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This Article Full Text Full Text (PDF) All Versions of this Article: 291/5/H2533    most recent 00472.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (11) Citing Articles via Google Scholar Google Scholar Articles by Eckle, T. Articles by Eltzschig, H. K. Search for Related Content PubMed PubMed Citation Articles by Eckle, T. Articles by Eltzschig, H. K.

INNOVATIVE METHODOLOGY

Systematic evaluation of a novel model for cardiac ischemic preconditioning in mice

¹Department of Anesthesiology and Intensive Care Medicine and ²Department of Pharmacology and Toxicology, Tübingen University Hospital; and ³Berufsgenossenschaftliche Unfallklinik, Eberhard-Karls-Universität, Tübingen; and ⁴Klinik und Poliklinik für Anästhesiologie, Julius-Maximilian-University, Würzburg, Germany

Submitted 9 May 2006 ; accepted in final form 7 June 2006

Cardioprotection by ischemic preconditioning (IP) remains an area of intense investigation. To further elucidate its molecular basis, the use of transgenic mice seems critical. Due to technical difficulty associated with performing cardiac IP in mice, we developed an in situ model for cardiac IP using a hanging-weight system for coronary artery occlusion. This technique has the major advantage of eliminating the necessity of intermittently occluding the coronary artery with a knotted suture. To systematically evaluate this model, we first demonstrated correlation of ischemia times (10–60 min) with infarct sizes [3.5 ± 1.3 to 42 ± 5.2% area at risk (AAR), Evan’s blue/triphenyltetrazolium chloride staining]. IP (4 x 5 min) and cold ischemia (27°C) reduced infarct size by 69 ± 6.7% and 84 ± 4.2%, respectively (n = 6, P < 0.01). In contrast, lower numbers of IP cycles did not alter infarct size. However, infarct sizes were distinctively different in mice from different genetic backgrounds. In addition to infarct staining, we tested cardiac troponin I (cTnI) as marker of myocardial infarction in this model. In fact, plasma levels of cTnI were significantly lower in IP-treated mice and closely correlated with infarct sizes (R² = 0.8). To demonstrate transcriptional consequences of cardiac IP, we isolated total RNA from the AAR and showed repression of the equilibrative nucleoside transporters 1–4 by IP in this model. Taken together, this study demonstrates highly reproducible infarct sizes and cardiac protection by IP, thus minimizing the variability associated with knot-based coronary occlusion models. Further studies on cardiac IP using transgenic mice may consider this technique.

cardioprotection; targeted gene deletion; murine; ischemia; reperfusion; heart

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