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 Ϯ 1.3 to 42 Ϯ 5.2% area at risk (AAR), Evan's blue/triphenyltetrazolium chloride staining]. IP (4 ϫ 5 min) and cold ischemia (27°C) reduced infarct size by 69 Ϯ 6.7% and 84 Ϯ 4.2%, respectively (n ϭ 6, P Ͻ 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 (R 2 ϭ 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 A CARDIOPROTECTIVE EFFECT by preconditioning with ischemia was first described in 1986 by Murry et al. (22), who demonstrated that pretreatment with short time periods of intermittent myocardial ischemia resulted in a marked reduction of myocardial infarct size in dogs. Since then, multiple studies have attempted to identify molecular mechanisms involved in cardioprotection by ischemic preconditioning (IP). Despite these efforts, many aspects of the molecular mechanisms involved in cardioprotection by IP remain unknown. In addition, it appears difficult to translate these concepts into a clinical setting. In fact, a profound reduction of morbidity and mortality from acute myocardial infarction, as would be expected from the initial observation (22), has not been achieved in patients yet. However, recent advances in designing transgenic mice with targeted gene deletion has revived the hope of revealing mechanisms of cardioprotection by IP. Moreover, the use of "floxed" (9, 16) or chimeric (27) mice may yield additional insight into the contribution of individual tissues or cell lines (e.g., endothelial, myeloid, or cardiac myocytes) to cardioprotection. This information may be particularly important for the design of pharmacological approaches, as pharmacokineti...

These data suggest that desflurane-induced APC is mediated in part by activation of mitochondrial large-conductance K(Ca) channels, and that activation of these channels by desflurane is mediated by PKA.

The results demonstrate that anesthetic preconditioning is mediated by the beta1-adrenergic pathway, whereas this pathway is not essential for ischemic preconditioning. These results indicate important differences in the mechanisms of anesthetic and ischemic preconditioning.

The two small heat shock proteins (sHSPs), alphaB-crystallin and HSPB2, have been shown to translocate within a few minutes of cardiac ischemia from the cytosol to myofibrils; and it has been suggested that their chaperone-like properties might protect myofibrillar proteins from unfolding or aggregation during stress conditions. Further evidence of an important role for HSPs in muscle function is provided by the fact that mutations of the alphaB-crystallin gene cause myopathy and cardiomyopathy. In the present study, we subjected isolated papillary muscles of alphaB-crystallin/HSPB2-deficient mice to simulated ischemia and reperfusion. During ischemia in alphaB-crystallin/HSPB2-deficient muscles, the development of contracture started earlier and reached a higher value compared to the wildtype mice. The recovery of contracture of alphaB-crystallin/HSPB2-deficient muscles was also attenuated during the simulated reperfusion period. However, twitch force was not significantly altered at any time of the experiment. This suggests that during ischemic insults, alphaB-crystallin/HSPB2 may not be important for the contraction process itself, but rather serve to maintain muscular elasticity.