The regulation of membrane cofactor protein (CD46) expression in transgenic mice: the importance of the first 125 BP of the 3' untranslated region.
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Biomedical subjects
Publications and source records attributed to R Shirakura.
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A new method of assessing left ventricular (LV) systolic function without terminating assisted circulation (AC) was investigated using a LV volume catheter (conductance catheter) in canine cardiopulmonary bypass (CPB) (Group 1, n = 7) and left heart bypass (LHB) (Group 2, n = 5) models. The hearts were subjected to either 20 min of global ischemia (IS), with a subsequent 80 min of reperfusion under CPB, or regional IS under LHB. Instantaneous LV pressure-volume data acquisitions were repeated during transient (15 sec) acute volume loading without terminating bypass. The relationship between the stroke work (SW), determined as the area of the pressure-volume loop, and the end-diastolic volume (EDV), were highly linear at every study point (mean: r = 0.956-0.986 in Group 1, r = 0.974-0.987 in Group 2). The slopes of SW and EDV (preload recruitable stroke work: PRSW) significantly decreased after IS, in both Group 1 and Group 2. In conclusion, measurement of PRSW without terminating bypass seemed to be useful in evaluating LV systolic function in patients under AC.
Organ procurement from non-heart-beating donors (NHBDs) may expand donor pools. In this study, the method of reanimation of heart, lung, and kidney in NHBDs by percutaneous cardiopulmonary support (PCPS) was evaluated. Thirteen beagles were asphyxiated after being given prostacyclin analogue, verapamil, propranolol, and nafmostat mesilate intravenously. Thirty minutes after cardiac arrest, the body was reperfused by PCPS for 1 hr. PCPS priming fluid contained the four drugs above and KCl. Eight hearts immersed in University of Wisconsin (Madison, WI) solution for 24 hr were transplanted orthotopically using leukocyte depleted blood cardioplegia, five left lungs immersed in modified Collins solution were transplanted orthotopically, and five kidneys immersed in University of Wisconsin solution were transplanted heterotopically. All donor hearts arrested without ventricular fibrillation. All transplanted hearts beat spontaneously, and all animals were weaned from cardiopulmonary bypass without inotropic support. The oxygen and carbon dioxide pressure of pulmonary vein blood in the donor lung were no different from those in the recipient lung. All transplanted kidneys made urine soon after reperfusion. These data suggested that hearts, lungs, and kidneys from NHBDs pretreated with four drugs and reanimated with PCPS can be transplanted successfully and that this method may expand the donor pool.
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Early donor heart failure is one of the serious problems in heart transplantation. This heart failure may be related to myocardial change during brain death before implantation of the heart. Actually, a gradual increment in catecholamine requirement to maintain hemodynamics is not infrequently seen in patients with brain death. This may presumably be related to alterations in the myocardial beta-adrenergic receptor system. In this experimental study, we investigated the changes in myocardial beta-adrenergic receptors after brain death induced by intracranial hypertension in dogs. To maintain the mean arterial pressure higher than 60 mm Hg after brain death, massive crystalloid infusion (group A) or 0.4 to 1.3 micrograms/kg/min of adrenaline infusion (group B) was applied. Blood adrenaline levels and myocardial beta-adrenergic receptor (receptor number and affinity with [125I]iodocyanopindolol binding) were measured at 3 hours (group A-3H or group B-3H, n = 5, respectively) and 6 hours (group A-6H or group B-6H, n = 5, respectively) after brain death. Blood adrenaline levels reduced in group A-6H and elevated in group B-3H and group B-6H. Beta-adrenergic receptor affinity was not different among each group. Beta-adrenergic receptor number decreased in group B-6H. Myocardial beta-adrenergic receptor density decreased in the adrenaline group during 6 hours of hemodynamic maintenance after brain death, whereas myocardial beta-adrenergic receptors did not change in the crystalloid group. Our data suggest that the large doses of catecholamines used to maintain hemodynamics in donors with brain death may depress myocardial beta-adrenergic receptors.
Canine hearts immersed in modified Collins solution were transplanted heterotopically (n = 23) and orthotopically (n = 15) to evaluate the effect of terminal warm-blood cardioplegia with or without leukocyte depletion. As the index for graft function, preload recruitable stroke work was measured in both series before harvesting (control) and after transplantation (percentage). The heterotopic hearts were divided into four groups (group 1 to 4) according to the preservation method; hearts were preserved for 3 hours in group 1 and for 24 hours in groups 2, 3, and 4. Simple terminal warm-blood cardioplegia was applied in group 3, and terminal warm-blood cardioplegia with leukocyte depletion was used in group 4. In the orthotopic series, five hearts were transplanted soon after harvesting (group 5) to simulate on-site transplantation, and the remaining ten hearts were transplanted after 24 hours of hypothermic preservation without and with terminal warm-blood cardioplegia with leukocyte depletion (groups 6 and 7, respectively). Among the heterotopic transplants, the percentage of preload recruitable stroke work was highest in group 4 (91% +/- 6%, 51% +/- 4%, 83% +/- 10%, 140% +/- 11% in groups 1, 2, 3 and 4, respectively). All orthotopic transplants in groups 5 and 7 were weaned from cardiopulmonary bypass without inotropic support and without significant differences in cardiac function between groups 5 and 7 (percentage of preload recruitable stroke work, 99% +/- 10% versus 102% +/- 2%; cardiac output, 122 +/- 10 versus 140 +/- 22 ml/kg/min). No orthotopic transplants in group 6 could be weaned from cardiopulmonary bypass, even with inotropic support.(ABSTRACT TRUNCATED AT 250 WORDS)
Twenty four-hour heart-lung preservation with Belzer-UW solution was studied in the canine heterotopic heart-lung transplant model. Four pairs of mongrel dogs were used. The donor heart was arrested with cardioplegic solution. The heart and the lung were flushed with UW solution, then excised en bloc and immersed in 4 degrees C UW solution for 24 hours. The graft was transplanted heterotopically into the left pneumonectomized recipient. The transplant procedure consisted of end-to-end anastomosis of two left main bronchi, end-to-side anastomosis of the descending aortas, and end-to-end anastomosis of the donor's superior vena cava to the recipient's left pulmonary artery. The recipient's right pulmonary artery was ligated after an observation period, and cardiopulmonary functions were measured during room air ventilation. In all four transplanted dogs the grafts were able to sustain the recipient's circulation. The prepreservation and posttransplant cardiac output was 71.2 +/- 21.6 ml/min/kg and 96.4 +/- 44.4 ml/min/kg; the arterial PO2 was 80.8 +/- 12.9 mm Hg and 74.1 +/- 2.7 mm Hg; and the arterial PCO2 was 25.6 +/- 5.5 mm Hg and 35.9 +/- 13.3 mm Hg, respectively. There were no significant differences between the prepreservation and posttransplant values. Posttransplant myocardial water content was within the normal range. Pulmonary vascular resistance increased significantly, to 13.8 +/- 3.7 from 8.8 +/- 5.2. Wood units, and the wet/dry ratio of the lung increased significantly, to 8.3 +/- 1.6 from 4.4 +/- 0.6. In conclusion, heart-lung grafts preserved in UW solution for 24 hours were able to sustain the recipient's circulation. Significant pulmonary edema, however, could not be prevented.
Activated leukocytes may have an important role in developing complement-related lung injury, with pulmonary leukocyte sequestration in the presence of blood-material interaction in cardiopulmonary bypass and hemodialysis. The authors evaluated the effects of a new cAMP phosphodiesterase inhibitor (DN-9693) on leukocyte aggregation in vitro, utilizing canine heparinized blood and pulmonary leukocyte sequestration during extracorporeal circulation (ECC) in dogs. On in vitro evaluation, DN-9693 inhibited the leukocyte aggregation response to leukotriene B4 in a dose response manner; the aggregation response elicited by contact with a membrane lung was inhibited by a 50% inhibition dose of approximately 0.2 mumol/L. Leukocyte kinetics were assessed in a venovenous bypass system with a silicone hollow fiber membrane lung. The control group (n = 6) without DN-9693 developed a reduction in the arterial leukocyte count of 55 +/- 17% at 2 minutes of ECC. The transpulmonary difference in leukocyte count (pulmonary artery count minus systemic artery count) was significantly increased (P less than 0.05) from -175 +/- 206/microliters at baseline to 1225 +/- 330/microliters after 2 minutes of ECC. In the DN-group (n = 4, DN-9693; 60-80 micrograms/kg/min), there was no significant reduction in the arterial leukocyte count during ECC, and the transpulmonary difference showed no significant increases (75 +/- 386/microliters; baseline, versus 125 +/- 263/microliters; 2 minutes of ECC). These results suggest that DN-9693 inhibits the aggregation of leukocytes in the presence of blood-material interaction in vitro, and also prevents pulmonary leukocyte sequestration induced by ECC, with attenuation of systemic leukocyte depletion.
Two patients with Budd-Chiari syndrome who underwent a new surgical procedure developed by Senning are reported. A 33-year-old man was diagnosed as having Budd-Chiari syndrome with a membranous obstruction of the inferior vena cava (IVC) and right hepatic vein and short segmental obstruction of the left hepatic vein. Removal of the obstruction by dorsocranial resection of the liver and reconstruction of the veins by hepatoatrial anastomosis was carried out. In a 53-year-old female, the same procedure was carried out for a short segmental obstruction of the IVC and left hepatic vein. In both patients, postoperative examination revealed good patency of the IVC and the hepatic veins and increased portal venous flow as measured by Doppler-echography. This procedure is considered the method of choice for Budd-Chiari syndrome with membranous and/or short segmental obstruction of the IVC and hepatic veins.
Component failure of a mechanical valve is an extremely serious complication. We experienced strut fracture and disc embolization of a 27 mm Björk-Shiley convexo-concave mitral valve prosthesis implanted one year and 9 months previously. The emergency operation was successful. In the follow-up of patients with Björk-Shiley convexo-concave models manufactured before March 1982, the possibility of strut fracture should be kept in mind.
Twelve patients (pts) with coronary and/or valvular heart disease and preoperative creatinine clearance (Ccr) below 30 ml/min underwent cardiac surgery using cardiopulmonary bypass (CPB) with pulsatile (P:n = 7) and nonpulsatile (NP:n = 5) perfusion. Preoperative Ccr was 15.8 +/- 4.4 ml/min in the P group and 26.5 +/- 4.7 ml/min in the NP group. After surgery, the NP group showed significant increases in BUN and serum creatinine within a week, but the P group showed significant increase in BUN only. The NP group had a significant decrease in Ccr on the 7th postoperative day, but there was no significant change in the P group. Three patients, 2 from the NP group and one from the P group, died from complications (operative mortality: 14 vs 40%). These data suggested that P-CPB appeared to be advantageous in patients with preoperatively impaired renal function with low Ccr although many other factors might influence the outcome.
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