[Reconstruction of pulmonary blood flow in the Norwood procedure; Blalock-Taussig shunt; from bench to surgery].

Although the right-ventricle to pulmonary artery( RV-PA) shunt as a source of pulmonary blood supply of Norwood procedure has improved early outcomes, disadvantages including right ventricular dysfunction or arrhythmias have been reported. So it has been still remained controversial whether BT shunt or RV-PA conduit should be selected. We examined the influence of Blalock-Taussig( BT) shunt size on regulation of the pulmonary blood flow in experimental model of a univentricular heart to determine the specific guidelines regarding suitable shunt size in the Norwood procedure. The canine univentricular heart model with the ratio of shunt size to body weight (SS/BW) of 0.8 to 1.1 showed significant negative correlation between the pulmonary/systemic blood flow ratio( Qp/Qs)and arterial PCo2, but those with SS/BW of 1.1 to 1.4 did not. Similar phenomena were shown with the grouped data on relationship between the Qp/Qs and inspired oxygen fraction. These findings imply that when SS/BW is 0.8 to 1.1, the Qp/Qs is controllable by physiologic respiratory manipulations. In the context of our clinical experiences, SS/BW of 0.9 to 1.0 is considered a useful index for suitable BT shunt in the Norwood procedure.

Role of hypoxia-inducible factor 1alpha in T cells as a negative regulator in development of vascular remodeling.

BACKGROUND AND PURPOSE: Recent studies have shown that the cellular immune response in the development of vascular remodeling modulates the resulting pathological alterations. We show that hypoxia-inducible factor 1 (Hif-1) (specifically expressed in T cells) is involved in the immune response to vascular remodeling that accompanies arteriosclerosis. METHODS AND RESULTS: To study the role of T cells in the development of vascular remodeling, femoral arterial injury induced by an external vascular polyethylene cuff was examined in mice lacking Hif-1 (specifically in T cells). We found that cuff placement caused prominent neointimal hyperplasia of the femoral artery in Hif-1- (T-cell)-deficient mice compared with that in control mice and that infiltration of inflammatory cells at the adventitia was markedly increased in the mutant mice. Studies to clarify the mechanism of augmented vascular remodeling in the mutant mice showed enhanced production of cytokines by activated T cells and augmented antibody production in response to a T-dependent antigen in the mutant mice. CONCLUSIONS: The results of this study revealed that Hif-1alpha in T cells plays a crucial role in vascular inflammation and remodeling in response to cuff injury as a negative regulator of T cell-mediated immune response. Potential new therapeutic strategies that target Hif-1alpha are described.

A successful transatrial repair in redo surgery of postinfarction inferoposterior ventricular septal rupture.

A successful transatrial repair in redo surgery of postinfarction posterior ventricular septal rupture (VSR) was performed after an infarct exclusion technique through left ventriculotomy incision of the infarcted area. For the infarct lesion, this approach provides excellent results with sufficient closure of the VSR and prevention of the ventricular remodeling for five years. A right atrial approach for postinfarction posterior VSR is very useful for avoiding any further ventriculotomy in an already impaired ventricle, securing a stable suture, and preserving the left ventricular geometry and function.

Iliac access conduit facilitates endovascular aortic aneurysm repair and ipsilateral iliofemoral bypass.

It may be difficult to access a route to deliver a stent-graft for abdominal aortic aneurysm in high-risk patients with bilateral iliofemoral occlusive disease. These two patients underwent both endovascular aortic aneurysm repair by a modified iliac access conduit technique and sequential ipsilateral iliofemoral artery bypass using the conduit, which provided excellent results. The iliac access conduit facilitates endovascular aortic aneurysm repair and ipsilateral iliofemoral bypass of high-risk patients with abdominal aortic aneurysm and bilateral iliofemoral occlusive disease.

Delayed-onset severe heparin-induced thrombocytopenia after total arch replacement under cardiopulmonary bypass.

An extremely rare case with delayed-onset heparin-induced thrombocytopenia (HIT) is described. A 46-year-old man underwent arch replacement for aortic dissection under cardiopulmonary bypass and initial exposure of unfractionated heparin. In post operative 7 days, persistent atrial fibrillation was occurred, so a continuous infusion of heparin (10000 IU/day) and Vitamine K antagonist (Warfarin) taking was started for preventing thrombosis. By 32 days after the operation, his platelet count had fallen (3×10(3)/µL) and oral hematoma and ecchymoma of bilateral lower legs were occurred. The value of HIT antibodies and the IgG antibody was 2.485 and 1.586 on 32-postoperative day, respectively. Heparin was immediately discontinued, and argatroban administrated. Platelet exceeded above 100×10(3)/µL on 12 days of the therapy. To our knowledge, few cases of delayed-onset severe HIT associated with CPB surgery have been reported in Japan.

Autologous peripheral blood-derived mononuclear cells induced by erythropoietin improve critical ischemic limbs.

PURPOSE: Efficient and secure collection of CD34+ cells are crucial for the angiogenic therapies. We have developed autologous peripheral blood-mononuclear cell (MNC) transplantation induced by erythropoietin (rhEPO) for critical ischemic limbs. METHODS: Seven patients, including five with arteriosclerosis obliterans, one with Buerger's disease and one with progressive systemic sclerosis, underwent ten cell therapies. The first administration of rhEPO was performed two weeks before apheresis, and the second administration and blood donation were performed one week before apheresis to activate bone marrow. MNCs including CD34+ cells, isolated from peripheral blood by apheresis, were immediately injected intramuscularly into ischemic limbs. RESULTS: The number of peripheral blood-CD34 + cells had significantly increased from 1.32 ± 0.83/microL, before the rhEPO induction, to 1.86 ± 0.94/microL, before the apheresis. The number of transplanted MNCs ranged between 0.5 × 10(9) and 16.5 × 10(9), and that of CD34+ cells, between 0.1 × 10(6) and 12.7 × 10(6), accounting for 0.02%-0.1% of MNCs. There were no serious complications. Finger ulcers with Buerger's disease were significantly improved one month after the transplantations, but the same or other ulcer(s) appeared 2-6 months later. Three patients had an improvement in rest pain, and one patient extended maximum pain-free walking distance. CONCLUSIONS: Erythropoietin-induced autologous peripheral blood-MNC transplantation is a useful and safe alternative for ischemic limbs.

Functional restoration of endothelial cells of the cryopreserved heart valve.

PURPOSE: Although several approaches have been tried to improve the durability of cryopreserved valves, cellular restoration after thawing remains to be investigated. The aim of our study was to assess the functional restoration of endothelial cells of cryopreserved heart valves by in vitro culture for an alternative step to improving longevity. METHODS: Cryopreserved human umbilical vein endothelial cells (HUVECs) and porcine aortic cusps were cultivated for 14 days after thawing. Then the cellular activity of the enzymes cytosolic esterase and mitochondrial dehydrogenase was measured. The cellular viability of cryopreserved cusps was also assessed using confocal laser scanning microscopy. RESULTS: The number of viable HUVECs decreased markedly after cryopreservation and thawing but recovered to pre-cryopreservation level after 14 days of culture. In contrast, the enzyme activity of the cryopreserved porcine aortic cusps showed recovery at 7 days of in vitro tissue culture after thawing. Confocal laser scanning microscopy findings showed that the cellular cytosolic esterase activity of cryopreserved cusps deteriorated after thawing but displayed considerable recovery by day 14 of culture. CONCLUSION: The functional recovery of endothelial cells in cryopreserved heart valves seems to require tissue culture of at least 14 days. Ex vivo endothelial restoration of cryopreserved heart valves may add to heart valve durability.

Successful early resection of cardiac papillary fibroelastomas.

Two adult patients with previous transient cerebral ischemic attacks (TIAs) or chest oppression were referred for further investigation. A swaying pedicled tumor was detected in the left atrium of the former patient and in the left coronary cusp of the latter by echocardiography. The TIA, or angina-like attack, was anticipated to be caused by thromboembolism of the tumor. Both patients underwent tumor extirpation. The histological findings demonstrated that both tumors were benign papillary fibroelastoma limited to the endocardium/endothelium layer. In conclusion, early surgical resection of a cardiac papillary fibroelastoma should be performed.

Ezetimibe monotherapy ameliorates vascular function in patients with hypercholesterolemia through decreasing oxidative stress.

AIM: Ezetimibe, an inhibitor of cholesterol intestinal absorption, is a lipid lowering agent. However, anti-atherogenic effects of ezetimibe have not been fully elucidated. Therefore, the objective in this study was to clarify the vascular protective effects of ezetimibe in patients with hypercholesterolemia. METHODS: Ezetimibe was administered to 20 patients with hypercholesterolemia (group E), and 20 age- and sex-matched patients with hypercholesterolemia were followed as controls (group C). Difference in metabolic profiles and cardiovascular surrogate markers before ezetimibe treatment and after 12 weeks of ezetimibe treatment were statistically evaluated. RESULTS: Ezetimibe treatment significantly reduced serum levels of low-density lipoprotein cholesterol (LDL-C) and malondialdehyde-modified low-density lipoprotein (MDA-LDL). In addition, the values of body mass index, body weight, waist circumference, plasma HbA1c and urinary albumin were significantly decreased in group E compared to those in group C. On the other hand, high-density lipoprotein cholesterol (HDL-C) and adiponectin levels were significantly increased in group E compared to those in group C. The values of brachial-ankle pulse wave velocity (ba-PWV), mean arterial blood pressure (m-ABP), and % of flow-mediated dilation (FMD) were significantly improved in group E. Furthermore, ultrasonic studies demonstrated amelioration of the vascular stiffness of common carotid arteries in group E but not in group C. These vascular protective effects of ezetimibe were statistically correlated with the decreased values of MDA-LDL and MDA-LDL-to-LDL-C ratio but not with those of LDL-C. CONCLUSION: Ezetimibe has a lipid lowering-independent vascular protective effect in patients with hypercholesterolemia through decreasing oxidative stress.

Syngeneic bone marrow mononuclear cells improve pulmonary arterial hypertension through vascular endothelial growth factor upregulation.

BACKGROUND: We investigated the effects and possible mechanism of syngeneic bone marrow mononuclear cell (BM-MNC) transplantation on pulmonary arterial hypertension induced by monocrotaline. METHODS: Monocrotaline (80 mg/kg body weight) was administrated to C57BL/6 mice, and pulmonary arterial hypertension was induced 4 weeks later. Bone marrow mononuclear cells harvested from syngeneic donor mice were injected intravenously into those mice 4 weeks after monocrotaline administration. The ratio of right ventricular to septum plus left ventricular weight, the number of small pulmonary arteries, and medial thickness of pulmonary arteries were measured. Western immunoblotting of the lung tissue was performed to observe vascular endothelial growth factor and its receptor expression 1 week after BM-MNC transplantation. Vascular endothelial growth factor receptor-2 inhibitor was administered to pulmonary arterial hypertension mice simultaneously with BM-MNC transplantation. RESULTS: The ratio of right ventricular to septum plus left ventricular weight increased, the number of pulmonary arteries decreased, and medial thickness increased significantly 4 weeks after monocrotaline injection compared with those of vehicle-injected mice. These indices of monocrotaline-injected mice improved significantly 4 weeks after BM-MNC transplantation compared with those of mice at 8 weeks after monocrotaline injection (0.22 +/- 0.02 versus 0.31 +/- 0.02; 17.1 +/- 2.6 versus 8.2 +/- 1.7; 7.7% +/- 2.2% versus 20% +/- 2.1%, respectively; p < 0.01). However, BM-MNCs were not incorporated into the lung at 1 week after transplantation, and significant vascular endothelial growth factor upregulation and without receptor expression was observed in lung tissue 1 week after transplantation. Improvement of pulmonary arterial hypertension was inhibited by simultaneous administration of vascular endothelial growth factor receptor-2 inhibitor with BM-MNC transplantation. CONCLUSIONS: These results indicate that syngeneic BM-MNC transplantation improves monocrotaline-induced pulmonary arterial hypertension by favorable pulmonary artery remodeling through vascular endothelial growth factor upregulation.

Significance of peritoneal fluid drainage in management after repair of complex heart defects in infancy: cytokine dynamics in vivo.

BACKGROUND: In vivo redundancy of pro-inflammatory cytokines results in a vicious cycle of systemic inflammatory response syndrome and low cardiac output syndrome (LOS). The purpose of this study was to elucidate the influence of peritoneal fluid (PF) drainage on cytokine dynamics in vivo and the significance of early induction for infants with LOS. METHODS AND RESULTS: Seven infants, who underwent early PF drainage to manage LOS after repair of complex heart defects under cardiopulmonary bypass, were enrolled. The serum and PF levels of the pro- and antiinflammatory cytokines, interleukin (IL)-6, -8, -10 and tumor necrosis factor (TNF)-alpha, were measured during the perioperative period. Clinical outcomes were observed simultaneously. There were no cases of early or late death, or infectious complications. Drainage volume of PF peaked just after operation, and decreased completely. The amount of proinflammatory cytokines in the PF increased for 3 days after operation. Of the proinflammatory cytokines in the PF IL-6 increased the earliest and cleared the fastest. The amount of cleared IL-8 and TNF-alpha peaked on the 3rd postoperative day and resembled the course of C-reactive protein (CRP). Serum levels of CRP and proinflammatory cytokines in patients with PF drainage decreased significantly more than those without PF drainage. CONCLUSIONS: Early initiation of PF drainage is useful in the postoperative critical care of infants with LOS by improving cytokine dynamics in vivo, although there are differences between the severity of patients undergoing PF drainage and those who do not.