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Biomedical subjects

R Tominaga

Publications and source records attributed to R Tominaga.

At least 19 recordsLinked to original sources

Application of chimerism-based drug-induced tolerance to rat into mouse xenotransplantation.

The current critical shortage of human donor organs has stimulated the feasibility of the xenogenic transplantation, such as swine to primate. We have previously reported the induction of donor-specific tolerance in MHC-disparated recipient mice by using our cyclophosphamide (CP)-induced tolerance conditioning. In this study, we examined the efficacy of our CP-induced tolerance conditioning in xenogenic transplantation model. F344 rats and B10 mice were used as donors and recipients. Recipient mice were treated with donor spleen cells, CP, Busulfan and bone marrow cells, with or without prior NK-cell depletion. Donor mixed chimerism, and the presence of donor reactive T-cell population were analysed by flow cytometry. The survival of the donor skin grafts were observed after the conditioning. Donor mixed chimerism was temporary induced but terminated at 10 weeks after treatments. Donor-specific prolongation of the skin graft survival was observed after the treatments, however, grafts were rejected in the long term. NK-cell depletion, prior to the treatments, did not affect the levels of the mixed chimerism or graft prolongation. The donor-reactive recipient T-cell population was remained the same level as the untreated mice, suggesting the failure of the induction of the central T-cell tolerance. Thus, partial efficacy of our CP-induced tolerance treatments in the rat to mice xenotransplantation was observed. Our results suggested that the additional treatments were required to establish the stable xenogenic tolerance.

Animals↗

Effect of phosphodiesterase III inhibitor on contractility, afterload, and vascular capacitance during right heart bypass preparation.

OBJECTIVES: Phosphodiesterase III inhibitors, which have both positive inotropic and vasodilatory effects, occasionally cause hypotension due to afterload reduction and possibly due to preload reduction caused by the increase in vascular capacitance. METHODS: Six open-chest adult mongrel dogs were used to compare the effects on left ventricular contractility, afterload, and vascular capacitance of the phosphodiesterase III inhibitor, olprinone, with those of dobutamine using a right-heart-bypass model. Contractility and afterload were evaluated by the left ventricular pressure-volume relations with the use of a conductance catheter to derive the end-systolic elastance (Ees) and the effective arterial elastance (Ea). Vascular capacitance change was evaluated by reservoir volume change under a constant bypass flow (80 ml/kg per minute). RESULTS: Ees increased significantly both with dobutamine (7.6 +/- 2.8 to 14.3 +/- 4.8 mmHg/ml, p < 0.05) and with olprinone (7.6 +/- 2.9 to 11.5 +/- 4.2 mmHg/ml, p < 0.05). Ea did not change with dobutamine (14.4 +/- 3.5 to 14.5 +/- 3.6 mmHg/ml, p = 0.9), whereas it decreased with olprinone (14.0 +/- 4.1 to 11.4 +/- 3.8 mmHg/ml, p = 0.093). Reservoir volume increased after the infusion of dobutamine (-94.0 +/- 39.8 ml), and decreased after the infusion of olprinone (-114.0 +/- 62.3 ml). The difference was statistically significant (p = 0.007). The reservoir volume change indicated that vascular capacitance decreased with dobutamine, and increased with olprinone. CONCLUSIONS: Pre- and afterload reduction of olprinone combined with the positive inotropic effect are useful in treating congestive heart failure and managing low cardiac output syndrome after cardiac surgery.

3',5'-Cyclic-AMP Phosphodiesterases↗

Early and late results of total correction of congenital cardiac anomalies in infancy.

OBJECTIVE: We evaluated long-term results of surgical correction of congenital cardiac anomalies in infancy. METHODS: We reviewed cases of 856 patients who underwent complete correction of major cardiac anomalies in the first year of life during last 24 years at our institution, and analyzed results. Surgery involved ventricular septal defect (n = 453), tetralogy of Fallot (n = 92), atrioventricular canal defect (n = 93), and complete transposition of the great arteries (n = 218). RESULTS: Operative mortality was 2.2% in ventricular septal defect, 0% in tetralogy of Fallot, 8.6% in atrioventricular canal defect, and 4.1% in complete transposition of the great arteries. Freedom from reoperation at 20 years was 96.5 +/- 2.0% and actuarial survival was 94.2 +/- 1.3% in ventricular septal defect. Freedom from reoperation at 15 years was 90.5 +/- 3.9% in tetralogy of Fallot and 86.6 +/- 4.4% in atrioventricular canal defect. Actuarial survival at 15 years was 97.8 +/- 1.6% in tetralogy of Fallot, 85.7 +/- 3.7% in atrioventricular canal defect, and 89.9 +/- 2.2% in complete transposition of the great arteries. Actuarial survival in complete transposition of the great arteries was significantly better in arterial than in atrial switch operations. CONCLUSIONS: Total correction of ventricular septal defect, tetralogy of Fallot, atrioventricular canal defect, and complete transposition of the great arteries in infancy was conducted safely, but the incidence of reoperation in late follow-up must be reduced.

Endocardial Cushion Defects↗

Confirmation of correct placement of the endocardial lead in cardiodefibrillator implantation by intraoperative transesophageal echocardiography.

Correct positioning of the endocardial lead in the apex of the right ventricle during the insertion of an implantable cardiodefibrillator (ICD) under general anesthesia, when cardiac function is generally poor, is most important. We describe herein a method of using intraoperative esophageal echocardiography in combination with fluoroscopy to confirm fixation of the endocardial ICD lead in the right ventricular apex.

Cardiac Catheterization↗

Atherosclerotic aneurysm in the circumflex retroesophageal right aortic arch.

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.

Aorta, Thoracic↗

Impacts of pulsatile systemic circulation on endothelium-derived nitric oxide release in anesthetized dogs.

BACKGROUND: The effects of pulsatile flow on endothelium-derived nitric oxide-mediated vasodilation are not fully elucidated in an in vivo model. METHODS: A left ventricular assist device was established in 10 anesthetized dogs with a centrifugal pump and an air-driven pneumatic pump. The systemic circulation was subjected to step changes in the frequency of pulse (0, 30, 60, and 120 bpm with a fixed pulse pressure of 50 mm Hg), and in the amplitude of pulse (0, 20, and 50 mm Hg with a fixed pulse rate of 120 bpm). Hemodynamic variables and calculated total systemic vascular resistance were compared before and after the administration of N(G)-Nitro-L-arginine Methyl Ester (L-NAME) (20 mg/kg). Plasma NO2-/NO3- concentration levels were also measured. RESULTS: Total systemic vascular resistance significantly decreased while plasma NO2-/No3- concentration increased in response to the rise in both pulse rate and pulse pressure. However, L-NAME significantly diminished these effects of pulsatile flow. CONCLUSIONS: Both the frequency and the amplitude of pulse wave in the systemic circulation are significant independent stimuli for endothelium-derived nitric oxide-mediated vasodilation in vivo.

Animals↗

Systemic effects of hyperthermic isolated lower limb perfusion with carboplatin and interferon-beta.

The changes in systemic circulation during hyperthermic isolated lower limb perfusion with carboplatin and interferon-beta were investigated in 19 patients with malignant melanoma. The cardiac output (CO) increased significantly (p < 0.01) from 3.81 +/- 0.22 L/min before the procedure to 5.30 +/- 0.49 L/min 1 h after hyperthermic perfusion. The double product (mean arterial pressure x heart rate) also increased significantly (p < 0.01) from 5,145 +/- 372 mm Hg/min to 6,760 +/- 486 mm Hg/min. In some patients, it increased to more than twice the control value. These changes were accompanied by an increase in body temperature, presumably caused by the systemic leakage of both warmed blood and interferon-beta. Blood chemistry data demonstrated no significant changes in the liver or renal function. However, the serum CPK level increased markedly on the first postoperative day, and persisted for 1 week, thus suggesting that some muscle damage occurred during the procedure. There was no operative death or severe complications. From these data, we concluded that hyperthermic isolated limb perfusion with interferon-beta is a relatively safe therapeutic method for malignant melanoma of the extremities. However, care should be taken in patients with ischemic heart disease who may suffer a heart attack due to the rapid increase in cardiac work during the procedure.

Adult↗

Influence of cyclic variation of right ventricular volume on left ventricular mechanical parameters measured with conductance catheter.

The conductance catheter is widely used for the continuous measurement of the left ventricular (LV) pressure-volume loops. Cyclical change of the right ventricular (RV) volume may alter the parallel conductance volume, thereby affecting the LV mechanical parameters. Using 8 open-chest adult mongrel dogs, multiple LV pressure-volume loops were obtained by 2 methods: first with a vena cava occlusion (VCO) method, which involved RV volume alteration, and second with a right-heart-bypass (RHB) preparation, which decompressed the right ventricle completely. The slope of the end-systolic pressure-volume relation (Ees), the end-systolic volume associated with the end-systolic pressure of 100 mmHg (V100,es), stiffness constant (beta), and the end-diastolic volume associated with the end-diastolic pressure of 9 mmHg (V9,ed) were calculated from each loop. There was minimal influence from RV volume alteration on systolic-phase indices [Ees (VCO method, 6.37 +/- 1.91 mmHg/ml; RHB preparation, 6.60 +/- 1.66mmHg/ml; p=0.356), and V100,es (VCO method, 18.4 +/- 9.3ml; RHB preparation, 17.8 +/- 9.0 ml; p=0.681)], but there was a significant influence on diastolic-phase indices [beta (VCO method, 0.0599 +/- 0.0152; RHB preparation, 0.0839 +/- 0.0150; p=0.007), and V9,ed (VCO method, 35.6 +/- 11.3 ml; RHB preparation, 31.9 +/- 12.3 ml; p=0.001)]. The increase in the RV volume in the diastolic phase increased the parallel conductance volume, causing overestimation of the LV diastolic volume measured by the conductance catheter.

Animals↗

Current techniques of hyperthermic isolated limb perfusion for malignant melanoma.

A retrospective study was conducted examining 25 patients with malignant melanoma who were treated by our new protocol for hyperthermic isolated limb perfusion. The characteristics of our techniques include: a lower priming volume of the extracorporeal circuit; a therapeutic temperature range of 40-41 degrees C with 60 min hyperthermic perfusion; a nominal perfusion flow rate of 500 ml/min in the lower limb and 200 ml/min in the upper limb; and combined carboplatin with interferon-beta as the adjuvant chemotherapy drug. In the lower extremity group, the arterial cannula size ranged from 8 to 14 F, while the venous cannula size ranged from 14 to 16 F. In the upper limb group, the arterial cannula size ranged from 6 to 8F and the venous cannula size ranged from 10 to 12F. No patient required any homologous blood transfusion postoperatively. No operative death or major complications occurred during the early postoperative period, confirming the safety of this treatment. Both optimal cannula size selection and maintaining perfusion temperature below 41 degrees C were judged to be important in elimination of vascular and deep tissue injury.

Adult↗

The differential cardioprotective effects of nucleoside transport inhibitor on moderate and deep hypothermic ischemia with cold cardioplegia.

The differences in the cardioprotective effects of nucleoside transport inhibitor (NTI) which is known to accumulate endogenous adenosine, on moderate and deep hypothermic ischemia, were examined. Using the Langendorff model, isolated, perfused rat hearts were arrested with cold cardioplegia and subjected to 90 min of global ischemia followed by 40 min of reperfusion. The temperature during ischemia was maintained at either 10 degrees C (groups 1 and 2) or 25 degrees C (groups 3 and 4). In groups 2 and 4, NTI in the form of R75231, 1 mg/l, was added to the cardioplegic solution. The intramyocardial adenosine triphosphate content at the end of ischemia was significantly lower in the moderate hypothermia groups than in the deep hypothermia groups. In the moderate hypothermia groups, NTI significantly enhanced the adenosine accumulation at the end of ischemia. Moreover, the recovery of both the contractile function and coronary flow rate in group 4 was superior to that in group 3, and was similar to those in groups 1 and 2. The addition of NTI to the cardioplegic solution generated a sufficient cardioprotective effect in moderate hypothermic ischemia, but not in deep hypothermic ischemia. The mechanism of this discrepancy is attributed to the differences in the levels of endogenous adenosine accumulated during ischemia.

Adenine Nucleotides↗

Successful implantation of a bipolar epicardial lead and an autocapture pacemaker in a low-body-weight infant with congenital atrioventricular block: report of a case.

A permanent pacemaker system was successfully implanted into a low-body-weight infant with congenital atrioventricular (AV) block, using a bipolar epicardial CapSure Epi lead and an autocaptured Pacesetter Solus-micro VVIR pacemaker. The calculated life span of the pacemaker generator is 5 years with a heart rate of 120/min and an output of 1.2 V (0.31 ms), and fortunately, its threshold was autocaptured. Thus, we can conclude that the combination of a steroid-eluted bipolar epicardial lead and the smallest possible autocaptured pacemaker generator is most suitable for a neonate or young infant.

Cardiac Pacing, Artificial↗

Coronary artery bypass grafting on the beating heart evaluated with integrated backscatter.

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 = 6, poor collateral group n = 9). RESULTS: In all patients, CV increased significantly after revascularization (8.56+/-2.50 to 11.47+/-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+/-2.21 to 3.23+/-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.

Aged↗

Pulsatile flow enhances endothelium-derived nitric oxide release in the peripheral vasculature.

The effects of pulsatility in blood flow on endothelium-derived nitric oxide (EDNO) release in the peripheral vasculature were investigated. The basal and flow-stimulated EDNO release were compared between pulsatile and nonpulsatile systemic flows before and after the administration of NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA). Peripheral vascular resistance (PVR) was significantly lower in pulsatile flow than in nonpulsatile flow, but this difference disappeared after L-NMMA. The percent increase in PVR by L-NMMA was significantly larger in pulsatile flow. In reactive hyperemia in the hindlimb, the peak flow did not differ; however, both the repayment flow and the duration were significantly larger in pulsatile flow. Percent changes of these parameters by L-NMMA were significantly larger in pulsatile flow. These data indicated that pulsatility significantly enhances the basal and flow-stimulated EDNO release in the peripheral vasculature under in vivo conditions. We also studied the involvement of the Ca(2+)-dependent and Ca(2+)-independent pathways in flow-induced vasodilation using calmodulin inhibitor calmidazolium and tyrosine kinase inhibitor erbstatin A. PVR was significantly elevated by erbstatin A but not by calmidazolium, suggesting that flow-induced vasodilation was largely caused by tyrosine kinase inhibitor-sensitive activation of NO synthase.

Angiotensin II↗

Effects of nonpulsatile left heart bypass on renal sympathetic nerve activity in rabbits.

To determine the effects of nonpulsatile left heart bypass (LHB) on sympathetic nerve activity the renal sympathetic nerve activity (RSNA) was directly measured in rabbits. In anaesthetized rabbits (n=6), LHB was instituted with a centrifugal pump. Before and during LHB, heart rate (HR), arterial pressure (AP), central venous pressure (CVP), left atrial pressure (LAP) and spike counts of RSNA were measured. After bilateral vagotomy (section of the afferent inputs of the cardiac reflex arc) the same parameters were measured before and during LHB. Data were obtained at the same level of mean AP before and during LHB. Mean AP and CVP were not changed by LHB before and after vagotomy. LAP was significantly decreased by LHB before and after vagotomy. RSNA and HR were not significantly changed by LHB before and after vagotomy. Our results clarify the complex baroreflex control during nonpulsatile LHB and indicate that RSNA is not altered by LHB.

Action Potentials↗

Effects of intra-aortic ballon pumping on renal sympathetic nerve activity and renal circulation in dogs.

BACKGROUND: Little is known on how intra-aortic balloon pumping (IABP) affects neural circulatory regulation, even though many studies have been done to clarify the effects of IABP on hemodynamics. Although IABP is used clinically in patients with severe heart failure, whose sympathetic nerve activity is increased, there are no previous reports that demonstrate the effects of IABP on neural regulation in heart failure. The aim of this study is to determine the effects of IABP on neural regulation of renal circulation with both normal and failing heart condition in dogs. METHODS: We directly measured renal sympathetic nerve activity and hemodynamic parameters (heart rate, central venous pressure, distal aortic pressure, proximal aortic pressure, left ventricular pressure, renal sympathetic nerve activity, ascending aortic flow, and renal arterial flow) before and during IABP driving in both normal and failing heart condition in dogs (n=7). Acute heart failure models were made by coronary ligation. RESULTS: IABP driving inhibits renal sympathetic nerve activity and improves renal circulation in failing heart condition, while these phenomena do not occur in normal heart condition. CONCLUSIONS: These findings suggest that IABP may show its full effect on renal circulation via neural regulation especially in failing heart condition.

Animals↗

Benign mediastinal teratoma complicated by cardiac tamponade: report of a case.

We present herein the case of a 48-year-old woman with a benign mediastinal teratoma that had been followed up for 3 years, who developed acute cardiac tamponade. The patient had initially undergone an exploratory sternotomy, at which time the tumor was histologically diagnosed as a benign mature teratoma that could not be resected due to its severe, wide adhesion to the surrounding organs. However, following the development of cardiac tamponade, both sternotomy and right intercostal thoracotomy were employed, and the tumor could be excised with cardiopulmonary bypass standby. High levels of amylase and carbohydrate antigen 19-9 were revealed in the pericardiac effusion fluid. The mRNA expression of inflammatory cytokines including interleukin-1 (IL-1), IL-6, and IL-8 in the tumor tissue was also demonstrated by a reverse transcriptase-polymerase chain reaction analysis. This case illustrates the ultimate natural course of benign mediastinal teratoma and emphasizes the importance of early surgical excision, even when this tumor is asymptomatic.

Base Sequence↗

Fate of atrial flap used in repair of total anomalous pulmonary venous connection.

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.

Cardiac Surgical Procedures↗

Surgical treatment of tricuspid regurgitation caused by Löffler's endocarditis.

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.

Adult↗