL vs. 73.8 +/- 15.0 microL [P < 0.001], all values shown as mean +/- SD; for MRI, mean of end-diastolic and end-systolic volumes are given), whereas they did not for their wild-type littermates (MRI: 106.2 +/- 12.3 microL vs. 94.7 +/- 14.6 microL [P = 0.214]; PET: 82.6 +/- 20.9 microL vs. 65.0 +/- 16.9 microL [P = 0.185]). CONCLUSION: Evaluation and quantitation of LV dilation in both control and cardiomyopathic mice can be reliably and serially performed using small-animal PET and (18)F-FDG, yielding useful functional information in addition to metabolic data.

Aging↗
PubMed2004

High-density lipoprotein stimulates myocardial perfusion in vivo.

BACKGROUND: Several clinical studies have demonstrated a close association between plasma HDL cholesterol levels and endothelium-dependent vasodilation in peripheral arteries. In isolated arteries, HDL has been shown to mediate vasodilation via NO release. In vivo, administration of reconstituted HDL restored abnormal endothelial function of the brachial artery in hypercholesterolemic patients. However, no data are currently available on the effect of HDL on myocardial perfusion. METHODS AND RESULTS: In this study, administration of human HDL enhanced incorporation of the perfusion tracer 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) into the murine heart in vivo by approximately 18%. This increase was completely abolished in mice deficient for endothelial NO synthase. Because we have recently identified sphingosine 1-phosphate (S1P) as an important vasoactive component contained in HDL, we measured myocardial perfusion after administration of S1P in vivo. We observed an approximately 25% decrease in myocardial MIBI uptake, which was abolished in mice deficient for the S1P receptor S1P3. In S1P3-/- mice, the stimulatory effect of HDL on myocardial perfusion was preserved. CONCLUSIONS: HDL increased myocardial perfusion under basal conditions in vivo via NO-dependent mechanisms, whereas S1P inhibited myocardial perfusion through the S1P3 receptor. Thus, HDL may reduce coronary risk via direct NO-mediated vasodilatory effects on the coronary circulation.

Animals↗
PubMed2004

Functional changes after partial left ventriculectomy and mitral valve repair assessed by gated perfusion SPECT.

UNLABELLED: A myocardial remodeling in dilated cardiomyopathy (DCM) after partial left ventriculectomy (PLV) has been previously discussed. The aim of this study was to investigate the functional changes in the follow-up of patients with DCM undergoing PLV using electrocardiographically triggered perfusion SPECT (gated SPECT). METHODS: Twelve DCM patients (10 men, 2 women; 56 +/- 9 y [mean +/- SD]), after successful PLV and mitral valve repair (PLV-MVR), were monitored by gated SPECT and echocardiography. Gated SPECT quantified end-diastolic volumes (EDV), end-systolic volumes (ESV), myocardial and scar volumes, as well as ejection fraction (EF) preoperatively, early (38 +/- 28 d), and late (296 +/- 130 d) after PLV-MVR. RESULTS: EDV and ESV showed an immediate reduction after PLV-MVR (EDV from 542 +/- 90 mL to 350 +/- 81 mL, P < 0.001; ESV from 452 +/- 91 mL to 254 +/- 79 mL, P < 0.001) with no significant change in the late follow-up (EDV late, 316 +/- 63 mL; ESV late, 207 +/- 63 mL; both P = not significant vs. early follow-up). PLV-MVR immediately improved EF (preoperative, 16.8% +/- 5.5%; early, 28.8% +/- 7.6%; P = 0.003) with no significant change in the late follow-up (36.0% +/- 9.4%; P = not significant vs. early follow-up). CONCLUSION: In this highly selected DCM patient group, gated perfusion SPECT assessed early responses in volumes and EF after PLV-MVR. However, although statistically nonsignificant in the small patient group, ESV and EDV were further decreased, whereas EF improved toward 1 y, coinciding with the improvement of clinical symptoms (New York Heart Association), potentially indicating a functional remodeling after PLV-MVR. Further studies in larger patient cohorts and longer follow-up are warranted.

Adult↗