Biomedical subjects

Masahiko Tokumine

Publications and source records attributed to Masahiko Tokumine.

6 recordsLinked to original sources

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

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↗

PubMed2002

Effects of a p38 mitogen-activated protein kinase inhibitor as an additive to Euro-Collins solution on reperfusion injury in canine lung transplantation1.

BACKGROUND: The activation of p38 mitogen-activated protein kinase (MAPK) plays an important role in the development of ischemia/reperfusion injury. FR167653 is a novel p38 MAPK inhibitor. This study evaluated the effects of p38 MAPK inhibition during cold ischemia on subsequent reperfusion injury using FR167653 as an additive to Euro-Collins solution in canine lung transplantation. METHODS: Canine orthotopic left lung transplantation was performed after 12-hr cold storage using Euro-Collins solution, with or without FR167653. Fifteen minutes after reperfusion, the right pulmonary artery and the right stem bronchus were ligated, and the animals were observed for 4 hr after reperfusion. Left pulmonary vascular resistance (L-PVR), cardiac output (CO), arterial oxygen pressure (Pao2), and alveolar-arterial oxygen pressure difference (A-aDo2) were measured. Lung specimens were harvested for wet-to-dry lung weight ratio (WDR) measurements, histopathologic studies, and polymorphonuclear neutrophil (PMN) counts. The activities of p38 MAPK in lung grafts were evaluated. RESULTS: The addition of FR167653 significantly (P<0.05) improved Pao2, A-aDo2, L-PVR, CO, and WDR and suppressed PMN infiltration after transplantation. FR167653 also ameliorated histologic damage to the lung graft. During cold storage, p38 MAPK was not activated in the lung graft, whereas it was markedly activated 30 min after reperfusion. FR167653 significantly (P<0.05) inhibited p38 MAPK activation 30 min after reperfusion. CONCLUSIONS: The addition of FR167653 to Euro-Collins solution improved lung graft viability associated with the inhibition of p38 MAPK activation. These results suggest that inhibiting p38 MAPK activation may attenuate ischemia/reperfusion injury in lung transplantation.

Animals↗

PubMed2002

The optimal pressure for initial flush with UW solution in heart procurement.

OBJECTIVE: University of Wisconsin (UW) solution is widely used in organ preservation. Some investigators have reported that high pressure during initial flush with UW solution may induce vasoconstriction and endothelial damage, because of its high potassium content and high viscosity. However, using lower pressure during the initial flush may lead to irregular distribution of the solution and incomplete flushing of blood components from coronary vascular beds. This experimental study evaluated the effects of a range of initial flush pressures during heart procurement, followed by orthotopic transplantation of the graft after 12 hours of preservation. MATERIALS AND METHODS: Twelve pairs of adult mongrel dogs, weighing 9 to 14 kg, formed the recipient-donor combinations. After determining hemodynamic status by measuring cardiac output, left ventricular pressure (LVP), and maximum positive and negative change in LVP (+/-LVdP/dt), donor hearts were excised. Coronary vascular beds were flushed with 4 degrees C UW solution at a pressure of 60 mm Hg in the low-pressure group (n = 6) and at 120 mm Hg in the high-pressure group (n = 6). After 12 hours of cold preservation, orthotopic transplantation was performed using cardiopulmonary bypass (CPB). The hemodynamics of the transplanted graft were assessed by comparing recovery rates (%) from donor hearts 2 hours after weaning from CPB. Endothelin-1 (ET-1) levels were measured in the blood obtained from the coronary sinus 30 minutes after reperfusion. The transplanted grafts were then harvested for histologic study and measurement of adenosine triphosphate (ATP) content. RESULTS: Cardiac output, LVP, LVdP/dt and myocardial tissue ATP content were significantly better (p < 0.05) in the high-pressure group than in the low-pressure group. We found no significant differences in ET-1 levels between the groups. Transmission electron microscopic findings revealed that degeneration of the mitochondria was less extensive in the high-pressure group than in the low-pressure group. We observed no obvious ultrastructural damage to the endothelial cells in either group. CONCLUSION: When using UW solution in heart procurement, high pressure is better to completely wash out the blood components and distribute the solution.

Adenosine↗

PubMed2002

Effects of a bradykinin B(2) receptor antagonist, FR173657, on pulmonary ischemia-reperfusion injury in dogs.

BACKGROUND: This study investigated the effects of a bradykinin B(2) receptor antagonist, FR173657 (FR), on pulmonary ischemia-reperfusion (I/R) injury. METHODS: Twenty-four mongrel dogs were divided into four groups (n = 6 each). In Groups I, II and III, FR doses of 33, 100 and 300 nmol/kg per hour, respectively, were administered continuously beginning 30 minutes before ischemia and continuing for 2 hours after reperfusion. In Group IV, vehicle alone was administered. 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. Fifteen minutes after reperfusion, the right pulmonary artery and bronchus were ligated. Left pulmonary vascular resistance (L-PVR), cardiac output (CO), arterial oxygen pressure (PaO(2)) and the alveolar - arterial oxygen pressure difference (A-aDO2) were measured for 4 hours after reperfusion. Lung tissue was harvested for wet-to-dry weight ratio (WDR) measurements, histopathologic studies and polymorphonuclear neutrophil (PMN) counts. Serum thromboxane (TX) B(2), 6-keto-prostaglandin (PG) F(1alpha) and leukotriene (LT) B(4) levels were also measured. RESULTS: PaO(2), A-aDO2, L-PVR and CO were significantly (p < 0.05) improved and WDR was significantly (p < 0.05) lower in Groups II and III than in Group IV. Histologic tissue edema was mild, and PMN infiltration was significantly (p < 0.05) reduced in Groups I, II and III compared with Group IV. TXB(2) levels were significantly (p < 0.05) lower in Group II than in Group IV, whereas 6-keto-PGF(1alpha) levels were not significantly different. LTB(4) levels were significantly (p < 0.05) lower in Groups II and III than in Group IV. CONCLUSIONS: FR appears to have a protective effect on pulmonary I/R injury stemming from the inhibition of eicosanoid release.

Animals↗

PubMedDate not supplied

The effects of a bradykinin B2 receptor antagonist in extended liver resection with ischemia in dogs.

BACKGROUND/AIMS: In liver surgery, total clamping of the portal triad (Pringle's procedure) is commonly used, and sometimes causes liver failure. This study evaluated the effects of a bradykinin B2 receptor antagonist, FR173657 (FR), on ischemia-reperfusion injury during liver resection in dogs. METHODOLOGY: Experimental animals were divided into two groups. In the FR group (n=6), FR (100 nmol/kg/hr) was administered continuously via the portal vein from 30 min before the onset of ischemia until 2 hr after reperfusion. In the control group (n=6), vehicle was injected in the same manner. The right portal pedicle was clamped for 60 min, while the left portal branch was left patent to avoid portal congestion. Following reperfusion, the non-ischemic lobes were resected, and remnant liver function was evaluated. RESULTS: AST and ALT were significantly (p<0.05) lower in the FR group than in the control group. Hepatic tissue blood flow 30 min after reperfusion was significantly (p<0.05) higher in the FR group than in the control group. Histological tissue damage was mild, and polymorphonuclear neutrophil infiltration was significantly (p<0.05) reduced in the FR group compared with the control group. CONCLUSIONS: A bradykinin B2 receptor antagonist ameliorated the ischemia-reperfusion injury caused by Pringle's procedure during extended liver resection.

Analysis of Variance↗