Data on uncoupling protein-3 levels, hypoxia, low flow ischemia, and insulin stimulation in dystrophin-deficient mdx mouse hearts.

The data contain body weights, plasma free fatty acids concentrations and cardiac uncoupling protein-3 protein levels for wild-type and mdx mice. The data provide heart rates, left ventricular contractile functions, coronary flow, phosphocreatine concentrations, and adenosine 5'-triphosphate (ATP) concentrations throughout hypoxia in mdx mouse hearts. This data article also provides left ventricular contractile functions after low flow ischemia with and without glucose, glycogen levels before ischemia or hypoxia, glucose uptake rates during low flow ischemia and insulin stimulation, and insulin-stimulated phospho-Akt protein levels, a protein in insulin signaling, in mdx mouse hearts.

Dystrophin- and MLP-deficient mouse hearts: marked differences in morphology and function, but similar accumulation of cytoskeletal proteins.

In humans, cytoskeletal dystrophin and muscle LIM protein (MLP) gene mutations can cause dilated cardiomyopathy, yet these mutations may have different effects in mice, owing to increased accumulation of other, compensatory cytoskeletal proteins. Consequently, we characterized left-ventricular (LV) morphology and function in vivo using high-resolution cine-magnetic resonance imaging (MRI) in 2- to 3-month old dystrophin-deficient (mdx) and MLP-null mice, and their respective controls. LV passive stiffness was assessed in isolated, perfused hearts, and cytoskeletal protein levels were determined using Western blot analyses. In mdx mouse hearts, LV-to-body weight ratio, cavity volume, ejection fraction, stroke volume, and cardiac output were normal. However, MLP-null mouse hearts had 1.2-fold higher LV-to-body weight ratios (P<0.01), 1.5-fold higher end-diastolic volumes (P<0.01), and decreased ejection fraction compared with controls (25% vs. 66%, respectively, P<0.01), indicating dilated cardiomyopathy and heart failure. In both models, isolated, perfused heart end-diastolic pressure-volume relationships and passive left-ventricular stiffness were normal. Hearts from both models accumulated desmin and beta-tubulin, mdx mouse hearts accumulated utrophin and MLP, and MLP-null mouse hearts accumulated dystrophin and syncoilin. Although the increase in MLP and utrophin in the mdx mouse heart was able to compensate for the loss of dystrophin, accumulation of desmin, syncoilin and dystrophin were unable to compensate for the loss of MLP, resulting in heart failure.

In vivo cardiac 1H-MRS in the mouse.

The mouse is the predominant animal model to study the effect of gene manipulations. Imaging techniques to define functional effects on the heart caused by genomic alterations are becoming increasingly routine in mice, yet methods for in vivo investigation of metabolic phenotypes in the mouse heart are lacking. In this work, cardiac 1H-MRS was developed and applied in mouse hearts in vivo using a single-voxel technique (PRESS). In normal C57Bl/6J mice, stability and reproducibility achieved by dedicated cardiac and respiratory gating was demonstrated by measuring amplitude and zero-order phase changes of the unsuppressed water signal. Various cardiac metabolites, such as creatine, taurine, carnitine, or intramyocardial lipids were successfully detected and quantified relative to the total water content in voxels as small as 2 microl, positioned in the interventricular septum. The method was applied to a murine model of guanidinoacetate N-methyltransferase (GAMT) deficiency, which is characterized by substantially decreased myocardial creatine levels. Creatine deficiency was confirmed noninvasively in myocardium of anesthetized GAMT-/- mice. This is the first study to report the application of cardiac 1H-MRS in mice in vivo.

The mechanism underlying the positive inotropic effect of angiotensin II in the isolated perfused rabbit heart: a 31P NMR study.

Activation of the Na(+)/H(+) exchanger may play an important role in the development of cardiac hypertrophy. Isolated ventricular myocyte studies have suggested that angiotensin II (AII) has direct positive inotropic effect caused by intracellular alkalinization due to increased Na(+)/H(+) exchange, but whether this occurs in the whole heart is unknown. Consequently, we have used non-invasive 31P NMR spectroscopy to determine whether AII stimulation alters energetics or intracellular pH (pH(i)) in the intact beating rabbit heart. Heart rate (HR) and developed pressure (DP) were recorded continuously in isolated perfused rabbit hearts, simultaneously with pH(i) and high energy phosphate metabolite levels measured using 31P NMR spectroscopy. AII (11 nM) increased developed pressure by 14+/-2 mmHg (P<0.05) and increased pH(i) by 0.08+/-0.03 pH units (P<0.05, n=6). There were no significant changes in myocardial phosphocreatine (PCr), ATP or Pi concentrations throughout the protocol. Inhibition of Na(+)/H(+) exchange with 1 microM Hoe642 (n=7) abolished the increase in pH(i), but did not prevent the increase in developed pressure, caused by AII. Inhibition of protein kinase C (PKC) using 25 microM chelerythrine chloride prevented the positive inotropic and alkalinizing effects of AII (n=5). We conclude that the positive inotropic effect of AII is associated with, but not caused by, a decreased proton concentration due to stimulation of Na(+)/H(+) exchange in the whole rabbit heart.