Stimulation of cardiac  1 -adrenergic receptors is the main mechanism that increases heart rate and contractility. Consequently, several pharmacological and gene transfer strategies for the prevention of heart failure aim at improving the function of the cardiac -adrenergic receptor system, whereas current clinical treatment favors a reduction of cardiac stimulation. To address this controversy, we have generated mice with heart-specific overexpression of  1 -adrenergic receptors. Their cardiac function was investigated in organ bath experiments as well as in vivo by cardiac catheterization and by time-resolved NMR imaging. The transgenic mice had increased cardiac contractility at a young age but also developed marked myocyte hypertrophy (3.5-fold increase in myocyte area). This increase was followed by progressive heart failure with functional and histological deficits typical for humans with heart failure. Contractility was reduced by Ϸ50% in 35-week-old mice, and ejection fraction was reduced down to a minimum of Ϸ20%. We conclude that overexpression of  1 -adrenergic receptors in the heart may lead to a short-lived improvement of cardiac function, but that increased  1 -adrenergic receptor signalling is ultimately detrimental.
This work shows that MR systems with a vertical bore design can be used to accurately measure cardiac function in both normal and chronically failing mouse hearts within one hour. The increased signal-to-noise ratio (SNR) due to the higher field strength could be exploited to obtain higher temporal and spatial resolution compared to previous studies that were performed on horizontal systems with lower field strengths.
Temporal changes in respiration could influence navigator-echo (NE)-gated MR coronary angiography (MRCA), but systematic investigation of the effects of such variations and how to limit them has not been performed. We addressed these issues by studying the influence of time in the magnet on diaphragm position and respiratory patterns using NE diaphragm monitoring in volunteers and a phantom model. NE diaphragm monitoring was performed at .5 T in 10 subjects over a total period of 35 minutes. The end-expiratory position was sustained for longer (1.1 vs .4 seconds, P < .001) and with greater position stability (SD 1.9 vs 5.9 mm, P = .01) than the end-inspiratory position. Drift of the end-expiratory position occurred over time, causing a fall in scan efficiency (44-28%, P = .01). Up-drift of the end-expiratory position was most common. Loss of scan efficiency was worse with up-drift because of loss of the end-expiratory pause from the NE window (up-drift 10% mm-1, down-drift 7% mm-1, both P = .03). Scan efficiency also was reduced during sleep (to a nadir of 0%), secondary to loss of the end-expiratory pause, periodic breathing with oscillating end-expiratory position, and periods of apnea. The phantom model used actual diaphragm traces to evaluate the artifact resulting from diaphragm motion during acquisition. Artifact was considerably reduced by NE adaptive motion correction compared with NE gating alone (ghosting ratio 2.0 vs 2.8, P < .01). Artifact also was significantly reduced with up-drift if scan efficiency was maintained above 35% (P = .05). For optimal NE-gated MRCA, the following features are important: the NE window should be placed around the end-expiratory position; subjects should not sleep; scan efficiency should be monitored and the NE window should be repositioned if scan efficiency falls below 35%; and adaptive motion correction should be used.
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