[Atrial fibrillation after isolated coronary bypass surgery].

Postoperative atrial fibrillation (Af) remains a significant source of morbidity after coronary artery bypass grafting (CABG). Prophylactic therapy with beta-adrenergic blockers or amiodarone hydrochloride is reported to reduce the incidence of Af. We studied the incidence of Af retrospectively and considered the risk factors for it. Ninety-three patients who underwent isolated CABG from April 2003 to March 2004 are included in this study. Postoperative Af was observed in 22 (25%) patients. Ten of them were operated on off-pump procedure, and 14 had any type of beta-adrenergic blockers preoperatively. The mean age of the group of postoperative Af is 69.7 +/- 9.2 years old (older than the non-Af group: 65.5 +/- 10 years old, p = 0.087). And the preoperative left atrial size was larger in the Af group than in the non-Af group (43.4 +/- 6.1 versus 40.6 +/- 5.4mm, p = 0.064) Major embolic complication occurred in only 1 (1.1%) patient of non-Af group. We observed postoperative Af in 25% of patients after CABG. Older age and larger left atrial size may relate to the incidence of Af, and appropriate anticoagulant therapy and medication of beta-blockers are important for the patients who have such risk factors.

[Operative decision for acute type A aortic dissection; ascending aorta or arch replacement].

Operative technique of acute type A aortic dissection remains controversial. We adopted the strategy to replace the aortic arch only when the entry of the dissection was found in the aortic arch, or atherosclerotic arch aneurysm existed. The purpose of the current study was to elucidate the feasibility of the ascending aorta and hemiarch replacement and to follow the fate of the patent false lumen distal to the anastomosis after surgery. Nineteen patients operated from 2000 to 2004 were included in this study. Ascending or hemiarch replacement were performed in 15/19 (78.9%) patients. The early mortality rate was 10.5% (2/19). The causes of death included major brain infarction and rupture of the descending aortic aneurysm 25 +/- 23 days after surgery. Thrombosed distal false lumen of the thoracic aorta was observed in 60% (9/15) of patients of De Bakey type I dissection. Thus our strategy for acute type A aortic dissection including entry closure and the ascending or hemiarch replacement is a reasonable option especially for the elderly patients in acute phase. Our results also indicated that the thrombosis of the false lumen distal to the anastomosis can be expected and the enlargement of the distal aorta is minimal.

[Evaluation of a combination chemotherapy with nedaplatin and 5-FU for oral cancers].

Nedaplatin (cis-diammine-glycolato platinum: CDGP) is a platinum compound with a molecular weight of 303.18 that was recently developed in Japan. There have been reports of the antineoplastic effects of Nedaplatin on cancers in the cranio-cervical region, lung, esophagus, urinary bladder, testis, ovary, and uterus. In this study, we performed combined therapy of CDGP and fluorouracil (5-FU) for 8 patients with oral cancers, and evaluated the results to elucidate the clinical effect and adverse side effects. The subjects were 8 patients with squamous cell carcinoma (5 males and 3 females aged 33-65 years). The primary carcinoma regions were the tongue in 5 patients, oral floor in 2 patients, and mandibular gingiva in 1 patient. The T-classification was T2 in 6 patients and T4 in 2 patients, and the clinical staging was Stage II in 5 patients, Stage III in 1 patient and Stage IV in 2 patients. We first administered 700 mg/m2 5-FU per day from day 1 to day 5 (total dose 3,500 mg/m2), then 90 mg/m2 CDGP on day 5. The clinical effect was evaluated as a partial response in all cases, showing a 100% success rate. The histopathological findings of resected tumors were evaluated by Ohboshi and Shimozato's classification. One patient was Grade IIA, 5 patients Grade IIB, and 2 patients Grade III. The adverse side effects were slight myelotoxicity, gagging, nausea, alopecia, and stomatitis less than Grade II. Although the oral cancers in this study were extroverted superficial ulcerative cancers, and the number of patients was low at 8, this combined therapy is considered useful and worth evaluating in further accumulated cases.

Recombinant adenoviral mediated CD39 gene transfer prolongs cardiac xenograft survival.

BACKGROUND: Extracellular ATP and ADP may be important mediators of vascular inflammation and thrombosis. Nucleoside triphosphate diphosphohydrolase (NTPDase or CD39) is a vascular ectoenzyme that hydrolyses ATP and ADP; however, this activity is lost during reperfusion injury. We show that the supplementation of NTPDase activity within xenograft vasculature using CD39 recombinant adenoviruses (AdCD39) has protective effects in vivo. METHODS: Recombinant adenoviruses containing human CD39 or beta-galactosidase (Adbeta-gal) encoding genes were constructed. Hartley guinea pig coronary arteries were perfused ex vivo with University of Wisconsin solution containing 10(9) plaque-forming units of the recombinant adenovirus. Infected grafts were then implanted in the abdomen of complement depleted Lewis rats. RESULTS: NTPDase activities decreased in all grafts within the first 24 hr and subsequently recovered only in those hearts infected with AdCD39. Immunohistological examination of AdCD39-infected grafts confirmed successful CD39 gene transfer into the endocardium and macrovasculature. Expression of CD39 modestly prolonged graft survival (90.2+/-5.4 hr, mean+/-SD, n=5) when compared with Adbeta-gal-infected grafts (67.4+/-5.4 hr, P<0.005) and perfusion controls (66.4+/-5.2 hr; P<0.005). CONCLUSIONS: Recombinant adenoviral infection can induce expression of CD39 within cardiac xenografts and provide survival benefits in vivo. Our data show that ex vivo infection by recombinant adenovirus vectors can result in vascular expression of a potential therapeutic agent.

Suppression of delayed xenograft rejection by specific depletion of elicited antibodies of the IgM isotype.

BACKGROUND: Hamster hearts transplanted into untreated rats undergo delayed xenograft rejection (DXR). This acute inflammatory response is associated with the deposition of anti-graft antibodies of the immunoglobulin (Ig)M isotype in the vasculature. We have previously shown that these antibodies are generated in a T cell-independent manner. In this study, we tested whether the generation of anti-graft IgM antibodies is involved in the pathogenesis of DXR. In addition, we tested whether the suppression of this antibody response would overcome DXR. METHODS: Hamster hearts were transplanted into rats treated with an anti-mu monoclonal antibodies (mAb) to deplete circulating IgM or with an isotype-matched control mAb recognizing the dinitrophenyl epitope. T cell immunosuppression was achieved with cyclosporin A (CsA). RESULTS: Depletion of circulating IgM by anti-mu mAb inhibited DXR, whereas the control mAb had no effect on DXR. In anti-mu-treated rats, xenografts were rejected 5-7 days after transplantation through a T cell-dependent mechanism associated with the generation of antibodies of the IgG isotype. Combination of anti-mu with CsA suppressed the anti-graft IgM and IgG response and resulted in long-term xenograft survival (> 50 days). Xenograft long term survival occurred despite the return of anti-graft IgM antibodies to the circulation, a phenomenon referred to as accommodation. CONCLUSION: This study demonstrates that the pathogenesis of DXR can be initiated by anti-graft antibodies of the IgM isotype, which are generated in a T-cell independent manner. In addition, we show that under T cell immunosuppression, specific depletion of this IgM response by anti-mu mAb administration results in xenograft long-term survival and accommodation.

Accommodated xenografts survive in the presence of anti-donor antibodies and complement that precipitate rejection of naive xenografts.

Hamster hearts transplanted into transiently complement-depleted and continuously cyclosporin A (CyA)-immunosuppressed rats survive long-term despite deposition of anti-donor IgM Abs and complement on the graft vascular endothelium. This phenomenon is referred to as "accommodation." The hypothesis tested here is that accommodated xenografts are resistant to IgM Abs and complement that could result in rejection of naive xenografts. After first hamster hearts had been surviving in cobra venom factor (CVF) + CyA-treated rats for 10 days, a time when the anti-donor IgM Ab level was maximal and complement activity had returned to approximately 50% of pretreatment levels, naive hamster hearts or hamster hearts that had been accommodating in another rat for 14 days were transplanted into those rats carrying the surviving first graft. The naive hearts were all hyperacutely rejected. In contrast, a majority of regrafted accommodating hearts survived long-term. There was widespread Ab and activated complement deposition on the vascular endothelium of accommodating first hearts, second accommodating hearts, and rejected second naive hearts. However, only the rejected naive hearts showed extensive endothelial cell damage, myocardial necrosis, fibrin deposition, and other signs of inflammation. Accommodating first and second hearts but not rejected second naive hearts expressed high levels of the protective genes A20, heme oxygenase-1 (HO-1), bcl-2, and bcl-xL. These data demonstrate that accommodated xenografts become resistant to effects of anti-donor IgM Abs and complement that normally mediate rejection of xenografts. We hypothesize that this resistance involves expression by accommodated xenografts of protective genes.

Abdominal aortic aneurysms in aged patients: analysis of risk factors in non-ruptured cases.

BACKGROUND AND METHODS: A retrospective analysis of 304 patients (274 males and 30 females) surgically treated for non-ruptured, infrarenal abdominal aortic aneurysm (AAA) to determine the relative contribution of preoperative, operative, and postoperative factors to mortality and to the development of postoperative complications. 1) Risk factors, hospital mortality and long-term survival rate were compared between patients aged 75 or older (- group I; n=79) and those under 75 years of age (group II; n=225). 2) These risk factors were subjected to univariate and multivariate analysis to determine their relative contribution to patient hospital mortality and to the development of major postoperative complications in aged patients. RESULTS: Maximum diameter of AAA, the prevalence of respiratory dysfunction, diabetes mellitus and the total volumes of intraoperative blood loss were significantly different between the two groups. A higher hospital mortality was noted in the aged patients (10.1% versus 3.1%, p<0.05). The majority of deaths in group I resulted from organ dysfunctions, especially involved with respiratory failure. The long term survival rate at 3 and 5 years was not different between operative survivors in the two groups. Incremental risk factors for hospital death in aged patients included the presence of symptomatic AAA, the maximum diameter of AAA, the postoperative development of myocardial infarction, respiratory complications and gastrointestinal bleeding. Operation time and the volumes of intraoperative blood loss significantly correlated with the postoperative development of respiratory failure, renal failure and multiple organ failure. CONCLUSIONS: 1) A higher operative mortality and higher prevalence of postoperative complications were noted in aged patients with AAA. 2) To reduce operation time and the volumes of intraoperative blood loss would be essential to improve surgical results of AAA in aged patients.

Rejection of cardiac xenografts by CD4+ or CD8+ T cells.

We recently showed that brief complement inhibition induces accommodation of hamster cardiac transplants in nude rats. We have reconstituted nude rats carrying an accommodated xenograft with syngeneic CD4+ or CD8+ T cells to investigate the cellular mechanism of xenograft rejection. We show that CD4+ T cells can initiate xenograft rejection (10 +/- 1.7 days) by promoting production of IgG xenoreactive Abs (XAb). These XAb are able to activate complement as well as to mediate Ab-dependent cell-mediated cytotoxicity. Adoptive transfer of these XAb into naive nude rats provoked hyperacute xenograft rejection (38 +/- 13 min). The rejection was significantly (p < 0.001) delayed by cobra venom factor (CVF; 11 +/- 8 h in four of five cases) but was still more rapid than in control nude rats (3.3 +/- 0.5 days). CVF plus NK cell depletion further prolonged survival (>7 days in four of five cases; p < 0.01 vs CVF only). CD8+ T cell-reconstituted nude rats rejected their grafts later (19.4 +/- 5.8 days) and required a larger number of cells for transfer as compared with CD4+ T cell-reconstituted nude rats. However, second xenografts were rejected more rapidly than first xenografts in CD8+ T cell-reconstituted nude rats (9 +/- 2 days), indicating that the CD8+ T cells had been activated. This study demonstrates that CD4+ and CD8+ T cells can both reject xenografts. The CD4+ cells do so at least in part by generation of helper-dependent XAb that act by both complement-dependent and Ab-dependent cell-mediated cytotoxicity mechanisms; the CD8+ cells do so as helper-independent cytotoxic T cells.

Modulation of nucleoside [correction of nucleotide] triphosphate diphosphohydrolase-1 (NTPDase-1)cd39 in xenograft rejection.

BACKGROUND: There is increasing evidence showing that extracellular nucleosides [corrected] may be important mediators of vascular inflammation. Nucleoside [corrected] triphosphate diphosphohydrolase-1 (NTPDase-1, identical to CD39), the major vascular endothelial ectonucleotidase, is responsible for the hydrolysis of both extracellular ATP and ADP in the blood plasma to AMP. Studies were therefore conducted to evaluate the role of vascular NTPDase-1/cd39 in modulating platelet activation and vascular injury in cardiac xenografts. MATERIALS AND METHODS: Cardiac xenografts from both wild-type and cd39 knockout mice (C57BL/6 x 129 Svj) were transplanted into Lewis rats. Alterations in cd39 mRNA transcripts and NTPDase activity expression were evaluated in wild-type grafts in untreated rats and then following complement depletion and immunosuppression. Rejection responses were studied with both mutant and wild-type grafts in the following models: presensitization with or without complement depletion, complement depletion alone, and with chronic immunosuppression to induce long-term graft survival. RESULTS: NTPDase biochemical activity in wild-type xenografts rapidly decreased after transplantation but soon rebounded with graft survival. Elevated levels of cd39 mRNA with associated increases in NTPDase activity were observed in all long-term surviving wild-type grafts. Hyperacute xenograft rejection times were comparable in wild-type and mutant grafts but cd39-deficient grafts were subject to more rapid rejection and exhibited pronounced vascular injury in complement-depleted, presensitized rats. The cd39-deficient grafts in immunosuppressed recipients were subject to increased intravascular platelet sequestration and fibrin deposition; this resulted in focal myocardial infarction in long-term surviving mutant xenografts. CONCLUSIONS: Augmentation of NTPDase-1 activity may be an important adaptive response for graft survival. Our results suggest that NTPDase-1/cd39 influences pathways of vascular injury in cardiac xenografts.

[Surgical treatment for perforated aorta caused by mediastinitis after bidirectional Glenn shunt and closure of atrial septal defect--a case report].

A 24-year-old man with Ebstein anomaly underwent a bidirectional Glenn shunt and closure of an atrial septal defect. Postsurgical prulent mediastinitis was treated by irrigation and drainage, but was followed by rupture of the ascending aorta. During emergency surgery, hypothermic circulatory arrest became necessary due to massive bleeding. Since he had undergone a bidirectional Glenn shunt, left heart venting was essential to obtain deep hypothermic circulatory arrest without cardiac distention and was successfully performed via an anterior thoracotomy approach. The perforated site of the ascending aorta was repaired with a Xeromedica patch. The anterior mediastinum was wrapped with the omentum. Transthoracic left heart venting via an anterior thoracotomy is an useful approach when hypothermic circulatory arrest is required to perform a median sternotomy and to approach the heart.

Evaluation of 18-hour lung preservation with oxygenated blood for optimal oxygen delivery.

BACKGROUND: Previous studies have shown that availability of oxygen during lung preservation to maintain aerobic metabolism may be essential for the optimal viability of preserved lung tissue. The purpose of this study was to evaluate lung preservation with oxygenated blood for optimal oxygen delivery to the lung graft in a rabbit model. METHODS: Eighteen excised rabbit lungs were flushed and stored for 18 hours at 10 degrees C with one of the following: Euro-Collins solution (EC; n=6), oxygenated homologous blood (OB; n=6), or low-potassium dextran solution (LPD; n=6). Poststorage lung functions were evaluated with isolated, blood-perfused lung model for 10 minutes. RESULTS: The mean oxygen tensions after reperfusion for the EC, OB, and LPD groups (47.0+/-2.8, 76.9+/-13.1, 96.2+/-10.9 mm Hg at 10 minutes, respectively) were significantly different throughout the perfusion period (EC < OB < LPD, p < 0.05; EC < LPD, p < 0.01). Pulmonary artery pressure during the reperfusion period in the EC group (35.8+/-4.4 mm Hg at 10 minutes) was higher than that in the OB and LPD groups (29.8+/-4.3 and 22.4+/-2.2 mm Hg, respectively) (EC > OB, EC > LPD, p < 0.05). However, the E-selectin level in the reperfused blood in the OB group (5.04+/-0.24 ng/mL) was significantly elevated compared with that in other groups (EC, 3.56+/-0.54; LPD, 2.92+/-0.35 ng/mL, p < 0.05), which indicated enhanced neutrophil recruitment in the OB group. Comparisons of thrombomodulin and endothelin among the three groups did not reach statistical significance. CONCLUSIONS: We conclude that OB may enhance lung preservation as compared with EC solution, probably through its enriched oxygen delivery during storage and extracellular composition. However, the availability of oxygenated blood does not exceed that of LPD solution because of augmented neutrophil recruitment, which may activate neutrophil-endothelial interactions.

Expression of heme oxygenase-1 can determine cardiac xenograft survival.

The rejection of concordant xenografts, such as mouse-to-rat cardiac xenografts, is very similar to the delayed rejection of porcine-to-primate discordant xenografts. In concordant models, this type of rejection is prevented by brief complement inhibition by cobra venom factor (CVF) and sustained T-cell immunosuppression by cyclosporin A (CyA). Mouse hearts that survive indefinitely in rats treated with CVF plus CyA express the anti-inflammatory gene heme oxygenase-1 (HO-1) in their endothelial cells and smooth muscle cells. The anti-inflammatory properties of HO-1 are thought to rely on the ability of this enzyme to degrade heme and generate bilirubin, free iron and carbon monoxide. Bilirubin is a potent anti-oxidant, free iron upregulates the transcription of the cytoprotective gene, ferritin, and carbon monoxide is thought to be essential in regulating vascular relaxation in a manner similar to nitric oxide. We show here that the expression of the HO-1 gene is functionally associated with xenograft survival, and that rapid expression of HO-1 in cardiac xenografts can be essential to ensure long-term xenograft survival.

Surgical experiences with peripheral arterial aneurysms due to vasculo-Behçet's disease.

BACKGROUND: Vascular involvement of Behçet's disease is currently considered as an important sign of the clinical evolution of patients with Behçet's disease. In addition, Behçet's disease is important in that it causes peripheral arterial aneurysms. METHODS: In this report, 4 patients with vasculo-Behçet's peripheral arterial aneurysms are presented. These aneurysms were distributed in the carotid artery (n=1), popliteal artery (n=1) and femoral arteries (n=3). Operative procedures included patch closure of a perforated wall for the carotid aneurysm, arterial reconstruction with the autogenous saphenous vein for the femoral and popliteal aneurysms. RESULTS: All four patients tolerated the operation well, however, two of four patients required re-operation due to anastomotic insufficiency later. CONCLUSIONS: Aneurysms associated with Behçet's disease have a sudden onset in many cases and often result in rupture. Appropriate operative procedures, including an adequate choice of anastomotic sites and reinforcement of the suture, may reduce the incidence of complications in patients with arterial aneurysms due to Behçet's disease.

Complement-fixing elicited antibodies are a major component in the pathogenesis of xenograft rejection.

Hamster to rat cardiac xenografts undergo delayed rejection as compared with the hyperacute rejection of discordant xenografts. Elicited xenoreactive Abs (EXA) are thought to initiate hamster to rat cardiac xenograft rejection. In this study, we demonstrate that following transplantation of a hamster heart, rats generated high levels of EXA. Adoptive transfer into naive recipients of purified IgM, IgG2b, or IgG2c, but not IgG1 or IgG2a EXA, induced xenograft rejection in a complement-dependent manner. Ability of EXA to cause rejection correlated with complement activation, platelet aggregation, and P-selectin expression in the xenograft endothelium. Cyclosporin A (CyA) administration, after transplantation, totally suppressed IgG1, IgG2a, IgG2b, and IgG2c EXA, and inhibited IgM EXA production, but failed to overcome rejection. Administration of cobra venom factor (CVF), 1 day before and at the time of transplantation, resulted in complement inhibition during 3 days after transplantation, which failed to overcome rejection. Combination of CyA and CVF, which we have previously shown to overcome rejection, resulted in suppression of IgG EXA production and in the return of IgM XNA to preimmunization serum levels, 3 to 7 days after xenotransplantation, while complement remained inhibited. Thus, under CyA/CVF treatment, complement activation by hamster cells was suppressed following xenotransplantation, and presumably for this reason xenograft rejection did not occur. In conclusion, our data demonstrate that EXA play a pivotal role in the pathogenesis of xenograft rejection and that CyA and CVF suppress xenograft rejection by preventing exposure of xenograft endothelial cells to complement activation by EXA.

Application of the reversed elephant trunk technique during total thoracoabdominal replacement in patients with Marfan's syndrome.

The reversed elephant trunk operation has been applied in patients with extensive aortic involvement as a scheduled staged operation. We report application of the same technique in two patients with Marfan's syndrome. The two patients underwent total replacement of the thoracoabdominal aorta for a DeBakey IIIb aortic dissection. The proximal end of the prosthetic graft was invaginated to facilitate future proximal operation. No complication related to the trunk had been observed during the follow-up period.

Takayasu's arteritis complicating annuloaortic ectasia (AAE) treated with modified Bentall procedure.

A case report and a brief review of the literature on Takayasu's arteritis complicating annuloaortic ectasia are presented. The patient successfully underwent modified Bentall procedure during the inactive stage of the disease. Piehler's method is recommended for coronary reconstruction in the presence of severe periaortic adhesions resulting from Takayasu's arteritis.

[A case report of correction for total anomalous pulmonary venous connection in adult--usefulness of the superior approach].

In the repair of total anomalous pulmonary venous connection (TAPVC), some reports suggest that atrial arrhythmia was occurred as a late post-operative complication when the extended incision over the both atria was made by lateral approach, while the posterior approach in adult case often is difficult to expose operative field. A 42-year-old female patient with supracardiac type of TAPVC, Darling Ia type, was successfully corrected using superior approach. During procedure, the excellent operative field was obtained and large size of anastomosis between the posterior wall of left atrium and the common pulmonary vein could be carried out without lifting up the apex of the heart or the extensive incision of the both atria. The post-operative angiogram revealed no stenosis or distortion at the anastomotic site. We reviewed the 17 adult cases of supracardiac type of TAPVC repair in Japan, however, the superior approach was not reported. Our experience would suggest the superior approach is useful in the adult patient to repair supracardiac type of TAPVC. In addition to surgical approach, the pitfall of the post-operative hemodynamic changes in adult case of TAPVC repair was discussed.

[CPE chemotherapy for tongue carcinoma--clinical effects and side effects].

UNLABELLED: Recent advances in chemotherapy have markedly improved the treatment results for oral cancer. Among many chemotherapeutic regimens, the usefulness of multiple combination chemotherapy with cisplatin as the primary drug has been frequently reported. During the past 6-year period, we have performed combination chemotherapy with cisplatin as the primary drug, peplomycin, and etoposide (CPE chemotherapy) as one of the chemotherapeutic regimens for oral cancer. The subjects were 11 patients (7 males and 4 females) with tongue cancer treated by CPE chemotherapy as neoadjuvant chemotherapy at our department between March, 1990 and April, 1995. RESULTS: PR in 8 (73%), and NC in 3 (27%). No patient showed CR and PD. The side effects observed were reversible findings such as transient myelosuppression, nausea-vomiting, and alopecia. No patient showed severe or persistent suppression of hematopoietic function.