Takeshi Uzuka

Bcl-xL Gene Transfer Inhibits Bax Translocation and Prolongs Cardiac Cold Preservation Time in Rats

Background—Apoptosis is an important cause of early graft loss after heart transplantation. Bcl-xL was reported to protect the heart against normothermic ischemia and reperfusion injury. In this study, we determined whether overexpression of Bcl-xL could inhibit tissue injury resulting from prolonged cold preservation followed by warm reperfusion of heart transplants. Methods and Results—Lewis rat hearts were transduced with an adenovirus vector harboring Bcl-xL cDNA (AxCAhBclxL) 4 days before collection of tissue. After preservation in University of Wisconsin solution at 4°C for 24 hours, the heart was either perfused with a Langendorff device ex vivo or used for heterotopic heart transplantation in vivo. Bcl-xL gene transfer significantly reduced the infarct size (23.0±2.6% versus 47.7±7.0% in saline control and 48.6±6.1% in vector control, P<0.01) after 2-hour reperfusion at 37°C with the Langendorff device and significantly decreased creatine kinase release (0.82±0.27 IU, versus 1.57±0.33 and 1.50±0.37 IU in saline and vector controls, respectively; P<0.05). In heart transplantation, overexpresson of Bcl-xL inhibited Bax translocation from the cytosol to the mitochondria, resulting in decreased cytochrome c release from the mitochondria; it also significantly decreased cardiac cell apoptosis and improved graft survival rate after long cold preservation, followed by warm reperfusion. Conclusions—Bcl-xL gene transfer inhibited the translocation of Bax and prolonged the cold preservation time of cardiac transplants. This may be a potential therapeutic method in clinical practice.

Surgery of giant right coronary artery aneurysm complicated with coronary artery fistula to left ventricle

Coronary artery aneurysms (CAA)may exceed 5 cm, commonly involve the right coronary artery (RCA), may occur in close proximity to the left main trunk, andmay result in pulmonary artery fistulae or compress the right atrium and present as a pericardial mass. We present images of a CAA of the RCA with a fistula to the left ventricle (LV). A 64-year-old female was evaluated for palpitations and found on computed tomography (CT) scan to have a 6-cm right CAA (RCAA)with a fistula to the posterior LV (Figures 1A and 1B). At the time of surgery, cardiopulmonary bypass was instituted by aortic and bicaval cannulation. The aorta was crossclamped and the heart arrested with retrograde cold blood cardioplegia. The RCCA was opened, the fresh clot removed, and the orifices of the branches were suture ligated (Figures 2A and 2B). The RCCA fisutula was closed with a pericardial patch and the ostium of the RCA was closed with a Dacron patch (Figure 2C). An end-side anastomosis was performed to the posteriolateral branch using a segment of saphenous vein, followed by a sideside anastomosis to the posterior descending artery, and a proximal anastomosis to the ascending aorta (Figure 2D). The patient tolerated the procedure well. A postoperative CT angiogram showed a patent vein graft and closure of the RCCA orifice and fistula (Figure 1C). The histology of the RCCA showed atherosclerotic changes and disruption of the tunica media.

Giant intercostal aneurysm complicated by Stanford type B acute aortic dissection in patients with type 1 neurofibromatosis

Vascular involvement is rare in neurofibromatosis type 1 (NF1). It is often missed because it is usually asymptomatic. We report a case of a 42 years old male with neurofibromatosis type 1 who presented with left back discomfort. CT angiography revealed a massive 42 mm aneurysm of left 11th intercostal artery. After a discussion between radiologists and cardiothoracic surgeons, endovascular coil embolization was chosen to treat this patient. Percutaneous aneurysm embolization was successfully performed. However, the procedure was complicated by Stanford type B acute aortic dissection. Stanford type B acute aortic dissection was medically managed and patient remained well after discharge. Fragile vascular nature was thought to be one of the causes of this unreported complication.

Idiopathic bronchial hemorrhage: a rare but catastrophic complication in cardiac surgery.

BackgroundHemoptysis is a common complication in all kinds of surgery. However, it is rarely critical because it resolves with or without intervention.Case presentationHere the authors present what is believed to be an unprecedented report of a case involving a fatal idiopathic bronchial hemorrhage complication during cardiac surgery. Eighty-five-year-old female with severe aorticvalve stenosis had elective aortic valve replacement. Subsequently, she developed diffuse bilateral severe idiopathic bronchial hemorrhage which required maximum intervention such as external bronchial ligation, V-A ECMO, coil embolization of bronchial artery and internal airway blockage by spigot.ConclusionsAirway bleeding is not a rare complication in cardiac surgery, but this case should increase awareness of this potentially life threatening perioperative complication.

Repeat conduit replacement in the pulmonary position without sternal resplitting for the patient with repaired Tetralogy of Fallot and the absent inferior caval vein

Recently, sternal reentry has been performed with low perioperative mortality and morbidity. In some patients, however, there are specific problems leading to life-threatening events during sternal reentry. A 27-year-old woman with repaired Tetralogy of Fallot and the absent inferior caval vein was referred to our department for pulmonary conduit replacement. Preoperative computed tomography disclosed the dominant right coronary artery and the ascending aorta longitudinally running just beneath the midline of the sternum. Therefore, we selected bilateral antero-lateral thoracotomy as the alternative approach to avoid the injury of these vital organs. The left axillar and right femoral artery were used for arterial perfusion sites. Venous drainage could be obtained from the left superior caval vein and the isolated hepatic vein via the left antero-lateral thoracotomy, and the right superior caval vein via the right antero-lateral thoracotomy. We successfully performed the repeat conduit replacement via the right antero-lateral thoracotomy.

Conversion to Open Repair from Emergency EVAR in a Patient with Ruptured AAA: Report of a Case

A 77-year-old woman with a ruptured abdominal aortic aneurysm (AAA) was transferred to our hospital. Due to a severe comorbidity, endovascular aortic repair of the ruptured AAA was proposed. During the operation, although a Zenith(®) AAA endovascular graft was deployed, digital subtracted angiography revealed an enhancement of the endoleak, and the patient became hemodynamically unstable. Therefore, we decided to convert to graft replacement of the abdominal aorta through a median laparotomy. During the postoperative period, the patient suffered from ischemic colitis, which resolved with conservative therapy. She was discharged after 33 postoperative days.

189. Sendai Virus Mediated Angiopoietin-1 Gene Therapy for Cardiovascular Diseases

Background: Sendai virus (SeV) is negative-stranded RNA virus, which is classified as a type I parainfluenza virus belonging to the family of Paramyxoviridae. SeV has been known as rodent respiratory virus, however it is considered to be non-pathogen for humans. Recently, efficient gene transduction into various types of cells and tissue has been reported. Angiopoietin-1 (Ang1) is a critical angiogenic factor for vascular maturation and enhances vascular endothelial growth factor (VEGF)-induced angiogenesis in a complementary manner. Previously we reported Ang1 gene therapy clearly promoted myocardial angiogenesis and prevented remodeling in a rat AMI model. In the present study, we created recombinant Sendai virus vector (SeVV) encoding human Ang1 and evaluated therapeutic effect in the cardiovascular diseases. We also evaluated the angiogenic effect of mesenchymal stem cells (MSCs) transplantation with SeVV-mediated Ang1 gene modification.

938. Myocardial Administration of Adenoviral Vector Encoding VEGF Induces Severe Pleural and Pericardial Effusion in Rat

Background: Clinical trials for severe coronary ischemia and critical limb ischemia using vascular endothelial growth factor (VEGF) gene have been on going for several years. However, the indication of VEGF therapy for ischemic heart disease is only limited to chronic ischemia, and acute myocardial infarction (AMI) is exception for this therapy at present. High levels of circulating VEGF were reported to arise following AMI in a short period after the ischemic event and surmised that it protects the blood vessels from apoptosis, modulates vasomotor response, and supports vessel formation in the ischemic area, and to contribute to quick recovery from the ischemic state. In this regard, we attempted adenoviral VEGF gene therapy for rat myocardial infarction model. However, we found the increase mortality of animals receiving adenoviral VEGF. Therefore, we re-evaluated the adverse effect of myocardial administration of adenoviral vector encoding VEGF in AMI rat.