[Dissection of descending aorta with spinal paralysis].

A 56-year-old man had undergone ascending aorta and total arch replacement because of aortic dissection (Stanford type A) in 1997. He had onset of diplegia of the lower limb and vesicorectal disability. Computed tomography (CT) showed serpentine aneurysm in the descending aorta, it was seen between the left subclavian artery and diaphragm level. It was 80 mm of maximum diameter. Magnetic resonance imaging (MRI) was performed for identified Adamkiewicz artery, but we could not identify it. We performed a graft replacement. The 8th intercostal artery was reconstructed with a branch graft. The postoperative course was uneventful. We conclude that graft replacement for spinal ischemia can be effective.

[Surgical angioplasty of isolated left coronary ostial stenosis].

A 42-year-old female had suffered from chest pain for approximately 1 month, and was admitted with unstable angina pectoris. Emergent coronary angiography showed an isolated 75% stenosis of the left coronary ostium. Repair of ostial stenosis by vein patch angioplasty was done by the transactional superior approach. Postoperative catheterization revealed an expanded left coronary orifice and the patient was discharged without any complications. We have experienced 2 other patients of isolated left coronary ostial stenosis, who had undergone double coronary artery bypass grafting. Long-term coronary angiography showed regression of ostial stenosis in 1 patient, and no progression of new lesions in either. These results suggest that direct vein patch angioplasty of the ostial lesion is an alternative procedure for isolated left coronary ostial stenosis.

Overexpression of tumor necrosis factor- alpha activates both anti- and pro-apoptotic pathways in the myocardium.

We have previously reported that mice with cardiac-specific overexpression of tumor necrosis factor (TNF)- alpha develop myocardial inflammation, cardiac hypertrophy, and dilated cardiomyopathy. TNF- alpha is reported to induce apoptosis in cultured cardiac myocytes. To investigate the role of apoptosis in this transgenic model, wild-type controls (WT) and transgenic mice (TG) at the age of 1, 8, and 40 weeks were analyzed. Increased incidence of apoptosis in TG was indicated by DNA laddering. TUNEL assays revealed that the frequencies of apoptotic cells were increased in the TG myocardium at all ages. However, as revealed by histochemical and immunofluorescent methods, most of the apoptotic cells appeared to be non-myocytes even in the mice with overt congestive heart failure. To elucidate the signaling pathways responsible for TNF- alpha induced apoptosis, expression of apoptosis-related genes were evaluated by multi-probe RNase protection assays. Transcripts for death-domain-related proteins, including TNFR1, Fas, FADD, TRADD, and RIP, were constitutively expressed in WT and upregulated in the TG myocardium. Expression of caspase-1 through -8 was also enhanced in TG. While both anti- and pro-apoptotic Bcl-2 family genes were constitutively expressed in WT, TNF- alpha overexpression strongly induced anti-apoptotic A1 in the myocardium. Furthermore, TNF- alpha overexpression activated NF- kappa B, a mediator of anti-apoptotic pathways, in the myocardium. Thus, overexpression of TNF- alpha activated both anti- and pro-apoptotic pathways in the myocardium, resulting in an increase of apoptosis, primarily in non-myocytes. These results suggest that TNF- alpha by itself is not sufficient to induce apoptosis in cardiac myocytes in vivo.

Expression of proinflammatory cytokines in the failing human heart: comparison of recent-onset and end-stage congestive heart failure.

BACKGROUND: Plasma levels of proinflammatory cytokines, including tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, are elevated in patients with congestive heart failure (CHF). Recent studies suggest that the failing human heart is a source of proinflammatory cytokines in the end-stage failing heart. However, the relevance of plasma levels to those of the myocardium remains undefined. We sought to compare cytokine expression in early and end-stage CHF, and to evaluate the correlation of tissue expression to plasma levels. METHODS: Two patient populations were studied: patients with recent-onset CHF, all with symptoms less than 6 months (n = 17, duration of symptoms 2.1 +/- 1.6 months, range of New York Heart Association (NYHA) 1 to 3), and end-stage heart-failure patients (n = 7) who underwent left-ventricular assist-device (LVAD) implantation (Duration of symptoms 47.1 +/- 28.0 months, all NYHA class 4). Plasma levels of TNF-alpha and IL-6 proteins were evaluated by an Enzyme-Linked Immuno-Sorbent Assay (ELISA), while myocardial levels of cytokine transcripts were assessed by ribonuclease (Rnase) protection assay. RESULTS: In patients with end-stage heart failure, TNF-alpha and IL-6 were increased in the plasma as well as in the myocardium (plasma: TNF-alpha = 7.7 +/- 2.3 pg/ml, IL-6 = 45.0 +/- 47.1 pg/ml; myocardium: TNF-alpha = 0.31 +/- 0.15% of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) expression, IL-6 = 1.56 +/- 1.54% ). In contrast, despite elevated plasma levels of TNF-alpha and IL-6, the myocardium of patients with the recent onset of symptoms demonstrated minimal expression of TNF-alpha and IL-6 messenger ribonucleic acid (mRNA) (plasma: TNF-alpha = 4.3 +/- 1.7 pg/ml, IL-6 = 3.3 +/- 1.8 pg/ml; myocardium: TNF-alpha = 0.13 +/- 0. 04%, IL-6 = 0.02 +/- 0.04%). Plasma levels of TNF-alpha were significantly correlated with those in the myocardium when both populations were combined. (r = 0.69, p < 0.001). CONCLUSIONS: Cytokines are expressed in the myocardium in end-stage heart failure to a much greater degree than in patients with the recent-onset of symptoms. This suggests that induction of cytokines in the myocardium is a relatively late event in the pathogenesis of CHF. Furthermore, plasma levels of TNF-alpha correlates with mRNA expression in the myocardium and thus may serve as an appropriate marker of myocardial cytokine activation. Whether the production of cytokines in the failing human heart precedes the elevation of cytokines in the plasma remains undefined. Therefore, we studied expression of TNF-alpha and IL-6 in the myocardium as well as in the plasma in patients with early and end-stage CHF. The results have demonstrated that cytokines are expressed in the myocardium in end-stage heart failure to a much greater degree than in patients with the recent onset of symptoms. This suggests that induction of cytokines in the myocardium is a relatively late event in the pathogenesis of CHF.

Soluble tumor necrosis factor receptor abrogates myocardial inflammation but not hypertrophy in cytokine-induced cardiomyopathy.

BACKGROUND: Transgenic mice with cardiac-specific overexpression of tumor necrosis factor (TNF)-alpha develop dilated cardiomyopathy. The present study was designed to evaluate therapeutic effects of adenovirus-mediated neutralization of TNF-alpha on this model. METHODS AND RESULTS: An adenovirus encoding the 55-kDa TNF receptor-IgG fusion protein (AdTNFRI) was injected intravenously into 6-week-old transgenic mice, which resulted in high levels of TNFRI in both plasma and myocardium. AdTNFRI did not reverse cardiomegaly but abrogated myocardial inflammation. Furthermore, AdTNFRI blocked the myocardial expression of intercellular adhesion molecule-1 and downstream cytokines, including interleukin-1beta and monocyte chemotactic protein-1. Downregulation of alpha-myosin heavy chain was restored by the treatment, whereas upregulation of beta-myosin heavy chain was not reversed. In contrast, the downregulation of sarcoplasmic reticulum Ca(2+)-ATPase and phospholamban was normalized by AdTNFRI. Echocardiographic measurements showed that left ventricular end-systolic diameter was significantly larger in transgenic mice than in control mice, and this increase was reversed by the AdTNFRI treatment. However, left ventricular wall thickening was not reversed. CONCLUSIONS: These results suggest that anti-TNF therapy may hold promise in the treatment of end-stage heart failure.

Mid-term follow up results of Japanese heart transplant patients operated in UCLA Medical Center.

UNLABELLED: Japanese candidates have been accepted for heart transplantation by the UCLA Medical Center in the US since 1993 due to the lack of donors available from brain-dead patients. OBJECTIVES AND METHODS: We monitored to patients who underwent such heart transplantation and have been seen at the out-patient clinic at Tokyo Women's Medical University following transplantation. Pre-operative diagnosis was dilated cardiomyopathy in all patients. One patient underwent Novacor implantation as a bridge to heart transplant. All patients underwent cardiac echocardiography and cardiac catheterization including intraluminal echography. RESULTS: All patients survived with an actuarial survival curve of 100% at 1 year, 100% at 3 years and 87% at 5 years in 4.15 years of average follow-up. Two patients died due to liver dysfunction and cerebral emboli. The postoperative functional status of patients was New York Heart Association classification I in 8 (100%). Immunosuppressive therapies included triple drug therapy using either cyclosporin or tacrolimus. The incidence of acute rejection (/pt) exceeding grade 3 was 4% within three months, 3.5% in 3-6 months, and no significant rejection episode more than 6 months after transplantation. Posttransplantation coronary artery disease was seen in 2 patients, but no progression was seen after diltiazem therapy. CONCLUSION: Our postoperative follow-up after cardiac transplantation appears to be satisfactory.

Neutrophil accumulation and damage to the gastric mucosa in resuscitated hemorrhagic shock is independent of inducible nitric oxide synthase.

Polymorphonuclear leukocytes (PMN) and inducible nitric oxide synthase (iNOS) appear to play important roles in the liver and in lung injury induced by hemorrhagic shock. Their precise roles in hemorrhagic shock-induced acute gastric mucosal lesions (AGML), however, are still poorly understood. In this study, we investigated the effect of neutropenia on hemorrhagic shock-induced AGML. We also examined the roles of iNOS in PMN infiltration into the mucosa and AGML during hemorrhagic shock by using L-N6-(1-iminoethyl)-lysine, a potent inhibitor of iNOS, and by reverse transcriptase polymerase chain reaction. Remarkable gastric mucosal damage occurs after hemorrhagic shock. PMN depletion caused by Vinblastine pretreatment significantly attenuates this AGML. Although low-dose L-N6-(1-iminoethyl)-lysine (50 microg/kg, iNOS inhibition) has no effect on AGML, high-dose L-N6-(1-iminoethyl)-lysine (250 microg/kg, iNOS + endothelial NOS inhibition) significantly exacerbates AGML without increasing PMN infiltration into the mucosa. The mRNA expression of iNOS in the stomach during hemorrhagic shock cannot be detected by reverse transcriptase polymerase chain reaction. We conclude that PMN play a pivotal role in hemorrhagic shock-induced AGML, iNOS does not regulate PMN infiltration into the mucosa, and endothelial NOS provides important protection against AGML during hemorrhagic shock.

An implantable centrifugal blood pump with a recirculating purge system (Cool-Seal system).

A compact centrifugal blood pump has been developed as an implantable left ventricular assist system. The impeller diameter is 40 mm, and pump dimensions are 55 x 64 mm. This first prototype, fabricated from titanium alloy, resulted in a pump weight of 400 g including a brushless DC motor. The weight of a second prototype pump was reduced to 280 g. The entire blood contacting surface is coated with diamond like carbon (DLC) to improve blood compatibility. Flow rates of over 7 L/min against 100 mm Hg pressure at 2,500 rpm with 9 W total power consumption have been measured. A newly designed mechanical seal with a recirculating purge system (Cool-Seal) is used for the shaft seal. In this seal system, the seal temperature is kept under 40 degrees C to prevent heat denaturation of blood proteins. Purge fluid also cools the pump motor coil and journal bearing. Purge fluid is continuously purified and sterilized by an ultrafiltration unit which is incorporated in the paracorporeal drive console. In vitro experiments with bovine blood demonstrated an acceptably low hemolysis rate (normalized index of hemolysis = 0.005 +/- 0.002 g/100 L). In vivo experiments are currently ongoing using calves. Via left thoracotomy, left ventricular (LV) apex descending aorta bypass was performed utilizing an expanded polytetrafluoroethylene (ePTFE) vascular graft with the pump placed in the left thoracic cavity. In 2 in vivo experiments, the pump flow rate was maintained at 5-9 L/min, and pump power consumption remained stable at 9-10 W. All plasma free Hb levels were measured at less than 15 mg/dl. The seal system has demonstrated good seal capability with negligible purge fluid consumption (<0.5 ml/day). In both calves, the pumps demonstrated trouble free continuous function over 6 month (200 days and 222 days).

Experience of patients with end-stage heart failure who underwent heart transplant at UCLA.

From 1993 to 1997, nine Japanese heart transplant candidates were accepted by the University of California at Los Angeles (UCLA) Medical Center, because no donor heart was available in Japan from a brain-dead patient. In all nine heart transplant patients described in this investigation, the preoperative diagnosis was dilated cardiomyopathy. One patient underwent implantation with a Novacor left ventricular assist device (Baxter Japan, Tokyo, Japan) as a bridge to heart transplant. All patients survived surgery and for a long-term period. The actuarial 1-year and 3-year survival curves of these patients were both 100%. The postoperative functional status was New York Heart Association Class 1 in all patients (100%). Immunosuppressive triple drug therapy (azathioprine, steroids, and cyclosporine) was given in seven patients; in two patients, cyclosporine was withdrawn and replaced by FK506 due to refractory rejection. The incidence of acute rejection per patient of more than grade 3 according to the International Society for Heart and Lung Transplantation was 6% within 3 months and 4.5% in 3-6 months; there was no rejection episode more than 6 months after transplantation. Post-transplant coronary artery disease was seen in two patients. However, no disease progression was seen after diltiazem therapy. These results may encourage heart transplantation in Japan.

Less blood damage in the impeller centrifugal pump: a comparative study with the roller pump in open heart surgery.

A centrifugal pump with an impeller (Nikkiso Centrifugal Pump, Model HPM15; Nikkiso Co. Ltd.) was applied to cardiopulmonary bypass (CPB) in 14 patients who underwent elective coronary artery bypass grafting. Serum hemoglobin level, platelet count, and serum beta-thromboglobulin (beta TG) level were measured during CPB. The results were compared with those obtained in a comparative roller pump (RP) group (n = 10). There was no difference in the time on CPB between the NP (109 min) and RP (121 min) groups. The serum beta TG level (ng/ml) was lower in the NP group than in the RP group (obtained 90 min after the initiation of CPB). The plasma-free hemoglobin level also was lower in the NP group than in the RP group (obtained 90 min after the initiation of CPB, 120 min after the initiation of CPB, immediately after the termination of CPB, 3 h after termination of CPB; p < 0.01). There was no significant difference in platelet depletion. The HPM15 pump showed excellent hemodynamic performance with less blood trauma compared with the roller pump in its clinical application to open heart surgery.