We recently demonstrated that ischemic preconditioning (PC) induced by cyclic episodes of short duration of ischemia and reperfusion potentiates a signal transduction cascade involving Janus kinase (JAK) 2 and signal transducer and activator of transcription 3 (STAT3). A rapid activation of JAK and several STATs, including STAT3, STAT5A, and STAT6 also occurred during myocardial ischemia and reperfusion. This study sought to examine whether STAT5A and STAT6 were also involved in PC. Two different animal models were used: isolated perfused working rat hearts and STAT5A and STAT6 knockout mouse hearts. The results of our study indicated phosphorylation of STAT 5A and STAT6 in the preconditioned myocardium. Tyrphostin AG490, a JAK2 inhibitor, or 4-amino-5-(4-methylphenyl)-7-(t-butyl)-pyrazolo-3,4-d-pyrimidine (PPI), a Src kinase blocker, blocked STAT5A phosphorylation, whereas STAT6 phosphorylation was blocked only with tyrphostin. As expected, significant cardioprotection was achieved in the preconditioned heart as evidenced by reduced myocardial infarct size and decreased number of apoptotic cardiomyocytes. PC-mediated cardioprotection was partially abolished when hearts were pretreated with tyrphostin, PPI, or LY-294002, a phosphatidylinositol (PI)-3 kinase inhibitor. Studies with STAT5A and STAT6 knockout mouse hearts revealed that STAT6 knockout mouse hearts, and not STAT5A knockout mouse hearts, were resistant to myocardial ischemia-reperfusion injury. The hearts from STAT5A knockout mice could not be preconditioned, whereas those from STAT6 knockout mice were easily preconditioned. The results of the present study demonstrate that STAT5A, and not STAT6, plays a role in ischemic PC. For the first time, the results also indicated a role of Src kinase pathway in STAT5A PC and PI-3 kinase-Akt pathways appear to be the downstream regulator for STAT5A-STAT6 signaling pathway.

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Free-floating left atrial thrombi are rare. Here we report a case of a 75-year-old woman with atrial fibrillation who was admitted for treatment of acute myocardial infarction. A free-floating left atrial thrombus was found incidentally on echocardiography. Ten days after percutaneous coronary intervention, the patient had mild faintness with transient hypotension, and it was found that the left atrial thrombus had developed intermittent entrapment in the mid-ventricle during diastole, with abrupt rebound back to the left atrial cavity during systole. Urgent removal of the thrombus was performed successfully. Although the free-floating thrombus had appeared to be spherical, like a ball thrombus, on echocardiography, the excised thrombus was pedunculated. A cut section revealed a laminated thrombus with an onion-skin-like appearance.