The Experts below are selected from a list of 1758 Experts worldwide ranked by ideXlab platform

Shintaro Nishio - One of the best experts on this subject based on the ideXlab platform.

  • Pharmacological and clinical properties of Beraprost sodium, orally active prostacyclin analogue
    Nihon yakurigaku zasshi. Folia pharmacologica Japonica, 2001
    Co-Authors: Shintaro Nishio, Hajimu Kurumatani
    Abstract:

    Prostacyclin is an endogeneous eicosanoid synthesized by vascular endothelial cells, and has potent inhibitory effects on platelet adhesion/aggregation and vasoconstriction. However, its therapeutic use is restricted by its extremely short half-life. Beraprost sodium (Beraprost) is the first orally active prostacyclin analogue developed by TORAY Industries, Inc. Beraprost possesses a phenol moiety instead of the exo-enol ether moiety, which is the cause of the instability of prostacyclin, and has a modified omega-side chain that contributes to dissociating antiplatelet action from adverse reactions. In 1992, Beraprost was approved as a drug for chronic arterial occlusion. Beraprost is now widely used clinically as "Dorner" or "Procylin". The indication for "primary pulmonary hypertension" was also approved in 1999. Recently in Europe, a placebo controlled trial named "Beraprost et Claudication Intermittent-2 (BERCI-2)" was performed, and it was reported that Beraprost improved the walking distances of the patients. Beraprost has a variety of biological activities such as antiplatelet effects, vasodilation effects, antiproliferative effects on vascular smooth muscle cells, cytoprotective effects on endothelial cells and inhibitory effects on the production of inflammatory cytokines. On the basis of basic and clinical research, it has been suggested that Beraprost is also effective for many intractable diseases. We expect that the relationship between reduced prostacyclin level and these diseases would be clarified and the beneficial effects of Beraprost would be demonstrated by controlled clinical trials in the future.

  • Anti-inflammatory effects of Beraprost sodium, a stable analogue of PGI2, and its mechanisms.
    Prostaglandins, 1997
    Co-Authors: Yuji Ueno, Hiroshi Koike, Shigeyasu Annoh, Shintaro Nishio
    Abstract:

    Abstract We examined whether Beraprost sodium (Beraprost), a stable analogue of PGI2, has an anti-inflammatory effect on the permeability barrier through endothelial cells in vivo. The injection of collagen (5 μg/head) plus epinephrine (0.6 μg/head) showed time-dependently the increased Evans blue dye leakage of the lung in mice for 60 min. Beraprost significantly suppressed this leakage dose-dependently (control; 11.26 ± 1.64 μg/lung, Beraprost 10 μg/kg; 7.49 ± 1.36 μg/lung, 30 μg/kg; 5.33 ± 0.71 μg/lung, 100 μg/kg; 5.52 ± 0.79 μg/lung). Pulmonary thromboembolism-induced Evans blue dye leakage was also reduced significantly by aspirin (5 mg/kg), but PGE1 (170 μg/kg) showed a tendency to potentiate the edematogenic response. One week after the injection of same dosage of collagen plus epinephrine in mice, pulmonary thromboembolism showed the increase of wet-to-dry weight ratio of the lung (normal; 3.84 ± 0.01, control; 3.96 ± 0.04) and right ventricular hypertrophy (normal; 28.2 ± 0.9%, control; 32.3 ± 0.9%) compared to normal mice. Beraprost significantly suppressed lung edema and hypertrophy dose-dependently, and over 30 μg/kg/day of Beraprost, the effects were statistically significant (Beraprost 30 μg/kg/day; 3.85 ± 0.02 and 27.8 ± 1.4%, 100 μg/kg/day; 3.85 ± 0.02 and 27.3 ± 1.1%). Beraprost significantly reduced 5-hydroxytryptamine (5-HT; 17 nmol/paw)-induced rat paw edema dose-dependently (5-HT alone; 100%, Beraprost 10−13 mol/paw; 91.19 ± 2.22%, 10−12 mol/paw; 85.79 ± 4.85%, 10−11 mol/paw; 78.49 ± 3.95%). 5-HT-induced edema was also suppressed significantly by the co-injection of (−)-isoproterenol (10−12 mol/paw), but PGE1 (10−11 mol/paw) significantly potentiated the edematogenic response. From these results, we propose that the anti-inflammatory effect of Beraprost may be contributed, in part, to the permeability barrier through end othelial cells in vivo. © 1997 by Elsevier Science Inc.

  • Research and development of Beraprost sodium, a new stable PGI2 analogue
    Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan, 1997
    Co-Authors: Shintaro Nishio, Hiroshi Nagase, Kanji Kanou, Shigeru Aoki, Yoshinori Kanbayashi
    Abstract:

    A novel prostaglandin I2 (PGI2) analogue, Beraprost sodium, is the first launched drug as an orally active PGI2. PGI2 was discovered in 1976, and has attracted much attention as a medicine for cardiovascular diseases such as strokes and heart attacks because of its potent antiplatelet and vasodilating effect. However, PGI2 is extremely unstable for the use as practical medicines. Thus, stable PGI2 analogues have been explored by a large number of researchers in the world. Just after the discovery of PGI2, we started a research on chemically and metabolically stable PGI2 derivatives with longer duration of action and less adverse reaction. We invented a novel class of stable PGI2, 5,6,7-trinor-4,8-inter-m-phenylenePGI2 analogues that have the phenol moiety instead of the enolether moiety of PGI2. Further efforts were devoted to enhance the efficacy of the PGI2 analogues and to eliminate their side effects, and an orally active analogue, Beraprost sodium, was obtained. In order to establish the synthetic route of Beraprost sodium, various novel processes were invented, including ortho-selective metalation of bromoanisoles by means of Grignard reagents, copper-catalyzed SN2' cyclization to prepare cyclopenta[b]benzofuran, and stereo-selective elongation of the omega-side chain by Prins reaction. Beraprost sodium inhibit platelet aggregation induced by adenosine 5'-diphosphate (ADP), collagen and arachidonic acid. It was shown that the drug has a potent antiplatelet effect both in vitro and ex vivo in human and several animal species. In clinical studies, Beraprost sodium exerted a marked effect to improve arteriosclerosis obliterans. No serious adverse effects related with the drug have been reported. It was highly evaluated as an orally active PGI2 by pharmaceutical companies overseas as well, and now clinical trials are under way in U.S.A. and Europe.

  • Positive inotropic and chronotropic effects of Beraprost sodium, a stable analogue of prostacyclin, in isolated guinea pig myocardium
    General pharmacology, 1996
    Co-Authors: Yuji Ueno, Seiji Okazaki, Shintaro Nishio, Masafumi Isogaya, Hikaru Tanaka, Yoshimitsu Kato, K Shigenobu
    Abstract:

    Abstract 1. 1. Inotropic and chronotropic effects of Beraprost sodium (Beraprost), a chemically stable prostacyclin analogue, were examined in isolated myocardial preparations of guinea pigs. 2. 2. In the left atria, 10−9-10−7 M Beraprost had no significant effect on the contractile force, but 10−6 and 10−5 M produced a concentration-dependent positive inotropic response. This effect was antagonized by S-145, a potent and selective thromboxane A2 (TXA2) receptor antagonist, but not by propranolol. 3. 3. Beraprost, from 10−9 to 10−5 M, had no significant inotropic effect in the right ventricular papillary muscles. 4. 4. In the right atria, 10−9 and 10−8 M Beraprost had no significant effect, but 10−7-10−5 M caused an increase in beating rate; this effect was not affected by S-145. 5. 5. The present study demonstrates that Beraprost has positive inotropic and chronotropic effects at high doses on isolated guinea pig atria. The inotropic effect may be mediated by the TXA2 receptor, but some mechanism other than the TXA2 receptor is responsible for the chronotropic effect.

  • Protective effect of Beraprost sodium, a stable prostacyclin analogue, in development of monocrotaline-induced pulmonary hypertension.
    Journal of cardiovascular pharmacology, 1996
    Co-Authors: Masayuki Miyata, Shintaro Nishio, Yuji Ueno, Hiroshi Koike, Hideharu Sekine, Osamu Ito, Fumitaka Sakuma, Tomoe Nishimaki, Reiji Kasukawa
    Abstract:

    Experimental pulmonary hypertension (PH) was induced by a single injection of monocrotaline (MCT), a pyrrolizidine alkaloid extracted from Crotalaria spectabilis. The effect of Beraprost sodium, a stable prostacyclin analogue, on the development of MCT-induced PH in rats was studied. Chronic administration of Beraprost sodium at a dose of 30 micrograms/kg/day initiated on the same day as MCT injection decreased the degree of PH determined by weight ratio of right ventricular free wall to that of left ventricle plus septum depending on the duration of administration. Although the injection of prostaglandin E1 (PGE1) at a dose of 200 micrograms/kg/day initiated 1 week after MCT injection did not decrease the degree of PH significantly, Beraprost sodium administration at doses of 30 and 100 micrograms/kg/day decreased the degree of PH significantly. The cytoprotective effect of Beraprost sodium against endothelial cell (EC) damage is believed to be involved in inhibiting development of PH in MCT-injected rats. The amounts of cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF) produced by alveolar macrophages decreased in accordance with the inhibiting effect of Beraprost sodium on development of PH, indicating that Beraprost sodium inhibited the development of PH in MCT-injected rats not only through its effect of vasodilation and anti-platelet aggregation in pulmonary circulation but also through its antiinflammatory effects.

Soji Kasayama - One of the best experts on this subject based on the ideXlab platform.

  • effects of the prostaglandin i2 analogue Beraprost sodium on vascular cell adhesion molecule 1 expression in human vascular endothelial cells and circulating vascular cell adhesion molecule 1 level in patients with type 2 diabetes mellitus
    Metabolism-clinical and Experimental, 2003
    Co-Authors: Kayoko Goya, Michio Otsuki, Soji Kasayama
    Abstract:

    Abstract Beraprost sodium is an orally active prostaglandin (PG)I 2 analogue, which has antiplatelet and vasodilating properties. In this study, we investigated the effects of Beraprost on the expression of vascular cell adhesion molecule-1 (VCAM-1), one of the key molecules involved in atherosclerosis, in cultured vascular endothelial cells. In addition, we examined the effects of Beraprost on circulating VCAM-1 level and atherosclerosis progression in patients with type 2 diabetes mellitus. Beraprost significantly decreased tumor necrosis factor-α (TNF-α)–induced VCAM-1 expression in human vascular endothelial cells. Beraprost also repressed human monocytoid U937 cell adhesion to the vascular endothelial cells. Twenty-five patients with type 2 diabetes mellitus who had atherosclerotic change of carotid arteries were enrolled for an open prospective study: 11 patients received Beraprost for 3 years, while the other 14 did not. The 3-year changes of circulating VCAM-1 level, as well as those of carotid arterial intima-media thickness (IMT) were significantly lower in the patients receiving the Beraprost treatment than that in the patients without the treatment. Thus, Beraprost had an ability to repress the expression of VCAM-1 in human vascular endothelial cells. In addition, Beraprost lowered circulating VCAM-1 level and prevented the increase of carotid IMT in patients with type 2 diabetes mellitus. Considering that circulating VCAM-1 and IMT are predictive of future vascular events, Beraprost may have a beneficial effect on progression of atherosclerosis in diabetic patients. Copyright 2003, Elsevier Science (USA). All rights reserved.

Yuji Ueno - One of the best experts on this subject based on the ideXlab platform.

  • Anti-inflammatory effects of Beraprost sodium, a stable analogue of PGI2, and its mechanisms.
    Prostaglandins, 1997
    Co-Authors: Yuji Ueno, Hiroshi Koike, Shigeyasu Annoh, Shintaro Nishio
    Abstract:

    Abstract We examined whether Beraprost sodium (Beraprost), a stable analogue of PGI2, has an anti-inflammatory effect on the permeability barrier through endothelial cells in vivo. The injection of collagen (5 μg/head) plus epinephrine (0.6 μg/head) showed time-dependently the increased Evans blue dye leakage of the lung in mice for 60 min. Beraprost significantly suppressed this leakage dose-dependently (control; 11.26 ± 1.64 μg/lung, Beraprost 10 μg/kg; 7.49 ± 1.36 μg/lung, 30 μg/kg; 5.33 ± 0.71 μg/lung, 100 μg/kg; 5.52 ± 0.79 μg/lung). Pulmonary thromboembolism-induced Evans blue dye leakage was also reduced significantly by aspirin (5 mg/kg), but PGE1 (170 μg/kg) showed a tendency to potentiate the edematogenic response. One week after the injection of same dosage of collagen plus epinephrine in mice, pulmonary thromboembolism showed the increase of wet-to-dry weight ratio of the lung (normal; 3.84 ± 0.01, control; 3.96 ± 0.04) and right ventricular hypertrophy (normal; 28.2 ± 0.9%, control; 32.3 ± 0.9%) compared to normal mice. Beraprost significantly suppressed lung edema and hypertrophy dose-dependently, and over 30 μg/kg/day of Beraprost, the effects were statistically significant (Beraprost 30 μg/kg/day; 3.85 ± 0.02 and 27.8 ± 1.4%, 100 μg/kg/day; 3.85 ± 0.02 and 27.3 ± 1.1%). Beraprost significantly reduced 5-hydroxytryptamine (5-HT; 17 nmol/paw)-induced rat paw edema dose-dependently (5-HT alone; 100%, Beraprost 10−13 mol/paw; 91.19 ± 2.22%, 10−12 mol/paw; 85.79 ± 4.85%, 10−11 mol/paw; 78.49 ± 3.95%). 5-HT-induced edema was also suppressed significantly by the co-injection of (−)-isoproterenol (10−12 mol/paw), but PGE1 (10−11 mol/paw) significantly potentiated the edematogenic response. From these results, we propose that the anti-inflammatory effect of Beraprost may be contributed, in part, to the permeability barrier through end othelial cells in vivo. © 1997 by Elsevier Science Inc.

  • Positive inotropic and chronotropic effects of Beraprost sodium, a stable analogue of prostacyclin, in isolated guinea pig myocardium
    General pharmacology, 1996
    Co-Authors: Yuji Ueno, Seiji Okazaki, Shintaro Nishio, Masafumi Isogaya, Hikaru Tanaka, Yoshimitsu Kato, K Shigenobu
    Abstract:

    Abstract 1. 1. Inotropic and chronotropic effects of Beraprost sodium (Beraprost), a chemically stable prostacyclin analogue, were examined in isolated myocardial preparations of guinea pigs. 2. 2. In the left atria, 10−9-10−7 M Beraprost had no significant effect on the contractile force, but 10−6 and 10−5 M produced a concentration-dependent positive inotropic response. This effect was antagonized by S-145, a potent and selective thromboxane A2 (TXA2) receptor antagonist, but not by propranolol. 3. 3. Beraprost, from 10−9 to 10−5 M, had no significant inotropic effect in the right ventricular papillary muscles. 4. 4. In the right atria, 10−9 and 10−8 M Beraprost had no significant effect, but 10−7-10−5 M caused an increase in beating rate; this effect was not affected by S-145. 5. 5. The present study demonstrates that Beraprost has positive inotropic and chronotropic effects at high doses on isolated guinea pig atria. The inotropic effect may be mediated by the TXA2 receptor, but some mechanism other than the TXA2 receptor is responsible for the chronotropic effect.

  • Protective effect of Beraprost sodium, a stable prostacyclin analogue, in development of monocrotaline-induced pulmonary hypertension.
    Journal of cardiovascular pharmacology, 1996
    Co-Authors: Masayuki Miyata, Shintaro Nishio, Yuji Ueno, Hiroshi Koike, Hideharu Sekine, Osamu Ito, Fumitaka Sakuma, Tomoe Nishimaki, Reiji Kasukawa
    Abstract:

    Experimental pulmonary hypertension (PH) was induced by a single injection of monocrotaline (MCT), a pyrrolizidine alkaloid extracted from Crotalaria spectabilis. The effect of Beraprost sodium, a stable prostacyclin analogue, on the development of MCT-induced PH in rats was studied. Chronic administration of Beraprost sodium at a dose of 30 micrograms/kg/day initiated on the same day as MCT injection decreased the degree of PH determined by weight ratio of right ventricular free wall to that of left ventricle plus septum depending on the duration of administration. Although the injection of prostaglandin E1 (PGE1) at a dose of 200 micrograms/kg/day initiated 1 week after MCT injection did not decrease the degree of PH significantly, Beraprost sodium administration at doses of 30 and 100 micrograms/kg/day decreased the degree of PH significantly. The cytoprotective effect of Beraprost sodium against endothelial cell (EC) damage is believed to be involved in inhibiting development of PH in MCT-injected rats. The amounts of cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF) produced by alveolar macrophages decreased in accordance with the inhibiting effect of Beraprost sodium on development of PH, indicating that Beraprost sodium inhibited the development of PH in MCT-injected rats not only through its effect of vasodilation and anti-platelet aggregation in pulmonary circulation but also through its antiinflammatory effects.

  • Beneficial effects of Beraprost sodium, a stable prostacyclin analogue, in diabetic cardiomyopathy.
    Journal of cardiovascular pharmacology, 1995
    Co-Authors: Yuji Ueno, Hiroshi Koike, Shintaro Nishio
    Abstract:

    We examined whether Beraprost sodium (Beraprost), a stable prostacyclin analogue, prevented cardiomyopathy in diabetic rats in vivo. Diabetes was induced by a bolus injection of streptozotocin in rat-tail vein. Four weeks after the induction of diabetes, the animals were treated with Beraprost (30 micrograms/kg/day, p.o.) for 4 weeks until they were used for the measurement of hemodynamics, electrocardiogram (ECG), and plasma creatine phosphokinase (CK) activity. Nontreated diabetic rats have lower mean blood pressure, heart rate, left ventricular systolic pressure, and peak positive dP/dt at basal levels compared to age-matched normal rats. All of these changes were not improved in Beraprost-treated rats. The left ventricular end-diastolic pressure and ST/R ratio in the ECG were significantly increased in diabetic rats. These parameters were significantly improved by Beraprost compared with nontreated diabetic rats. Additionally, Beraprost significantly suppressed the elevation of plasma CK activity as compared with that in non-treated diabetic rats. Changes in peak positive dP/dt in response to isoproterenol were attenuated in nontreated diabetic rats as compared with age-matched normal rats and Beraprost-treated diabetic rats. These results suggest that Beraprost is capable of preventing diabetic cardiomyopathy without affecting hyperglycemic condition.

  • Effect of Beraprost sodium on changes in action potentials during hypoxia as compared with propranolol, diltiazem and glibenclamide in guinea-pig ventricular muscle.
    Archives internationales de pharmacodynamie et de therapie, 1994
    Co-Authors: Yuji Ueno, K Shigenobu, S Nishio
    Abstract:

    The inhibitory effect of Beraprost on the transmembrane action potentials was compared with other cardioprotective drugs during hypoxia in guinea-pig isolated right ventricular muscle. Glibenclamide, like Beraprost, inhibited the decrease of the action potential duration, but propanolol and diltiazem did not affect this decrease during hypoxia. In Beraprost-treated preparations, the decrease of the myocardial K+ content during hypoxia was inhibited. Furthermore, Beraprost prevented the action potential shortening during metabolic inhibition by 2,4-dinitrophenol. It is suggested that Beraprost may inhibit the hypoxia- and 2,4-dinitrophenol-induced shortening of the action potential duration by preserving the muscular ATP level. Accordingly, Beraprost may have beneficial effects both during hypoxia and metabolic inhibition.

Shoki Takahashi - One of the best experts on this subject based on the ideXlab platform.

  • treatment of in stent restenosis with Beraprost sodium an experimental study of short and intermediate term effects in dogs
    Clinical and Experimental Pharmacology and Physiology, 2009
    Co-Authors: Kazumasa Seiji, Masashi Tsuda, Toshio Matsuhashi, Kei Takase, Hideo Miyachi, Takayuki Yamada, Tadashi Ishibashi, Shuichi Higano, Shoki Takahashi
    Abstract:

    SUMMARY 1. The aim of the present study was to evaluate the inhibitory effects of the short-term administration of Beraprost sodium, a stable prostaglandin I2 analogue, on neointimal thickening after stenting. 2. To examine the immediate and short-term effects, Z-stents were placed in the iliac veins of 12 dogs, which were randomly assigned to either a Beraprost-treated or control (saline) group. Beraprost (0.35 lg/kg per min) or saline (1.5 mL/min) was administered 30 min before stenting and was continued for 5 h thereafter. Platelet aggregation was measured before and after drug administration. At 3, 7 and 14 days after stenting, dogs were killed and immunohistochemical staining for proliferating cell nuclear antigen was used to quantify the proliferation of vascular smooth muscle cells (SMC). To evaluate intermediate-term effects, a Z-stent was placed in the right iliac vein in 10 dogs, followed by Beraprost treatment. Three days later, a second Z-stent was placed contralaterally with saline infusion as a control. After 4 weeks, dogs were killed and neointimal thickness was measured under a light microscope to calculate the intima : media area ratio. 3. Platelet aggregation was more significantly suppressed in the Beraprost-treated than in the control group (P ¼ 0.01). In addition, SMC proliferation was significantly lower in the Beraprost-treated group 7 and 14 days after stenting (P <0 .05). Over the intermediate term, the intima : media area ratio was significantly lower in the Beraprost-treated vein compared with control (P < 0.05). 4. In conclusion, short-term Beraprost treatment during

  • Treatment of in‐stent restenosis with Beraprost sodium: An experimental study of short‐ and intermediate‐term effects in dogs
    Clinical and experimental pharmacology & physiology, 2009
    Co-Authors: Kazumasa Seiji, Masashi Tsuda, Toshio Matsuhashi, Kei Takase, Hideo Miyachi, Takayuki Yamada, Tadashi Ishibashi, Shuichi Higano, Shoki Takahashi
    Abstract:

    SUMMARY 1. The aim of the present study was to evaluate the inhibitory effects of the short-term administration of Beraprost sodium, a stable prostaglandin I2 analogue, on neointimal thickening after stenting. 2. To examine the immediate and short-term effects, Z-stents were placed in the iliac veins of 12 dogs, which were randomly assigned to either a Beraprost-treated or control (saline) group. Beraprost (0.35 lg/kg per min) or saline (1.5 mL/min) was administered 30 min before stenting and was continued for 5 h thereafter. Platelet aggregation was measured before and after drug administration. At 3, 7 and 14 days after stenting, dogs were killed and immunohistochemical staining for proliferating cell nuclear antigen was used to quantify the proliferation of vascular smooth muscle cells (SMC). To evaluate intermediate-term effects, a Z-stent was placed in the right iliac vein in 10 dogs, followed by Beraprost treatment. Three days later, a second Z-stent was placed contralaterally with saline infusion as a control. After 4 weeks, dogs were killed and neointimal thickness was measured under a light microscope to calculate the intima : media area ratio. 3. Platelet aggregation was more significantly suppressed in the Beraprost-treated than in the control group (P ¼ 0.01). In addition, SMC proliferation was significantly lower in the Beraprost-treated group 7 and 14 days after stenting (P

Stanley C Jordan - One of the best experts on this subject based on the ideXlab platform.

  • a stable prostacyclin analog Beraprost sodium attenuates platelet accumulation and preservation reperfusion injury of isografts in a rat model of lung transplantation
    Transplantation, 1998
    Co-Authors: Yoshinori Okada, Alberto M Marchevsky, Robert M Kass, Jack M Matloff, Stanley C Jordan
    Abstract:

    Background. Recent studies have shown that the extent of platelet accumulation in the vasculature of transplanted organs correlates with the degree of preservation-reperfusion injury. In this study, we examined the effect of a stable prostacyclin analog, Beraprost sodium, which possesses potent antiplatelet activity, on parameters of platelet accumulation and preservation-reperfusion injury of isografts in a rat model of lung transplantation. Methods. The heart-lung blocks of donor rats were flushed with and preserved in modified Euro-Collins solution at 4°C for 6 hr or 24 hr. The left lung was transplanted into recipient rats and reperfused for 1 hr. Lung injury was evaluated by the pulmonary blood flow ratios to the lung isografts, the weight gain of the isografts, and histological examination. Small portions of the lung isografts were excised and stained with an antibody specific for rat platelets. A scoring system was developed to semiquantitate the intensity of antibody staining (score 0-4). The recipient rats received oral administration of Beraprost sodium (0.3 mg/kg) before lung transplantation. Control animals received no Beraprost sodium. Results. In the 6-hr preservation study, administration of Beraprost sodium significantly reduced the score for platelet accumulation (1.8±0.4 vs. 3.3±0.5, P<0.01). This observation was accompanied by a significantly decreased degree of preservation-reperfusion injury as evidenced by an increased blood flow ratio (13.7±2.6% vs. 4.5±3.6%, P<0.01) and a reduced weight gain (0.7±0.2 g vs. 1.1±0.2 g, P<0.01). Histological examination revealed severe capillary congestion in three of six cases in the control group, while no capillary congestion was observed in the Beraprost group. In the 24-hr preservation study, no differences were seen in platelet accumulation scores or parameters of lung injury. Conclusion. Beraprost sodium, an antiplatelet agent, reduces platelet accumulation and preservation-reperfusion injury of lung transplants at 6 hr in this rat isograft model.

  • A stable prostacyclin analog, Beraprost sodium, attenuates platelet accumulation and preservation-reperfusion injury of isografts in a rat model of lung transplantation.
    Transplantation, 1998
    Co-Authors: Yoshinori Okada, Alberto M Marchevsky, Robert M Kass, Jack M Matloff, Stanley C Jordan
    Abstract:

    Background. Recent studies have shown that the extent of platelet accumulation in the vasculature of transplanted organs correlates with the degree of preservation-reperfusion injury. In this study, we examined the effect of a stable prostacyclin analog, Beraprost sodium, which possesses potent antiplatelet activity, on parameters of platelet accumulation and preservation-reperfusion injury of isografts in a rat model of lung transplantation. Methods. The heart-lung blocks of donor rats were flushed with and preserved in modified Euro-Collins solution at 4°C for 6 hr or 24 hr. The left lung was transplanted into recipient rats and reperfused for 1 hr. Lung injury was evaluated by the pulmonary blood flow ratios to the lung isografts, the weight gain of the isografts, and histological examination. Small portions of the lung isografts were excised and stained with an antibody specific for rat platelets. A scoring system was developed to semiquantitate the intensity of antibody staining (score 0-4). The recipient rats received oral administration of Beraprost sodium (0.3 mg/kg) before lung transplantation. Control animals received no Beraprost sodium. Results. In the 6-hr preservation study, administration of Beraprost sodium significantly reduced the score for platelet accumulation (1.8±0.4 vs. 3.3±0.5, P