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91.
Shuzo Oshita Yoshiki Fujiwara Hisashi Tamura Takefumi Sakabe Hiroshi Takeshita 《Journal canadien d'anesthésie》1994,41(6):534-541
To gain a better understanding of the direct actions of halothane on myocardial function in ischaemia, we studied the effects
of increasing extracellular potassium concentration and decreasing extracellular pH (acidosis), alone or in combination with
halothane, on the contractile force and resting tension in isolated atria. Guinea pig left atria were superfused with Tyrode’s
solution and stimulated at 1 Hz. Isometric contractile force and resting tension were measured using a force displacement
transducer. Perfusate potassium concentrations were increased from 5.4 mmol · L−1 to either 8.1 mmol · L−1 or 10.8 mmol · L−1 by adding KCl to the standard Tyrode’s solution, and its pH was decreased from 7.4 to either 7.0 or 6.5 by decreasing bicarbonate.
In standard Tyrode’s solution (potassium 5.4 mmol · L−1, pH 7.4), halothane 0.5–2% reduced contractile force in a dose-dependent manner (P < 0.05); the effective concentration of
halothane for 50% inhibition of contractile force (IC50) was 1.3%. Both increasing extracellular potassium and decreasing extracellular pH decreased the contractile force in a potassium-or
pH-dependent fashion. The negative inotropism of halothane (1%) was not altered by increasing potassium concentrations, whereas
1% halothane caused a greater decrease in contractile force at pH 6.5 than at pH 7.4. Halothane (1%) enhanced the acidosis
(pH 6.5)-induced increases in resting tension. Arrhythmias were produced in one of eight preparations during acidosis, while
four of eight preparations demonstrated arrhythmias during acidosis in the presence of halothane. These data suggest that
acidosis and halothane may have a synergistic interaction on the contractile force and resting tension of the atria. The increase
in resting tension observed during acidosis/ halothane conditions suggests than an increase in cytosolic calcium is associated
with these synergistic interactions between acidosis and halothane.
Pour mieux comprendre l’action direct de l’halothane sur la fonction myocardique pendant l’ischémie, nous avons étudié les
effets de l’augmentation du potassium extracellulaire et de la diminution du pH extracellulaire (acidose), seuls ou en association
avec l’halothane, sur la force contractile et la tension de repos d’oreillettes isolées. Des oreillettes gauches de cobaye
furent perfusées avec une solution de Tyrode et stimulées à 1 Hz. La force contractile isométrique et la tension de repos
ont été mesurées avec un transducteur de force de déplacement. Les concentrations de potassium perfusées ont été augmentées
de 5,4 mmol · L−1 à 8,1 mmol · L−1 ou à 10,8 mmol · L−1 par l’ajout de KCl à la solution standard de Tyrode, et son pH abaissé de 7,4 à 7,0 ou 6,5 par baisse des bicarbonates. Avec
la solution standard de Tyrode (potassium 5,4 mmol · L−1, pH 7,4), l’halothane (0.5–2%) diminue la force contractile proportionnellement à la dose (P < 0,05); la concentration efficace
d’halothane requise pour produire une inhibition de 50% de la force contractile (IC5O) a été de 1,3%. L’augmentation du potassium extracellulaire et la diminution du pH extracellulaire réduisent toutes les deux
la force contractile proportionnellement au potassium ou au pH. L’inotropisme négatif de l’halothane (1%) n’est pas modifié
par l’augmentation de la concentration de potassium alors que l’halothane produit une diminution plus importante de la force
contractile à un pH de 6,5 que de 7,4. L’halothane (1%) exagère l’augmentation de la tension de repos induite par l’acidose
(pH 6,5). Des arrythmies sont apparues sur une des huit préparations pendant l’acidose en présence d’halothane. Ces données
suggèrent que l’acidose et l’halothane pourraient avoir une activité synergique sur le force contractile et la tension de
repos des oreillettes. L’augmentation de la tension de repos observée pendant l’acidose combinée à l’halothane suggère l’association
d’une augmentation du calcium cytosolique avec des interactions synergiques entre l’acidose et l’halothane. 相似文献
92.
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94.
Matsumoto G Sunamura M Shimamura H Kodama T Hashimoto W Kobari M Kato K Takeda K Yagita H Okumura K Hamada H Matsuno S 《Surgery》1999,125(3):257-264
BACKGROUND: To explore effective therapeutic strategy against cancer of the gastrointestinal tract, tumor vaccination using fibroblasts secreting interleukin-12 (IL-12) was developed as an adjuvant therapy against murine tumor after surgical resection. METHODS: Initially, IL-12 was genetically engineered into fibroblasts (IL-12/3T3 cells), and then we evaluated in vivo and in vitro antitumor effects. In the vaccination model, irradiated C-26 tumor mass was reinoculated intradermally with IL-12/3T3 cells in mice as a tumor vaccine to examine how much it suppresses tumor recurrence. RESULTS: IL-12/3T3 cells producing 7.2 ng/10(6) cells/24 h murine IL-12 in vitro exerted dose-dependent potent tumor suppression when coinoculated with C-26 cells in vivo. Specific immunity was also acquired in 63% of mice in vivo. In the vaccination model, protective immunity was developed in 70% of mice that were inoculated with irradiated tumor mass and IL-12/3T3 cells. In addition, local recurrence was not observed in vaccinated mice, although 44% of control mice had recurrence. CONCLUSIONS: Coinoculation of genetically engineered fibroblasts secreting IL-12 with irradiated tumor mass was proved to be an effective tumor vaccine. This system of vaccination is easily applicable to clinical situations, particularly to human gastrointestinal tract cancers. 相似文献
95.
Key words cardiac arrhythmias - oxygen uptake - carbon dioxide elimination 相似文献
96.
97.
Kazuhiro Takahashi Yoshiki Mori Hideshi Yamamura Toshio Nakanishi Makoto Nakazawa 《Pediatrics international》2003,45(6):671-675
OBJECTIVE: Although long-term prostacyclin(PGI2) therapy in patients with severe pulmonary hypertension (PH)reduces pulmonary vascular resistance (PVR), there have been no reports on its therapeutic effects in patients with mild PH. We investigated the chronic effect of beraprost sodium (BPS), an oral PGI2 analog, in children with mild PH. METHODS: We studied 20 patients who were destined for a Fontan procedure with a mean pulmonary arterial pressure(PAP) of>20 mmHg and/or PVR of>3.0 Wood units. Both the PAP and the PVR in these cases were too high for patients to undergo a successful Fontan procedure. Seven patients received BPS (PG group) and 13 did not (control group). All patients underwent repeat cardiac catheterization to examine pulmonary hemodynamics. RESULTS: In the PG group, the pulmonary-to-systemic flow ratio (Qp/Qs) did not change after BPS administration(1.1 +/- 0.6 vs 1.3 +/- 0.9);however, the mean PAP decreased significantly (25.3 +/- 8.2 vs 19.9 +/- 6.5 mmHg; P < 0.05),as did PVR (3.7 +/- 1.3 vs 2.3 +/- 0.9 Wood units; P < 0.05), whereas the pulmonary artery (PA) index increased significantly (312 +/- 136 vs 375 +/- 165; P < 0.05). In the control group, the mean PAP decreased significantly (24.9 +/- 4.7 vs 19.8 +/- 6.3 mmHg; P < 0.05)and the PA index increased significantly (295 +/- 72 vs 362 +/- 114; P < 0.05). No significant changes in Qp/Qs (1.5 +/- 0.8 vs 1.4 +/- 0.6)or PVR (2.9 +/- 1.3 vs 2.5 +/- 0.8 Wood units) were observed. CONCLUSION: We conclude that long-term BPS administration probably reduces PVR in potential candidates for a Fontan procedure with mild PH. This treatment would reduce the risks associated with the Fontan procedure and would also improve its outcome. 相似文献
98.
Induction of unresponsiveness to islet xenograft by MMC treatment of graft and blockage of LFA-1/ICAM-1 pathway 总被引:7,自引:0,他引:7
Grochowiecki T Gotoh M Dono K Takeda Y Sakon M Yagita H Okumura K Miyasaka M Monden M 《Transplantation》2000,69(8):1567-1571
BACKGROUND: Induction of unresponsiveness to graft is one of major interest in xenotransplantation. Two different modalities [direct graft treatment by mitomycin C (MMC) and blockage of the lymphocyte function-associated antigen-1/intracellular adhesion molecule-1 (LFA-1/ICAM-1) pathway in recipients by species-specific mAbs] were tested for their ability to produce unresponsiveness to secondary islet xenografts. METHODS: Collagenase-digested WS (RT1k) rat islets, purified by Ficoll density gradient, were incubated for 30 min with MMC 10 microg/ml, cultured for 20 hr, and transplanted into the renal subcapsular space of streptozotocin-induced diabetic C57BL/6 (H-2b) mice. Recipient mice were divided into experimental groups according to anti-rat ICAM-1 and/or anti-mouse LFA-1 mAb treatment and transplantation of MMC-treated or nontreated islets. RESULTS: MMC pretreatment alone prolonged graft survival, with a mean survival time (MST) of 23.0+/-7.4 days, compared with that of cultured islets (12.4+/-2.7 days; P<0.01). MMC treatment of islets significantly augmented graft survival, compared with that of crude islet grafts under treatment with anti-donor ICAM-1 mAb (MST: >41.3+/-30 vs. 16.6+/-5.4 days, P<0.01), anti-recipient LFA-mAb (MST: >70.3+/-28.9 vs. 30.4+/-10.4 days, P<0.001), or both mAbs (MST: >88.1+/-24.1 vs. 23+/-7.4 days, P<0.0001). One of six, four of nine, and six of eight animals accepted MMC-treated islet xenografts over 100 days after treatment with anti-rat ICAM-1, anti-mouse LFA-1, or both mAbs treatments, respectively, whereas none of the animals accepted nontreated islets under the same treatment. When the mice bearing long-term functioning xenografts were challenged with the secondary graft from the original donor strain, the animals previously treated with anti-recipient LFA-1 and anti-donor ICAM-1 mAbs were more prone to accept it than animals given anti-recipient LFA-1 mAb alone (MST: 55.8+/-25.7 vs. 15+/-2.4 respectively; P<0.001), although they rejected the third-party xenograft and allograft acutely. CONCLUSIONS: In the xenogeneic islet transplantation model, MMC graft pretreatment and blockage of the ICAM-1/LFA-1 pathway constitute a potent protocol for inducing unresponsiveness to islet xenografts. 相似文献
99.
100.