Biomedical subjects

T Genda

Publications and source records attributed to T Genda.

At least 19 recordsLinked to original sources

PubMed2001

Improved survival with oral administration of enteric-coated tegafur/uracil for advanced stage IV-A hepatocellular carcinoma.

BACKGROUND AND AIMS: There is currently no proven chemotherapy regimen for hepatocellular carcinoma (HCC). The principal chemotherapeutic approach in most cases is infusion therapy into the hepatic arteries feeding the tumors. However, the clinical effects of chemotherapy are extremely poor. Therefore, in the present study, we conducted a prospective randomized trial of the efficacy of oral administration of enteric-coated tegafur/uracil for advanced HCC. METHODS: From 1994 to 1999, a total of 56 consecutive patients with unresectable stage IV-A HCC were studied prospectively to examine the efficacy of enteric-coated tegafur/uracil in HCC and to determine the significant prognostic factors. Twenty-eight patients were treated only with enteric-coated tegafur/uracil without other anticancer treatment. Another 20 patients were given conservative management only. The remaining eight patients withdrew from the study. RESULTS: In the group treated only with enteric-coated tegafur/uracil, the median survival time and 1 and 2 year survival rates were 12.13 months and 55.3 and 36.9%, respectively. In the control group, the median survival time and 1 year survival rate were 6.20 months and 5.5%, respectively. By both univariate analysis and multivariate analysis using Cox's proportional hazards model, treatment with enteric-coated tegafur/uracil was shown to be the factor most significantly favoring a better prognosis. CONCLUSIONS: Although the prognosis of most patients with stage IV-A HCC is poor, administration of enteric-coated tegafur/uracil induces long-term survival and is an effective treatment for stage IV-A HCC.

Administration, Oral↗

PubMed2001

Inhibition of intrahepatic metastasis of human hepatocellular carcinoma by Rho-associated protein kinase inhibitor Y-27632.

Intrahepatic metastasis is one of the most important prognostic factors for patients with hepatocellular carcinoma (HCC). Cell motility mediated by Rho- and p160 Rho-associated coiledcoil forming protein kinase (p160ROCK) signaling pathways has recently been shown to play a critical role in intrahepatic metastasis in human HCC. Furthermore, the stable introduction of dominant-negative p160ROCK into Li7 cells resulted in a reduced metastatic rate in mice with severe combined immunodeficiency (SCID). To investigate whether the specific p160ROCK inhibitor, Y-27632, could also inhibit intrahepatic metastasis, the effect of Y-27632 on the cell motility and intrahepatic metastasis of Li7 was investigated. Y-27632 markedly blocked actin reorganization and motility of Li7 cells mediated by lysophosphatidic acid (LPA). Y-27632 was administered continuously into the peritoneal cavity using a micro-osmotic pump, together with orthotopic implantation of Li7 cells into the liver of SCID mice. Phosphate-buffered saline (PBS) alone was administered as the control. The incidence of mice with metastatic nodules decreased in the Y-27632-treated group. The primary tumor volume at the site of injection was smaller in the Y-27632-treated group compared with the control group, but the difference was not statistically significant. Histologically, control tumors showed infiltrative growth into the sinusoidal area at the tumor boundary, whereas Y-27632-treated tumors showed expansive growth and low invasiveness. These findings confirm the importance of the Rho/p160ROCK signaling pathway in intrahepatic metastasis of human HCC, and indicate that Y-27632 may be useful for the prevention of intrahepatic metastasis of human HCC.

Actins↗

PubMed2001

Involvement of c-Src in carcinoma cell motility and metastasis.

Carcinoma cells exhibit dysfunction / dysregulation of cell adhesion systems that correlates with their abilities to migrate, invade, and metastasize. Here we show that the tyrosine kinase c-Src is required for motility and metastasis of two carcinoma cell lines. Adherent KYN-2 cells having a high level of c-Src kinase activity become scattered, extend lamellipodia, and exhibit high motility. Expression of a dominant-negative mutant form of c-Src caused formation of stress fibers and focal adhesions, and markedly reduced motility. HCT15 cells extended lamellipodia and became scattered in response to lysophosphatidic acid stimulation in parallel with transient activation of c-Src, which was inhibited by expression of a dominant-negative mutant form of c-Src or treatment with a specific Src kinase inhibitor. Furthermore, implantation of dominant-negative c-Src transfectants into the peritoneal cavity of SCID mice resulted in reduced peritoneal dissemination compared with control transfectants. These findings indicate that c-Src activation is critically involved in carcinoma cell migration and metastasis.

Adenocarcinoma↗

PubMed2000

Loss of cell-cell contact is induced by integrin-mediated cell-substratum adhesion in highly-motile and highly-metastatic hepatocellular carcinoma cells.

The cadherin-mediated cell-cell adhesion system plays a critical role in normal development and morphogenesis. Inactivation of this system is thought to be responsible for cancer invasion and metastasis. A human hepatocellular carcinoma (HCC) cell line, KYN-2, was observed to have great potential for intrahepatic metastasis when orthotopically implanted into the liver of SCID mice. In vitro cultures of KYN-2 cells showed that they formed trabecular structures in suspension but lost tight cell-cell adhesion and became scattered when attached to a substratum such as collagen or fibronectin. In response to adhesion to the substratum, subcellular colocalization of E-cadherin and actin filaments were shown to be reduced, and a significant amount of alpha-catenin was dissociated from the E-cadherin-catenin complex in KYN-2 cells. These changes of cell-cell adhesion were blocked by inhibitory monoclonal antibodies against beta1 and beta5 integrins. We found that c-Src was coimmunoprecipitated with E-cadherin-catenin complex and was tyrosine-dephosphorylated and activated in the adherent cells. The tyrosine dephosphorylation of c-Src was induced by cell adhesion to the substratum and inhibited by addition of inhibitory monoclonal antibodies against beta1 and beta5 integrins. These findings indicate that integrin-mediated cell-substratum adhesion inhibits cadherin-mediated cell-cell adhesion, possibly through c-Src activation, and suggest that this cross-talk mediates transient inactivation of the cadherin system and plays an important role in intrahepatic metastasis of human HCC. Modulation of this interaction might provide a new approach to prevent metastasis and recurrence of HCC.

CSK Tyrosine-Protein Kinase↗

PubMed2000

Margin clearance and HPV infection do not influence the cure rates of early neoplasia of the uterine cervix by laser conization.

A lesion existing in the endocervical and/or ectocervical conized margin and HPV-DNA existing in a conized specimen are reported to be at risk of persistence or recurrence of early neoplasia of the cervix when treated by conization. The aim of this study was to investigate whether margin clearance and HPV infection influenced the outcome in our series of laser conization. Excisional conization with the KTP/YAG Surgical Laser System or Nd-YAG laser was performed in this study. Eighty patients with cervical neoplasias were included: 47 with dysplasia, 25 with carcinoma in situ (CIS) and eight with microinvasive carcinoma. The endocervical and ectocervical conized margins were examined microscopically. HPV-DNA was analyzed with the primer for types 16, 18, 31, 33, 35, 52b and 58 amplified by the PCR method. The margins of the conized specimens were confirmed histopathologically to be clear in 58 cases (73%), whereas in 22 cases (27%) they were involved by neoplasia. HPV-DNA was positive in 38% of dysplasias, 40% of CISs and 50% of microinvasive carcinomas. The overall rate of the initial cure at 10 weeks after treatment appeared to be 100% in all 80 cases. Primary cure rates were 100% for 47 cases with dysplasia, 96% for 24 cases with CIS and 100% for four cases with microinvasive carcinoma regardless of margin positivity and HPV-DNA status. Involved margins and HPV infection did not influence the cure of early neoplasia of the uterine cervix achieved by our laser conization procedure. The favorable results may be due to the procedure of vaporizing the cut surface forming a dome-shaped tissue defect.

Conization↗

PubMed1999

Cell motility mediated by rho and Rho-associated protein kinase plays a critical role in intrahepatic metastasis of human hepatocellular carcinoma.

Human hepatocellular carcinoma (HCC) can invade the portal vein and metastasizes to other parts of the liver even at a relatively early stage of the disease, with less tumor spread occurring outside the liver. This intrahepatic metastasis is the main cause of liver failure and death in HCC patients. To analyze the mechanisms of intrahepatic metastasis we have constructed metastatic models using orthotopic implantation of human HCC cell lines. Five HCC cell lines formed liver tumors after injection into the livers of SCID mice, and of those 5 cell lines, Li7 and KYN-2 cells also resulted in vascular tumor thrombi and intrahepatic metastasis. These 2 cell lines had markedly higher cell motilities than the other 3 cell lines in vitro. Their motilities appeared to be Rho-mediated; serum and lysophosphatidic acid (LPA) evoked actin reorganization and motility of Li7 cells, and C3 exoenzyme exposure reduced the motility of both serum-stimulated Li7 cells and KYN-2 cells. Dominant negative and active forms of p160 Rho-associated coiled-coil forming protein kinase (p160ROCK), one of the downstream effectors of Rho, were separately and stably introduced into Li7 cells. Dominant active p160ROCK transfectants showed increased motility that was independent of serum and LPA, and dominant negative p160ROCK transfectants showed reduced motility under stimulation. Furthermore, implantation of dominant negative p160ROCK transfectants resulted in a reduced metastatic rate in vivo compared with the parent cells or a control transfectant. These findings indicate that cell motility mediated by the Rho/p160ROCK signaling pathway plays a critical role in intrahepatic metastasis of human HCC.

ADP Ribose Transferases↗

PubMed1999

Beta-catenin accumulation and mutation of exon 3 of the beta-catenin gene in hepatocellular carcinoma.

A study was conducted to clarify the contribution of beta-catenin accumulation and mutation of the beta-catenin gene to hepatocarcinogenesis. Beta-catenin accumulation was examined immunohistochemically in 38 paired samples of hepatocellular carcinoma (HCC) and corresponding non-cancerous liver tissue. Gene mutation was analyzed by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and direct sequencing using intronic primers encompassing exon 3. Neither accumulation nor mutation was detected in non-cancerous liver tissues that showed no remarkable histological features, chronic hepatitis or liver cirrhosis. Accumulation of beta-catenin was seen in the nucleus, cytoplasm or cell membrane in 15 of 38 (39%) HCC samples, and gene mutation was seen in 9 of 38 (24%) HCC samples. Although there was a significant correlation between accumulation and mutation (P<0.01), six HCCs without mutation also showed accumulation. Samples of early HCC showed neither accumulation nor mutation, and accumulation and mutation were each correlated significantly with portal vein tumor involvement (P<0.05). The present results indicate that (1) mutation of exon 3 of the beta-catenin gene can lead to beta-catenin accumulation, although other mechanisms of accumulation may also operate in HCC, and (2) beta-catenin accumulation and mutation of the beta-catenin gene are not early events in hepatocarcinogenesis, and may be associated with the malignant progression of HCC.

Adult↗

PubMed1998

Hyperplastic foci reflect the risk of multicentric development of human hepatocellular carcinoma.

BACKGROUND/AIMS: Identification of the risk factors of multicentric hepatocarcinogenesis is important for the clinical management of hepatocellular carcinoma. We investigated hyperplastic foci in non-cancerous liver parenchyma, and clarified their pathological features and clinical significance. METHODS: Hyperplastic foci were defined as hypercellular areas, which architecturally and cytologically resembled early hepatocellular carcinoma or adenomatous hyperplasia but did not form macroscopically detectable nodules. Surgically resected livers from 155 patients with hepatocellular carcinoma were examined histopathologically and immunohistochemically. RESULTS: Hyperplastic foci were found in 26 of 155 patients (16.8%). All the patients with hyperplastic foci had chronic liver diseases, and the incidence did not differ between those with chronic hepatitis and those with liver cirrhosis. Six of 92 (6.5%) patients with single primary hepatocellular carcinoma nodules, 8 of 42 (19.0%) with two nodules, and 12 of 21 (57.0%) with more than three nodules had hyperplastic foci. The incidence of hyperplastic foci showed a significant positive correlation with the multiplicity of hepatocellular carcinoma nodules. Immunohistochemically, hyperplastic foci were masses of proliferative hepatocytes similar to adenomatous hyperplasia and early hepatocellular carcinoma. CONCLUSIONS: Hyperplastic foci reflect the risk of multicentric hepatocarcinogenesis. Our results suggest strongly that hyperplastic foci are precursors of adenomatous hyperplasia or hepatocellular carcinoma.

Adult↗

PubMed1998

[The effects of sevoflurane, isoflurane or enflurane on the pattern of phrenic nerve discharge in rabbits].

In order to estimate primary action of anesthetic agents on the central neural mechanisms of respiratory control and the ventilatory response to an acute increased ETCO2, the effect of sevoflurane (SEV), isoflurane (ISO) or enflurane (ENF) on the pattern of phrenic nerve discharge (Phr.N.A.) was studied in adult rabbits which had been vagotomized, paralyzed and ventilated artificially with 100% oxygen. Throughout the course of experiment, ETCO2 and the rectal temperature of animals were maintained around physiological values. Depressant effects of these anesthetics on Phr. N.A. which consisted of inspiratory slope (SLO), peak amplitude (AMP), inspiratory (Ti) and expiratory (Te) time, I/E ratio (I/E) and respiratory cycle (Tc) were evaluated and compared with each anesthetic. At 0.5 MAC administration, SEV and ISO reduced SLO and AMP without a remarkable change in Tc, but ENF did with a prolongation in Tc. Inhalation of each anesthetic with 1 MAC caused a marked respiratory slowing with a more reduction of SLO and AMP than those occurred at 0.5 MAC; SEV increased Te more than Ti, but ENF prolonged Ti more than Te, while ISO enhanced both Ti and Te without any change of I/E. An acutely increased ETCO2 after the respiratory arrest (RA test) induced the change of Phr.N.A which was characterized by a marked prolongation in Tc with a prolonged Te, an increased SLO and an augmented AMP. The prolonged Tc induced by RA test was diminished by the inhalation of anesthetics, and a new response, shortening in Ti was produced by ENF and ISO. Based on these results, it might be concluded that there are both quantitative and qualitative differences in these anesthetic effects on the central pattern generator of respiration and the mechanism of CO2 responses at equipotent anesthetic concentrations.

Action Potentials↗

PubMed1997

Intravascular ultrasound findings after successful primary angioplasty for acute myocardial infarction: predictors of abrupt occlusion.

OBJECTIVES: This study sought to evaluate the intravascular structure as depicted by intravascular ultrasound after successful primary angioplasty (i.e., without thrombolytic therapy) for acute myocardial infarction and to investigate the related predictors of acute coronary occlusion. BACKGROUND: The usefulness of primary angioplasty for acute myocardial infarction is still limited by early reocclusion. There are few data regarding the intravascular ultrasound findings after primary angioplasty. METHODS: Intravascular ultrasound was performed in 27 patients after successful primary angioplasty. Repeat coronary angiography was performed 15 min later, on the following day and 1 month after angioplasty. RESULTS: Abrupt occlusion occurred in 8 of 27 patients. Angiographic variables in patients with versus those without abrupt occlusion were not significantly different. Intravascular ultrasound disclosed a significantly smaller lumen area ([mean +/- SD] 2.49 +/- 0.72 vs. 5.06 +/- 1.52 mm2, p < 0.001) and a significantly greater percent plaque area (80.5 +/- 9.1% vs. 63.7 +/- 7.8%, p < 0.001) in patients with abrupt occlusion. There was no significant difference in external elastic membrane cross-sectional area. We classified the ultrasound appearance of the intravascular structure as smooth, irregular or filled. Abrupt occlusion occurred in none of 6 patients with a smooth intravascular structure, 24% of 17 patients with an irregular structure and in all 4 with a filled structure (p < 0.05). In the latter group, the lumen was filled with bright speckled or low echogenic material, although angiography revealed excellent coronary dilation in all these arteries. CONCLUSIONS: Intravascular ultrasound revealed a narrow lumen in coronary arteries showing abrupt occlusion after successful primary angioplasty, even though angiography disclosed successful dilation. Arteries with a lumen filled with bright speckled or low echogenic material frequently develop abrupt occlusion.

Aged↗

PubMed1996

Fetal circulatory responses during maternal bleeding.

The purpose of this study was to investigate the fetal circulatory responses during maternal hemorrhage. Five pregnant goats with fetuses with a mean gestational age of 132 +/- 2 days were used. The maternal blood was withdrawn at 350 ml/h for 2 hours (e.g. 700 ml, 11.9 ml/kg maternal weight) and reinfused at the same speed. During maternal bleeding, maternal arterial pressure (MAP) gradually decreased. As a result of this maternal hypotension, fetal arterial pO2 and pH decreased, and PCO2 increased. After the reinfusion, fetal pO2 recovered but pH and PCO2 did not recover. Fetal arterial pressure (FAP) increased and heart rate (FHR) decreased during maternal bleeding and returned to the control level, after the reinfusion. Fetal arginine vasopressin (AVP) concentration increased to 401.2 +/- 318.5 pg/ml at the maximum bleeding. There were significant positive correlation between AVP concentration and FAP, and negative correlation between AVP and FHR during maternal bleeding. Therefore, we concluded that 700 ml maternal bleeding for 2 hours resulted the decrease in fetal pH, pO2, and FHR, and increase in PCO2, FAP, and AVP concentration. Fetal pH, PCO2, and AVP did not return to the control level in spite of reinfusion.

Animals↗

PubMed1996

[Comparison of fetal circulatory responses during maternal bleeding and fetal bleeding].

The purpose of this study was to compare the fetal circulatory responses during maternal hemorrhage and fetal hemorrhage. Four pregnant goats, gestational age 131 +/- 7 days for the fetal hemorrhage and 5 goats, 132 +/- 2 days (term 145 days) for the maternal hemorrhage were used. The amounts of hemorrhage were 700ml per 2 hours for the maternal hemorrhage and 40ml per 2 hours for the fetal hemorrhage. Although fetal arterial pH decreased during both hemorrhages, fetal arterial pO2 increased during the fetal hemorrhage and decreased in the maternal hemorrhage. The fetal arginine vasopressin concentration and plasma renin activity increased during both hemorrhages, but the rates of change in the hormone concentrations were higher during the fetal hemorrhage. The fetal aldosterone concentration decreased during maternal hemorrhage but increased during fetal hemorrhage. FAP increased and FHR decreased during maternal hemorrhage. FAP and FHR were significantly correlated to the AVP concentration. These relationships were not found during fetal hemorrhage. We therefore concluded that fetal responses were completely different in pO2, FAP and FHR during the maternal and fetal hemorrhages.

Aldosterone↗

PubMed1995

Non-secretory alpha chain disease involving stomach, small intestine and colon.

A case of alpha chain disease, involving stomach, small and large intestine, and caecum with poor prognosis is reported. Endoscopic examination revealed gastric erosion, edematous mucosa with enlarged villi of duodenum and jejunum, multiple hyperplastic lymph follicles of terminal ileum and thickening mucosa of caecum. Light microscopy revealed a conspicuous infiltration of plasma cells and lymphocytes in gastric, duodenal, jejunal and caecal lamina propria. Immunohistochemistry demonstrated alpha heavy chain protein devoid of light chain in these plasma cells. The patient developed paralytic ileus and died of septic shock on the 179th hospital day.

Colon↗

PubMed1995

[Halothane reduces the inhibition of dorsal horn lamina V type neuronal activity induced by bradykinin injection into the femoral artery contralateral to the recording site].

Effect of halothane (0.2%, 0.5%, and 1.0%) on spinal function were studied in lamina V type cells responding to noxious and light touch applied at their cutaneous receptive field on the foot pad of the left hind paw. Extracellular unit activities of lamina V type cells were recorded at the lumbar level in six cats and thirteen spinal cats. When intra-arterial injection of bradykinin (BK) 10 micrograms into the femoral artery ipsilateral to the recording sites was used as the noxious test stimuli, six of these cells (100%) were found to have inhibitory response in six intact cats and thirteen of these cells (100%) were found to have excitatory response in thirteen spinal cats. On the other hand, when the injection of 10 micrograms into the femoral artery contralateral to the recording sites was used as the noxious test stimuli, six of these cells (100%) were found to have inhibitory response in six intact cats and six of these cells (46%) were found to have inhibitory response in thirteen spinal cats. We studied the effect of halothane on the inhibition induced by BK injection into the femoral artery contralateral to the recording sites in six intact cats and six spinal cats. Halothane 0.2%, 0.5% and 1.0% reduced the inhibition of dorsal horn lamina V type neuronal activity induced by BK injection.

Animals↗

PubMed1994

[Effect of isoflurane on spinal dorsal horn WDR neuronal activity in cats].

The effects of isoflurane (0.5% and 1.5%) on the spinal dorsal horn wide dynamic range (WDR) neuronal activity were studied in either spinal cord intact or spinal cord-transected cats. Extracellular activity was recorded in the dorsal horn from single WDR neurons responding to noxious and non-noxious stimuli applied to the cutaneous receptive fields on the left hind foot pads of intact or decerebrate, spinal cord transected (L1-2) cats. When bradykinin (BK) 10 micrograms was injected into the femoral artery ipsilateral to the recording site as the noxious test stimulus in the spinal cat, all of 17 WDR neurons gave excitatory responses which were not depressed by 0.5% isoflurane but were depressed significantly by 1.5%. On the other hand, when the injection of BK 10 micrograms into the femoral artery ipsilateral to the recording site was used in the intact cat, 13 of 24 WDR neurons (54%) gave excitatory responses, which were significantly depressed by 0.5% and 1.5% isoflurane, and 11 of 24 WDR neurons (46%) gave inhibitory responses, which were significantly depressed by 0.5% and 1.5% isoflurane. We have found that isoflurane reduces the excitation as well as the inhibition of dorsal horn WDR neuronal activity induced by BK injection.

Action Potentials↗

PubMed1993

[Effects of sevoflurane on spinal dorsal horn WDR neuronal activity in cats].

The effects of sevoflurane (S) (0.5%, 1.5%, and 2.5%) on the spinal dorsal horn wide dynamic range (WDR) neuronal activity were studied in either spinal cord intact or spinal cord transected cats. Extracellular activity was recorded in the dorsal horn from single WDR neurons responding to noxious and non-noxious stimuli applied to the cutaneous receptive fields on the left hind paw foot pads of intact or decerebrate and spinal cord transsected (L1-2) cats. When BK 10 micrograms was injected into the femoral artery ipsilateral to the recording site as the noxious test stimulus in the spinal cat, 7 of 8 WDR neurons gave excitatory responses which were not depressed by sevoflurane 0.5% and 1.5% but were depressed significantly by 2.5%. On the other hand, when BK 10 micrograms was injected into the femoral artery ipsilateral to the recording site in the intact cat, 6 of 13 WDR neurons (46%) gave excitatory responses, which were significantly depressed by sevoflurane 0.5%, 1.5% and 2.5%, and 7 of 13 WDR neurons (54%) gave inhibitory responses, which were significantly depressed sevoflurane at 0.5%, 1.5%, and 2.5%. In conclusion, we have found that sevoflurane reduces the excitation as well as the inhibition of dorsal horn WDR neuronal activity induced by BK injection.

Animals↗

PubMed1991

[Effects of halothane on spinal dorsal horn WDR(wide dynamic range) neuronal activity in cats].

The effects of halothane (0.2%, 0.5%, and 1.0%) on the spinal dorsal horn wide dynamic range (WDR) neuronal activity was studied in either spinal cord intact or spinal transected cats. Extracellular activity was recorded in the dorsal horn from single WDR neurons responding to noxious and non-noxious stimuli applied to the cutaneous receptive fields on the left hind foot pads of intact or decerebrate, spinal cord transected (L 1-2) cats. When 10 micrograms of bradykinin was injected into the femoral artery ipsilateral to the recording site as the noxious test stimulus in the spinal cat, all of 7 WDR neurons gave excitatory responses which were not depressed by 0.2% and 0.5% halothane but were depressed significantly by 1.0%. On the other hand, when the injection of 10 micrograms of bradykinin into the femoral artery ipsilateral to the recording site was used in the intact cat, 7 of 14 WDR neurons (50%) gave excitatory responses, which were not depressed by 0.2% halothane but were significantly depressed by 0.5% and 1.0% halothane, and 7 of 14 WDR neurons (50%) gave inhibitory responses, which were significantly depressed by 0.2%, 0.5%, and 1.0% halothane. We have found that halothane reduces the excitation as well as the inhibition of dorsal horn WDR neuronal activity induced by bradykinin injection.

Animals↗

PubMed1991

[Effects of prostaglandins on pulmonary circulation].

Effects of prostacyclin (PGI2) and thromboxane A2 (TxA2) on pulmonary circulation and pulmonary edema were studied in 24 dogs. The heart and lungs were provided with an autoperfusion circulation. Mean aortic pressure and cardiac output were maintained at 80 mmHg and 40 ml.kg-1.min-1, respectively. The animals were divided evenly into 4 groups: group 1, control; group 2, PGI2-analog loaded; group 3, TxA2-analog loaded; and group 4, TxA2-antagonist loaded. The heart-lung tissues were autoperfused for 4 hours. During the experimental period, respiratory parameters (PaCO2 and PaO2) showed no significant change, but significant elevations of mean pulmonary arterial pressure and mean left atrial pressure were observed in group 3. The radiological pulmonary dilution curve changed significantly during autoperfusion. The half-life and the mean transit time were both prolonged significantly in groups 1, 3 and 4, but unchanged in group 2. Characteristic pathological pulmonary vascular changes, intravascular leukocyte sequestration, capillary dilatation and perivascular edema were observed in groups 1 and 3. Those changes were attenuated in group 4 and prevented in group 2. In conclusions, pulmonary circulation was impaired by TxA2, whereas maintained by PGI2. These findings show that TxA2 and PGI2 may modify blood-vessel interaction, and organ damage may occur in the case of TxA2 and organ may be preserved in the case of PGI2.

Animals↗