Contractile cardiac grafts using a novel nanofibrous mesh.

Cardiomyoctes are terminally differentiated cells and therefore unable to regenerate after infarction. The use of autologous bioengineered cardiac grafts has been suggested to replace infarcted myocardium and enhance cardiac function. Here we report the development of an in vitro system for engineered myocardium. Cardiac nanofibrous meshes (CNM) were developed by culturing cardiomyocytes from neonatal Lewis rats on electrospun, nanofibrous polycaprolactone (PCL) meshes. The mesh had an ECM-like topography and was suspended across a wire ring that acted as a passive load to contracting cardiomyocytes. The cardiomyocytes started beating after 3 days and were cultured in vitro for 14 days. The cardiomyocytes attached well on the PCL meshes and expressed cardiac-specific proteins such as alpha-myosin heavy chain, connexin43 and cardiac troponin I. The results demonstrate the formation of contractile cardiac grafts in vitro. Using this technique, cardiac grafts can be matured in vitro to obtain sufficient function prior to implantation. It is conjectured that cardiac grafts with clinically relevant dimensions can be obtained by stacking CNMs and inducing vascularization with angiogenic factors.

Endovascular stent-grafting via the aortic arch for distal aortic arch aneurysm: an alternative to endovascular stent-grafting.

OBJECTIVE: We have experienced transaortic stent-grafting for treating distal arch aneurysm or type B dissection. This paper is to mainly report the surgical aspect of these procedures. METHODS: Fifteen patients underwent this surgery, including 12 men and three women ranging from 47 to 83 years. Twelve had aneurysms and three aortic dissection. Concomitant surgery was necessary in seven patients (coronary artery bypass grafting in five, tricuspid annuloplasty in one, and replacement of ascending aorta and/or total arch replacement in three cases). A stent graft (Gianturco Z-stent and Intervascular prosthesis) was loaded in a 30-F sheath catheter. Under circulatory arrest, selective cerebral perfusion was established, and the sheath catheter was inserted through aortotomy into descending aorta and the stent graft was deployed at an appropriate level. The proximal end of graft was sutured to the aorta just distal to the left subclavian artery with inclusion method at the posterior wall. Concomitant surgery was done during cooling or rewarming period. TEE was utilized to visualize every endovascular manipulation to avoid unintended intimal injury or misplacement of graft and to assess the surgical results in the operative theater. RESULTS: Aneurysm was successfully excluded except in one patient who had a proximal endoleak and distal endoleak due to underestimation of aortic diameter. There was one operative mortality caused by cerebral infarction, possibly due to debris from femoral arterial cannulation. In the remaining patients, there was no enlargement of residual aneurysm. The excluded aneurysmal sac gradually regressed and disappeared within 2 years in five patients and the thrombosed false lumen completely shrunk within 1 year in two patients. One patient had paraplegia, possibly because the graft was intentionally advanced deeply to cover the thick and fragile atheromatous layer in order to avoid destruction of the atheroma by an expanded graft. CONCLUSIONS: Endovascular stent graft via the aortic arch is an acceptable treatment for distal arch aneurysms close to or involving left subclavian artery or type B dissections, especially for those cases requiring other cardiac procedures. It can lead to regression and disappearance of aneurysm or dissection in the mid-term follow-up.

Pulmonary vein orifice isolation for eliminating paroxysmal atrial fibrillation after ICD implantation.

We treated a patient with dilated cardiomyopathy (DCM) and sustained ventricular tachycardia by an implantable cardioverter defibrillator (ICD). He then suffered from inappropriate ICD shocks triggered by paroxysmal atrial fibrillation (AF). We successfully performed pulmonary vein orifice isolation to eliminate paroxysmal AF. The pulmonary vein orifice isolation was a simple and useful procedure for eliminating paroxysmal AF in patient with decreased left ventricular (LV) function after ICD implantation.

Electrophysiological analysis of chronic atrial fibrillation associated with mitral valve disease by using spectral analysis.

Several authors have suggested that periodic activation is related to maintenance of atrial fibrillation (AF). The aim of this study was to examine periodic electrical activations in both atria that may lead to the generation and maintenance of AF associated with valvular diseases by means of fast Fourier transform (FFT) analysis. Atrial electrograms (AEGs) were analyzed in 15 persistent AF patients, who underwent pulmonary vein orifice (PVO) isolation with mitral valve surgery. Intraoperatively, AEGs of 4 seconds duration were acquired at 48 epicardial sites, 24 each from the right and left atrium (RA, LA). Dominant peaks (DPs) examined using FFT were present in 26% of all sampling points (380/1440). Prominent clustering of DPs was mostly observed on the LA. The mean AF cycle length (mAFCL) estimated from DP frequency was significantly shorter in LA than that in RA (178 +/- 32 msec vs 247 +/- 58, p = 0.0003). The shortest AF cycle length in each patient was mainly found in the LA. The PVO isolation procedures successfully eliminated AF in 87% of patients (13/15). In cases of recurred AF (2/15), the difference in mAFCL between bilateral atria was significantly smaller than in the case of successful AF elimination (17 +/- 7 msec vs 76 +/- 56, p = 0.042). FFT analysis of intraoperative mapping data clarified that periodic activity was present predominantly in LA. It may be possible to predict the efficacy of surgical procedures for eliminating AF using this technique.

Efficacy of pulmonary vein isolation for the elimination of chronic atrial fibrillation in cardiac valvular surgery.

BACKGROUND: Haissaguerre and colleagues emphasize the importance of the pulmonary veins as a source of ectopic foci for initiating paroxysmal atrial fibrillation (AF). We hypothesized that ectopic foci from the pulmonary veins could also act as drivers for maintaining chronic AF, and that surgical ablation of the pulmonary vein orifices could terminate chronic AF. METHODS: Using a computerized 48-channel mapping system, we performed intraoperative atrial mapping in 12 patients with chronic AF associated with mitral valve disease. Patient age ranged from 24 to 82 years (mean, 60.4 years). AF duration ranged from 3 to 240 months (mean, 92+/-84 months). Simple surgical isolation of the pulmonary vein orifices was performed during the mitral valve operation. RESULTS: Regular and repetitive activation was found in the left atria of 9 out of 12 patients, and irregular and chaotic activation was found in both atria of 3 out of 12 patients. Chronic AF in the 9 patients (75%) with regular and repetitive activation of their left atria was successfully treated by a simple surgical isolation of the pulmonary vein orifices. The other 3 patients did not recover sinus rhythm after this procedure. In 1 case of recurrent AF, the patient recovered sinus rhythm during the follow-up period (AF-free rate, 83%). CONCLUSIONS: Surgical ablation of the pulmonary vein orifices was effective in the treatment of chronic AF associated with mitral valve disease. Intraoperative mapping may be useful in predicting the efficacy of a single pulmonary vein orifice isolation procedure.

Ruptured sinus valsalva with infectious endocarditis: a technique of defect closure with an autologous-xenologous pericardial sandwich patch.

We report a case of ventricular septal defect with acquired rupture of sinus Valsalva induced by infectious endocarditis. After irrigati on of all infectious tissues, the defect was closed twice using two different patches. One was an autologous pericardial patch from the right ventricle and the other was a composite patch made of an autologous pericardium and axenologous pericardium from the left ventricle. As a result, the xenologous pericardium was sandwiched between autologous pericardiums. We thought that this "sandwiched patch" would compensate for the shortcomings of each type of pericardium and resist left ventricular pressure and infection. Despite the development of antibiotic therapy, infectious endocardit is (IE) is still one of the most difficult disease to cure. In the case of a rupture of sinus Valsalva, because of the rapid spread of infection into any of the cardiac chambers, surgical intervention is necessary. In this report, we describe a case treated successfully.

Treatment of established collagen induced arthritis with prostaglandin E1 incorporated in lipid microspheres.

OBJECTIVE: In view of evidence obtained from in vitro and in vivo experiments that prostaglandin E1 (PGE1) has regulatory effects on disordered immune responses and inflammation, we investigated whether lipo-PGE1, an efficient drug delivery system incorporating PGE1 into lipid microspheres, can ameliorate arthritis in the collagen induced arthritis (CIA) model of rheumatoid arthritis (RA). METHODS: DBA/1J male mice were immunized with bovine type II collagen in adjuvant, and treated daily from onset of clinical arthritis with intravenous administration of lipo-PGE1 (5-50 microg/kg) or lipid vehicle as a control. Arthritis was assessed over a 10 day treatment period by monitoring for paw swelling and clinical score. Histopathology of the arthritic hind paws was also evaluated. Lipo-PGE1 accumulation in arthritic joint tissues was measured using 3H labeled PGE1 incorporated in lipid microspheres. RESULTS: Arthritis was significantly suppressed in lipo-PGE1 treated mice compared with lipid vehicle treated controls (p < 0.05, p < 0.016, respectively) in a dose-dependent manner. Histopathological assessment showed a significant reduction of pannus formation and joint destruction in lipo-PGE1 treated mice compared with controls (p < 0.05). Lipo-PGE1 preferentially accumulated in arthritic joints for a longer period than free PGE1. CONCLUSION: Using an efficient drug delivery system, PGE1 can suppress CIA, and lipo-PGE1 may have a potential therapeutic role in RA.

Echocardiography-assisted surgery in transaortic endovascular stent grafting: role of transesophageal echocardiography.

OBJECTIVE: Transesophageal echocardiography was applied to visualizing endovascular procedures during transaortic stent grafting for aneurysm and dissection at the distal arch, and the use of transesophageal echocardiography was evaluated. METHODS: The 16 consecutive patients (13 with aneurysms and 3 with dissections) were examined. Transesophageal echocardiography was used for (1) determining graft size, (2) guiding placement of the catheter in the descending aorta at an appropriate position without intimal damage, (3) guiding graft tailoring with a balloon catheter, and (4) examining the results after the procedures. RESULTS: Visualization was disturbed in one patient who had undergone a previous operation. The graft size was appropriate, except in one patient as a result of underestimation. Transesophageal echocardiography was helpful for navigating the graft placement and tailoring without intimal damage. We tried to keep a distance from the diaphragm of 9 cm and an attachment portion of 4 cm. In one patient the graft was placed too distally (7 cm from the diaphragm) to cover the thick atheromatous plaque with the graft. The patient had paraplegia. Transesophageal echocardiographic assessment of endoleak and thromboexclusion was identical to that of postoperative computed tomography or angiography, with a sensitivity of 100% (1/1) and a specificity of 100% (13/13). Leakage at the proximal suture and graft kinking were found in 3 patients. Successful thromboexclusion by transesophageal echocardiographic assessment (13 patients) was predictive of subsequent regression of aneurysm and dissection in the midterm follow-up period: there was complete and partial regression in 5 and 8 patients, respectively. CONCLUSION: Transesophageal echocardiography enables echocardiography-assisted operations with secure step-by-step endoluminal procedures and immediate intraoperative assessment, which is predictive of the postoperative results.

Aortic arch branches are no longer a blind zone for transesophageal echocardiography: a new eye for aortic surgeons.

OBJECTIVES: Branch arteries of the aortic arch have been a blind zone for transesophageal echocardiography. Information regarding blood flow, which is important in both planned and emergency operations on the aorta, has therefore been limited. We have established a technique for visualizing these arteries in nearly all cases. METHODS: In 25 consecutive patients requiring either planned or emergency operations on the aorta, the branch arteries were visualized whenever cerebral malperfusion was suspected. Lateral flexion of the probe tip was used when the trachea interfered with visualization of the arteries. RESULTS: The left subclavian, left and right common carotid, right subclavian, innominate, and left and right vertebral arteries were visualized in 96% (24/25), 92% (23/25), 96% (24/25), 100% (25/25), 84% (21/25), 92% (22/24), and 88% (21/24), respectively. The origin of the innominate artery was visualized in 36% (9/25). In some cases, dissection extended into branch arteries during surgery or during conservative therapy. When the subclavian artery was clamped, retrograde flow was detected in the vertebral artery (steal flow). The cannula for selective cerebral perfusion occasionally was entered into the right common carotid or subclavian artery and obstructed the other branch with a balloon. CONCLUSIONS: The branch arteries of the aortic arch, including the vertebral artery, are no longer a blind zone for transesophageal echocardiography. The information obtained with our new transesophageal echocardiography technique is helpful for diagnosis, monitoring, and decision making during aortic surgery and in critical care medicine. Visualizing these vessels is worth the effort.

[Three cases of Munchausen's syndrome mimicking connective tissue diseases].

Three young women were admitted to our hospital because of severe anemia and fever of unknown origin. The patients had a long history of frequent hospitalizations and operations. During hospitalization, the patients complained of hematemesis, hematuria and fever, which were sometimes discrepant with their physical and laboratory findings. After the careful observation, the patients were diagnosed as Munchausen syndrome because of either discovery of the tools used to make their symptoms or the patient's confession that these symptoms were made by herself. The patients with Munchausen syndrome sometimes show various symptoms and signs of multisystem inflammatory diseases, which mimick the clinical feature of connective tissue diseases. It is important for rheumatologists to be aware of the existence of Munchausen syndrome among the differential diagnosis of connective tissue diseases.

[Early repair of ventricular septal rupture in patients over 80 years of age: infarction exclusion technique].

Since 1994, three patients more than 80 years of age underwent early repair of ventricular septal rupture complicating acute myocardial infarction at our hospital. The infarction exclusion technique introduced by David and Komeda was employed. Average aortic clamp time, cardiopulmonary bypass time and operation time were 83 minutes, 129 minutes and 228 minutes, respectively. No hemostatic suture were required to the left ventricular suture line. All patients survived. One patient with posterior ventricular septal rupture had residual shunt and necessitated transient hemodialysis but recovered. Thus, the infarction exclusion technique seems to be useful in the elderly with unfavorable tissue fragility.

[A case of extracardiac noncoronary sinus Valsalva aneurysm associated with aortic regugitation].

A case of extracardiac noncoronary sinus Valsalva aneurysm was reported. A 11-year-old male with history of mild AR was admitted to the hospital due to severe AR. Echocardiography revealed that the severe AR and an aneurysm in the posterior part of the ascending aorta. Angiography revealed that the origin of the aneurysm was noncoronary sinus. Operative findings showed that the aneurysm sized 23 mm by 25 mm was an extracardiac type which grew posteroinferiorily at the left side of noncoronary sinus and that the dilation. Neither aortic valve nor the aortic route showed degenerative change. The ptosis of the valvular ring due to aneurysmal dilation of the noncoronary sinus caused AR. Then, valve repair composed by commissuroplasty and commissural suspension was carried out. And intraluminal patch closure technique in which the longitudinal diameter of patch was half of that of the aneurysm was effective on suspension of the valvular ring. Postoperative echocardiography showed decreasing of AR.

[Remission induction after pentoxifylline treatment in a patient with rheumatoid arthritis].

Pentoxifylline (POF) has been shown to have anti-inflammatory and immunomodulatory effects. including suppression of TNF-alpha production by activated macrophages, Th-1 response of T cells, and fibroblasts' proliferation and metalloproteinase production. Pentoxifylline was also reported to possess therapeutic properties in 50% of severe refractory RA in an open study. We experienced a 64 year-old man with seronegative RA, stage 2, class 3. He showed 23 swollen joints, 32 painful joints, ADL score 37/40, and ESR 135 mm/h. All these parameters were dramatically improved 3 weeks after administration of POF 300 mg/d and prednisolone 5 mg/d. Discontinuation of POF resulted in rapid exacerbation of RA. POF was restarted and the patient showed complete recovery from arthritis with normalization of ESR within 3 months and was maintained a complete remission for another 1 year. This case further supports a potential antirheumatic effect of POF on some patients with RA.

[The significance of heparin concentration measurement during cardiopulmonary bypass--effect of heparin-coated circuit during normothermic bypass].

Recently, use of heparin-coated circuits during normothermic cardiopulmonary bypass has become a trend in cardiovascular surgery. In light of this, heparin administration protocols during bypass should be reevaluated. In twenty patients who underwent cardiac surgery using a heparin-coated circuit under normothermia, heparin concentration was measured with Hepcon/HMS. Before initiating bypass, 300 IU/kg of heparin was administered with additional heparin to maintain activated clotting time (ACT) at more than 400 seconds. The heparin dose response (HDR) was measured before heparin administration. HDR is a heparin concentration calculated to correspond to an ACT of 480 seconds. As an index of heparin control during bypass, average heparin concentration/HDR (HC/HDR) was calculated. HC/HDR was correlated with Fibrinogen degradation products E (R = -0.52). D dimer (R = -0.45). Thrombin antithrombin complex (R = -0.54). Antithrombin III (R = 0.50) and platelet number (R = 0.44), but not with 24-hour postoperative blood loss. In conclusion, even when using a heparin-coated circuit plasma coagulation activity was not sufficiently suppressed by use of a conventional ACT monitoring protocol during normothermic bypass. Therefore, the maintenance of HC/HDR at a higher level may be indicated.

[Surgical treatment for subacute left ventricular free wall rupture complicating acute myocardial infarction--pericardial patch gluing method].

We reviewed 22 cases with surgical repair for subacute left ventricular free wall rupture complicating acute myocardial infarction. Different operative technique was used. Direct closure or patch repair with infarctectomy was preformed in first patients with a great difficulty in hemostasis. Since 1988 we sutured a large pericardial patch covering the infarcted myocardium under extra corporeal circulation in 11 patients (pericardial patch suture technique). From 1993 we began to glue a pericardial patch with Aron alpha without cardiopulmonary bypass (pericardial patch gluing technique). There were eight early death and four late death. Most common cause of death was low cardiac output syndrome (LOS). With medical therapy 13 patients in cardiogenic shock improved before surgery and only three developed postoperative LOS, but all six patients with sustained shock developed LOS without survivor (p = 0.007). Two of the five patients underwent direct closure or infarctectomy and seven of the 11 employed pericardial patch suture technique developed LOS, but none of the six used pericardial patch gluing technique developed LOS. Medical treatment such as intraaortic balloon pumping, catecholamine and subxyphoid drainage in order to improve hemodynamic condition before surgery is extremely important. Pericardial patch gluing technique seems to be useful since cardiac function would be maximally preserved.