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Background: Genetically engineered mouse models of human cardiovascular disease provide an opportunity to understand critical pathophysiological mechanisms. Cardiovascular magnetic resonance (CMR) provides precise reproducible assessment of cardiac structure and function, but, in contrast to echocardiography, requires that the animal be immobilized during image acquisition. General anesthetic regimens yield satisfactory images, but have the potential to significantly perturb cardiac function. The purpose of this study was to assess the effects of general anesthesia and a new deep sedation regimen, respectively, on cardiac function in mice as determined by CMR, and to compare them to results obtained in mildly sedated conscious mice by echocardiography., Results: In 6 mildly sedated normal conscious mice assessed by echo, heart rate was 615 +/- 25 min-1 (mean +/- SE) and left ventricular ejection fraction (LVEF) was 0.94 +/- 0.01. In the CMR studies of normal mice, heart rate was slightly lower during deep sedation with morphine/midazolam (583 +/- 30 min-1), but the difference was not statistically significant. General anesthesia with 1% inhaled isoflurane significantly depressed heart rate (468 +/- 7 min-1, p < 0.05 vs. conscious sedation). In 6 additional mice with ischemic LV failure, trends in heart rate were similar, but not statistically significant. In normal mice, deep sedation depressed LVEF (0.79 +/- 0.04, p < 0.05 compared to light sedation), but to a significantly lesser extent than general anesthesia (0.60 +/- 0.04, p < 0.05 vs. deep sedation). In mice with ischemic LV failure, ejection fraction measurements were comparable when performed during light sedation, deep sedation, and general anesthesia, respectively. Contrast-to-noise ratios were similar during deep sedation and during general anesthesia, indicating comparable image quality. Left ventricular mass measurements made by CMR during deep sedation were nearly identical to those made during general anesthesia (r2 = 0.99, mean absolute difference < 4%), indicating equivalent quantitative accuracy obtained with the two methods. The imaging procedures were well-tolerated in all mice., Conclusion: In mice with normal cardiac function, CMR during deep sedation causes significantly less depression of heart rate and ejection fraction than imaging during general anesthesia with isoflurane. In mice with heart failure, the sedation/anesthesia regimen had no clear impact on cardiac function. Deep sedation and general anesthesia produced CMR with comparable image quality and quantitative accuracy.