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Biomedical subjects

M Kusagawa

Publications and source records attributed to M Kusagawa.

157 records · Page 9Linked to original sources

Histologic changes in donor bronchi may explain the reduced mucosal blood flow seen during acute lung allograft rejection.

We assessed the histologic changes in donor and recipient bronchi from 15 dogs that had received a lung transplant and related these changes to the severity of acute rejection seen in the parenchyma of these same lungs. Minimal rejection was associated with no abnormal change in either the donor or the recipient bronchi. In mild lung rejection, mononuclear cell cuffings were seen around bronchial arteries in donor bronchial adventitia, although few mononuclear cell infiltrates were seen in the submucosa. Moderate lung rejection was associated with more prominent mononuclear cell cuffings in the donor bronchial adventitia and mucosal infiltrates of mononuclear cells in the membranous portion. In cases of severe lung rejection, the mononuclear cell infiltrates were also apparent in the cartilaginous portion of the donor bronchial mucosa. Moreover, submucosal edema and detachment of bronchial epithelium were seen. These histologic changes were not observed in the recipient bronchi during acute rejection, nor were they seen in the donor and the recipient bronchi during lung infection without rejection. They might, therefore, reflect acute rejection in the donor bronchus. These results might provide the histologic support for our previous observation of decreased bronchial mucosal blood flow measured by the laser Doppler flowmeter in relation with the extent of acute lung rejection.

Acute Disease↗

Administration of haptoglobin during cardiopulmonary bypass surgery.

A study was undertaken to evaluate hemolysis and subsequent renal damage in 14 patients undergoing cardiopulmonary bypass (CPB) surgery. In all patients, free haptoglobin disappeared completely 30 to 90 minutes into CPB, while free hemoglobin (Hb) levels increased progressively. The NAG index and alpha 1M index also increased progressively, indicating renal tubular injury due to hemolysis (Study 1). An additional 20 patients were monitored intraoperatively for plasma free Hb levels by a newly developed colorimetric method using a haptoglobin coated strip. Free Hb levels during CPB exceeded 30 mg/dl in 14 patients, who were immediately given haptoglobin. This treatment eliminated plasma free Hb within 30 minutes, and effectively prevented hemoglobinuria. Haptoglobin treatment brought significant decreases in the NAG index and alpha 1M index, suggesting a protective effect on renal function (Study 2).

Acetylglucosaminidase↗

Nafamostat mesilate administration during cardiopulmonary bypass decreases postoperative bleeding after cardiac surgery.

The hemostatic effect of nafamostat mesilate (FUT-175) was evaluated in patients undergoing cardiopulmonary bypass (CPB) surgery. Thirty patients undergoing aortocoronary bypass grafting were divided into two groups. In the control group, anticoagulation was achieved with an initial dose of heparin (3 mg/kg). In the FUT-175-treated group, in addition to the ordinary treatment with heparin, FUT-175 was infused continuously into the circuit throughout the procedure at a rate of 100 mg/hr. Thrombin-antithrombin III complex (TAT), fibrinopeptide A (FPA), and fibrin degradation products (FDP-D) dimer increased in both groups as CPB proceeded. In the FUT-175-treated group, these parameters remained lower and decreased more rapidly after the end of CPB. Alpha 2 plasmin inhibitor/plasmin complex (PIC) increased progressively during CPB in the control group; no such significant increases were seen in the FUT-175-treated group. Postoperative blood loss was significantly lower in the FUT-175-treated group than in the control group. It was concluded that FUT-175 reduces postoperative blood loss by inhibiting both coagulation and fibrinolysis during CPB.

Adult↗

Significance of bronchial mucosal blood flow for the monitoring of acute rejection in lung transplantation.

Bronchial mucosal blood flow (BMBF) was measured with a laser-Doppler flowmeter in a canine model (n = 20), and the measurement was evaluated to see if it was a useful method for diagnosing allografted lung rejection. The ratio of the value of BMBF at the level of the donor second carina against that at the level of carina (the L/C ratio, an index of BMBF of donor bronchus) decreased in accordance with the extent of lung rejection, and it increased and entered the normal range with the reversal of lung rejection. Compared with the L/C ratio and the rejection grade by histologic changes in open-lung biopsy, the L/C ratio at grade 0 (latent phase) was 0.91 +/- 0.07; at grade Ia (early vascular phase), 0.86 +/- 0.05; at grade Ib (late vascular phase), 0.68 +/- 0.10; at grade II (early alveolar phase), 0.60 +/- 0.14; and at grade III (late alveolar phase), 0.50 +/- 0.15. A significant difference was noted between grades Ia and Ib (p less than 0.01) and between grades Ib and III (p less than 0.01). The sensitivity and the specificity in the detection of early rejection before grade Ib were 96% and 92%, with only one false-negative and two false-positives resulting from 51 measurements of BMBF. In three cases of serious lung infections, the L/C ratio did not fall, and the rejection could be distinguished from infection. These results suggest that measurement of the BMBF is useful for detecting the early rejection of transplanted lungs.

Animals↗

New diagnostic method for pulmonary allograft rejection by measurement of bronchial mucosal blood flow.

We investigated the relationship between the rejection of lung allografts and the bronchial mucosal blood flow with a laser flowmeter. Nineteen mongrel dogs underwent left lung allotransplantation and were given daily oral immunosuppressive therapy with azathioprine and cyclosporine. The bronchial mucosal blood flow at the carina and the bifurcation of left upper and lower bronchi were measured on days 14, 21, and 28 after left lung transplantation. The bronchial mucosal blood flow of the transplanted lungs was expressed as the ratio of bronchial mucosal blood flow at the bifurcation of left upper and lower bronchi to the bronchial mucosal blood flow at the carina (L/C ratio) instead of the absolute value because bronchial mucosal blood flow was affected by the depth of anesthesia of the dogs. We classified the histologic appearance of the transplanted lung tissue into one of five grades: 0, 1a, 1b, 2, and 3. No rejection was in grade 0, and as the rejection process progressed the higher grades were used in order. The mean L/C ratios for grades 0, 1a, 1b, 2, and 3 were 0.95 +/- 0.03, 0.82 +/- 0.05, 0.68 +/- 0.04, 0.58 +/- 0.07, and 0.30 +/- 0.07, respectively. Thus the L/C ratio decreased as the rejection process progressed. The histologic changes of the donor main bronchus in each rejection grade were investigated. Mononuclear cell infiltration and edema around the small vessels was seen in early rejection. These same histologic changes appeared in muscular arteries as rejection progressed, and the damage to the small vessels and muscular arteries was more severe in late rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

New technique for intrathoracic heart-lung transplantation in the rat.

A technique for intrathoracic heart-lung transplantation in the rat is described. The combined heart and left lung were transplanted into the recipient's thorax in place of the excised left lung. The graft's aorta was anastomosed end to side to the recipient's descending aorta. The bronchial anastomosis was made by the telescoping technique. When the aortic anastomosis was carried out, a total aortic clamp was used in group 1 (26 animals), and an internal shunt was used in group 2 (20 animals). One rat in group 1 and seven rats in group 2 survived with well-functioning grafts for more than 7 days after transplantation. This model of intrathoracic heart-lung transplantation appears to be suitable for investigations of rejection because the grafted lung is ventilated through the anastomosed bronchus. Our internal shunt method makes it possible for this system to be used as an experimental model.

Anastomosis, Surgical↗

Preoperative evaluation and surgical treatment for tricuspid regurgitation associated with acquired valvular heart disease. The Kay-Boyd method vs the Carpentier-Edwards ring method.

This study compared the results of annuloplastic repair of tricuspid regurgitation (TR) using Doppler echocardiography. Sixty-three patients who underwent tricuspid annuloplasty were studied. Thirty-four patients received Kay-Boyd annuloplasty and 29 Carpentier-Edwards ring annuloplasty. A new classification of TR based on the direction and area of regurgitation flow on Doppler echocardiogram was applied preoperatively. In the Kay-Boyd group, 10 cases showed massive TR and 24 cases showed localized TR preoperatively. Localized TR was well controlled in all cases, but 8 of 9 cases of massive TR showed grade III residual TR. In the C-E group, 21 cases showed massive TR and 8 cases showed localized TR. All cases were well controlled postoperatively. We conclude that (1) although the Kay-Boyd method is acceptable for localized TR, the C-E method should be employed for massive TR; (2) analyzing the regurgitant pattern of TR by Doppler echocardiogram is useful in selecting an appropriate surgical technique.

Adult↗

Effects of inhaled nitric oxide in single lung transplantation in rats with monocrotaline-induced pulmonary hypertension.

BACKGROUND: The edema of grafted lungs during the early postoperative period is one of the serious complications of single lung transplantation for primary pulmonary hypertension. METHODS: The effectiveness of inhaled nitric oxide in single lung transplantation for primary pulmonary hypertension during the early postoperative period was evaluated with the use of rats with monocrotaline-induced pulmonary hypertension. In the inhaled nitric oxide group, rats were given 60 parts par million of nitric oxide for 24 hours just after left lung transplantation; in the no inhaled nitric oxide group, rats were kept without nitric oxide inhalation; in the control group, normal rats received left isografts. RESULTS: Three hours after transplantation, the mean pulmonary artery pressure of the no inhaled nitric oxide group (28.0 +/- 4.6) was significantly higher than that of the control group (23.3 +/- 0.9, p < 0.05) and the inhaled nitric oxide group (22.7 +/- 1.7, p < 0.05). On the first postoperative day, the mean left-to-right pulmonary blood flow ratio in the inhaled nitric oxide group was 0.34 +/- 0.03; it showed no significant difference to those of the other two groups, whereas that of the no inhaled nitric oxide group (0.42 +/- 0.14) was significantly elevated compared with that of the control group (0.14 +/- 0.03, p < 0.05). Histopathologically, the edema of the grafted lungs 24 hours after operation in the inhaled nitric oxide group was less severe than that in the no inhaled nitric oxide group. CONCLUSIONS: The postoperative use of inhaled nitric oxide is effective to reduce the pulmonary edema of the grafts in single lung transplantation for pulmonary hypertension by reducing acute pulmonary blood flow shift toward grafts after transplantation.

Administration, Inhalation↗

Selective cerebral perfusion in patients with aortic aneurysms involving the aortic arch.

Patients with aortic arch aneurysms underwent surgery using a selective cerebral perfusion (SCP) method. For this purpose, a protocol for SCP was established on the basis of an animal experimental study. Our SCP procedure is performed at a perfusion rate of 6 ml/kg/min with the patient under deep hypothermia at 20 degrees C. The subject group in the current study included 36 patients, 28 men and eight women, ranging in age from 23 to 84 years (mean, 61). There were five operative deaths (13.9%). The mean cardiopulmonary bypass time was 288 minutes, and the mean aortic clamp time was 135 minutes. Mean SCP time was 89 minutes, exceeding 90 minutes in 17 cases. The mean blood pressure during SCP was 43 mmHg and oxygen saturation rate in the internal jugular vein was at least 90%. There was no definite production of lactate in the brain. Cerebral disorders considered to have been caused by SCP occurred in only two cases. It appears that cerebral metabolism can be maintained safely, and that our SCP method is useful during surgery for aortic arch aneurysms.

Adult↗

Effects of nafamostat mesilate on platelets and coagulofibrinolysis during cardiopulmonary bypass surgery.

The effect of nafamostat mesilate (FUT-175) on platelet membrane glycoproteins and the coagulofibrinolytic system were analyzed. Twenty-five patients undergoing aorto-coronary bypass surgery were randomly distributed into an FUT treated group and a control group. In the control group, anticoagulation was achieved with sodium heparin (3 mg/kg) immediately before cardiopulmonary bypass (CPB). In the FUT treated group, in addition to the usual treatment with heparin, FUT-175 was infused continuously at a rate of 2 mg/kg/hr. In the control group, alpha 2 plasmin inhibitor/plasmin complex (PIC) and fibrinogen/fibrin degradation products (FDP) D-dimer increased significantly during CPB, reaching 6.1 +/- 5.1 micrograms/ml and 576 +/- 200 ng/ml, respectively, at 60 min of CPB. PIC and FDP D-dimer remained significantly lower in the FUT treated group than in the control group. GPIb on platelets decreased significantly in both groups, but remained higher in the FUT treated group (81 +/- 5% vs. 56 +/- 21% at 60 min of CPB, P < 0.01). There were no significant changes in GPIIb/IIIa on platelets throughout the procedure in either group. Blood loss after CPB was significantly lower in the FUT treated group than in the control group (778 +/- 277 ml vs. 1,342 +/- 426 ml, P < 0.01). The authors conclude that FUT-175 improves hemostasis after CPB, not only by inhibiting fibrinolysis, but also by preserving platelet GPIb during CPB.

Adult↗

Platelet dysfunction during cardiopulmonary bypass surgery. With special reference to platelet membrane glycoproteins.

Changes in platelet membrane glycoproteins (GPIb, GPIIb/IIIa, and GMP-140) were evaluated using flow cytometry after binding with monoclonal antibodies in 22 adult patients undergoing cardiopulmonary bypass (CPB) surgery. The amount of GPIb on platelets decreased significantly during CPB, reaching a minimum level of 64 +/- 26% of the pre CPB value at 120 min of CPB. There was no significant change in the amount of GPIIb/IIIa on platelets. In accordance with these changes, ristocetin induced agglutination decreased to 56.7 +/- 16.2% of the pre CPB value during CPB. However, there were no significant changes in ADP and collagen induced aggregation throughout the procedure. The number of the activated platelets expressing GMP-140 on their surfaces increased significantly during CPB. There was an upper limit to the amount of GMP-140 expression on each platelet in the circulating blood, suggesting that excessively activated platelets are removed from the circulation. The authors conclude that CPB reduces the amount of GPIb on platelets, which results in platelet dysfunction. In addition, removal of excessively activated platelets from the circulation may lead to thrombocytopenia after CPB.

Adult↗