Koji Onoda

Effects of Cilostazol, a Selective cAMP Phosphodiesterase Inhibitor on the Contraction of Vascular Smooth Muscle

The effects of cilostazol (OPC-13013, 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydro-2(1H)-quin olinone) on cyclic nucleotide metabolism and Ca2+-induced contraction of intact and skinned rabbit arterial smooth muscles were investigated. The concentrations of cilostazol producing 50% inhibition of cyclic adenosine monophosphate phosphodiesterase and Ca2+-dependent cyclic nucleotide phosphodiesterase were 0.4 microM and above 100 microM, respectively. This compound has no significant effect on adenylate cyclase in concentrations of up to 100 microM. Addition of cilostazol increased significantly the cAMP content without significant effect on cyclic guanosine monophosphate level of rabbit thoracic aorta in the presence of forskolin. Moreover, the ED50 value of cilostazol in relaxation of rabbit mesenteric arterial strips was decreased selectively by addition of 0.01 microM forskolin, which alone at this concentration has no effect on vascular contraction. Cilostazol of up to 30 microM did not suppress the Ca2+-induced contraction of the chemically skinned rabbit mesenteric artery. Therefore, cilostazol may produce the relaxation of intact vascular smooth muscle by its inhibition of cyclic adenosine monophosphate hydrolysis.

Changes in False Lumen After Transluminal Stent-Graft Placement in Aortic Dissections Six Years’ Experience

Background—Transluminal stent-graft placements (TSGPs) are a new, less invasive procedure now recognized as the choice for aortic disease repair. Treatment of aortic dissections with TSGPs has resulted in good early results, but the long-term results and changes in the false lumen have not been elucidated in detail. Methods and Results—TSGPs were performed in 49 patients with primary tears in their descending aortas, and the follow-up period ranged from 4 months to 6 years. The patients were divided into 32 acute-onset and 17 chronic dissections; of the acute-onset cases, there were 15 Stanford type A retrograde dissections. Periodic enhanced spiral CT was conducted after TSGP. The false lumen in the ascending aorta in 14 (93%) of the Stanford type A cases was obliterated completely within 3 months. The CT study was continued for >2 years for 17 acute-onset dissection and 11 chronic dissection patients. The average false lumen diameters of the proximal, middle, and distal descending aorta before treatment were 15.9, 16.2, and 15.6 mm in the acute-onset dissection group and 28.1, 25.2, and 21.0 mm in the chronic dissection group, respectively. The false lumen diameters 2 years after treatment were 3.0, 3.7, and 3.1 mm in the acute-onset dissection group and 10.6, 10.5, and 11.9 mm in the chronic dissection group, respectively. Two years after TSGPs, the false lumen of the thoracic aorta totally disappeared in 76% of the acute-onset dissection group and 36% of the chronic dissection group. No cases showed rupture after TSGP. Conclusions—Complete obliteration of the false lumen is more likely in acute-onset cases than in chronic cases.

Long-Term Follow-up After Carpentier-Edwards Ring Annuloplasty for Tricuspid Regurgitation

BACKGROUND Use of flexible rings for tricuspid ring annuloplasty is becoming popular. This study was undertaken to evaluate Carpentier-Edwards (C-E) rigid ring annuloplasty for tricuspid regurgitation (TR), secondary to mitral valve disease and clinical outcome on a long-term basis. METHODS From December 1985 to March 1996, 45 patients with secondary TR underwent C-E ring annuloplasty. Thirty-nine patients (95.1%) were in New York Heart Association (NYHA) functional class III or IV. The mean follow-up was 96.7+/-48.5 months or 362.6 patient-years. RESULTS There were three in-hospital and nine late deaths that were not related to tricuspid annuloplasty. Actuarial survival at 10 years was 68.3%. Echocardiographic studies showed that TR was well controlled within grade 2+ in all survivors. Residual pulmonary hypertension (PH) was recognized in 9 of 21 patients (42.9%) with preoperative PH, however, no TR was seen in 6 patients. A TR grade of 2+ was observed in 3 patients. Thirty of the total survivors (96.8%) were in NYHA class I and II, but 1 patient was in NYHA class III. The actuarial rate of freedom from tricuspid valve reoperation after 10 years was 97.5%. CONCLUSIONS C-E ring annuloplasty is acceptable for repair of secondary TR and improvement in clinical status on a long-term basis.

Expression and degeneration of tenascin-C in human lung cancers.

Tenascin-C is an extracellular matrix glycoprotein produced in response to epithelial-mesenchymal interactions during organogenesis and tissue remodelling. It has therefore been proposed as a stromal marker for epithelial malignancy. To test this hypothesis, 30 human lung cancers, presenting a variety of clinicopathological features, and six specimens of normal tissue were examined by Western and Northern blotting of tenascin-C protein and mRNA. The results obtained were: (1) elevated tenascin-C expression was detected in all 30 cases by Western blotting, with mRNA increase in 22 of them; (2) mRNA for a large isoform of tenascin-C, including an alternatively spliced sequence, was expressed in lung cancer tissues but not in normal lungs; and (3) metastasis to lymph nodes was frequently found in cases whose tenascin-C was degraded into small fragments. These results suggest that tenascin-C degradation can be used as a marker for metastatic potential of a tumour.

Silicone-coated polypropylene hollow-fiber oxygenator : Experimental evaluation and preliminary clinical use

BACKGROUND A membrane oxygenator consisting of a microporous polypropylene hollow fiber with a 0.2-microm ultrathin silicone layer (cyclosiloxane) was developed. Animal experimental and preliminary clinical studies evaluated its reliability in bypass procedures. METHODS Five 24-hour venoarterial bypass periods were conducted on dogs using the oxygenator (group A). In 5 controls, bypass periods were conducted using the same oxygenator without silicone coating (group B). As a preliminary clinical study, 14 patients underwent cardiopulmonary bypass with the silicone-coated oxygenator. RESULTS Eight to 16 hours (mean, 12.2 hours) after initiation of bypass, plasma leakage occurred in all group B animals, but none in group A. The O2 and CO2 transfer rates after 24 hours in group A were significantly higher than at termination of bypass in group B (p < 0.005 and p < 0.03, respectively). Scanning electron microscopy of silicone-coated fibers after 24 hours of bypass revealed no damage to the silicone coating of the polypropylene hollow fibers. In the clinical study, the oxygenator showed good gas transfer, acceptable pressure loss, low hemolysis, and good durability. CONCLUSIONS This oxygenator is more durable and offers greater gas transfer capabilities than the previous generation of oxygenators.

Ultrafiltration of the priming blood before cardiopulmonary bypass attenuates inflammatory response and improves postoperative clinical course in pediatric patients.

ABSTRACT The priming solution using in cardiopulmonary bypass (CPB) for infants undergoing cardiac surgery includes considerable amounts of stored blood. Our objective was to test the hypothesis that ultrafiltration (UF) of the stored blood before CPB reduces the unfavorable effects of stored blood and the production of inflammatory cytokines. Fifty pediatric patients with congenital heart defects took part in this study. The patients were randomly divided into two groups: the UF (27 pediatric patients who received UF) and control (23 pediatric patients who did not receive UF) groups. UF was performed with a polysulphone ultrafiltrator before CPB. Blood samples were collected immediately before, during, and 1 h after CPB. The levels of cytokines (TNF‐&agr;, IL‐1&bgr;, IL‐8), NH3, and bradykinin were determined. The serum concentrations of NH3 and bradykinin decreased significantly after UF. Compared with the control group, the UF group had significantly lower cytokine production. Water balance in UF group was better than that of control group. The UF group received significantly less inotropic support and shorter duration of ventilator support and ICU stay. We conclude that removal of bradykinin and a decrease in the levels of NH3, potassium, and pH play a significant role in reducing water retention and postoperative lung injury. UF of the blood used to prime the circuit for CPB is a safe and efficient method for use in open heart surgery in small pediatric patients.

Biocompatibility of silicone-coated oxygenator in cardiopulmonary bypass

BACKGROUND This study was designed to analyze the biocompatibility of silicone-coated oxygenators using inflammatory response as the outcome measure, and to investigate whether the silicone-coated oxygenators perform better in terms of postoperative organ dysfunction. METHODS The 32 patients who underwent cardiopulmonary bypass (CPB) were divided into 3 groups: group A (n = 10), heparin-coated circuit with silicone-coated oxygenator; group B (n = 11), whole heparin-coated circuit; and group C (n = 11), whole untreated circuit. The plasma concentrations of the proinflammatory markers, made of inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, interleukin-8), terminal complement complex (C5b-9), and polymorphonuclear elastase (PMN-E), were measured by enzyme-linked immunosorbant assay. RESULTS All proinflammatory markers were significantly lower in groups A and B than in group C, especially C5b-9 and PMN-E concentrations, which were significantly lower in group A than in group B. The alveolar-arterial oxygen gradients (A-aDO2) and the respiratory index were significantly better in group A than in group C. In group B, however, only the A-aDO2 was significantly better than in group C. The duration of intubation and the length of stay in the intensive care unit stay were significantly shorter in groups A and B than in group C. CONCLUSIONS Silicone-coated oxygenators are biocompatible and prevent postoperative organ dysfunction.

Coronary artery aneurysm in a patient with Marfan syndrome

True aneurysm of the coronary artery in Marfan syndrome is very rare. We present a patient with Marfan syndrome who had aneurysms from the ascending aorta to the thoracoabdominal aorta and a large aneurysm of the left main coronary artery after an original Bentall operation. Prosthetic graft replacement of total aorta, coronary artery bypass grafting, and removal of the aneurysm of the left main coronary artery were successfully performed.

Effects of inhaled nitric oxide in rats with chemically induced pulmonary hypertension.

To determine the model animal with pulmonary hypertension in which nitric oxide (NO) inhalation reduces pulmonary arterial pressure (PAP), we examined the inhalation of 20-100 ppm NO gas on normal rats and rats with monocrotaline induced pulmonary hypertension. In the control group, mean PAP showed no change after spontaneous breathing of NO at the concentration of 20 to 100 ppm for 5 min. On the contrary, in both the severe (mean PAP > 40 mmHg) and moderate (mean PAP < 40 mmHg) pulmonary hypertensive groups, NO inhalation produced a prompt reduction of the mean PAP which had been elevated by monocrotaline. 20 ppm NO inhalation reduced mean PAP from 64.4 +/- 3.7 mmHg to 56.2 +/- 4.4 mmHg (mean +/- SEM, P < 0.01) in the severe pulmonary hypertensive group, from 31.0 +/- 2.0 mmHg to 24.2 +/- 0.9 mmHg in the moderate pulmonary hypertensive group (mean +/- SEM, P < 0.05). The onset of the reduction of mean PAP occurred within 30 sec after the start of NO inhalation and maximum reduction occurred within 4 min. 20 ppm NO inhalation significantly reduced mean PAP, and mean PAP was reduced dose-dependently at the concentration of 20 to 60 ppm and reaction to NO was almost constant at the concentrations of over 60 ppm.

Monoclonal antibody recognition of two subtype forms of protein kinase C in human platelets.

Using a hydroxylapatite column chromatographic technique, we obtained the evidence for two subtype forms of protein kinase C in human platelets. These subtypes had a similar chromatographic property to Type II, Type III protein kinase C from the rabbit brain. In addition, in monoclonal antibodies (MC-1a, 2a, 3a) (1) which reacted with specifically Type I, II, III rabbit brain protein kinase C, respectively, only MC-2a and MC-3a reacted with human platelet protein kinase C. All these brain and platelet subtypes have a similar Km value for ATP, the range being from 8.0 to 20.0 microM and a similar IC50 value with regard to the effect of the protein kinase C inhibitor, H-7. Thus, the possibility that specific functions of platelet may be derived from a deficiency of Type I protein kinase C warrants attention.