We tested the hypothesis that activation Jak2, which is prominently involved in the up-regulation of the renin-angiotensin system (RAS), constitutes a focal point in relaying signals triggered by a Angiotensin II (Ang II) and hypoxia/reoxygenation separately to cause an enhanced susceptibility of cardiac myocyte to apoptotic cell death. Ang II-treated adult cardiomyocytes in culture exhibited an increased level of apoptosis that accompanied activation of pro-apoptotic as well as anti-apoptotic signaling pathways. We observed increased phosphorylation of Jak2 kinase, Stat1, JNK, with increased expression of Bax protein, followed by an increase in caspase-1 and caspase-3 activity. Activation of these pro-apoptotic pathways was blocked by the Jak2 pharmacological inhibitor, Tyrphostin AG490. We also observed an increase in phosphorylation of cardioprotective pathway components, namely S6 ribosomal protein, and heat shock protein 27 (HSP27). Likewise, the oxidative stress, via the hypoxia/reoxygenation treatment of rat adult cardiomyocytes, produced apoptosis that was dependent upon activation of Jak2. The apoptotic response was not only reduced by Losartan, an inverse agonist of the AT1, receptor, but by treatment with AG490 as well. Taken together, these observations provide clear evidence in favor of Jak2 signaling as mediator of the apoptotic response in cardiomyocytes. However, there was a concomitant induction of cytoprotective signaling that presumably provides a negative feedback to the deleterious effects of the agonist. D

C ORONARY ARTERY DISSECTIONS are rare but potentially life threatening. 1,2 They can occur either spontaneously or as a complication of percutaneous coronary interventions. 1,3 Management can be either catheter based or surgical and is determined by the extent of the dissection, hemodynamic status, and the number and extent of the vessels involved. 1,2 The case presented here involves a patient with a catheter-induced dissection of the left anterior descending (LAD) artery, which was managed with off-pump coronary artery bypass graft surgery. The authors highlight the use of epiaortic sonography to image the coronary artery before and after repair. CASE REPORT A 61-year-old man with a past medical history of systemic hyper-tension presented with a 1-month history of exertional chest pain and shortness of breath. A cardiac nuclear stress test showed exercise-induced anteroseptal, apical, and inferoposterior ischemia with a left ventricular ejection fraction of 36%. Coronary arteriography then was performed showing triple-vessel coronary artery disease. There were chronic total occlusions of the right coronary artery and the mid-LAD. The obtuse marginal arteries 1 and 2 also were found to have 50% to 60% stenosis. No obvious collaterals were shown on the coronary angiogram. The patient initially refused coronary artery bypass graft (CABG) surgery. The LAD lesion was crossed with a guidewire, but attempts at angioplasty resulted in an iatrogenic LAD dissection (Fig 1). The procedure was aborted, and the patient was referred for urgent surgery. He remained hemodynamically stable. Intraoperatively, the transesoph-ageal echocardiogram (TEE) showed 1 mitral regurgitation and inferior septal hypokinesis. Upon inspection of the epicardial surface, the midportion of the LAD had a bluish discoloration. An L15-7io epiaortic probe (Phillips Medical, Andover, MA) was placed into a sterile sheath and used to evaluate the vessel. A dissection and intramural hematoma were visualized originating in the midportion of the LAD with no flow in the false lumen (Figs 2 and 3). The LAD was stabilized and opened (Fig 4). The layers of the wall at the site of the arteriotomy were reapproximated to eliminate the false lumen. A left internal mammary artery to LAD anastomosis then was constructed. Repeat ultrasound evaluation showed excellent laminar flow through the anastomosis and in the distal LAD (Fig 5). The right internal mammary artery then was anastomosed to the right coronary artery, and vein grafts were placed to the 2 obtuse marginal arteries. The immediate postprocedure TEE showed no significant change. The patient remained hemodynamically stable with no postoperative electrocardiographic or enzymatic changes and had an uneventful postoperative recovery. He remains asymptom-atic 3 years after surgery. DISCUSSION Coronary artery dissections are a rare but well-recognized life-threatening condition. 1,3-5 They are classified as either spontaneous or catheter-induced. 1,3 These patients typically present in the form of acute coronary syndrome with unstable angina or myocardial infarction with ST-segment changes on the electrocardiogram. 1 Early diagnosis via angiography is of the utmost importance. In this patient, probably because of the pre-existing complete total occlusion of the LAD, ischemic changes did not occur. Catheter-induced coronary artery dissection is a rare but well-recognized complication of percutaneous coronary intervention. The true incidence may be unknown because there is From the Fig 1. A cardiac catheterization image of LAD dissection. Fig 2. Epiaortic sonography visualizes the intramural hematoma and mid-LAD dissection.