Antisense Cdc2 kinase oligonucleotide inhibits adhesion molecule expression in cardiac allograft arteriopathy.
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Animals↗
Biomedical subjects
Y Sawa
Publications and source records attributed to Y Sawa.
Normothermia has beneficial effects in cardiopulmonary bypass attenuating inflammatory reactions.
"Post perfusion syndrome" after cardiopulmonary bypass (CPB) has been known to be evoked by inflammatory reactions. To elucidate the effect of perfusate temperature during CPB on subsequent inflammatory reactions, serum levels of interleukin (IL)-6, IL-8, tumor necrosis factor-alpha, IL-1 beta, and polymorphonuclear (PMN) elastase were measured before and after (0, 12 hours, and 24 hours after) CPB in adult patients undergoing cardiac operations. Patients were divided into two groups: the normothermic CPB group (NOR, 34 degrees C perfusate temperature, n = 8) and hypothermic CPB group (HYP, 28 degrees C perfusate temperature, n = 8). In both groups, IL-6, IL-8, and PMN elastase levels were elevated during CPB, while the increase of tumor necrosis factor-alpha and IL-1 beta was not detected. The increase in IL-8 and PMN elastase levels at 12 hours after CPB was significantly less in NOR than in HYP (IL-8; NOR versus HYP, 15.1 +/- 12.9 versus 62.5 +/- 30.6 pg/ml, p < 0.05, PMN elastase; 394 +/- 200 versus 1085 +/- 523 micrograms/L, p < 0.05) while neither group showed any difference in IL-8 and PMN elastase at 24 hours after CPB. There was no difference in IL-6 between the two groups, and no significant increase in tumor necrosis factor-alpha and IL-1 beta levels were detected in either group after CPB. These results demonstrate that although CPB activated inflammatory reactions detected by IL-8 and PMN elastase activity, post operative persistence of these reactions were attenuated by warm CPB.
Adult↗
Clinical experience with long-term use of the Toyobo left ventricular assist system.
The Toyobo-NCVC extracorporeal pneumatic left ventricular assist system (LVAS) was used in four patients with advanced dilated cardiomyopathy. The duration of support ranged from 46 to 390 days (mean, 206 days). In all patients, stable hemodynamics were achieved with 3.5-5.5 L/min flow rates. Two patients survived long term. One was transported to the United States by a chartered jet while on LVAS and successfully underwent heart transplantation after 119 days of support. The other is on LVAS and is doing well for 390 days. The remaining two patients died of multi-organ failure while their hemodynamics were quite stable under LVAS. In these two patients, severe hepatic failure had developed before LVAS implantation. Minor cerebral embolisms occurred in the two survivors, but neither of them experienced permanent neurologic deficits. In only the initial patient were major thrombi noted on the diaphragm of the pump; the thrombi required pump exchange four times during 119 days. In the patient supported for 390 days, a small tear in the diaphragm was observed after 209 days of support, and the pump was safely exchanged. It is suggested that the Toyobo LVAS can provide consistent and reliable performance for long-term use.
Adolescent↗
Nitric oxide gas infusion to the oxygenator enhances the biocompatibility of heparin coated extracorporeal bypass circuits.
Heparin coated bypass circuits have been reported to improve the biocompatibility of extracorporeal circulation, although it is still insufficient and improvable. Nitric oxide (NO) is known to inhibit platelet activation and inflammatory reactions. In this study, the authors evaluated exogenous NO infusion in enhancing the effect of a heparin coated bypass circuit on the biocompatibility of an extracorporeal circuit, especially in view of the attenuation of the inflammatory response. A miniature closed bypass circuit, including an oxygenator (BioActive surface; Carmeda, Stockholm, Sweden) was primed with fresh human heparinized blood and perfused with a centrifugal pump. Either pure N2 gas (control group: n = 7) or NO gas (NO group [100 ppm in N2]: n = 7) was infused to the oxygenator. NO metabolites (nitrite and nitrate), platelet count, thrombin-antithrombin III complex (TAT), alpha2-plasmin-plasminogen inhibitor complex (PIC), beta-thromboglobulin (beta-TG), platelet factor 4 (PF4), serotonin, complement 3 activation products (C3a), granulocyte elastase, and bradykinin were measured at 0, 30, 60, 120, and 180 min after starting perfusion. At every sampling point, platelet counts were significantly higher, and TAT, beta-TG, and bradykinin were lower in the NO group than in the control group. PF4, C3a, and granulocyte elastase were significantly lower in the NO group at 60, 120, and 180 min. These results suggest that NO gas infusion to the oxygenator enhances the biocompatibility of heparin coated extracorporeal circuits.
Biocompatible Materials↗
Endovascular stent graft placement for patients with aortic aneurysm and end-organ dysfunction.
Endovascular stent grafts (ESGs) for the treatment of aortic aneurysm is becoming popular because it is less invasiveness for the patient. This new modality seems to be especially useful for treating high risk patients, such as those with end-organ dysfunction. In this study we retrospectively analyzed the results of ESG placement for patients with renal or hepatic dysfunction. From January 1996 to December 1997, six patients with end-organ dysfunction (two with descending thoracic aneurysm and four with abdominal aneurysm) underwent ESG placement. Five of these patients had renal dysfunction, with serum creatinine levels of 2.0 mg/dl or greater, and the remaining patient had hepatic dysfunction with a prothrombin time less than 60%. One of the patients also had severe atherosclerotic disease with a history of multiple brain infarctions. All the patients received custom made endovascular spiral Z stents covered with a woven Dacron (DuPont Co., Wilmington, DE) graft, which was delivered via a femoral artery under local anesthesia. None of the patients showed significant changes in renal or hepatic function after the procedure. None of the five patients with renal dysfunction needed hemodialysis after ESG placement, although the mean preoperative level of serum creatinine and blood urea nitrogen was 3.4 mg/dl and 42.0 mg/ dl, respectively. All the patients left the recovery room on postoperative day 1. These results indicated that endovascular stent graft placement is extremely useful in the treatment of aortic aneurysm patients with end-organ dysfunction.
Aged↗
P-selectin monoclonal antibody may attenuate the whole body inflammatory response induced by cardiopulmonary bypass.
Cardiopulmonary bypass (CPB) is known to induce an inflammatory response in association with neutrophil mediated lung injury. P-Selectin has been reported to be involved in the initiation of this inflammatory response by promoting the adhesion of neutrophils to endothelial cells in postcapillary venules. However, the role of P-selectin in the inflammatory response induced by CPB has never been clarified. To elucidate its role, we evaluated the effect of an anti-rat specific P-selectin monoclonal antibody (ARP2-4; Sumitomo Pharmaceutical) on the response of inflammatory cytokines and lung injury in a rat-CPB model. Twenty Sprague-Dawley rats underwent CPB for 30 minutes (80 ml/kg per minute, 34 degrees C) under one of two conditions. In group P, ARP2-4 (3 mg/kg) was added to the priming solution of the bypass circuit (n = 10). Saline alone was given to group C (n = 10). Inflammatory cytokines (tumor necrosis factor-alpha [TNF-alpha], interleukin[IL]-1beta, IL-6, and IL-8) and respiratory index (RI) as a marker of pulmonary gas-exchange ability were measured 1) before the initiation of CPB, 2) at the termination of CPB, and 3) 2 hours after the termination of CPB. Neither TNF-alpha nor IL-1beta was detected during the experimental period in either group. The plasma levels of IL-6 and IL-8 increased after CPB in both groups, but they were significantly lower in group P than in group C. The RI value increased in a pattern similar to that of the inflammatory cytokines and was significantly lower in group P. These data demonstrate that the addition of an anti-rat specific monoclonal antibody inhibits the abnormal release of inflammatory cytokines and attenuates CPB induced lung injury in rats. Thus, P-selectin may play a role in the augmentation of CPB induced inflammatory response, and the use of its inhibitory monoclonal antibody seems to be a promising strategy for the treatment of CPB induced lung injury.
Animals↗
Application of ultra short acting beta blockade (esmolol) in pediatric open heart surgery: a trial in total anomalous pulmonary venous return.
BACKGROUND: In the repair of total anomalous pulmonary venous return (TAPVR) under cardiopulmonary bypass, esmolol, ultra short acting beta blocker, was applied to obtain low heart rate and weak ventricular contraction under mild hypothermic cardiopulmonary bypass. METHODS: Five infants aged from 14 to 158 days with an average of 70 days, underwent a primary or palliative repair of TAPVR. The type of anomalous return was supracardiac type (2), infracardiac (2), and intracardiac (1). A primary repair was done in three for isolated TAPVR with bypass time of 65 to 76 minutes, and a palliative repair for two with complex anomalies with bypass time of 64 and 87 minutes. RESULTS: There was one operative death from cerebral bleeding in an infant with complex TAPVR who underwent simultaneous pulmonary banding. CONCLUSION: This strategy seems to be applicable in pediatric cardiac surgery when aortic cross-clamping is better to be avoided and the surgery is mainly limited to the atrial level.
Adrenergic beta-Antagonists↗
Predictive value of preoperative serum cholinesterase concentration in patients with liver dysfunction undergoing cardiac surgery.
OBJECTIVE: There are an increasing number of patients with severe liver dysfunction subjected to open heart surgery. This retrospective study was designed to assess operative results and clarify the degree of liver injury in patients with liver dysfunction undergoing open heart surgery. In addition, determinants influencing their prognosis were assessed. METHODS: In a 9-year period from 1988 to 1996, we operated on 31 patients with posthepatitis liver dysfunction and 16 with chronic passive congestion of the liver. This group was 2.3% and 1.6% of the 1368 patients undergoing cardiac surgery in the same period. We compared several perioperative factors between survivors and nonsurvivors to determine risk factors affecting mortality. RESULTS: In the group with posthepatitis liver dysfunction, the postoperative course of 5 patients among 31 (16.1%) was poor. Serum cholinesterase concentration was lower only in the nonsurvivor group (nonsurvivor vs survivor: 1979+/-949 vs 3515+/-1424 IU/I, p < 0.05). All patients with cholinesterase < 2000 IU/L died. The duration of CPB (212+/-53 vs 150+/-54 minutes, p < 0.03) and ACC time (151+/-38 vs 96+/-40 minutes, p < 0.02) was longer in the nonsurvivor group. In the group with chronic passive congestion, the postoperative course of 5 of 16 (31.3%) patients with valvular disease was poor. Serum cholinesterase concentration was lower only in the nonsurvivor group (nonsurvivor vs survivors: 2006+/-435 vs 3483+/-1442 IU/L, p < 0.02), and all patients with cholinesterase < 2000 IU/L died. Postoperative bleeding was greater in the nonsurvivor group (3327+/-2106 vs 1428+/-643 mL, p < 0.05). Multivariate logistic regression analysis including the described pre- and intraoperative factors identified only serum cholinesterase concentration (F = 9.18) as significant. CONCLUSIONS: A low value of preoperative serum cholinesterase (< 2,000 IU/L) is thought to be the predictor of prognosis after open heart surgery in patients with severe posthepatitis and congestive liver dysfunction. Operative factors (cardiopulmonary time in posthepatitis liver dysfunction and postoperative bleeding in the congestive liver dysfunction) also influenced the prognosis.
Adolescent↗
Endoscopic resection of small rectal carcinoid tumours using an aspiration method with a transparent overcap.
Rectal carcinoid tumours are often small and rarely metastatic. Endoscopic resection may, therefore, be the best treatment for small tumours. We diagnosed rectal carcinoid tumours in four women and three men (mean age 53 years; range, 43 - 63) between 1994 and 1999. Tumour depth was evaluated using a high-frequency ultrasonographic probe in five of the seven patients. All tumours were resected by endoscopic mucosal resection using an aspiration method with a transparent overcap. Histologically, all tumours were located within the submucosal layer. Tumour cells were found at the resected margin of the lateral side in one patient, and at the bottom of the margin in another. Both patients were followed up with frequent endoscopy, and no local recurrences have been detected at 1-year or 4-year follow-ups. Ultrasonographic examination before resection is useful to estimate tumour depth. Endoscopic resection by an aspiration method with a transparent overcap is safe and effective for the treatment of small rectal carcinoid tumours.
Adult↗
Effects of terminal cardioplegia with leukocyte-depleted blood on heart grafts preserved for 24 hours.
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)
Animals↗
Circular dichroism studies of the coenzyme environment in the active sites of mutant forms of the beta-subunit in the tryptophan synthase alpha 2 beta 2 complex.
The circular dichroism has been used to evaluate the effect of mutation on the environment of the pyridoxal phosphate coenzyme in the active site of the beta-subunit in the tryptophan synthase alpha 2 beta 2 complex from Salmonella typhimurium. Seven mutant forms of the alpha 2 beta 2-complex with single amino acid replacements at residues 87, 109, 188, 306, and 350 of the beta-subunit have been prepared by site-directed mutagenesis, purified to homogeneity, and characterized by absorption and circular dichroism spectroscopy. Since the wild type and mutant alpha 2 beta 2 complexes all exhibit positive circular dichroism in the coenzyme absorption band, pyridoxal phosphate must bind asymmetrically in the active site of these enzymes. However, the coenzyme may have an altered orientation or active site environment in five of the mutant enzymes that display less intense ellipticity bands. The mutant enzyme in which lysine 87 is replaced by threonine has very weak ellipticity at 400 nm. Since lysine 87 forms a Schiff base with pyridoxal phosphate in the wild type enzyme, our results demonstrate the importance of the Schiff base linkage for rigid or asymmetric binding. Although the mutant enzymes display spectra in the presence of L-serine that differ from that of the wild type enzyme, addition of alpha-glycerol 3-phosphate converts the spectra of two of the mutant enzymes to that of the wild type enzyme. We conclude that this alpha-subunit ligand may produce a conformational change in the alpha-subunit that is transmitted to the mutant beta-subunits and partially corrects conformational alterations in the mutant enzymes.
Base Sequence↗
Attenuation of pulmonary leukocyte sequestration during extracorporeal circulation by a new c-AMP phosphodiesterase inhibitor.
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.
3',5'-Cyclic-AMP Phosphodiesterases↗
Common pulmonary vein atresia: a successfully corrected case.
Common pulmonary vein atresia is a rare congenital cardiac anomaly in which there is no communication between the confluence of the pulmonary veins and the heart or the major systemic venous system. We successfully treated this disease in a 5-day-old boy by performing an anastomosis of the left atrium to the common pulmonary vein. Only one patient with this lesion who survived this procedure has been reported in the literature. Early recognition of this lesion and immediate surgical intervention are the only way to save the patient's life.
Echocardiography↗
Hemodynamic effect of inhaled nitric oxide in dilated cardiomyopathy patients on LVAD support.
Recently it has been shown that inhaled nitric oxide (NO), which has been proven to contribute to improvement in critical pulmonary hypertension, may provide a favorable effect early after left ventricular assist device (LVAD) support. To improve right ventricular function, inhalation of NO was added to treatment with conventional catecholamines for four consecutive dilated cardiomyopathy (DCM) patients following institution of LVAD. In two patients 1 hr after inhalation of NO, central venous pressure (CVP), mean pulmonary arterial pressure (PAm), and pulmonary vascular resistance (PVR) were improved. These results led to better LVAD output and resulted in an adequate cardiac index. On the other hand, a right VAD (RVAD) was implemented in one patient whose high CVP, PAm, and PVR continued; he was weaned after 8 days of RVAD support. Another patient who had a high CVP but normal PAm and PVR before and after inhalation of NO had no improvement in his hemodynamic state. These data suggest that inhaled NO may improve systemic circulation by reducing right ventricular afterload and may become a promising and convenient therapy before placing RVAD in DCM patients under LVAD support. RVAD should be conducted in patients with right ventricular failure or when pulmonary hypertension is associated with impaired right ventricular reserve, even after inhalation of NO.
Administration, Inhalation↗
Portable cardiopulmonary support system as a bridge to left ventricular assist system implantation. A new strategy for the treatment of end stage cardiac disease.
The key to the successful implantation of a left ventricular assist system (LVAS) for patients with end stage cardiac disease is whether the functions of other vital organs are irreversibly damaged or not. The portable cardiopulmonary support system (PCPS) is not only as convenient as, but is more powerful than, the intra-aortic balloon pump (IABP) in resuscitating impaired end organ function. To investigate the efficacy of PCPS in end stage cardiac disease, end organ function before and after the application of PCPS was retrospectively analyzed for end stage cardiac disease. From 1992 to 1996, five cardiomyopathy patients with deterioration in end organ function, despite application of IABP, underwent PCPS support before implantation of LVAS. Urine volume and levels of liver enzymes (sAST and sALT) and serum creatinine were determined before and after institution of PCPS. After the start of PCPS, the urine output increased significantly (1,840 +/- 450-4,340 +/- 470 ml/day, p < 0.01), and levels of sAST, sALT, and serum creatinine decreased significantly (630 +/- 220-150 +/- 50 IU/L, 630 +/- 260-260 +/- 130 IU/L, and 2.9 +/- 0.5-1.2 +/- 0.1 mg/dl, respectively; p < 0.05). All five patients were successfully bridged to LVAS implantation, and none died of multiple organ failure caused by pre-existing cardiac failure. These results indicate that PCPS before LVAS implantation is useful in resuscitating impaired end organ function and improving the survival rate with LVAS implantation for end stage cardiac disease.
Adult↗
Hepatic sinusoid endothelial dysfunction plays a role in hyperbilirubinemia in patients following implantation of an LVAD.
To clarify the mechanism of hyperbilirubinemia in the setting of a left ventricular assist device (LVAD), the change in hepatocellular function, hepatic sinusoid endothelial microcirculation, and inflammatory response before and after LVAD implantation were evaluated. Eight consecutive patients underwent the placement of an LVAD, and serum levels of total bilirubin (TB), transaminases [alanine transaminase (ALT), aspartate transaminase (AST)], interleukin (IL-6, IL-8), and hyaluronic acid (HA), an indicator of hepatic sinusoidal circulation, were measured before and after LVAD implantation. The TB of all patients increased significantly in the first post operative week (p < 0.05 vs. pre-operatively). In five patients, the elevated TB (4.6 +/- 4.1 mg/dl) returned to pre-operative levels (2.7 +/- 2.0 mg/dl) by the 14th post operative day (Group R), but in the other three patients who died of multiple organ failure, the level of TB increased to 39.9 +/- 16.4 mg/dl (Group A). Levels of HA and IL-8 had good correlation with the level of TB (HA: r = 0.60, p < 0.05; IL-8: r = 0.55, p < 0.05). However, AST, ALT, and IL-6 were not related to changes in TB. These results suggest that hepatic sinusoid endothelial dysfunction and inflammatory reaction may play a significant role in hepatic failure in patients following implantation of an LVAD.
Adult↗