Search

As a result of improvements in medical management, patients suffering from hemophilia have a life expectancy approaching that of the normal population. An increased life expectancy, however, brings an increased risk of developing age-related disorders. Several article have reported elective cardiac operations successfully performed on hemophiliacs. To our knowledge, there are no articles describing such patients undergoing emergent aortic surgery. Our report describes the successful management of an individual with hemophilia A undergoing emergent total arch replacement for acute aortic dissection (Stanford A). We used a continuous infusion of factor VIII concentrate during the perioperative period. The patient was discharged without bleeding complications.

Off-pump coronary artery bypass surgery is considered to be less invasive compared with a conventional coronary artery bypass surgery, while objective assessment of its invasiveness has not been well established. The grade of invasiveness of off-pump CABG was evaluated by biochemical markers released from the myocardium.Perioperative serial changes of myocardial enzyme leakage (creatine kinase-MB isoenzyme and troponin T) were evaluated in 217 patients who underwent coronary artery bypass surgery (28 off-pump CABG patients and 189 conventional CABG patients). Serial changes of atrial natriuretic peptide and brain natriuretic peptide secretion as markers of heart failure were also evaluated in 12 off-pump CABG patients and 49 conventional CABG patients.Myocardial enzyme leakage was significantly less in the off-pump CABG group, while increase of brain natriuretic peptides secretion were similar in both groups with its peak at the first postoperative day (246+/-46 pg/ml in the off-pump CABG group and 312+/-57 pg/dl in the conventional CABG group).Although off-pump CABG seems to be less invasive to the myocardial cells from the aspect of enzyme leakage, ischemic stress to the heart assessed by brain natriuretic peptide secretion was similar to that of conventional CABG. Careful monitoring and management throughout postoperative period is mandatory even in off-pump CABG procedure.

Objectives: Elastic property of the proximal aorta plays an important role in reducing pulsatile load to the ventricle. When a stiff vascular prosthesis is used for the proximal aorta, the pulsatile load increases. We designed this study to elucidate whether the increase in pulsatile load caused left ventricular hypertrophy. Methods: We created an ascending aorta-abdominal aorta bypass in 9 dogs with a noncompliant vascular prosthesis. The aortic arch proximal to the left subclavian artery was occluded to direct blood flow into the bypass. Closed chest studies were performed after a median of 139 days (range 45-588) days. We assessed the pulsatile load of the ventricle by calculating characteristic impedance from pressure and flow velocity in the ascending aorta. The left ventricle was weighed, normalized with body weight, and compared with the control group, which had sham operations (7 dogs). Results: Characteristic impedance of the bypassed dogs was 175% higher than the control (0.146 ± 0.056 vs 0.053 ± 0.014 mm Hg · s · mL−1, P =.009), which resulted in wider pulse pressure (57 ± 11 vs 25 ± 11 mm Hg, P

Objectives: There are an increasing number of reports concerning mitral valve repair by reconstruction of the chordae tendinae with the use of expanded polytetrafluoroethylene (PTFE) sutures. However, little information is available about the extended application or results of this technique for extended prolapse of bilateral mitral leaflets, which is considered to be difficult to repair. Methods: Between October 1993 and May 1998, 17 patients (age range 16‐74 years) who had from moderate to severe mitral regurgitation as the result of a prolapse of bilateral leaflets underwent mitral valve repair by reconstruction of artificial chordae with CV-4 expanded PTFE sutures. Either bilateral or unilateral Kay’s suture annuloplasty was also performed to correct annular dilatation in all patients. Results: No operative death or late mortality was observed. Before discharge, immediate postoperative echocardiography showed less than moderate mitral regurgitation in 16 of 17 patients. The follow-up was completed in all cases by a clinical examination and serial echocardiograms, and the median follow-up period was 52 months (range 27‐82 months). There was one failure that required re-operation because of worsening mitral regurgitation (elongation of the anchored side of papillary muscle). When the re-operated patient was excluded from the following data, the degree of mitral regurgitation, estimated by echocardiography performed at recent follow-up, was none in four patients, trivial in eight patients, and mild in four patients. The systolic and diastolic dimensions of the left ventricle decreased significantly (P , 0:01). Conclusions: Because replacement of artificial chordae was not complicated and seemed to preserve fine relationships among leaflet tissues, chordae, and papillary muscles, we therefore suggest that the extensive use of PTFE artificial chordae appears to be a promising procedure for the repair of all kinds of mitral lesions causing mitral regurgitation. q 2002 Elsevier Science B.V. All rights reserved.

The vibrational wave superimposed on the load-deflection curve recorded by the instrumented Charpy impact test was analyzed and the effect of specimen, dimension on the vibrational wave was investigated. Moreover, the change in fracture toughness values with changing loading rate was studied. Furthermore, the validity of the use of shock-absorbing material, which can suppress the generation of the vibrational wave at impact, was examined. Lastly, the time history of the stress intensity factor evaluated by the one-point bend test was compared with the one in the impact response curve in the instrumented impact test, and the differences in fracture toughness values between the one-point bend test and the Charpy impact test were discussed. The results of present study are summarized as follows. (1) The vibrational wave can be prevented by the use of a smaller specimen which shortens the period of the vibrational wave. (2) The load value is lowered by the use of shock-absorbingmaterial. (3) The differences in the impact response curves and the fracture times evaluated from the instrumented Charpy impact test and the one-point bend test are rather large at the lower impact velocity of 3.10 m/s; however, the obtained K Id values are nearly coincident.

The load calibration in instrumented Charpy impact testing was performed to develop an accurate measurement method of impact load. A decrease in specimen, thickness results in a slight decrease of the calibration factors. This was attributed to strain localization, near the region in which strain gages were attached. The results strongly suggested that the system must be calibrated for the different thicknesses of specimens to know the accurate impact load. The accurate impact load was not measured from the gage around the end of the slit which was introduced to release the constraining effect of deformation of the gage position from surrounding hammer; the effect of the vibration of the hammer appeared strongly around this position. However, it was possible to prevent the effect of such vibration by attaching the gage away from such position.

The use of multiplane transesophageal echocardiography (TEE) to reconstruct 3-dimensional (3D) images is limited by time-consuming, multiplane image acquisition and the need for offline processing. To overcome these limitations, a 3D fully sampled matrix array transducer was recently developed to allow real-time acquisition and online display of 3D images. In this case, real-time 3D transesophageal echocardiography produced clear image of a small paraprosthetic leak point. Although the surgical view from the left atrium was poor due to severe adhesions, we were able to perform optimal repair of the small leak after intraoperative confirmation of the location of the leak that was identified by preoperative real-time 3D transesophageal echocardiography.

Purpose Transplantation of healthy regenerative cardiomyocytes into the injured heart is effective option to improve cardiac function. The optimal transplantation of cardiomyocytes must be developed. The aim of this study is to fabricate scaffold-free 3-Dimensional pulsatile cardiac tissue by nobel tissue engineering technology. Methods and Materials Approximately two thousands of mouse embryonic stem cells (ESc) derived cardiomyocyte were formed into spheroids. To construct 3-dimensional cardiac tissue, a large number of spheroids are fused via our nobel technology, named bio-rapid prototyping system (BRP). This technolog is based on the original characteristic of cells to form spheroid cell aggregates. The constructs were produced semi-automatically by stabbing spheroids with numerous needles. Finally, we succeeded in fabricating scaffold-free contractile cardiac tissue 3×1×1mm in diameter. Electrophysiological and histological analysis are performed to evaluate the function of the constructs. Results Electrophysiological studies revealed that electrical spikes detected on the construct. Immunofluorescent images with anti-connexin43 antibody demonstrated that gap junctions also established within the construct within 24 hours. This constructs continued pulsation for two weeks in vitro. Figure options Download full-size image Download high-quality image (99 K) Download as PowerPoint slide Conclusions These results demonstrate that electrically communicative pulsatile 3-D cardiac constructs were achieved in vitro by fusing cardiomyocytes spheroids. We concluded that cardiac tissue engineering based on this technology may prove useful for heart model fabrication and cardiovascular tissue repair.

Although protein arginine methyltransferase 5 (PRMT5) has been implicated in various cancers, its expression pattern in lung adenocarcinoma cell lines and tissue samples has not yet been elucidated in detail. In this study, microarray data analysis of 40 non-small cell lung carcinoma cell lines showed that PRMT5 was a candidate histone methyltransferase gene that correlated with epithelial-mesenchymal transition. Immunocytochemical analysis of these cell lines indicated that the expression of PRMT5 was frequently localized to the cytoplasm of E-cadherin-low and vimentin-high cell lines, while it was predominant in the nucleus and faint in the cytoplasm of E-cadherin-high and vimentin-low cell lines. Immunohistochemical analysis of 130 cases of lung adenocarcinoma revealed that the expression of PRMT5 was high in the cytoplasm of 47 cases (36%) and the nuclei of 34 cases (26%). The high cytoplasmic expression of PRMT5 was frequently observed in high grade subtypes such as the solid adenocarcinoma component with low expression of thyroid transcription factor-1 (TTF-1, the master regulator of lung) and low expression of cytokeratin 7 and E-cadherin (two markers for bronchial epithelial differentiation), while the high nuclear expression of PRMT5 was frequently noted in the lepidic growth component, a low-grade subtype. The cytoplasmic expression of PRMT5 was correlated with vessel invasion and poor prognosis. We herein highlighted the importance of PRMT5 expression, especially its cytoplasmic expression, in the process of epithelial-mesenchymal transition and loss of the bronchial epithelial phenotype of lung adenocarcinoma. Citation Format: Daisuke Matsubara, Reem Ibrahim, Wael Osman, Akteru Goto, Teppei Morikawa, Shigeki Morita, Shumpei Ishikawa, Hiroyuki Aburatani, Masashi Fukayama, Toshiro Niki, Yoshinori Murakami. Expression of PRMT5 in lung adenocarcinoma and its significance in epithelial-mesenchymal transition. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1036. doi:10.1158/1538-7445.AM2014-1036

Lung cancer is the leading cause of cancer mortality worldwide, and novel therapeutic targets and molecular diagnostic markers are highly warranted. Micro RNAs (miRNAs) are a class of small non-coding RNAs associated with a variety of cancer. miRNA-21 is an “oncomiR” and upregulated in many cancers, including lung cancer, and high miR-21 levels have been associated with poor prognosis. To determine the localization of miR-21 and to compare its expression levels, we performed in situ hybridization of miR-21 on 89 mixed subtypes of lung adenocarcinoma. miR-21 was predominantly expressed in cancer associated fibroblasts (CAF)s expressing α-SMA, with no difference in expression between non-invasive and invasive component. In addition, stromal miR-21 expression was significantly associated with decreased overall survival (p=0.0021). In functional analyses of miR-21 in vitro, miR-21 was overexpressed in lung fibroblasts to assess migration and invasion. miR-21 expression in lung fibroblasts promoted migration and invasion. Moreover, the proliferation of lung cancer cells was accelerated by conditioned medium of miR-21-expressing lung fibroblasts. These results suggest that miR-21 overexpression in CAFs of lung adenocarcinoma might serve as a prognostic biomarker and be involved in cancer cell proliferation through interactions with cancer cells. Citation Format: Akiko Kunita, Shigeki Morita, Masashi Fukayama. Expression of miR-21 in cancer associated fibroblasts in lung adenocarcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 535. doi:10.1158/1538-7445.AM2014-535

1. Background: Vandetanib is a multikinase inhibitor of EGFR, VEGFR and RET, and is now clinically used for advanced medullary thyroid carcinoma treatment. KIF5B-RET fusion is reported to be novel oncogenic genomic translocation accounting for about 5% of lung cancers. However, overexpression of RET has not been well studied. 2. Material and methods: a) We performed quantitative RT-PCR of 82 surgically resected adenocarcinomas. And using tissue micro array we performed immunohistochemistry (IHC) assay of 379 surgically resected lung cancer (151 squamous cell carcinomas(SCC), 210 adenocarcinomas, 6 large cell carcinomas, 6 pleomorphic carcinomas and 6 small cell carcinomas). b) We performed a retrospective prognosis survey of 82 patients with surgically resected adenocarcinomas, stratifying based on RET overexpression and EGFR mutation. c) Using lentiviral vectors, we generated RET-overexpressed A549, NCI-H23, and NCI-H1650. Then, we measured IC50 values for gefitinib and vandetanib in original cell lines, and RET-overexpressed cell lines using WST-8. Relative resistance index for gefitinib and vandetanib was calculated by dividing the IC50 value in RET-overexpressed cell by IC50 in original cell line. 3. Results: a) RET was overexpressed in 4.6% of SCC, 17.1% of adenocarcinomas, and none of other histological type of lung cancers by using IHC assay. Quantitative RT-PCR also revealed that RET was overexpressed in 13.4% of adenocarcinomas. c) Multivariate analysis showed that RET overexpression was more likely in patients with EGFR mutation (p=0.004, t-test). Among patients with EGFR mutation, RET-overexpression was a poor prognostic factor (p=0.001, Log Rank test). c) In all the three cell lines, IC50 value for vandetanib was higher than that for gefitinib; the ratio was 1.25, 1.21 and 1.33, respectively. These data indicate that overexpression of RET leads to the development of resistance to gefitinib, and using vandetanib is a possible way to overcome the resistance. 4. Conclusions: RET overexpression is a poor prognostic factor among lung adenocarcinomas with EGFR mutation. Acquired resistance to gefitinib due to RET overexpression may explain this clinical data. This study indicated that instead of EGFR-TKI it is better to use vandetanib, which inhibits both EGFR and RET, for treating lung cancer with EGFR mutation and RET overexpression. To confirm this, a prospective randomized trial focusing on RET overexpression is needed. Citation Format: Mitsuhiro Sunohara, Shigeki Morita, Masanori Kawakami, Kousuke Watanabe, Hidenori Kage, Yousuke Amano, Rie Ishikawa, Masahisa Fukayama, Takahide Nagase, Nobuya Ohishi, Daiya Takai. Can lung cancer with overexpression of RET-proto oncogene be a good candidate for vandetanib treatment? [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr B22.

A 63-year-old man had a distal arch aneurysm combined with a circumflex retroesophageal right aortic arch, which is a rare form of vascular ring. By using combined median sternotomy and left thoracotomy under deep hypothermia and retrograde cerebral perfusion, total arch replacement with a vascular graft was successful. We describe our surgical strategy for arch aneurysm associated with an uncommon congenital vascular malformation.

The use of a left ventricular assist device (LVAD) as a bridge to transplant is associated with a 52% incidence of RV failure requiring additional inotropic or mechanical support (RVAD). This study evaluated the differential performance of the RV free wall and septum to identify the need for additional RV support. Cross-sectional views of the RV were obtained immediately before, and 1 hr after, Novacor LVAS implantation in 12 consecutive patients using transesophageal echocardiography. Each image was divided into a free wall portion (FW) and a septal portion (SP) by grids drawn from the center of gravity of the end-diastolic endocardial outline to the junction between the FW and the SP. Percentage change between preimplant and postimplant for RV ejection fraction (RVEF), fractional area change for the FW (FAC-FW) and the SP (FAC-SP), and fractional shortening of the FW to SP distance (F-S) is reported for patients based upon the need for RV support: minimal (Group 1), maximal (Group 2). After LVAS implantation, patients showed a reduction in SP fractional area change. However, this reduction was most pronounced in Group 2. The degree of SP impairment may explain the mechanism of RV failure in patients on an LVAD.

We report a case of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis induced by propylthiouracil (PTU), and review the literature concerning to anti-thyroid drug-induced ANCA-associated vasculitis. A 45-year-old man treated with PTU developed fever and arthralgia without pulmonary, skin or eye involvement. These symptoms persisted for a long period without specific symptom, sign or laboratory data of other arthritis. Laboratory findings of urine and blood were normal, except for positive MPO-ANCA (191EU) and PR3-ANCA (37EU) findings. After PTU was discontinued without steroids or immune modulating drugs, both symptoms disappeared. Our patient had a high titer of MPO-ANCA. Moreover, titers of ANCA fell in correlation with the course of symptoms after the cessation of PTU, and we diagnosed PTU-induced ANCA-associated vasculitis. Most patients with pulmonary renal syndrome receive anti-thyroid drugs over a prolonged period, but the duration of our case was shorter than those of these patients. It is suggested that our patient was diagnosed at an early stage of ANCA-associated vasculitis before the start of pulmonary or renal involvement.

Background. In beating heart coronary artery bypass grafting (CABG) the effect of ischemic insult during coronary occlusion could not be evaluated immediately. Using transesophageal echocardiography, myocardial performance can be evaluated with analysis of integrated backscatter. Methods. In 15 beating heart CABGs, cyclic variation (CV) of integrated backscatter of the anterior wall before, during, and after the left internal thoracic artery to left anterior descending (LAD) branch anastomosis was measured with transesophageal echocardiography. The patients were divided into two groups according to collateral vessels status (good collateral group n 5 6, poor collateral group n 5 9). Results. In all patients, CV increased significantly after revascularization (8.56 6 2.50 to 11.47 6 3.32 dB, p < 0.0001). During LAD occlusion, significant decrease in CV was found in patients who had poor collateral arteries. At 15 minutes of LAD occlusion, CV decreased from the preocclusion value of 7.51 6 2.21 to 3.23 6 4.03 dB (p < 0.01). Conclusions. Measurement of CV can detect the ischemic insult during coronary occlusion and the effect of revascularization in beating heart CABG.

An 81-year-old Japanese woman visited our hospital because of abdominal discomfort. Physical examination revealed that she had an abdominal mass. A combination of ultrasonography, computed tomography, magnetic resonance imaging (MRI), and hepatic asialoglycoprotein scintigraphy was utilized to make a diagnosis. We found that she had a downward elongated hepatic lobe or Riedel's lobe which did not appear to be common in our district. The prevalence of Riedel's lobe in the Asian population has not been studied. Furthermore, this is the first report that describes the MRI and hepatic asialoglycoprotein scintigraphy features of Riedel's lobe of the liver.

A 25-year-old man with a history of bone-marrow-transplantation for the treatment of Löffler's endocarditis underwent surgery for massive tricuspid regurgitation with paroxysmal atrial flutter. Dense fibrosis in the right ventricular endocardium with complete obliteration of the apex was seen intraoperatively, and the right ventricular cavity was diminished. Annular dilatation of the tricuspid valve and entrapment of the posterior leaflet to the endocardial fibrosis were also seen. Annuloplication at the posterior leaflet was performed. In addition, the right atrial free wall was widely resected and the septal and inferior vena cava-tricuspid valve isthmi were cryoablated for the treatment of atrial flutter. Postoperative catheterization revealed rather high right ventricular end-diastolic pressure. However, tricuspid regurgitation disappeared with the increased cardiac output. Atrial flutter could not be induced by repetitive stimulation in the postoperative electrophysiological examination.

This report describes 2 cases of a type A acute aortic dissection combined with myocardial infarction caused by a retrograde dissection into the left main trunk of the coronary artery. Successful surgical treatments, including the replacement of the ascending aorta, aortic valve resuspension and coronary artery bypass grafting, were performed in both patients, and they recovered well from cardiogenic shock. However, left ventricular function of both patients remained depressed postoperatively, which limited their quality of life. Because no definite method for salvaging infarcted myocardium has yet been established, either more timely surgery or the preoperative placement of a perfusion catheter in the left main coronary artery is mandatory.

Histological changes in the right atrial flap used in repair of total anomalous pulmonary venous connection were observed when the patient underwent repair of peripheral pulmonary venous stenosis after two months. The flap, 35 mm in length and 15 mm in width, was thin and soft. Microscopically, endocardium and myocardium were preserved well, with only moderate thickening of the epicardium. We can anticipate the viability of the right atrial flap, but care should be taken to keep blood supply to the flap intact.

The effects of arresting donor hearts with University of Wisconsin solution was investigated. Donor dogs were divided into two groups according to the technique used for arresting the heart. In group I (n = 6) the heart was arrested with University of Wisconsin solution, whereas in group II (n = 6) extracellular-type cardioplegia (K+ = 20 mmol/liter) was used to induce cardioplegic arrest. Aortic root pressure was measured during the infusion of solution at constant flow. In both groups, the hearts were then flushed and stored in cold University of Wisconsin solution for 6 h. The hearts were transplanted orthotopically and disconnected from cardiopulmonary bypass. Left ventricular function was evaluated by pressure-volume relations using a conductance catheter. Peak aortic root pressure during the infusion was significantly higher in group I than in group II, although post-transplant left ventricular function was similar in both groups. Although there was no difference in cardiac function after implantation, donor hearts should be arrested by extracellular-type cardioplegia to prevent coronary vasoconstriction associated with preservation in University of Wisconsin solution.

Objective: There are an increasing number of reports concerning mitral valve repair by reconstructing the chordae tendineae with the use of expanded polytetrafluoroethylene sutures in adults. However, little information is available about application or results of this technique in children. Methods : Between January 1995 and December 1997, 16 children who had from moderate to severe mitral regurgitation mainly as the result of a prolapse of the anterior leaflet (age range, 5 months–12.8 years) underwent mitral valve repair by reconstruction of artificial chordae. Either unilateral or bilateral Kay-Reed annuloplasty was also performed to correct annular dilatation in all patients. Results: No operative death or morbidity was observed. Before discharge, immediate postoperative echocardiography showed less than trivial mitral regurgitation in all patients. The follow-up was complete in all cases by a clinical examination and serial echocardiograms, and the median follow-up period was 14.8 months (range, 1.3-26.4 months). There were no valve-related events during the entire follow-up period. The degree of mitral regurgitation, estimated by echocardiography performed at recent follow-up period, was none in 5 patients, trivial in 10 patients, and mild in 1 patient. The diastolic and systolic dimensions of the left ventricle decreased and were 95.0% and 96.2% of the normal values, respectively. Conclusions: Although further investigations and long-term results are still called for, mitral valve repair by reconstruction of the artificial chordae was found to be safe and effective even in infants and children. (J Thorac Cardiovasc Surg 1999;118:94-8)

A 76-year-old woman presented with multiple brain infarctions in the right middle cerebral artery and vertebral artery area. Carotid sonography revealed a large mobile pedunculated mass in the brachiocephalic artery, which showed rapid growth despite treatment with heparin and aspirin. Graft replacement of the brachiocephalic artery was performed under selective cerebral perfusion with deep hypothermia. Histology of the resected specimen revealed aortic atherosclerotic plaque.

Purpose The aim of our study is to develop completely scaffold-free, viable, contractile cardiac tissue which can be grafted to the damaged native heart. Methods and Materials Our technology is based on the fundamental characteristics of self-assembling nature of cells. We called these self-assembled spherical cell aggregates as “spheroids”. We created contractile cardiac spheroids by plating a mixture of 800 cells of rat neonate ventricular cardiomyocytes (RNVCM), 100 cells of human normal dermal fibroblasts (HNDFB), and 100 cells of human coronary micro-artery endothelial cells (HCMEC) in ultra-low-attachment plate. After 24 hr cultivation, prevascularized contractile cardiac spheroids were fabricated. Next, 10000 spheroids were fused into patch like construct with a maximum diameter of 1cm with 200μm in thickness. We evaluated morphological characteristics, and electro- and mechanical function. We also grafted the cardiac patch onto the heart of F344 nude rats, and performed histological study 3 weeks after transplantation. Results We confirmed synchronous beating of the cardiac patch electro-physiologically, and mechanically (video-motion analysis). Expression of connexin 43 (a component of gap junction) and micro network of endothelial cell in the construct were demonstrated. Histological study performed 3 weeks after transplantation showed that the grafts were viable with functioning micro-vascular structure inside the graft. [ figure 1 ] Conclusions We consider that applying our scaffold-free 3-Dimensinal tissue engineering technology to cardiac regeneration therapy is feasible. We expect that this technology will become a promising tool to treat end-stage heart failure.

Protamine sulfate often causes hypotension during heparin neutralization. The concept of ventricular-arterial coupling was applied to determine whether a negative inotropic effect or a vasodilating effect of protamine was the major contributing factor to this hypotension. Thirty-five patients who underwent cardiac operations were studied during operation by measuring instantaneous left ventricular pressure and aortic flow to examine the end-systolic pressure-volume relationship. We obtained end-systolic elastance and effective arterial elastance values in a beat-to-beat fashion with a single-beat estimation method. In 28 of the 35 patients (80%), mean arterial pressure decreased more than 10 mm Hg with protamine infusion. Parameters were compared at the following three points: before a decrease in mean arterial pressure (control), at maximally decreased mean arterial pressure (maximum), and at a middle point between control and maximum values (midpoint). At both midpoint and maximum, mean arterial pressure decreased significantly (control 79.6 ± 12.6 mm Hg, midpoint 66.5 ± 10.8 mm Hg, maximum 52.7 ± 9.9 mm Hg; p < 0.01). Similar changes were observed in effective arterial elastance (control 2.00 ± 0.75 mm Hg/ml, midpoint 1.60 ± 0.53 mm Hg/ml, maximum 1.31 ± 0.46 mm Hg/ml; p < 0.01). Although the decrease in end-systolic elastance at midpoint (control 3.08 ± 1.61 mm Hg/ml, midpoint 2.92 ± 1.68 mm Hg/ml) did not reach statistical significance, end-systolic elastance significantly decreased at maximum (2.63 ± 1.46 mm Hg/ml; p < 0.01). Continuous measurements showed that the decreases in mean arterial pressure and effective arterial elastance always preceded the depression of end-systolic elastance and that afterload reduction by vasodilating effect of protamine was the mechanism most likely to have initiated the hypotension. Delayed decrease in contractility may be ascribed to reduced coronary perfusion pressure caused by vasodilation or to a direct effect of protamine. (J Thorac Cardiovasc Surg 1996;112:462-71)

Background. Preoperative autologous blood donation is one of the most effective methods to avoid homologous blood transfusion in cardiac operations. However, there have been few reports about the safety and efficacy of autologous blood donation in children. Methods. Since 1986, we have instituted a blood conservation program including preoperative autologous blood donations in children. Eighty children as young as 3 years old (mean ± SD, 8.6 ± 3.9 years) and weighing as little as 12.3 kg (29.2 ± 14.5 kg) were enrolled in the program, and 735 ± 388 mL of blood was donated during an average of 3.1 ± 1.5 phlebotomies before the operations. Results. Two episodes of mild vasovagal reaction were observed in 2 patients as a complication of the phlebotomy. Seventy-six percent of the collected blood was stored by cryopreservation; the remaining 24% was preserved by liquid storage. Seventy-eight of these patients (97.5%) underwent operations using cardiopulmonary bypass. Seventy-five patients (94%) were operated on successfully without the need for a homologous blood transfusion. As for the other 5 patients, 2 received only platelet concentrate. Conclusion. Preoperative autologous blood donation is a safe and effective method to avoid homologous blood transfusion in pediatric cardiac operations.

It has been reported that various types of immunoactivators can induce Graves' disease. We describe here a case of Graves' disease during treatment with sizofiran, an immunoactivator. A 42-year-old woman who had previously been in an euthyroid state with Hashimoto's thyroiditis, experienced thyrotoxicosis during continuous administration of sizofiran as immunotherapy for endometrial carcinoma. Since the TSH receptor-antibody was positive, and a thyroid scintigram showed diffuse goiter and high uptake, she was diagnosed as having Graves' disease. It is suggested that the administration of sizofiran may be one of the triggers of Graves' disease.

The objective of this study was to determine the relationship of on-line measurements of left ventricular cavity area generated by echocardiographic automated border detection to true volume measured by an intraventricular balloon in an isovolumically contracting isolated canine heart preparation. Seven excised dog hearts had placement of an intraventricular balloon and were perfused in an ex vivo apparatus. Left ventricular area data from the midventricular short-axis plane and pressure data were recorded on a computer through a customized hardware and software interface with the ultrasound system. Left ventricular volumes were varied from 5 ml to maximal values (30 to 40 ml) at 1-milliliter increments. Three increasing and decreasing volume ramps were analyzed on each of seven hearts for a total of 1260 simultaneous measurements. Linear regression analysis correlated mean automated border detection area with absolute volume from each preparation. A predominantly linear relationship was observed with an average correlation of r = 0.97 (y = 0.16x-0.69, SEE = 0.31 cm2, p0.01). Left ventricular area measures for six of seven dogs varied little during isovolumic contraction (0.4 cm2) but did show a systematic cardiac cycle-related variability in one dog (28% change in area, maximum to minimum, over all volumes). In conclusion, the relationship between cross-sectional area and left ventricular volume was predominantly linear and varied little during isovolumic contractions in the normal canine left ventricle. Echocardiographic automated border detection appears to be a promising method to reflect changes in left ventricular volume.

The effect of retinoic acid (RA) on thyroid peroxidase (TPO) and thyroglobulin (Tg) gene expression was investigated in cultured human thyrocytes. Thyrocytes dispersed from Graves' thyroid tissues were incubated with TSH 5mU/ml and RA 0, 0.01, 0.1, 1.0 microM for 72 h respectively. The samples were then subjected to Northern gel analysis. Northern gel analysis using the specific cDNA probes showed that RA suppressed the accumulation of TPO and Tg mRNA stimulated by TSH in a time- and dose-responsive manner. Furthermore, RA inhibited forskolin and 8-Bromo-cyclic-AMP-induced TPO and Tg gene expression, suggesting a distal action site for these cAMP mediated gene expressions. Immunoprecipitation analysis using the specific monoclonal antibodies showed that TSH increased newly synthesized 100, 75, 36-kDa [35S] TPO. The increased de novo TPO was markedly inhibited by RA. Tg secretion from monolayer cultures was measured by radioimmunoassay. RA also inhibited TSH-induced Tg secretion in a dose dependent manner. RA did not affect [3H] thymidine uptake into primary cultured human thyrocytes. In conclusion, RA inhibits the synthesis of TPO and Tg via the suppression of thyroid-specific gene expression although the exact site of RA action on these genes in human thyroids remains to be further elucidated. These results suggest that RA may play a regulatory role in Tg and TPO gene expression, subsequently resulting in the suppression of thyroid hormone synthesis.

Right ventricular (RV) failure after the implantation of a left ventricular assist device (LVAD) limits the use of univentricular support for patients awaiting heart transplantation. An understanding of the mechanism responsible for RV failure after LVAD implantation is essential for determining patient selection for univentricular assist devices versus the total artificial heart as a bridge to transplantation. To examine the effect of LVAD implantation on the RV, we explored the relations among RV end-systolic elastance (Ees), effective pulmonary arterial elastance (Ea), and the energy transfer from the pressure-volume area (PVA) to external mechanical work (EW). Eight patients were studied intraoperatively before and after Novacor LVAD implantation, using a trans-esophageal echocardiogram and catheter tip micromanometer to construct a RV pressure-cross-sectional area loop, thereby measuring Ees, Ea, PVA, and EW. The Ees was obtained by transiently occluding the inferior vena cava. After the implantation, Ea/Ees was reduced from 10.4 ± 6.9 to 3.7 ± 2.5 and EW/PVA improved from 0.32 ± 0.51 to 0.51 ± 0.20. Ea/Ees was negatively correlated with EW/PVA (r = -0.75). Those who required mechanical RV assistance showed both an increase in Ea/Ees and a worsening of the mechanical efficiency of the right ventricle. The implantation of a LVAD brought about RV afterload reduction, which optimized ventricular/arterial coupling, thereby improving the mechanical efficiency of the RV.

The use of a left ventricular assist device (LVAD) as a bridge to transplant is associated with a 25% incidence of right ventricular (RV) failure requiring an additional extended inotropic support or mechanical support (RVAD). Loss of septal contribution may be partially responsible for RV failure. This study evaluated two quantitative methods to assess the differential performance of the RV free wall and septum. Cross-sectional echo views of the right ventricle were obtained immediately prior to and 1 h after Novacor LVAD implantation in 12 consecutive patients. Each image was divided into a free wall portion (FW) and a septal portion (SP) by grids drawn from the center of gravity of the end-diastolic endocardial outline (fixed axis system) or corresponding phase of outline (floating axis system) to the junction between the FW and the SP. Fractional area change for the FW (FAC-FW) and the SP (FAC-SP) are reported. The fixed axis system was superior to a floating axis system for detecting contraction defects. The fixed axis system showed a significant reduction in SP contraction after Novacor implantation.

11. Safian RD, Gelbfish JS, Erny RE, Schnitt SJ, Schmidt DA, Baim DS. Coronary atherectomy: clinical, angiographic, and histological findings and observations regarding potential mechi82:69-79. Kuntz R. Selmon M. Robertson G. Schnitt S, Safian R. Excision of deep wall components by directional cbronary atherectomy does not increase restenosis [Abstract]. Circulation 1991;84(suppl II):II-81. Garratt KN, Holmes DR, Bell MR, et al. Restenosis after coronary atherectomy: differences between primary atheromatous and restenosis lesions and influence of subintimal tissue resection. J Am Co11 Cardiol 1990;16:1665-71. Yakubov SJ, Dick RJ, Haudenschild CC, Rosenschein U. Deep tissue retrieval with coronary atherectomy is paradoxically associated with less restenosis [Abstract]. Circulation 1991; 84(suppl II):II-520. Hill JA, Margolis JR, Feldman RL, Conti CR, Pepine CJ. Coronary arterial aneurysm after balloon angioplasty. Am J Cardiol 1983;52:261-4. van Suylen RJ, Serruys PW, Simpson JB, de Feyter PJ, Strauss BH, Zondervan PE. Delayed rupture of right coronary artery after directional atherectomy for bail-out. AM HEART J 1991;121:914-6.

The new immunosuppressive agent FK 506 was used as primary immunotherapy in conjunction with low-dose steroids and azathioprine in 72 patients subsequent to orthotopic cardiac transplantation. Overall patient survival at a mean follow-up of 360 days was 92%. The number of episodes of cardiac rejection (grade 3A or greater) within 90 days of transplantation was 0.95 per patient. The actuarial freedom from rejection at 90 days was 41%. Achievement of this level of immunosuppression is comparable with that of cyclosporine-based triple-drug therapy with OKT3 immunoprophylaxis. Thirty percent of patients were tapered off all steroids, and the average steroid dose in the group who received steroids was 8.6 mg of prednisone per day. The incidence of infection reflected the diminished necessity for steroids: seven major infections (10%) and 11 minor infections (16%). Renal dysfunction occurred during the perioperative period in most patients in this trial. However, the incidence of hypertension was 54% compared with 70% during the cyclosporine era. Ten adults underwent successful rescue therapy with FK 506 after cardiac rejection refractory to conventional immunotherapy. Side effects of FK 506 were notably few, and the results of the trial are encouraging for the future of the cardiac transplant recipient.

1. To determine whether a persistent release of creatine kinase from the myocardium occurs in patients with hypertrophic cardiomyopathy, the activities of serum creatine kinase MM isoforms were measured in 22 patients with hypertrophic cardiomyopathy and in 14 normal control subjects. 2. Serum creatine kinase MB activity was significantly higher in patients with hypertrophic cardiomyopathy (7.8 ± 3.8 i.u./l) than in normal control subjects (0.4 ± 0.8 i.u./l; P < 0.01). 3. Serum MMa, MMb and MMc activities in patients with hypertrophic cardiomyopathy were 19.4 ± 4.1%, 26.7 ± 2.5% and 33.5 ± 7.0% of the total creatine kinase MM activity, respectively. These values for each isoform were significantly different from those in normal control subjects (11.3 ± 3.0%, 21.5 ± 4.4% and 40.7 ± 7.0%, respectively). The MMa/MMc activity ratio was significantly higher in patients with hypertrophic cardiomyopathy (0.61 ± 0.25) than in normal control subjects (0.30 ± 0.10; P < 0.01). 4. Our results indicate that a small amount of the myocardial tissue isoform of creatine kinase MM (MMa) is constantly released in many patients with hypertrophic cardiomyopathy.

A rare case of tracheopathia osteochondroplastica complicated with malignancy is reported. Further examination of hemosputum following thyroid cancer operation revealed an abnormal finding of the trachea, suggesting the recurrence of thyroid cancer. However, the serum level of thyroglobulin was within the normal range. In contrast, the findings of bronchofiberscopy and the histological analysis confirmed the presence of tracheopathia osteochondroplastica. Therefore, measurement of serum thyroglobulin level and the bronchofiberscopy procedure were valuable for the differential diagnosis of metastasis of thyroid cancer in this case. Additionally, case reports of tracheopathia osteochondroplastica in Japan are summarized.