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Target Discovery and Validation Reviews and Protocols

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274 Iversen <strong>and</strong> Sørensen<br />

the core of the body <strong>and</strong> the body surface. This regulation may affect the metabolic<br />

rate of the animal <strong>and</strong> consequently result in different experimental results<br />

compared with an animal in its thermoneutral zone. It is important that the environmental<br />

temperature is precisely defined <strong>and</strong> kept within the defined range. The<br />

temperature must be recorded <strong>and</strong> published. Environmental parameters are listed<br />

in Appendix A in the Convention of the Council of Europe. Most rodents may be<br />

kept at room temperatures between 20 <strong>and</strong> 24°C. It is important that the temperature<br />

is kept constant, <strong>and</strong> it must be recorded <strong>and</strong> published.<br />

2. Relative humidity should be kept in the range of 55±5%. Higher levels of relative<br />

humidity may lead to disturbances in the metabolic rate, <strong>and</strong> excessively high<br />

levels of relative humidity predispose for pathological conditions.<br />

3. The light cycle has an important effect on the animal’s physiology <strong>and</strong> behavior.<br />

Although most animals have their periods of highest activity during daylight<br />

hours, the majority of laboratory animals are nocturnal <strong>and</strong> sleep during day. In<br />

general 12 h of light <strong>and</strong> 12 h of dark is recommended for most laboratory animal<br />

species. The light intensity must be adjusted to the need of the species <strong>and</strong> should<br />

be constant in all parts of the room.<br />

4. Exposure to chemicals may be a part of the procedure in an experiment or it may<br />

be unintentional in the laboratory animal facility. The most important sources of<br />

chemical contamination are animal excretions, bedding, cage or enclosure materials,<br />

feed, <strong>and</strong> household chemicals.<br />

5. We prefer to study male mice because these are generally larger than the females.<br />

Size is a critical aspect because the induction of myocardial infarction requires<br />

surgery on the coronary vessels of the small murine heart.<br />

6. The ligature is tightened so the myocardial tissue is blanched on visual inspection.<br />

7. The use of microtipped transducer catheters is preferable to avoid pressure artifacts.<br />

8. Any weight should be adjusted for possible edema, e.g., by expressing the weight<br />

relative to a bone length.<br />

References<br />

1. McKee, P. A., Castelli, W. P., McNamara, P. M., <strong>and</strong> Kannel, W. B. (1971) The<br />

natural history of congestive heart failure: the Framingham study. N. Engl. J. Med.<br />

285, 1441–1446.<br />

2. Kh<strong>and</strong>, A., Gemmel, I., Clark, A. L., <strong>and</strong> Clel<strong>and</strong>, J. G. (2000) Is the prognosis of<br />

heart failure improving? J. Am. Coll. Cardiol. 36, 2284–2286.<br />

3. Kloner, R. A. <strong>and</strong> Rezkalla, S. H. (2004) Cardiac protection during acute myocardial<br />

infarction: where do we st<strong>and</strong> in 2004. J. Am. Coll. Cardiol. 44, 276–286.<br />

4. Torre-Amione, G., Kapadia, S., Lee, J., et al. (1996) Tumor necrosis factor-alpha<br />

<strong>and</strong> tumor necrosis factor receptors in the failing human heart. Circulation 93,<br />

704–711.<br />

5. Iversen, P. O., Nicolaysen, G., <strong>and</strong> Sioud, M. (2001) DNA enzyme targeting TNFalpha<br />

mRNA improves hemodynamic performance in rats with postinfarction<br />

heart failure. Am. J. Physiol. 281, H2211–H2217.

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