In this new method of MI induction, mice were anesthetized with 2% isoflurane inhalation with an isoflurane delivery system (Viking Medical, Medford, NJ) but not ventilated. Of course, prior to perfecting this surgical model we recommend using ventilation in mice until the surgeon can routinely perform the LCA ligation in less than 3 min. A small skin cut (1.2cm) was made over the left chest and a purse suture was made as shown in Fig. 1A-C. After dissection and retraction of the pectoral major and minor muscle, the 4th intercostal space was exposed (Fig. 1D). A small hole was made at the 4th intercostal space with a mosquito clamp to open the pleural membrane and pericardium (Fig. 1E). With the clamp slightly open, the heart was smoothly and gently “popped out” through the hole as show in Fig. 1F. The LCA was located, sutured and ligated at a site about 3 mm from its origin using a 6-0 silk suture (Fig. 1H-I). The ligation was deemed successful when the anterior wall of the LV turned pale (Fig. 1J). After ligation, the heart was immediately placed back into the intra-thoracic space followed by manual evacuation of air and closure of muscle and the skin, by means of the previously placed purse-string suture (Fig. 1K-L). The mouse was then allowed to breathe room air and monitored during the recovery period, which was generally complete within 3-5 minutes. No artificial respiratory aid was required during the recovery time. The sham group underwent the same surgical procedure except that the LCA was not occluded. A move of this new method of MI can be found in on-line Supplemental Methods.