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Stefan Neubauer

Publications and source records attributed to Stefan Neubauer.

94 records · Page 6Linked to original sources
PubMed2002

Mitochondrial creatine kinase is critically necessary for normal myocardial high-energy phosphate metabolism.

The individual functional significance of the various creatine kinase (CK) isoenzymes for myocardial energy homeostasis is poorly understood. Whereas transgenic hearts lacking the M subunit of CK (M-CK) show unaltered cardiac energetics and left ventricular (LV) performance, deletion of M-CK in combination with loss of sarcomeric mitochondrial CK (ScCKmit) leads to significant alterations in myocardial high-energy phosphate metabolites. To address the question as to whether this alteration is due to a decrease in total CK activity below a critical threshold or due to the specific loss of ScCKmit, we studied isolated perfused hearts with selective loss of ScCKmit (ScCKmit(-/-), remaining total CK activity approximately 70%) using (31)P NMR spectroscopy at two different workloads. LV performance in ScCKmit(-/-) hearts (n = 11) was similar compared with wild-type hearts (n = 9). Phosphocreatine/ATP, however, was significantly reduced in ScCKmit(-/-) compared with wild-type hearts (1.02 +/- 0.05 vs. 1.54 +/- 0.07, P < 0.05). In parallel, free [ADP] was higher (144 +/- 11 vs. 67 +/- 7 microM, P < 0.01) and free energy release for ATP hydrolysis (DeltaG(ATP)) was lower (-55.8 +/- 0.5 vs. -58.5 +/- 0.5 kJ/mol, P < 0.01) in ScCKmit(-/-) compared with wild-type hearts. These results demonstrate that M- and B-CK containing isoenzymes are unable to fully substitute for the loss of ScCKmit. We conclude that ScCKmit, in contrast to M-CK, is critically necessary to maintain normal high-energy phosphate metabolite levels in the heart.

Animals↗
PubMed2002

Analysis of right ventricular function in healthy mice and a murine model of heart failure by in vivo MRI.

Because of its complex geometry, assessment of right ventricular (RV) function is more difficult than it is for the left ventricle (LV). Because gene-targeted mouse models of cardiomyopathy may involve remodeling of the right heart, the purpose of this study was to develop high-resolution functional magnetic resonance imaging (MRI) for in vivo quantification of RV volumes and global function in mice. Thirty-three mice of various age were studied under isoflurane anesthesia by electrocardiogram-triggered cine-MRI at 7 T. MRI revealed close correlations between RV and LV stroke volume and cardiac output (r = 0.97, P < 0.0001 each). Consistent with human physiology, murine RV end-diastolic and end-systolic volumes were significantly higher compared with LV volumes (P < 0.05 each). MRI in mice with LV heart failure due to myocardial infarction revealed significant structural and functional changes of the RV, indicating RV dysfunction. Hence, MRI allows for the quantification of RV volumes and global systolic function with high accuracy and bears the potential to evaluate mechanisms of RV remodeling in mouse models of heart failure.

Animals↗
PubMed2002

Cardiac systolic rotation and contraction before and after valve replacement for aortic stenosis: a myocardial tagging study using MR imaging.

OBJECTIVE: Aortic stenosis leads to the derangement of cardiac function and contraction mode because of chronic pressure overload that is relieved after surgical valve replacement. The purpose of this study was to determine the changes in left ventricular systolic rotation and contraction using MR tagging in patients with aortic stenosis before and after surgical valve replacement compared with age-matched healthy volunteers. MATERIALS AND METHODS: Twelve patients with aortic stenosis were examined with an electrocardiographically triggered two-dimensional tagging sequence at 1.5 T before and 12 months after surgical valve replacement for the evaluation of wall function of the apical, mid ventricular, and basal levels. Eight healthy volunteers in the same age group served as the control group. RESULTS: Before surgery, all patients showed a significant increase of apical rotation (22.2 degrees +/- 5.9 degrees vs 10.3 degrees +/- 2.5 degrees, p < 0.0001) and overall left ventricular torsion (25.1 degrees +/- 6.6 degrees vs 14.5 degrees +/- 3.7 degrees, p < 0.001); basal rotation was not significantly different (-2.9 degrees +/- 2.1 degrees vs -4.2 degrees +/- 1.9 degrees, p = not significant) compared with the volunteer group. Apical rotation and torsion were negatively correlated with left ventricular mass (r = -0.73, p < 0.01, and r = -0.61, p < 0.05, respectively) and end-diastolic volume (r = -0.73, p < 0.01 and r = -0.64, p < 0.03, respectively). One year after surgery, basal rotation was reduced in the patients with aortic stenosis compared with the patients in the control group (-1.9 degrees +/- 1.8 degrees, p < 0.01). In comparison with preoperative values, apical rotation (14.2 degrees +/- 3.6 degrees, p < 0.01) also decreased but was still elevated, and this resulted in a normalization of left ventricular torsion (16.1 degrees +/- 3.7 degrees, p < 0.01). CONCLUSION: Surgical valve replacement for aortic stenosis leads to normalization of the left ventricular torsion 1 year after surgery. Pressure overload before surgery is associated with an increase of systolic left ventricular wringing motion, possibly serving as a compensatory mechanism. This mechanism declines with increasing left ventricular hypertrophy and dilatation.

Adult↗