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Aims To examine the effects of a 24-month treatment with ipragliflozin on carotid intima-media thickness (IMT) in type 2 diabetes patients. Methods and results In this multicenter, prospective, randomized, open-label, and blinded-endpoint investigator-initiated clinical trial, adults with type 2 diabetes and haemoglobin A1C (HbA1c) of 6.0–10.0% (42–86 mmol/mol) were randomized equally to ipragliflozin (50 mg daily) and non-sodium-glucose cotransporter-2 (SGLT2) inhibitor use of standard-care (control group) for type 2 diabetes and were followed-up to 24 months. The primary endpoint was the change in mean common carotid artery IMT (CCA-IMT) from baseline to 24 months. A total of 482 patients were equally allocated to the ipragliflozin (N = 241) and control (N = 241) groups, and 464 patients (median age 68 years, female 31.7%, median type 2 diabetes duration 8 years, median HbA1c 7.3%) were included in the analyses. For the primary endpoint, the changes in the mean CCA-IMT from baseline to 24 months were 0.0013 [95% confidence interval (CI), −0.0155–0.0182] mm and 0.0015 (95% CI, −0.0155–0.0184) mm in the ipragliflozin and control groups, respectively, with an estimated group difference (ipragliflozin-control) of −0.0001 mm (95% CI, −0.0191–0.0189; P = 0.989). A group difference in HbA1c change at 24 months was also non-significant between the treatment groups [−0.1% (95% CI, −0.2–0.1); P = 0.359]. Conclusion Twenty-four months of ipragliflozin treatment did not affect carotid IMT status in patients with type 2 diabetes recruited in the PROTECT study, relative to the non-SGLT2 inhibitor-use standard care for type 2 diabetes.

Cardiac involvement has been reported in patients with coronavirus disease 2019 (COVID-19). We herein report a 41-year-old man who presented with recurrent paroxysmal atrioventricular block without showing significant cardiac injuries or comorbidities. The patient was diagnosed with COVID-19 and admitted to our hospital, where he was noted to have paroxysmal atrioventricular block. Cardiac biomarkers, echocardiography, and cardiac magnetic resonance imaging findings were fairly normal. An endomyocardial biopsy performed before the implantation of a permanent pacemaker revealed mild myocardial fibrosis without inflammatory infiltrates. The unusual myocardial involvement of the novel coronavirus was suspected.

We performed infarct exclusion repair of ventricular septal perforation(VSP) in a 63-year-old woman who was diagnosed with acute myocardial infarction(AMI) of the inferior wall. As VSP existed behind a fragile posterior papillary muscle, we excised the papillary muscle and sutured a bovine pericardial patch to exclude the infarct area of the whole septum and a part of the inferior wall. Mitral valve replacement and coronary artery bypass were also performed. The postoperative course was uneventful. There was no residual shunt and the left ventricular function was preserved. Selection of surgical procedures taking account of complete closure of VSP is important.

We have evaluated the feasibility of a newly developed single-use, magnetically levitated centrifugal blood pump, MedTech Mag-Lev, in a 3-week extracorpo- real membrane oxygenation (ECMO) study in calves against a Medtronic Bio-Pump BPX-80. A heparin- and silicone-coated polypropylene membrane oxygenator MERA NHP Excelung NSH-R was employed as an oxy- genator. Six healthy male Holstein calves with body weights of about 100 kg were divided into two groups, four in the MedTech group and two in the Bio-Pump group. Under general anesthesia, the blood pump and oxygenator were inserted extracorporeally between the main pulmo- nary artery and the descending aorta via a fifth left thora- cotomy. Postoperatively, both the pump and oxygen flow rates were controlled at 3 L/min. Heparin was continuously infused to maintain the activated clotting time at 200-240 s. All the MedTech ECMO calves completed the study dura- tion. However, the Bio-Pump ECMO calves were termi- nated on postoperative days 7 and 10 because of severe hemolysis and thrombus formation. At the start of the MedTech ECMO, the pressure drop across the oxygenator was about 25 mm Hg with the pump operated at 2800 rpm and delivering 3 L/min flow. The PO2 of the oxygenator outlet was higher than 400 mm Hg with the PCO2 below 45 mm Hg. Hemolysis and thrombus were not seen in the MedTech ECMO circuits (plasma-free hemoglobin (PFH) 20 mg/ dL) and large thrombus were observed in the Bio-Pump ECMO circuits. Plasma leakage from the oxygenator did not occur in any ECMO circuits. Three-week cardiopulmo- nary support was performed successfully with the MedTech ECMO without circuit exchanges. The MedTech Mag-Lev could help extend the durability of ECMO cir- cuits by the improved biocompatible performances. Key Words: Magnetically levitated centrifugal blood pump— Silicone-coated polypropylene membrane oxygenator— Extracorporeal membrane oxygenation—Percutaneous cardiopulmonary support.

BACKGROUND Optimal ring size in tricuspid annuloplasty (TAP) surgery to treat functional tricuspid regurgitation (TR) was investigated because optimal ring size remains undefined. METHODS AND RESULTS Sixty seven patients who underwent TAP at our institution were retrospectively studied. Tricuspid Annuloplasty Ring size Index (TARI) was defined as implanted tricuspid annuloplasty ring size divided by body surface area (BSA). Different TARI cut-off values were tested to determine which value produced the greatest difference in TR improvement (TRI=preoperative minus postoperative TR grade) between patients with TARI smaller (group S) and larger (group L) than the cut-off. Group S was also subdivided by ring type: Cosgrove rings (SC) and MC3 rings (SM). TARI and TRI were negatively correlated (r=-0.307). A TARI threshold of 18.9 mm/m(2) produced the greatest and most significant difference (P

Purpose: We have been using the flanged composite aortic prosthesis and Carrel button technique to re-attach the coronary ostia in aortic root replacement procedures at our institution over the last twenty five years. Our objective was to evaluate the long-term results of aortic root replacement with this technique. Methods: A total of 73 patients from January 1984 to August 2010 were included in this study. The median age was 52.7 ± 14.4 years (range 28–80 years). There were 48 male and 25 female patients. 44 patients (60.3%) had annuloaortic ectasia, and 15 patients (20.5%) had acute type A aortic dissection. Marfan syndrome was recognized in 12 patients (16.5%). Results: The early mortality rate was 5.5% (n = 4). Causes of death were multiple organ failures in two patients and sepsis in another two patients. The actuarial survival rate was 84.2% at 5 years, 64.3% at 15 years and 51.9% at 25 years. Only one patient with aortitis needed a reoperation because of coronary pseudoaneurysm after 23 years from the previous operation. Conclusion: This modified Bentall procedure is reliable and safe, with superior long-term survival and a low rate of aortic reoperation.

The aim of this observational study was to determine the incidence of atrial fibrillation (AF) after coronary artery bypass grafting (CABG) in patients with or without preoperative pravastatin treatment. Between January 2005 and December 2007, a total of 195 patients (39 women, mean age 66.5 ± 10.2 years) who underwent CABG only were enrolled in this study. Patients were divided into three groups: nonstatin group (n = 111), atorvastatin group (n = 63), pravastatin group (n = 21). The endpoint of the study was the occurrence of new-onset AF during the first 14 days after CABG. Postoperative AF was less frequent in the pravastatin group (9.5%, 2/21 patients) than in the nonstatin group (34.2%, 38/111 patients; P = 0.0025) and the atorvastatin group (34.9%, 22/63 patients; P = 0.0257). C-reactive protein levels were lower in the pravastatin group 72 h after surgery (nonstatin vs. pravastatin, P = 0.0180; atorvastatin vs. pravastatin, P = 0.0383). The Kaplan-Meier analysis showed the protective effect of pravastatin against the risk of developing AF (nonstatin vs. pravastatin, P = 0.0369; atorvastatin vs. pravastatin, P = 0.0378). Multivariable analysis showed that pravastatin treatment conferred a reduced risk of AF (odds ratio 0.22, 95% confidence interval 0.05–0.92, P = 0.0172). Pravastatin treatment before CABG may decrease the incidence of postoperative AF.

Introduction Endomyocardial biopsy is the standard means of establishing cardiac allograft rejection diagnosis. The efficacy of this procedure in xenotransplantation has not been determined. In this study we compare the histology of right ventricular endomyocardial biopsy specimens with the corresponding full cross sections of explanted right ventricle (RV). We also compare RV with the related left ventricle (LV) cross sections. Methods Heterotopic CD46 pig-to-baboon cardiac xenotransplants (n = 64) were studied. RV endomyocardial biopsy specimens were taken at cardiac explant by using a standard bioptome (n = 24) or by sharp dissection (n = 40). Hematoxylin and eosin stained sections of RV and LV cross-section and RV endomyocardial biopsy specimens were compared in a blinded fashion. Characteristics of delayed xenograft rejection and a global assessment of ischemia were scored from 0 to 4 according to the percentage of myocardium involved (0, 0%; 1, 1%–25%; 2, 26%–50%; 3, 51%–75%; and 4, 76%–100%). Results Median graft survival was 30 days (range, 3–137 days). Linear regression analysis of histology scores demonstrated that specimens from both bioptome and sharp dissection equally represented the histology of the RV cross section. Global ischemic injury was strongly correlated between RV and RV endomyocardial biopsy ( R 2 = 0.84) and between RV and LV cross sections ( R 2 = 0.84). Individual characteristics of delayed xenograft rejection showed no significant variation between RV and RV endomyocardial biopsy or between RV and LV ( p Conclusions These results indicate that delayed xenograft rejection is a widespread process involving both right and left ventricles similarly. This study shows that histologic assessment of RV endomyocardial biopsy specimens is an effective method for the monitoring of delayed xenograft rejection after cardiac xenotransplantation.

A radial artery (RA) graft is frequently used for coronary artery bypass grafting (CABG), but little information exists regarding the early- and mid-term patency associated with the harvesting procedure. The objective of this study is to compare the early- and mid-term patency of the RA graft obtained using non-skeletonized and skeletonized harvesting.Altogether, 131 patients and 159 anastomoses were studied. In 85 patients the RA was harvested non-skeletonized (group A: procedures between September 2000 and November 2002), whereas in 46 patients the RA was harvested skeletonized (group B: procedures between November 2002 and April 2004). Angiography results were analyzed before discharge [A: postoperative day (POD) 14.7 +/- 2.9, 75 patients, 90 anastomoses; B: POD 13.7 +/- 1.9, 38 patients, 47 anastomoses], and after 1 year (A: POD 386.8 +/- 149.3, 44 patients, 51 anastomoses; B: POD 267.1 +/- 148.7, 11 patients, 13 anastomoses).There was no difference in patency between the two groups (group A vs group B, 96.7% vs 100%, P = not significant [NS], in the early-term, 96.2% vs 100%, P = NS, in the mid-term). However, the perfect patency rates for groups A and B were 86.7% and 98.1%, respectively, in the early-term (P = 0.034) and 77.5% and 100%, respectively, in the mid-term (P = 0.048). The location and severity of the target vessel did not influence the angiographic results.The early- and mid-term patency of RA grafts was excellent, and skeletonized harvesting improved the perfect patency rates at both time points.

The external lumen of a stent [defined as extra-stent lumen (ESL)] assessed by optical coherence tomography (OCT) may be related to the risk of thrombus formation after sirolimus-eluting stent (SES) implantation. An everolimus-eluting stent (EES) might provide relatively minimal inflammatory reaction and appropriate neointimal coverage. The purpose of this study was to compare the neointimal thickness and ESL between SES and EES. Patients who underwent OCT examination more than 7 months after either SES or EES implantation were enrolled. Stent area (SA), lumen area (LA), neointimal area (NIA) and neointimal thickness (NIT) of each strut were measured at 1-mm intervals between stented segments. The area, angle (summation per cross-section) and depth (maximum distance from adjacent vessel surface to the outline of stent) of ESL were analyzed. A total of 49 lesions were included (SES n = 20, EES n = 29). Mean follow-up period was 11 months. A total of 998 cross-sections and 9874 struts were analyzed. There were no differences in stent area, lumen area and neointimal area (SA: 6.01 ± 1.60 vs. 6.02 ± 1.40 mm2, p = 0.572, LA: 5.37 ± 1.52 vs. 5.29 ± 1.34 mm2, p = 0.692, NIA: 0.64 ± 0.49 vs. 0.72 ± 0.37 mm2, p = 0.493). Mean NIT of SES and EES were 0.11 ± 0.05 and 0.10 ± 0.05 mm, respectively (p = 0.367). Conversely, area, angle and depth of ESL in SES group were significantly greater than those in EES group (0.20 ± 0.39 vs. 0.03 ± 0.09 mm2, p

We have evaluated the feasibility of a newly developed single-use, magnetically levitated centrifugal blood pump, MedTech Mag-Lev, in a 3-week extracorporeal membrane oxygenation (ECMO) study in calves against a Medtronic Bio-Pump BPX-80. A heparin- and silicone-coated polypropylene membrane oxygenator MERA NHP Excelung NSH-R was employed as an oxygenator. Six healthy male Holstein calves with body weights of about 100 kg were divided into two groups, four in the MedTech group and two in the Bio-Pump group. Under general anesthesia, the blood pump and oxygenator were inserted extracorporeally between the main pulmonary artery and the descending aorta via a fifth left thoracotomy. Postoperatively, both the pump and oxygen flow rates were controlled at 3 L/min. Heparin was continuously infused to maintain the activated clotting time at 200-240 s. All the MedTech ECMO calves completed the study duration. However, the Bio-Pump ECMO calves were terminated on postoperative days 7 and 10 because of severe hemolysis and thrombus formation. At the start of the MedTech ECMO, the pressure drop across the oxygenator was about 25 mm Hg with the pump operated at 2800 rpm and delivering 3 L/min flow. The PO2 of the oxygenator outlet was higher than 400 mm Hg with the PCO2 below 45 mm Hg. Hemolysis and thrombus were not seen in the MedTech ECMO circuits (plasma-free hemoglobin [PFH]5 mg/dL), while severe hemolysis (PFH20 mg/dL) and large thrombus were observed in the Bio-Pump ECMO circuits. Plasma leakage from the oxygenator did not occur in any ECMO circuits. Three-week cardiopulmonary support was performed successfully with the MedTech ECMO without circuit exchanges. The MedTech Mag-Lev could help extend the durability of ECMO circuits by the improved biocompatible performances.

Non-ischemic mitral regurgitation( MR) is classified in degenerative MR, infective endocarditis( IE) and rheumatic MR. For degenerative MR, although 100% achievement of successful mitral valve plasty (MVP), it still important to evaluate mitral morphology preoperatively and to select suitable procedure.MR due to IE, the most important thing is to exclude vegetation completely. Then MVP is considered depends on its area of defect. Rheumatic MR is still difficult to accomplish MVP. Mitral valve replacement(MVR) is a main strategy for rheumatic MR.

Basic mechanism of ischemic mitral regurgitation (MR) is augmented leaflet tethering because of the out ward displacement of the papillary muscle by the left ventricular dilation. In 30% of ischemic MR, subvalvular procedure is necessary to eliminate MR. We propose subvalvular procedure aiming at a comprehensive remodeling of the entire mitral complex. This remodeling procedure consists of 3 major concepts; undersized mitral annuloplasty, division and reconstruction of secondary chords, and bilateral papillary muscle relocation. Subvalvular procedure under beating heart is effective to decide the length of artificial chord or papillary muscle relocation.

Owing to development of device technology, off-pump coronary artery bypass grafting (OPCAB) has become a safe, reproducible and reliable procedure. Surgeons must understand the advantages and limitations of each device and select appropriate devices in individual case to avoid device-related complication and a waste of cost. The directions and pitfalls of heart positioners, stabilizers and proximal anastomotic devices were described. With the improved heart positioners and stabilizers all coronary targets have been well visualized and accessible, maintaining hemodynamic stability. Automated proximal anastomotic devices and proximal anastomotic assist devices have reduced the occurrence of cerebral complications compared with the side-clamp of the ascending aorta. The appropriate use of devices in OPCAB would be a promising and cost-effective procedure for revascularization of ischemic heart disease.

Background Radioiodine is efficiently concentrated by tissues expressing the human sodium iodide symporter (hNIS). The aim of this study was to analyze the effects of 131I on acute cardiac allograft rejection after hNIS ex-vivo gene transfer in a rat model of cardiac allotransplantation.

BACKGROUND: In this investigation we studied the efficacy and durability of recombinant adeno-associated virus serotype 9 (rAAV9) vector-mediated gene transfer to the transplanted rat heart. METHODS: A rAAV9-CMV-lacZ vector diluted in cold (4 degrees C) University of Wisconsin solution was used to perfuse the rat coronary vasculature for 20 minutes prior to syngeneic heterotopic transplantation. Perfusion experiments (six groups, n = 3/group) were performed without rAAV9 and at four separate doses ranging from 2 x 10(9) to 2 x 10(12) viral genomes/ml. The transplanted heart was recovered 10 days or 3 months after transplantation and expression of lacZ assessed by histology, enzyme-linked immunoassay and real-time reverse transcript-polymerase chain reaction (RT-PCR). In a final group (n = 3), rAAV9 was administered systemically to compare the cardiac transduction efficiency and viral distribution to other organs. RESULTS: Transduction efficiency of perfused virus correlated with vector dose (p < 0.0001), with myocardial transduction ranging up to 71.74% at the highest dose. Cardiac expression of lacZ was equivalent at 10 days and 3 months. There was no evidence of viral gene transfer to other organs after heart transplantation. CONCLUSIONS: Our findings demonstrate efficient and durable rAAV9-mediated gene transfer to the transplanted heart after ex vivo perfusion and suggest that AAV9 is a promising vector for cardiac gene therapy.

Objective: We studied the concordance of transgene expression in the transplanted heart using bicistronic adenoviral vector coding for a transgene of interest (human carcinoembryonic antigen: hCEA — beta human chorionic gonadotropin: bhCG) and for a marker imaging transgene (human sodium iodide symporter: hNIS). Methods: Inbred Lewis rats were used for syngeneic heterotopic cardiac transplantation. Donor rat hearts were perfused ex vivo for 30 min prior to transplantation with University of Wisconsin (UW) solution (n = 3), with 10 9 pfu/ml of adenovirus expressing hNIS (Ad-NIS;n = 6), hNIS-hCEA (Ad-NIS-CEA; n = 6) and hNIS-bhCG (Ad-NIS-CG; n = 6). On postoperative day (POD) 5, 10, 15 all animals underwent micro-single photon emission computed tomography/computed tomography (SPECT/CT) imaging of the donor hearts after tail vein injectionof 1000 mCi 123 I and bloodsamplecollection forhCEA and bhCG quantification.Results:Significantlyhigherimageintensity wasnoted in the hearts perfused with Ad-NIS (1.1 0.2; 0.9 0.07), Ad-NIS-CEA (1.2 0.3; 0.9 0.1) and Ad-NIS-CG (1.1 0.1; 0.9 0.1) compared to UW group (0.44 0.03; 0.47 0.06) on POD 5 and 10 (p < 0.05). Serum levels of hCEA and bhCG increased in animals showing high cardiac 123 I uptake, but not in those with lower uptake. Above this threshold, image intensities correlated well with serum levels of hCEA and bhCG (R 2 = 0.99 and R 2 = 0.96, respectively). Conclusions: These data demonstrate that hNIS is an excellent reporter gene for the transplanted heart. The expression level of hNIS can be accurately and non-invasively monitored by serial radioisotopic SPECT imaging. High concordance has been demonstrated between imaging and soluble marker peptides at the maximum transgene expression on POD 5. # 2007 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

BACKGROUND: We evaluated the feasibility of noninvasive micro-single photon emission computed tomography (SPECT)/computed tomography (CT) imaging and quantification of cardiac gene expression after sodium iodide symporter (hNIS) gene transfer in cardiac transplantation. METHODS: Donor rat hearts were perfused ex vivo with adenovirus expressing hNIS (Ad-hNIS), Ad-Null, or University of Wisconsin (UW) solution prior to heterotopic transplantation into syngeneic recipients. In the first group of recipients, imaging of the transplanted hearts with micro-SPECT/CT on day 5 was followed by immediate explant of the organs for ex vivo analyses. Radioactivity counts in the explanted hearts were obtained ex vivo and expressed as a percentage of the injected dose per gram of tissue (%ID/g). Intensities of the SPECT images of the transplanted hearts were quantified and converted to radioactive counts using a standard equation. The second group of recipients was imaged sequentially after injection of I on days 2 to 14 after transplantation. RESULTS: Higher ex vivo radioiodine counts were noted in the hearts perfused with Ad-hNIS (1.04+/-0.2) compared to either the UW group (0.31+/-0.11, P

Background Adenovirus serotype 5 has remained the pre-eminent vector in pre-clinical gene therapy applications in cardiac transplantation. Concerns over the potential effects of adenoviral vectors on the later development of cardiac allograft vasculopathy (CAV) are addressed in this study. Methods Hearts ( n = 22) harvested from Brown Norway rats were perfused ex vivo with either University of Wisconsin (UW) solution with no virus, Ad-CMV-LacZ or Ad-CMV-Null. Donor hearts were transplanted heterotopically into the abdomen of Lewis rats. All recipients received cyclosporine for the duration of the experiment. Transplanted hearts were recovered for analysis at 120 days. Sections of the heart were stained with elastic–van Gieson stain for morphometric analysis of the vessels to ascertain the degree of vascular luminal occlusion. Hematoxylin–eosin staining facilitated diagnosis of chronic rejection. Results Seventy-seven percent of transplanted hearts showed signs of chronic rejection with no difference in the proportion of animals between groups ( p = 0.797). No difference was noted in the degree of vascular luminal occlusion between the Ad-Null (0.57 ± 0.22), Ad-LacZ (0.62 ± 0.19) and UW (0.47 ± 0.29) groups ( p = 0.653). Conclusions Vascularized cardiac allografts transplanted from Brown Norway to Lewis rats demonstrated cardiac allograft vasculopathy CAV at 120 days. Adenoviral perfusion of the donor heart ex vivo did not affect the development of CAV.

Efficient durable viral vector transduction of the transplanted heart remains elusive. This study assesses the potential of recombinant adeno-associated virus (rAAV) mediated gene delivery to the transplanted rat heart. rAAV serotype 1, 2 and 5 vectors encoding the green fluorescent protein (GFP) gene (1 x 10(11) viral particles/ml) were diluted in cold University of Wisconsin solution and circulated through the coronary vasculature of the donor organs for 30 min before syngeneic rat heterotopic heart transplantation was performed. Study 1: animals (n = 5 each serotype) were killed at 21 days post-transplant to evaluate the efficiency of GFP transduction using RT-PCR and expression by fluorescence microscopy. Study 2: using rAAV-1, animals (n = 5 each group) were killed at 7, 21 and 84 days to evaluate the durability of GFP expression. The maximum cardiac GFP expression at 21 days was observed in rAAV-1. GFP expression by rAAV-1 was detectable at 7 days, improved at 21 days, and was still evident at 84 days. This study demonstrates cardiac rAAV gene transduction with a cold perfusion preservation system of the donor heart. These data show that AAV-1 is superior to AAV-2 and AAV-5 for this purpose and that durable expression is achievable.

Isolated tricuspid valve regurgitation (TR) is a rare clinical entity. We report 2 patients, 80 and 74-year-old with isolated TR. They underwent valve replacement with the Carpentier-Edwards bioprosthesis because of resistance to medical treatment. The causes of insufficiency were suspected as congenital in case 1 and infective endocarditis in case 2, respectively. Postoperative course was free from major complications in both patients. Valvuloplasty and/or annuloplasty are recommended for TR, however, replacement of the tricuspid valve is sometimes necessary in isolated TR patients. The higher occurrence of thrombosis of mechanical prosthesis in the tricuspid position has been reported. The bioprosthesis in tricuspid position may reduce the rate of thromboembolism, thrombosis and structural dysfunction, therefore it may be an option for radical therapy in isolated TR especially in aged patients.

A 62-year-old man who underwent coronary artery bypass grafting (CABG) [left internal thoracic artery (LITA)-left anterior descending (LAD), saphenous vein graft (SVG) right coronary artery (RCA)] 13 years previously developed angina pectoris and congestive heart failure because of occlusion of SVG and native vessels. Coronary angiography (CAG) revealed that inflow to the coronary artery remained only from LITA. Repeat off-pump CABG (OPCAB) with SVG to the circumflex artery via left thoracotomy was performed. The proximal end of SVG was anastomosed to the left axillary artery because of the porcelain aorta and the patent LITA graft. The patient developed no complications and was discharged from hospital on postoperative day 21. OPCAB for circumflex artery by left thoracotomy is an effective and safe approach in redo CABG, particularly in instances of patent LITA.

Transthoracic and transeshophageal real-time three-dimensional (3D) echocardiographic technique provides a unique ‘en-face‘ view of the mitral leaflets and annulus by an easy acquisition of pyramidal images of whole beating heart. Conventional two-dimensional (2D) echocardiography has been greatly contributing in the clinical diagnosis of mitral valve diseases and it is certainly the standard in clinical echocardiography for the evaluation of mitral valve. Nevertheless, 2D has a disadvantage in the assessment of 3D morphology of the mitral valve complex, which is consisted of the saddle shaped annulus, four leaflets, chordae and papillary muscles. Although welltrained echocardiographers can reconstruct the 3D shape and position of the structures by multi-scanned 2D images (mental reconstruction), the newly-developed 3D echocardiographic system allows us to visually understand the configuration of the complex mitral valve morphology. Furthermore, the reconstructed 3D images can be quantitatively measured and analyzed in 3D spaces, which have never been done in 2D images. Three-dimensional evaluation of the mitral valve provides us important additional information in the clinical diagnosis of mitral valve diseases. In this session, I would like to introduce some clinical data regarding the assessment of ischemic mitral regurgitation by 3D echocardiography.

occurring during accelerated rejection of cardiac allografts in presensitized recipients. Methods and Materials: LEW rats (n 12) were sensitized with WF skin grafts, followed 7 days later by transplantation of WF hearts. Results: These grafts were rejected within 24 hours post transplantation. Lymphocytes from presensitized recipients showed significant host cell proliferation in MLR cytotoxicyty in LMC accompanied by the occurrence of anti-donor allo-antibodies in the recipients’ sera at the time of graft loss ( FACS analysis). Immunohistochemical studies of accelerately rejecting cardiac allografts revealed a dense infiltration with MHC class II bearing cells, monocytes and macrophages (ED1) as well as T-cells (R73). In addition, apoptosis was observed during accelerated rejection of cardiac allografts (but not in the recipients naive hearts) as demonstrated by DNA laddering and TUNEL assay. Western blot analysis revealed a marked down regulation of the survival gene Bcl-2 in accelerated rejecting allografts, in comparison to naive and isograft control hearts. Reduction of Bcl-2 protein levels seems to be mediated by a proteolytical degradation, since quantitative RT-PCR analysis disclosed no alteration of Bcl-2 mRNA levels. Conclusions: Apoptosis was discovered as a so far unknown effector mechanism in accelerated cardiac transplant rejection which accompanies combined cellular and humoral immune alloreactivity. Apoptotic cell death in accelerateled rejection as well as the cascade of upand downstream events leading to apoptosis should be considered as critical steps and potential therapeutical targets in the pathogenesis of accelerated rejection.

Purpose: The creation of pigs deficient in the -Gal antigen was widely anticipated to eliminate the need for -Gal polymers and perhaps extend cardiac xenograft survival by reducing the intensity of the overall immune response. Methods and Materials: GT-KO pigs were developed from porcine fetal fibroblasts containing a neomycin insertion that disrupts exon 9 of the -galactosyltransferase gene. All of the GT-KO animals produced to date have been healthy and show no evidence of cataracts, a phenotype initially reported in GT-KO mice. Production of the GT-KO genotype has been at or near the predicted Mendelian frequencies. A series of 8 GT-KO pig to baboon heterotopic heart transplants were done using a maintenance immunosuppressive regimen that matched a previous study using GT CD46 transplants in which the recipients were successfully treated with daily infusion of -Gal polymers to block anti-Gal function. Results: Unexpectedly one heart underwent hyperacute rejection (HAR). Flow cytometry using GT-KO porcine aortic endothelial cells confirmed the presence of preformed non-Gal IgM and IgG and the cytolytic nature of this preformed antibody. Histological analysis of the graft showed typical hyperacute rejection including widespread edema and hemorrhage with strong vascular deposition of IgM and C5b. The remaining transplants survived for a median of 27 days (range 2-128 days) with 5 of 7 grafts exhibiting graft failure and delayed xenograft rejection. Survival of these GT-KO organs was comparable to the survival of GT CD46 transgenic hearts in recipients treated with an -Gal polymer to control induction of anti-Gal antibody. Conclusions: GT-KO donors may be clinically useful since they may eliminate the need for intravenous -Gal polymers, however, the HAR of one graft and the uniform presence of vascular antibody in the remaining transplants illustrate the pathogenic potential of preformed non-Gal anti-pig antibody and suggest that non-Gal antibody response will dominate contemporary xenograft rejection.

A 43-year-old male was transferred to our institute. His heart rhythm on admission was ventricular fibrillation (VF) which was successfully defibrillated with a direct current shock (DC). A diagnosis of short QT syndrome (SQTS) was made on the basis of an abnormally short QT interval of 280 ms during the sinus rhythm. During treatment for mild total hypothermia, VF recurred repeatedly necessitating DCs. Nifekalant at a dose of 0.3 mg/kg was intravenously administered, the QT interval was prolonged from 280 to 370 ms and VF no longer recurred. Subsequently the patient underwent implantation of an implantable cardioverter defibrillator.