S. Neubauer

Age- and gender-specific differences in left and right ventricular cardiac function and mass determined by cine magnetic resonance imaging.

Abstract. We examined possible age- and gender-specific differences in the function and mass of left (LV) and right (RV) ventricles in 36 healthy volunteers using cine gradient-recalled echo magnetic resonance imaging. Subjects were divided into four groups (nine men and nine women in each): men aged under 45 years (32 ± 7), women aged under 45 (27 ± 6), men aged over 45 (59 ± 8), and women aged over 45 (57 ± 9). Functional analysis of cardiac volume and mass and of LV wall motion was performed by manual segmentation of the endocardial and epicardial borders of the end-diastolic and end-systolic frame; both absolute and normalized (per square meter body surface area) values were evaluated. With age there was a significant decrease in both absolute and normalized LV and RV chamber volumes (EDV, ESV), while LV and RV masses remained unchanged. Gender-specific differences were found in cardiac mass and volume (for men and women, respectively: LV mass, 155 ± 18 and 110 ± 16 g; LV EDV, 118 ± 27 and 96 ± 21 ml; LV ESV, 40 ± 13 and 29 ± 9 ml; RV mass, 52 ± 10 and 39 ± 5 g; RV EDV, 131 ± 28 and 100 ± 23 ml; RV ESV, 53 ± 17 and 33 ± 15 ml). Normalization to body surface area eliminated differences in LV volumes but not those in LV mass, RV mass, or RV function. Functional parameters such as cardiac output and LV ejection fraction showed nonsignificant or only slight differences and were thus largely independent of age and gender. Intra- and interobserver variability ranged between 1.4 % and 5.9 % for all parameters. Cine magnetic resonance imaging thus shows age- and gender-specific differences in cardiac function, and therefore the evaluation of cardiac function in patients should consider age- and gender-matched normative values.

Changes in left and right ventricular cardiac function after valve replacement for aortic stenosis determined by cine MR imaging.

The purpose of this study was to determine the changes in function of both the left and the right ventricles (LV, RV) before and after aortic valve replacement (AVR), compared with age‐matched healthy volunteers using magnetic resonance (MR) imaging. Fourteen patients with aortic stenosis underwent MR imaging (1.5 T) before and 3 (n = 14) and 12 (n = 9) months after surgical valve replacement. An electrocardiographically triggered two‐dimensional cine fast low‐angle shot sequence was used for the evaluation of absolute values and indices related to 1 m 2 body surface area for function, mass, and LV wall thickening. Fourteen age‐matched healthy volunteers served as controls. Before surgery, all patients showed significant abnormalities of LV mass and function, whereas RV mass and function were not different from those of volunteers and remained mostly unchanged. After surgery, normalization of LV ejection fraction, absolute mass, and end‐systolic wall thickness was observed, whereas the LV mass index failed to normalize, and LV volumes remained elevated. Aortic stenosis combined with a significant, but not severe reduction in LV function only affects the LV, whereas the RV remains unaffected at this stage of disease. AVR leads to improved LV function and reduced hypertrophy, but without normalization of LV volumes or the LV mass index within 1 year. J. Magn. Reson. Imaging 2000;12:240–246.

Altered energy metabolism after myocardial infarction assessed by 31P-MR-spectroscopy in humans

Abstract. The value of 31P-magnetic resonance spectroscopy (MRS) as a possible tool to distinguish viable from non-viable tissue after myocardial infarction was analysed in humans. Fifteen patients 3 weeks after anterior myocardial infarction were studied with breath-hold cine MRI and 3D-CSI MRS (1.5 T system). 31P-spectra were obtained from infarcted as well as non-infarcted myocardium (voxel size 25 cm3 each). Gold standard for viability was recovery of regional function, as determined by a control MRI 6 months after revascularization. Ten age-matched healthy volunteers served as control group. No significant difference was found between the phosphocreatine to adenosinetriphosphate (PCr/ATP) ratio of volunteers (SD 1.72 ± 0.31) and non-infarcted septal myocardium of patients. Cine MRI demonstrated recovery of regional function in 10 patients, i. e. 10 patients showed viable and 5 non-viable myocardium. In viable myocardium, the PCr/ATP ratio was 1.47 ± 0.38 (non-significant vs volunteers; p > 0.05). In the 5 patients with akinetic myocardium, PCr peaks could not be detected. Therefore, calculation of PCr/ATP ratios was not possible. However, a significant reduction of the ATP signal-to-noise ratio (SNR) was observed (2.92 ± 0.73 vs 6.68 ± 0.80; patients vs volunteers; p <0.05). The SNR of ATP of akinetic regions may predict recovery of function after revascularization in patients with myocardial infarction.

Reduced 1H-NMR visibility of creatine in isolated rat hearts

The aim of this study was to measure the concentration of creatine in Langendorff perfused rat hearts, both by quantitative 1H‐MRS and by high‐pressure liquid chromatography (HPLC). First, the relaxation times and other parameters affecting absolute quantification by MRS were determined. At 11.75 T, the relaxation times of myocardial creatine were T1 = 1.1 ± 0.29 sec (mean ± SD, n = 5) and T2 = 56.4 ± 6.2 ms (n = 9). In phantom experiments the MRS measurements gave accurate values for the known relative concentrations of the detected substances. In glucose‐perfused rat hearts, the creatine concentration measured by HPLC was 14.2 ± 1.9 mmol/kg wet weight (n = 8), in good agreement with literature values. The 1H‐MRS measurements, however, resulted in creatine concentrations of only approximately 60% of this value. The application of CHESS‐pulses for water suppression led to a further 30% reduction of the creatine MRS signal. These results indicate a reduced 1H‐NMR visibility of creatine in the myocardium, which suggests a compartmentation of myocardial creatine into various pools. Magn Reson Med 43:497–502, 2000.

Imaging of intracellular sodium with shift reagent aided 23Na CSI in isolated rat hearts

23Na chemical shift imaging (CSI) in conjunction with shift reagents was used to obtain images of intracellular (Nai) and extracellular sodium (Nae) in isolated rat hearts. It was demonstrated that the increase of Nai concentration in ischemic myocardium can be detected with this technique. 3D acquisition‐weighted 23Na CSI datasets with a nominal spatial resolution of 1.7 × 1.7 × 2.9 mm were acquired in 30 min in normoxic hearts and in globally or locally ischemic hearts. The shift reagent Tm(DOTP)5− was used to discriminate Nai and Nae signals. Nai maps could be generated in ischemic hearts, but not in normoxic hearts as the signal‐to‐noise ratio is too low. The Nai signal increased by more than 100% and the Nae signal decreased by more than 50% in myocardium of globally ischemic hearts (n = 3) compared to normoxic hearts (n = 3). In hearts with an acute occlusion of the left anterior descending coronary artery (n = 3), there was a local Nai signal increase in the anterior wall in the range of 60–110% compared to remote, normoxic tissue. Magn Reson Med 48:89–96, 2002.

Advances in human cardiac 31P-MR spectroscopy: SLOOP and clinical applications.

Phosphorus magnetic resonance spectroscopy (31P‐MRS) has revealed a lot about the biochemistry of physiological and pathological processes in the heart. Nevertheless, until today, cardiac 31P‐MRS has not had any clinical impact, albeit some pioneering studies demonstrated that 31P‐MRS can indeed provide diagnostic information. In this paper, the development of techniques for human cardiac 31P‐MRS over the past decade is reviewed, and the requirements for a reliable clinical measurement protocol are discussed. Spatial localization with optimal pointspread function (SLOOP) is a new method to achieve spatial localization and absolute quantitation. Its properties are detailed, and preliminary findings in patients with dilated cardiomyopathy or myocardial infarction are presented. J. Magn. Reson. Imaging 2001;13:521–527.

31P-Nuclear Magnetic Resonance Spectroscopy of Blood: A Species Comparison

31P-nuclear magnetic resonance (NMR) spectroscopy isfrequently used as a tool in the study of organs from various animal species and humans. Because signals arising from the presence of blood are visible in in vivo 31P-NMR spectra of blood-filled organs, such as the heart, it is necessary to correct these spectra for the contribution of blood to the signal. It is unknown whether species differences in 31P signals of blood exist. 31P-containing metabolites of blood from various species were therefore quantified by means of 31P-NMR spectroscopy. Signals of 2,3-bisphosphoglycerate (2,3-DPG); phosphodiesters (PDE); and gamma-, alpha-, and beta-ATP were detected in all 31P-NMR spectra of blood. 2,3-DPG/ATP ratios were significantly higher in dogs, rats, and guinea pigs than in humans but lower in sheep. Pig and rabbit were the only animals with a 2,3-DPG/ATP ratio similar to that of humans. PDE levels varied among species but were significantly lower than in humans only in guinea pigs. The PDE/ATP ratio was relatively similar among all species compared with humans, except dog and guinea pig, where it was significantly higher and lower, respectively. We conclude that because of large species differences, species-specific 31P metabolite ratios should be applied for the correction of in vivo 31P-NMR spectra.

Untersuchungen des kardialen Energiestoffwechsels bei Herzvitien mit der 31P-MR-Spektroskopie

ZusammenfassungZielsetzung: Mit einer linksventrikulären Hypertrophie einhergehende Herzvitien führen zu Veränderungen des kardialen Energiestoffwechsels, die mit der 31P-MR-Spektroskopie nichtinvasiv erfasst werden können. Ziel der vorliegenden Studie war es, zu untersuchen, ob nach chirurgischem Klappenersatz eine Normalisierung des Energiestoffwechsels beobachtet werden kann.nn Patienten und Methode: 10 gesunde Probanden und 10 Patienten mit Aortenklappenstenose (Druckgradient >60xa0mmHg) wurden untersucht. Zur Erfassung des kardialen Energiestoffwechsels wurde eine doppelt angulierbare 3D-CSI-Technik verwendet (Voxelgröße 25 ccm). 3 Monate nach Aortenklappenersatz (AKE) erfolgte bei 5 Patienten eine Nachkontrolle. Bei den Patienten wurden zusätzlich linksventrikuläre (LV) Funktionsparameter mittels cine-MRI-Technik analysiert.nn Ergebnisse: Vor Klappenersatz war bei den Patienten das Phosphokreatin-Adenosintriphosphat(PCr-ATP)-Verhältnis mit 0,80±0,25 signifikant im Vergleich zu Gesunden (1,65±0,21; p=0,0002) erniedrigt. 3 Monate nach AKE konnte eine signifikante (p=0,04) Verringerung der LV-Masse von 238±33xa0g auf 206±47xa0g nachgewiesen werden. Die LV-Ejektionsfraktion änderte sich jedoch nicht wesentlich (von 61±11% auf 65±7%; p=0,22). Zur selben Zeit zeigte sich ein signifikanter (p=0,04) Anstieg des PCr-ATP-Verhältnis von 0,80±0,25 auf 1,28±0,22 an. Für das Phosphodiester-ATP-Verhältnis zeigte sich eine geringe, jedoch nicht signifikante Reduzierung vor AKE, mit einer Tendenz zum Wiederanstieg nach AKE.nn Schlussfolgerungen: Nach Klappenersatz ist eine Tendenz zur Normalisierung des pathologisch veränderten Energiestoffwechsels zu beobachten. Weitere Nachkontrollen sind notwendig, um zu klären, ob es zu einem späteren Zeitpunkt zu einer vollständigen Normalisierung des Energiestoffwechsels kommt.SummaryPurpose: Heart valve disease combined with left ventricular hypertrophy leads to derangements in cardiac energy metabolism, which can be detected non-invasively by 31P-MR-spectroscopy. The purpose of the present study was to examine whether the derangements in cardiac metabolism are reversible after surgical valve replacement.nn Patients and methods: 10 healthy volunteers and 10 patients with aortic stenosis (pressure gradients >60xa0mmHg) were included. For assessment of energy metabolism, 31P-MR spectra were obtained with a double oblique 3D-CSI technique (voxel size 25xa0cm3). In 5 of 10 patients, follow-up examination was performed 3 months after surgical valve replacement (SVR). Left ventricular (LV) function was analyzed by cine MRI.nn Results: Before SVR the myocardial phosphocreatine to adenosinetriphosphate (PCr-ATP) ratio was significantly (p=0.0002) reduced to 0.80±0.25 in patients compared to 1.65±0.21 in volunteers. 3 months after SVR, LV mass had significantly (p=0.04) decreased from 238±33xa0g to 206±47xa0g. At the same time a significant (p=0.04) increase of the PCr-ATP ratio from 0.80±0.25 to 1.28±0.22 was observed. A slight, but not significant, reduction of the phosphodiester ATP ratio was observed before SVR, with a trend towards normalization after SVR.nn Conclusions: After SVR, the deranged energy metabolism shows a trend towards normalization. Further follow-up is necessary to determine whether complete normalization of the energetic derangement can be observed over longer periods of time following SVR.

Acute changes of myocardial creatine kinase gene expression under β-adrenergic stimulation

Creatine kinase (CK) plays a crucial role in myocardial energy metabolism. Alterations in CK gene expression are found in hypertrophied and failing heart, but the mechanisms behind these changes are unclear. This study tests the hypothesis that increased adrenergic stimulation, which is observed in heart failure, induces changes of myocardial CK-activity, -isoenzyme distribution and -gene expression that are characteristic of the failing and hypertrophied heart. Isolated rat hearts were perfused (constant pressure of 80 mmHg) with red cell suspensions. Following a 20-min warm-up period, perfusion for 3 h with 10(-8) M (iso 3 h) or without (control 3 h) isoproterenol was started or experiments were immediately terminated (control 0 h). Left ventricular tissue was analyzed for total CK-activity, CK-isoenzyme distribution and, by use of quantitative RT-PCR, for B-CK, M-CK, mito-CK and GAPDH- (as internal standard) mRNA. After beta-adrenergic stimulation (iso 3 h) but not after control perfusion (control 3 h) a roughly threefold increase in B-CK mRNA levels and a decrease in M-CK mRNA levels by 18% was found. There were no significant differences among the three groups in total CK-activity and in distribution of CK-MM, CK-BB, CK-MB and mito-CK. Thus, beta-adrenergic stimulation induces a switch in CK gene expression from M-CK to B-CK, which is characteristic for the hypertrophied and failing heart. This may be interpreted as an adaptive mechanism making energy transduction via CK more efficient at times of increased metabolic demand.

Mechanisms of the Effects of Nicorandil in the Isolated Rat Heart During Ischemia and Reperfusion: A 31P-Nuclear Magnetic Resonance Study

Nicorandil (SG75) is a potent K+-channel activator with an additional nitro moiety. In the present study we investigated the potential mechanisms (K+-channel activation and nitric oxide [NO] release) for the effects of nicorandil on isolated perfused rat hearts during total global ischemia using 31P-nuclear magnetic resonance. After a 10-min control perfusion, hearts were subjected to treatment with nicorandil-containing (100, 300, or 1000 microM) buffer for 10 min, 15 min of total global ischemia, and 30 min of reperfusion. At high dose (10(-3) M), nicorandil reduced ATP depletion during ischemia by 26% compared with untreated hearts. Blockade of K+ channels by glibenclamide prevented this protective effect. At all doses (10(-4) to 10(-3) M), nicorandil reduced the accumulation of protons during ischemia compared with untreated hearts (pH 6.22 +/- 0.03 vs. 6.02 +/- 0.05 in untreated hearts at the end of ischemia). This effect was preserved after blockade of K+ channels by glibenclamide. Hearts treated with nitroglycerine before ischemia also showed reduced proton accumulation. Therefore, NO release accompanied by increased coronary flow before ischemia, which is caused by the nitro moiety of nicorandil and nitroglycerine treatment, results in reduced proton accumulation. During reperfusion, a pro-arrhythmic effect was observed in hearts treated with the nonpharmacologically high dose of nicorandil (1000 microM). Thus, we conclude that the effects of nicorandil are caused by the simultaneous action of both mechanisms K+-channel activation and NO release. The activation of K+ channels prevents deterioration of ATP during ischemia, whereas NO release and increased coronary flow reduce the accumulation of protons--and thus the decrease in pH--during ischemia.