Background-Exercise training reduces the symptoms of chronic heart failure. Which exercise intensity yields maximal beneficial adaptations is controversial. Furthermore, the incidence of chronic heart failure increases with advanced age; it has been reported that 88% and 49% of patients with a first diagnosis of chronic heart failure are Ͼ65 and Ͼ80 years old, respectively. Despite this, most previous studies have excluded patients with an age Ͼ70 years. Our objective was to compare training programs with moderate versus high exercise intensity with regard to variables associated with cardiovascular function and prognosis in patients with postinfarction heart failure. Methods and Results-Twenty-seven patients with stable postinfarction heart failure who were undergoing optimal medical treatment, including ␤-blockers and angiotensin-converting enzyme inhibitors (aged 75.5Ϯ11.1 years; left ventricular [LV] ejection fraction 29%; V O 2peak 13 mL · kg Ϫ1 · min

Paramagnetic manganese (Mn) ions (Mn(2+)) are taken up into cardiomyocytes where they are retained for hours. Mn content and relaxation parameters, T(1) and T(2), were measured in right plus left ventricular myocardium excised from isolated perfused rat hearts. In the experiments 5 min wash-in of MnCl(2) were followed by 15 min wash-out to remove extracellular (ec) Mn(2+) MnCl(2), 25 and 100 micro M, elevated tissue Mn content to six and 12 times the level of control (0 micro M MnCl(2)). Variations in perfusate calcium (Ca(2+)) during wash-in of MnCl(2) and experiments including nifedipine showed that myocardial slow Ca(2+) channels are the main pathway for Mn(2+) uptake and that Mn(2+) acts as a pure Ca(2+) competitor and a preferred substrate for slow Ca(2+) channel entry. Inversion recovery analysis at 20 MHz revealed two components for longitudinal relaxation: a short T(1 - 1) and a longer T(1 - 2). Approximate values for control and Mn-treated hearts were in the range 600-125 ms for T(1 - 1) and 2200-750 ms for T(1 - 2). The population fractions were about 59 and 41% for the short and the long component, respectively. The intracellular (ic) R(1 - 1) and R(2 - 1) correlated best with tissue Mn content. Applying two-site exchange analyses on the obtained T(1) data yielded results in parallel to, but also differing from, results reported with an ec contrast agent. The calculated lifetime of ic water (tau(ic)) of about 10 s is compatible with a slow water exchange in the present excised cardiac tissue. The longitudinal relaxivity of Mn ions in ic water [60 (s mM)(-1)] was about one order of magnitude higher than that of MnCl(2) in water in vitro [6.9 (s mM)(-1)], indicating that ic Mn-protein binding is an important potentiating factor in relaxation enhancement.

The efficacy of manganese ions (Mn 2؉ ) as intracellular (ic) contrast agents was assessed in rat myocardium. T 1 and T 2 and Mn content were measured in ventricular tissue excised from isolated perfused hearts in which a 5-min wash-in with 0, 30, 100, 300, or 1000 M of Mn dipyridoxyl diphosphate (MnDPDP) was followed by a 15-min wash-out to remove extracellular (ec) Mn 2؉ . An inversion recovery (IR) analysis at 20 MHz revealed two T 1 components: an ic and short T 1-1 (650 -251 ms), and an ec and longer T 1-2 (2712-1042 ms). Intensities were about 68% and 32%, respectively. Tissue Mn content correlated particularly well with ic R 1-1. A two-site water-exchange analysis of T 1 data documented slow water exchange with ic and ec lifetimes of 11.3 s and 7.5 s, respectively, and no differences between apparent and intrinsic relaxation parameters. Ic relaxivity induced by Mn 2؉ ions in ic water was as high as 56 (s mM) - Key words: manganese; MnDPDP; heart; T 1 relaxation; R 1 relaxivity Recent studies (1-3) have shown that divalent manganese ions (Mn 2ϩ ) are promising intracellular (ic) contrast agents, and that Mn 2ϩ -releasing contrast media may be used for cardiac MRI in ischemic heart disease (4). The key factors in the potential success of these agents are that Mn-based MRI (MnMRI) utilizes physiological pathways, and Mn 2ϩ ions are tightly bound to both extracellular (ec) and ic proteins. Thus, cardiac cell uptake of Mn 2ϩ occurs in competition with the calcium ion (Ca 2ϩ ) (5), and Mn-MRI may mirror slow Ca 2ϩ channel function (2). Competition with Ca 2ϩ for cell efflux is less effective, since it may lead to cell Mn 2ϩ retention for hours, as well as to the possibility of delayed MRI. After uptake, Mn 2ϩ ions exert paramagnetic properties inside cardiac cells, and, as we recently demonstrated (3), proton relaxation is greatly enhanced compared to Mn 2ϩ ions in vitro-most probably due to extensive binding to slowly tumbling macromolecules (6). These unique endogenous properties of Mn 2ϩ ions may be exploited in both basic research and future clinical diagnostic techniques.The development of MnMRI has been hampered by the notion that Mn 2ϩ ions are cardiotoxic (7,8), since they may inhibit Ca 2ϩ channels in the cardiac cell membrane. However, recent studies have shown that the fear of cardiotoxicity in this case is largely unfounded (9 -11). Thus, while Mn 2ϩ entry in cardiomyocytes undoubtedly occurs via Ca 2ϩ channels (2,5,9,12), an inhibition of Ca 2ϩ influx that initiates cardiac contraction will not occur before ec [Mn 2ϩ ] exceeds ϳ25 M (1,3). However, extensive plasma protein binding ensures that only a very few M of Mn 2ϩ may exist in the free form in the blood pool or the interstitial space (13,14).We recently studied ic proton relaxation in rat myocardium with MnCl 2 present in the perfusate of isolated rat hearts (3). Relaxography performed after wash-in plus wash-out experiments revealed slow water exchange in the excised nonperfused cardiac tissue. Biexponential T 1 behavior dominated, and reve...

Improved understanding of how depot-specific adipose tissue mass predisposes to obesity-related comorbidities could yield new insights into the pathogenesis and treatment of obesity as well as metabolic benefits of weight loss. We hypothesized that three-dimensional contiguous “fat-water” MR imaging (FWMRI) covering the majority of a whole-body field of view (FOV) acquired at 3 Tesla (3T) and coupled with automated segmentation and quantification of amount, type and distribution of adipose and lean soft tissue would show great promise in body composition methodology. Precision of adipose and lean soft tissue measurements in body and trunk regions were assessed for 3T FWMRI and compared to DEXA. Anthropometric, FWMRI and DEXA measurements were obtained in twelve women with BMI 30–39.9 kg/m2. Test-retest results found coefficients of variation for FWMRI that were all under 3%: gross body adipose tissue (GBAT) 0.80%, total trunk adipose tissue (TTAT) 2.08%, visceral adipose tissue (VAT) 2.62%, subcutaneous adipose tissue (SAT) 2.11%, gross body lean soft tissue (GBLST) 0.60%, and total trunk lean soft tissue (TTLST) 2.43%. Concordance correlation coefficients between FWMRI and DEXA were 0.978, 0.802, 0.629, and 0.400 for GBAT, TTAT, GBLST and TTLST, respectively. While Bland Altman plots demonstrated agreement between FWMRI and DEXA for GBAT and TTAT, a negative bias existed for GBLST and TTLST measurements. Differences may be explained by the FWMRI FOV length and potential for DEXA to overestimate lean soft tissue. While more development is necessary, the described 3T FWMRI method combined with fully-automated segmentation is fast (<30 minutes total scan and post-processing time), noninvasive, repeatable and cost effective.

Water compartments were identified and equilibrium water exchange was studied in excised rat myocardium enriched with intracellular manganese (Mn 2؉ ). Standard relaxographic measurements were supplemented with diffusion-T 2 and T 1 -T 2 correlation measurements. In nonenriched myocardium, one T 1 component (800 ms) and three T 2 components (32, 120, and 350 ms) were identified. The correlation measurements revealed fast-and slow-diffusing water fractions with mean diffusion coefficients of 1.2 ؋ 10 -5 and 3.0 ؋ 10 -5 cm 2 s -1 . The two shortest T 2 components, which had different diffusivities, both originated from water in intracellular compartments. A component with longer relaxation time (T 1 Ϸ 2200 ms; T 2 Ϸ 1200 ms), originating from extra-tissue water, was also observed. The presence of this component may lead to erroneous estimations of water exchange rates from multiexponential relaxographic analyses of excised tissues. The tissue T 1 value is strongly reduced with increasing enrichment of Mn 2؉ , and eventually a second tissue T 1 component emerges, indicating a shift in the equilibrium water exchange between intra-and extracellular compartments from the fast-exchange limit to the slow-exchange regime. Using a two-site water exchange analysis, the lifetime of intracellular water, In biological tissues water is found in different compartments. In addition, equilibrium water exchange takes place between these compartments. In a single pixel of a proton MR image the observed signal is therefore a sum of signals from water molecules originating from different magnetic environments. In particular, since the MR contrast agent (CA) does not distribute homogeneously in the tissue, intercompartmental equilibrium water exchange can significantly affect the quantitative analysis of various in vivo MR parameters. One method of investigating equilibrium water exchange is to take advantage of the differences in the relaxation times, T i (i ϭ 1 or 2 for longitudinal or transverse relaxation, respectively) between tissue compartments in the presence of a contrast agent (CA) (1), known as "relaxography." The observed relaxation behavior will depend on the difference in relaxation rate between compartments, and to which extent the water in other compartments can access the CA through equilibrium water exchange. Biological tissue has intracellular (ic) and extracellular (ec) water compartments, with relaxation rates (R i ϭ 1/T i ) of R i-ic and R i-ec , respectively. The ec compartment further contains the intravascular (iv) and interstitial (is) compartments, with respective relaxation rates of R i-iv and R i-is. Depending on the type of CA used, equilibrium water exchange between some or all of these compartments have to be taken into consideration when analyzing an MR image.In the last decade there has been a growing interest in the use of manganese-enhanced MRI (MEMRI) to investigate tissue function and cell viability (2). In myocardium, manganese ions (Mn 2ϩ ) are known to enter the cell through calcium (Ca 2ϩ ) ch...