Biomedical subjects

Koshi Matsumoto

Publications and source records attributed to Koshi Matsumoto.

At least 19 recordsLinked to original sources

PubMed2006

Novel application of ProteinChip technology exploring acute rejection markers of rat small bowel transplantation.

BACKGROUND: Because no biomarker that reflects small bowel allograft rejection is available, we applied surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) to develop noninvasive markers required for routine diagnosis. METHODS: Heterotopic small bowel transplantation (SBT) was performed in rats, and they were divided into four experimental groups: sham-operated rats (sham), syngeneic transplants (syngeneic), allogeneic transplants (allogeneic), allogeneic transplants received FK506 (allo+FK). Plasma samples were analyzed with SELDI ProteinChip arrays to detect peaks that predominated in the allogeneic model. Possible biomarkers were identified in combination with SELDI retentate chromatography mass spectrometry (RCMS) and matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). The identified protein was further analyzed by immunohistochemistry. RESULTS: An increase in the level of a 14.8-kDa protein, identified as lysozyme, was observed specifically in the plasma of the allogeneic group; the levels of this protein remained unchanged in the plasma of the other groups. On the other hand, the levels of a 10.1-kDa and a 13.0-kDa protein, identified as migration inhibitory factor-related proteins (MRP), MRP-8 and MRP-14, respectively, began to increase from an early stage of acute rejection. We also observed that lysozyme-positive macrophages had strongly infiltrated the lamina propria during acute rejection. CONCLUSIONS: We identified three plasma proteins-MRP-8, MRP-14, and lysozyme-that increased during small bowel allograft rejection. The identified proteins appeared to be markers for inflammation associated with allograft rejection. This proteomic approach will be useful for the identification of candidate biomarkers.

Amino Acid Sequence↗

PubMed2006

Effect of the free radical scavenger MCI-186 on pulmonary ischemia-reperfusion injury in dogs.

BACKGROUND: Free radical scavengers and superoxide dismutase have been found to protect against cerebral ischemic damage, and it was suggested that oxygen free radicals contribute to ischemia-reperfusion injury induced by cerebral ischemic damage. MCI-186 (3-methyl-1-phenyl-2-pyrazolin-5-one) is a potent scavenger and inhibitor of hydroxyl radicals and protective agent of peroxidative injury. The purpose of this study was to evaluate the effects of MCI-186 on pulmonary ischemia-reperfusion injury in a simulated transplanted lung model. METHODS: Fourteen dogs were divided into two groups (n = 7 each). In the MCI group, MCI-186 was continuously administered at 3 mg/kg/hour intravenously (IV) from 30 minutes before reperfusion until 30 minutes after reperfusion (total administration time 1 hour). Vehicle was administered in the control group. Warm ischemia was induced for 3 hours by clamping the left pulmonary artery and veins. Simultaneously, the left stem bronchus was bisected and then anastomosed before reperfusion. The right pulmonary artery was ligated 15 minutes after reperfusion, and the right stem bronchus was then bisected. RESULTS: The respiratory gas exchange, hemodynamic changes, wet-to-dry weight ratio (WDR) and malondialdehyde (MDA) concentration in the tissue were significantly improved (p < 0.05) in the MCI group. The histologic damage was more severe in the control group and polymorphonuclear neutrophil (PMN) infiltration was reduced in the MCI group. CONCLUSION: MCI-186 has a protective effect on pulmonary ischemia-reperfusion injury through the inhibition of lipid peroxidation.

Animals↗

PubMed2006

Inhibition of cyclooxygenase-2 improves cardiac function following long-term preservation.

BACKGROUND: Cyclooxygenase (COX) is an intracellular enzyme that converts arachidonic acid to prostaglandin endoperoxide (PGG(2)). There are two isoforms of COX, namely constitutive COX-1 and inducible COX-2. It has been reported that COX-2 plays an important role in ischemia-reperfusion injury and that COX-2 mRNA and protein expression were up-regulated during cardiac allograft rejection. FK3311 is a suppressor of COX-2 activation. The purpose of this study was to evaluate the effectiveness of inhibiting COX-2 with FK3311 for the minimization of ischemia-reperfusion injury and for the improvement of donor heart function following transplantation in a canine model. MATERIALS AND METHODS: Adult mongrel dogs were used. After the measurement of hemodynamic parameters [cardiac output (CO), left ventricular pressure (LVP), and the maximum rates of increase and decrease in LVP (+/-LVdp/dt)], coronary vascular beds were washed out with a hypothermic (4 degrees C) University of Wisconsin (UW) solution following cardiac arrest in response to cold (4 degrees C) glucose-insulin-potassium solution. The heart was then excised and preserved in hypothermic (4 degrees C) UW solution for 12 h. FK3311 (3 mg/kg) was administered intravenously to five dogs prior to reperfusion, while vehicle was administered intravenously to a control group (n = 5). After 3 h of orthotopic transplantation using cardiopulmonary bypass, the hemodynamic parameters were compared with preoperative values of the donor animals under the condition of 10 mm Hg right atrial pressure and 5 mug/kg/min dopamine support. RESULTS: The recovery rates of CO and +/-LVdP/dt were significantly (P < 0.05) higher in the FK-treated dogs than in the controls (CO: 93 +/- 6 versus 66% +/- 4%; +LVdp/dt: 125 +/- 8 versus 77 +/- 10%; and -LVdp/dt: 81 +/- 7 versus 52 +/- 6%; for FK-treated versus control dogs, respectively). The recovery rate of LVP was higher in the FK-treated dogs than in the controls (90 +/- 5 versus 72 +/- 5%), but this difference was not statistically significant. Immunohistochemical staining revealed that COX-2 expression was reduced significantly in the myocardium of FK-treated dogs compared with controls. CONCLUSION: Hemodynamic parameters following transplantation were improved significantly in dogs treated with FK3311. Therefore, the inhibition of COX-2 improves transplanted cardiac function following long-term preservation.

Adenosine↗

PubMed2006

JNK (c-Jun NH2 terminal kinase) and p38 during ischemia reperfusion injury in the small intestine.

BACKGROUND: In small intestinal ischemia reperfusion injury, we investigated the pathophysiological role of c-Jun NH2 terminal kinase (JNK) and p38 in order to determine whether the dual inhibition of JNK and p38 was beneficial. METHODS: Ischemia reperfusion injury was induced by clamping the superior mesenteric artery for 30 min in Wistar male rats. The inhibition of JNK and p38 was achieved with LL-Z1640-2 as a novel JNK and p38 dual inhibitor in vivo. Between the non-treatment group (Control group) and the LL-Z1640-2 treatment group (LL-Z group), the following findings were compared; histological damage by hematoxylin and eosin (H. E.) staining, JNK and p38 activation by a kinase assay, the localization of apoptosis using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method, the localization of activated JNK and activated p38 based on immunohistochemistry. RESULTS: The activation of JNK and p38 increased remarkably after reperfusion according to a kinase assay. In immunohistochemistry for activated JNK and activated p38, a remarkable degree of positive staining was revealed in the nucleus of the detached epithelial cells from the tip of villi after reperfusion. In addition, many TUNEL positive cells were observed in the detached epithelial cells where JNK and p38 were activated. Pretreatment of LL-Z1640-2 inhibited the activation of JNK and p38, and also significantly improved the histological damage. CONCLUSIONS: These results suggest that JNK and p38 both play a key role during small intestinal ischemia reperfusion injury through a proapoptotic action on the tip of villi.

Animals↗

PubMed2006

A comparative study of long-term heart preservation using 12-h continuous coronary perfusion versus 1-h coronary perfusion following 11-h simple immersion.

PURPOSE: We previously reported the superiority of the continuous coronary perfusion method using apparatus developed in our department. However, myocardial edema was a serious problem following this method. The purpose of this study was to attempt a comparative study of 12-h continuous perfusion and 1-h perfusion following 11-h simple immersion to evaluate the suitable method for long-term heart preservation. MATERIALS AND METHODS: HBD dogs were used in this study. After measuring baseline hemodynamics, cardiac arrest was attained and the coronary vascular beds were washed out with 4 degrees C Celsior solution. The grafts were divided into the two groups. In the CP group (n = 6), the grafts were preserved by continuous perfusion with 4 degrees C Celsior solution, and in the SI + CP (n = 6) group, the grafts were preserved with 11 h of simple immersion followed by an additional 1 h of perfusion with the same solution. The hemodynamics after orthotopic transplantation were compared. We also performed a histopathologic examination. RESULTS: Hemodynamics after reperfusion were maintained in both groups, and there were no significant differences in CO, Emax, or the rate pressure product between the two groups. In contrast, the percentage water content was significantly lower in the SI + CP group than in the CP group. Histopathologically, the myocytes were well preserved in both groups. However, ischemia-reperfusion changes were observed more frequently in the CP group than in the SI + CP group. CONCLUSION: A short-term perfusion following the simple immersion method may provide satisfactory results compared to the continuous perfusion method in long-term heart preservation.

Animals↗

PubMed2006

Expression of keratinocyte growth factor receptor correlates with expansive growth and early stage of gastric cancer.

The keratinocyte growth factor receptor, also known as KGFR/FGFR2 IIIb, is mainly localized in epithelial cells, and participates in the proliferation of these cells. In contrast, a recent study has revealed that the overexpression of KGFR in salivary adenocarcinoma induces growth inhibition, cell differentiation and apoptosis. We attempted to clarify the expression and role of KGFR in normal and cancerous human gastric tissues and cancer cell lines. Reverse-transcription polymerase chain reaction and Western blot analyses showed KGFR mRNA and its protein expression in NUGC-4, KATO-III and MKN-7 gastric cancer cell lines, but not in the NS-8 cell line. Immunohistochemically, KGFR immunoreactivity was weakly detected in the luminal surface of normal gastric epithelial cells. In addition, KGFR immunoreactivity was strongly detected in the nucleus and cytoplasm of many parietal cells. In gastric cancer tissue, KGFR was expressed in the cell membrane and cytoplasm of cancer cells in 46 of 126 (36.5%) cases. KGFR expression in gastric cancer cells was significantly associated with early-type macroscopic findings, shallow invasion of the gastric wall and expansive growth type. KGFR expression tended to correlate with a good prognosis in gastric cancer. These findings indicate that KGFR expression plays important roles in the differentiation of normal gastric epithelial cells and parietal cell functions. Furthermore, a decreased expression level or the non-expression of KGFR in gastric cancer cells may be associated with the proliferation and invasion of gastric cancer cells and a poor prognosis for the patient.

Adult↗

PubMed2005

Identification of histological markers for malignant glioma by genome-wide expression analysis: dynein, alpha-PIX and sorcin.

Glioblastoma multiforme (GBM), the most malignant class of glial neoplasm (grade IV in WHO criteria), carries the worst clinical prognosis among primary brain tumors in adults. To identify a set of genes involved in the tumorigenesis of GBM, we evaluated expression profiles of GBM tissues from 11 patients using a cDNA microarray representing 25,344 human genes. By comparing the profiles with those of normal brain tissue, we identified a number of differentially expressed genes: 54 with increased expression and 45 with reduced expression in GBMs. Semi-quantitative RT-PCR experiments with 6 of those genes confirmed higher expression of DNCH2, ARHGEF6, NPM1 and SRI and lower expression of NRGN and TM4SF2 in GBM tumors. Immunohistochemical staining for 3 of the respective gene products, dynein (product of DNCH2), alpha-PIX (product of ARHGEF6), and sorcin (product of SRI) indicated that this technique might be useful for histological grading of glial tumors. To establish criteria for this diagnostic approach, we scored glial tumor tissues of different histological grades according to the staining results; the scores were significantly higher in anaplastic astrocytomas and GBMs than in diffuse astrocytomas or normal brain tissues. These findings indicated that levels of these three proteins might serve as histological markers for malignant glioma classification.

Biomarkers, Tumor↗

PubMed2005

Jejunectomy can reduce excessively elevated portal pressure after major hepatectomy in beagle dogs.

A number of factors can lead to the life-threatening liver dysfunction in the aftermath of an extended hepatectomy. Prominent among them is the high portal pressure induced by the concentrated flow of the entire stream of portal blood toward the small remnant liver. Twelve beagle dogs were randomly divided into group A (n=6, 70% hepatectomy) and group B (n=6, 70% hepatectomy after jejunectomy). Three dogs in each group were euthanized at 1 or 4 weeks after the operation and examined to evaluate hemodynamic changes, liver functions, and liver histology. One hour after the hepatectomy, the animals in group B exhibited a significantly lower portal pressure (P=0.002) and significantly higher hepatic arterial flow (P=0.004) than the animals in group A. As more time passed, the total hepatic flow and hepatic tissue flow both rose up to levels significantly higher than those in group A (P=0.037 and P=0.025, respectively). The alkaline phosphatase, total protein, albumin, and anti-thrombin III were all significantly better in group B than in group A on the 1st post-operative day. Liver specimens biopsied at 1 h after the hepatectomy showed significantly more swelling of the hepatocytes in group A than in group B. In addition, an immunohistochemical study using the TUNEL method for liver biopsy on the seventh post-operative day revealed numerous positive cells in group A but few in group B. Our results suggest that the portal pressure control by the enterectomy can forestall dysfunction of the remnant liver after extended hepatectomy, especially during the early post-operative period.

Animals↗

PubMed2005

KRP-203, a novel synthetic immunosuppressant, prolongs graft survival and attenuates chronic rejection in rat skin and heart allografts.

BACKGROUND: A novel immunomodulator, KRP-203, the molecular structure of which has some similarity to FTY720, has been developed for use in organ transplantation. The present study was designed to investigate the potency and safety of KRP-203 on allograft survival against both acute and chronic rejection in rat skin and heart transplantation. METHODS AND RESULTS: KRP-203 significantly prolonged skin or heart allograft survival of a minor histocompatibility complex (mHC)-disparate (LEW to F344) rat combination. Histopathological and immunohistochemical analysis at 100 days after mHC-disparate rat heart transplantation revealed that KRP-203 treatment significantly inhibited infiltration of inflammatory cells, including macrophages and T cells; expression of endothelin-1 and transforming growth factor-beta1; and IgG deposition and eventually attenuated neointimal formation and myocardial fibrosis. KRP-203 also prolonged heart allograft survival in a major histocompatibility complex (MHC)-incompatible (DA to LEW) rat combination, but the efficacy was not as significant. However, KRP-203 combined with a subtherapeutic dose of cyclosporin A synergistically prolonged the heart allograft survival. Flow cytometric analysis demonstrated that KRP-203 reduced the number of peripheral blood mononuclear cells (lymphocytes and monocytes) but not granulocytes and enhanced lymphocyte homing into peripheral lymph nodes. The influence of KRP-203 on heart rate changes in Hartley guinea pigs was examined. KRP-203 had less of a tendency to cause bradycardia than FTY720. CONCLUSIONS: These findings demonstrated that KRP-203 prolonged skin and heart allograft survival and significantly attenuated chronic rejection and bradycardia as an adverse effect. Therefore, KRP-203 offers considerable potential as a novel therapeutic immunosuppressant in patients with organ transplantation.

Animals↗

PubMed2005

Bradykinin B2 receptor antagonist FR173657 ameliorates small bowel ischemia-reperfusion injury in dogs.

Bradykinin mediates acute inflammation by increasing microvascular permeability, vasodilation, leukocyte migration and accumulation, and the production of arachidonic acid via phospholipase A2 activation. Arachidonic acid metabolites, or eicosanoids, are potent modulators of biological functions, particularly inflammation. Bradykinin exerts its inflammatory effects via the bradykinin B2 receptor. The aim of this study was to evaluate the effect of a bradykinin B2 receptor antagonist, FR173657 (FR), on intestinal ischemia-reperfusion (I/R) injury. Twenty-eight mongrel dogs were divided into four groups (n = 7 per group). Group I underwent I/R alone, Group II underwent I/R and received FR treatment, Group III was sham operated, and Group IV was sham operated and received FR treatment. The FR treatment consisted of FR continuously from 30 min prior to ischemia to 2 hr after reperfusion. In the I/R procedure, the superior mesenteric artery (SMA) and vein were clamped for 2 hr and then released to permit reperfusion for 12 hr. The intramucosal pH (pHi), SMA blood flow, and mucosal tissue blood flow were measured during the reperfusion period. The serum thromboxane B2 and 6-keto-prostaglandin F1alpha levels were determined, and tissue samples were examined histologically. Results showed that tissue blood flow, pHi, and SMA blood flow after reperfusion were maintained in Group II in comparison with Group I. Histopathological examination showed less severe mucosal damage after reperfusion in Group II than in Group I. The serum thromboxane B2 and 6-keto-prostagland in F1alpha levels were significantly lower in Group II than in Group I (P < 0.05). We conclude that FR treatment appears to have clear protective effects on small bowel I/R injury by inhibiting the release of eicosanoids.

6-Ketoprostaglandin F1 alpha↗

PubMed2005

Long-term preservation using a new apparatus combined with suppression of pro-inflammatory cytokines improves donor heart function after transplantation in a canine model.

OBJECTIVE: We developed a new apparatus for long-term heart preservation that combines simple immersion with coronary perfusion. In a previous study, we reported that suppression of pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta), improved results after transplantation. In this study, we evaluated whether long-term preservation using our apparatus for continuous coronary perfusion, combined with suppression of pro-inflammatory cytokines, improves donor heart function after transplantation in a canine model. METHODS: We used adult mongrel dogs in this study. Coronary vascular beds were washed with University of Wisconsin (UW) solution after arresting hearts with glucose-insulin-potassium solution. The heart was then excised and preserved for 12 hours with a combination of immersion and coronary perfusion using a preservation apparatus. Adult mongrel dogs were divided into 2 groups: the coronary perfusion (CP) group (n = 7) and the FR167653 (FR-CP) group (n = 6). In the CP group, we used a 4 degrees C UW solution for immersion and coronary perfusion. In the FR-CP group, we used a 4 degrees C UW solution supplemented with 20 mg/liter of the anti-inflammatory agent FR167653 for immersion and coronary perfusion. At 2 and at 3 hours after orthotopic transplantation, we compared hemodynamic parameters with pre-operative values in donor animals, with right atrial pressure at 10 mm Hg and with 5 microg/kg/min dopamine infusion. We compared serum concentrations of TNF-alpha from the coronary sinus and compared electron microscopic studies between the 2 groups. RESULTS: Three hours after transplantation, cardiac output (CO), left ventricular pressure (LVP), and -LVdp/dt were significantly greater (p < 0.05) in the FR-CP group than in the CP group (CO, 178% +/- 65% vs 93% +/- 40%; LVP, 115% +/- 22% vs 73% +/-26%; -LVdp/dt, 168% +/- 13% vs 61% +/- 17%, respectively). Electron microscopic studies showed that glycogen was well preserved in the FR-CP group compared with the CP group. Serum concentrations of TNF-alpha were decreased significantly in the FR-CP group compared with the CP group at 3 hours after reperfusion (161 +/- 54 pg/dl vs 642 +/- 636 pg/dl, respectively). CONCLUSION: Hemodynamics after transplantation were significantly better in the FR-CP group than in the CP group. The combined preservation method of continuous perfusion and immersion using our apparatus in conjunction with suppression of pro-inflammatory cytokines improves donor heart function after transplantation.

Animals↗

PubMed2004

Effects of adding P38 mitogen-activated protein-kinase inhibitor to celsior solution in canine heart transplantation from non-heart-beating donors.

BACKGROUND: The activation of p38 mitogen-activated protein kinase (MAPK) plays an important role in ischemia-reperfusion injury. This study evaluated the effects of p38 MAPK inhibition using FR167653, a novel p38 MAPK inhibitor, as an additive to Celsior solution in canine heart transplantation from non-heart-beating donors (NHBDs). METHODS: Donor hearts were left in situ for 20 minutes after cardiac arrest, which was induced by rapid exsanguination. Twelve donor-recipient pairs of mongrel dogs were divided into two groups: the control and FR167653 (FR) groups (n=6 each). In both groups, the grafts were subjected to coronary flushing and immersed in Celsior solution for 4 hours with or without FR167653. Orthotopic heart transplantation was then performed. Cardiac output (CO), left ventricular pressure (LVP), and end-systolic maximal elastance (Emax) were measured 2 hours after weaning from cardiopulmonary bypass (CPB), and the hearts were then harvested for histopathologic study. The activation of p38 MAPK was evaluated in another 20 mongrel dogs. RESULTS: In the FR group, CO, LVP recovery rate, and Emax were significantly (P<0.05) higher 2 hours after weaning from CPB, histopathologic damage was attenuated, and the activation of p38 MAPK was significantly (P<0.05) inhibited 10 minutes after reperfusion compared with the control group. CONCLUSIONS: The addition of FR167653 to Celsior solution improved heart-graft viability, probably by way of the inhibition of p38 MAPK activation, which may attenuate ischemia-reperfusion injury in heart transplantation from NHBDs.

Animals↗

PubMed2004

Cure of intractable pancreatic fistula by subcutaneous fistulojejunostomy.

Fistulojejunostomy was performed at the subcutaneous level in two patients with intractable pancreatic fistula that occurred after surgery for cancer of the ampulla of Vater and carcinoma of the lower bile duct. The treatment yielded mostly satisfactory results, though one patient incurred postoperative wound dehiscence, which was healed with conservative measures. Compared with conventional procedures, this method is technically easy to perform, as it does not involve surgical separation of the fistula up to a site deep within the abdominal cavity, rarely results in side injury, and poses few potential risks of cicatricial stenosis of the fistular lumen, because blood supply to the fistula is preserved. Subcutaneous fistulojejunostomy is considered to be recommendable for pancreatic fistulas that occur long after surgery and which are stenosed at the site of the pancreatojejunal stenosis and thus require surgical treatment.

Aged↗

PubMed2004

Large anomalous systemic arterial supply to basal segments of the left lung.

A 29-year-old man with a large anomalous systemic arterial supply to basal segments of the lower lobe was reported here. Pulmonary arteriography showed the absence of blood flow to basal segments. Aortography verified the anomalous artery from the descending thoracic aorta. Lobectomy was performed because the anastomosis between the anomalous and pulmonary arteries was anatomically difficult and segment 6 was small. The resected specimen showed that the anomalous artery had findings of pulmonary hypertension equivalent to grade V in the classification of Heath and Edwards. If the anastomosis between the anomalous and pulmonary arteries is anatomically feasible, pathological examination of open lung biopsy specimen is necessary to determine the operative procedures in this disease and two-staged operation is desirable.

Adult↗

PubMed2004

Metastasis to the thyroid from lung adenocarcinoma mimicking thyroid carcinoma.

We herein report a case of metastasis to the thyroid from lung adenocarcinoma mimicking thyroid carcinoma. The thyroid tumor was palpated in the left lobe of the thyroid and diagnosed as primary thyroid carcinoma by fine-needle aspiration cytology. The patient also had a large pulmonary tumor and tiny pulmonary nodules, which were respectively diagnosed as moderately differentiated adenocarcinoma of the lung and intrapulmonary metastases from the main large lung carcinoma by the pathological examination of the biopsy specimens obtained by video-assisted thoracic surgery. Hemithyroidectomy with radical neck dissection was performed. The thyroid tumor was diagnosed as metastasis to the thyroid from lung adenocarcinoma, because it showed mucin production, positive immunoreactivity for carcinoembryonic antigen and negative immunoreactivities for thyroglobulin and calcitonin. The patient received systemic chemotherapy and died of the disease 1 year and 7 months after the diagnosis was made.

Adenocarcinoma↗

PubMed2004

Sternal resection for metastasis from thyroid carcinoma and reconstruction with the sandwiched Marlex and stainless steel mesh.

A case of 69-year-old woman with a solitary sternal bone metastasis from thyroid carcinoma undergoing surgical therapy was reported here. On admission, most part of the body of the sternum was destroyed by tumor. Subtotal sternectomy was performed and a part of the major pectoral muscles adherent to the sternal tumor was also resected. The chest wall defect was reconstructed with a sandwiched Marlex and stainless steel mesh. Pathological examination of the resected specimen revealed metastatic papillary carcinoma of the thyroid. Her postoperative course was uneventful. The reconstruction with Marlex and stainless steel mesh seemed to be an appropriate procedure to prevent paradoxical movement of the thorax and protect the intrathoracic organs. Stainless steel mesh compensated for limited resiliency of Marlex mesh and remained rigid in all directions.

Aged↗

PubMed2004

Measuring platelet aggregation to estimate small intestinal ischemia-reperfusion injury.

BACKGROUND: The success of intestinal transplantation is affected by the extreme susceptibility of the small bowel to ischemia-reperfusion (I/R) injury. Currently, there is no quick, convenient method to estimate the extent of small bowel I/R injury. Although histological evaluation is reliable and accurate, it takes too long to allow favorable intervention in I/R injury. I/R causes the production of arachidonic acid products, oxygen free radicals, cytokines, and nitric oxide, which affect platelet function. OBJECTIVE: This study determined whether measuring platelet aggregation is useful for evaluating small bowel I/R injury. METHODS: Eighteen mongrel dogs were divided into three groups. In group A both the superior mesenteric artery (SMA) and vein (SMV) were occluded for 120 min. In group B the SMA was occluded for 60 min. Group C underwent a sham operation. Platelet aggregation was measured using a whole blood aggregometer (WBA analyzer), which readily handles small samples. Histological examination was performed. The correlation between platelet aggregation and histology was analyzed. RESULTS: Platelet aggregation was similar in all groups before reperfusion. After reperfusion, platelet aggregation was significantly lower in group A than in groups B and C (P < 0.05), and mucosal damage was most severe in group A (P < 0.05). After 1 and 3 h of reperfusion, there was a significant negative correlation between platelet aggregation and histological damage. CONCLUSIONS: Measuring platelet aggregation is rapid, easy, and useful for evaluating small bowel I/R injury.

Animals↗

PubMed2004

Effects of a bradykinin B(2) receptor antagonist on ischemia-reperfusion injury in a canine lung transplantation model.

BACKGROUND: This study investigated the effects of a bradykinin B(2) receptor antagonist, FR173657 (FR), on ischemia-reperfusion (I/R) injury in a canine lung transplantation model. METHODS: Eighteen pairs of weight-matched dogs were randomly divided into 3 groups. Six pairs were assigned to the FR(D+R) group, in which FR (100 nmol/kg/h) was administered to the transplant donor continuously beginning 30 minutes before ischemia until the onset of ischemia, and FR was administered to the transplant recipient beginning 30 minutes before reperfusion and continuing for 2 hours after reperfusion. Another 6 pairs of dogs were assigned to the FR(R) group, in which FR was administered only to the recipient in the same manner as in the FR(D+R) group. The other pairs were assigned to the control group, in which vehicle alone was administered. Orthotopic left lung transplantation was performed after 12-hour cold storage in Euro-Collins solution. Fifteen minutes after reperfusion, the right pulmonary artery and the right stem bronchus were ligated. The animals were measured for 4 hours after reperfusion for left pulmonary vascular resistance (L-PVR), cardiac output (CO), arterial oxygen pressure (PaO(2)) and alveolar-arterial oxygen pressure difference (A-aD(O(2))). Lung specimens were harvested for measurement of the wet-to-dry lung weight ratio (WDR), histopathologic studies and polymorphonuclear neutrophil (PMN) count. RESULTS: Compared with the control group, PaO(2), A-aDO(2), L-PVR and CO were all significantly (p < 0.05) improved and WDR significantly (p < 0.05) lower in both the FR(D+R) and FR(R) groups. Moreover, in the FR-treated groups, histologic tissue edema was mild, and PMN infiltration was significantly (p < 0.05) reduced. CONCLUSIONS: The bradykinin B(2) receptor antagonist, FR173657, ameliorates I/R injury in lung grafts, indicating that protection of lung grafts can be achieved by the administration of FR solely to the transplant recipient.

Animals↗