Journal
JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS
Volume 63, Issue 1, Pages 24-29Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.vascn.2010.04.002
Keywords
Cardiac; Small animal imaging; Lung; Micro-CT; Stress; Dobutamine
Categories
Funding
- NCRR National Biomedical Technology Research Center [P41 RR005959]
- NCI [U24 CA092656]
- GlaxoSmithKline
- NATIONAL CANCER INSTITUTE [U24CA092656] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [P41RR005959] Funding Source: NIH RePORTER
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Introduction: Dobutamine (DOB) stress in animal models of heart disease has been imaged so far using echocardiography and magnetic resonance imaging. The purpose of this study was to assess normal response to DOB stress in rats using anatomical and functional data using micro-computed tomography (CT). Methods: Ten normal adult male rats were first injected with a liposomal-based blood pool contrast agent and next infused with DOB via a tail vein catheter. Using prospective gating, 5 pairs of systole/diastole micro-CT images were acquired (a) pre-infusion baseline; (b) at heart rate plateau during infusion of 10 mu g/kg/min DOB; (c) at post-DOB infusion baseline; (d) at heart rate plateau during infusion of 30 mu g/kg/min DOB; and (e) after post-infusion return to baseline. Heart rate, peripheral and breathing distensions were monitored by oximetry. Micro-CT images with 88-mu m isotropic voxels were segmented to obtain cardiac function based on volumetric measurements of the left ventricle. Results: DOB stress increased heart rate and cardiac output with both doses. Ejection fraction increased above baseline by an average of 35.9% with the first DOB dose and 18.4% with the second dose. No change was observed in the relative peripheral arterial pressures associated with the significant increases in cardiac output. Discussion: Micro-CT proved to be a robust imaging method able to provide isotropic data on cardiac morphology and function. Micro-CT has the advantage of being faster and more cost-effective than MR and is able to provide higher accuracy than echocardiography. The impact of such an enabling technology can be enormous in evaluating cardiotoxic effects of various test drugs. (C) 2010 Elsevier Inc. All rights reserved.
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