The effect of FK506 on segmental pancreas allograft in mongrel dogs]

FK506 is a potent immunosuppressive agent on experimental and clinical organ transplantation. We studied the the effect of this agent on segmental pancreas allograft in mongrel dogs. Graft survival was prolonged significantly with continuous administration of FK506, 0.3mg/kg/day intramuscular and 1.0mg/kg/day orally. However such symptoms as loss of appetite, nausea and extreme emaciation were observed and caused death. While bolus therapy of FK506 (3 days administration with the dose of 1.0mg/kg i.m. from 4 to 6 day postoperatively) showed the same immunosuppressive effect as continuous therapy and less side effect. Furthermore it was suggested that FK506 plasma levels were concerned with the appearance of side effect. In conclusion, the administration of FK506 with plasma level monitoring was thought to be useful on pancreas transplantation.     

HA1077, a novel calcium antagonistic antivasospasm drug, increases both cerebral blood flow and glucose metabolism in conscious rats.

The effects of a novel calcium antagonistic antivasospasm drug, HA1077, on local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU) were studied in 33 anatomically discrete regions of the brain in conscious rats, using the quantitative autoradiographic [14C]iodoantipyrine and [14C]2-deoxyglucose techniques. HA1077 was infused i.v. over a 30-min period (1 or 3 mg/kg). HA1077 significantly increased LCBF in 9 of 33 sites in rats given 1 mg/kg, and in 14 of 33 sites in rats given 3 mg/kg compared to the control group given vehicle. Significant increases in LCGU were also noted in 16 of 33 sites in rats given 3 mg/kg. HA1077 increased both cerebral blood flow and glucose metabolism in conscious rats.     

Low-molecular-weight copolymers composed of L-lactic acid and various DL-hydroxy acids as biodegradable carriers

Biodegradable copolymers of L -lactic acid (L -LA) and DL -α-hydroxy acids with relatively low molecular weights, for example L -LA/DL -lactic acid (DL -LA), L -LA/DL -α-hydroxybutyric acid (DL -HBA), L -LA/DL -α-hydroxyisovaleric acid (DL -HIVA), and L -LA/DL -α-hydroxyisocaproic acid (DL -HICA), were synthesized by quantitative direct copolycondensation without catalysts at 200°C. The in vitro degradation, which was evaluated by measuring the weight loss of these copolymers in M/15 phosphate buffer solution (pH 7,2) without enzymes at 37°C, is strongly dependent on the kind and molecular weight of these copolymers, resulting in the formation of different degradation patterns such as parabola type (L -LA/DL -HBA system), linear type (L -LA/DL -LA system), and S type (L -LA/DL -HIVA and L -LA/DL -HICA systems).     

Heterogeneity of anticardiolipin antibody

The antibody to cardiolipin(ACA) was tested in patients with systemic rheumatic disease. The frequency of IgG ACA was 46/100(46.0%) in systemic lupus erythematosus(SLE). In other rheumatic disease, this was less than 20%. Significant correlation between the presence of IgG ACA and thrombosis and/or thrombocytopenia was found in patients with SLE. Eight sera containing high titered IgG ACA from lupus patients were selected for further inhibition study. Inhibitors were consisted of cardiolipin(CL), phosphatidyl(p-)serine, p-inositol, p-glycerol, p-ethanolamine, p-choline, ds-DNA, ss-DNA, fresh platelets(PLT)and fresh red blood cells(RBC). All sera were markedly inhibited by negatively charged phospholipids. In 4 sera(group B), there was moderate inhibition by ss-DNA, ds-DNA, PLT and RBC. In another 4 sera(group A), mild but significant inhibition was obtained by PLT alone. The number of platelet in group A was less than that in group B. There were some differences in inhibitory activity, suggesting heterogeneity of antibody to CL. It may be possible to speculate that heterogeneity of IgG ACA cause various combination of clinical features such as thrombocytopenia and thrombosis.     

Malfunction of arterial sarcoplasmic reticulum leading to faster and greater contraction induced by high-potassium depolarization in young spontaneously hypertensive rats.

The contribution of sarcoplasmic reticulum was studied with regard to the increase in arterial contraction induced by a high-potassium depolarization in spontaneously hypertensive rats (SHR). The 20 mmol/l potassium-induced contraction of femoral arteries was faster and greater in 6-week-old SHR than in age-matched normotensive Wistar-Kyoto (WKY) rats. Relaxation after washing the arteries with a Krebs solution was slower in SHR than in WKY rats. When the sarcoplasmic reticulum of SHR arteries had been depleted of calcium by caffeine in a calcium-free solution, the rate of high-potassium-induced contraction of the calcium-depleted SHR arteries was slowed, the same result as that with non-calcium-depleted WKY arteries. In ryanodine-treated arteries, the rate and magnitude of high-potassium-induced contraction were enhanced slightly in SHR and greatly in WKY rats, resulting in no final difference between SHR and WKY rats. Ryanodine slowed the relaxation rate in WKY rats but not in SHR. These results suggest that the diminution in ability of sarcoplasmic reticulum to sequester calcium may be responsible for the faster rate and greater magnitude of high-potassium-induced contraction with the slower relaxation in SHR arteries. We postulated that genetic malfunction of sarcoplasmic reticulum causes the increased contraction of arterial smooth muscle leading to the enhanced vasoconstriction and elevated blood pressure in SHR.     

Reoperation after aortic valvuloplasty for aortic regurgitation associated with ventricular septal defect

Five patients underwent reoperations because residual or recurrent aortic regurgitation occurred after aortic valvuloplasty for aortic regurgitation associated with ventricular septal defect. The mean age at reoperation was 22 years old, and the mean time interval between initial and second operation was 6 years, 10 months. The pathological findings of the aortic valves showed tears and perforation of repaired leaflets in four patients and a giant pseudoaneurysm of the Valsalva sinus in one. Aortic valvuloplasties were performed again in three patients, and aortic valves were replaced with prosthetic valves in two. Slight to moderate regurgitant murmurs are still audible in patients who underwent these valvuloplasties. Ventricular septal defects should be closed before aortic regurgitation develops. If it has developed, however, valvuloplasty should be considered as a first choice in young patients. For adult patients, aortic valve replacement is recommended.     

Hemodynamic consequences of right ventricular isolation: the contribution of the right ventricular free wall to cardiac performance

Surgical isolation of the right ventricular free wall was performed in 10 dogs to evaluate both the hemodynamic effects of the procedure and the postoperative contribution of right ventricular free wall contraction to overall cardiac performance. Following the procedure, there was no significant differences in peak right ventricular systolic pressure, right atrial pressure, right ventricular stroke volume, or cardiac index. Cardiac index remained at preoperative levels over a wide range of filling pressures. However, there was a significant decrease in right ventricular stroke work (6.0 +/- 1.3 gm-m/m2 to 5.1 +/- 0.5 gm-m/m2; p less than 0.05). Pacing the isolated right ventricular free wall resulted in marked hemodynamic improvement compared with an electrically silent right ventricular free wall. Cardiac index increased from 1.7 +/- 0.2 L/min/m2 to 2.6 +/- 0.2 L/min/m2 (p less than 0.0005), and right ventricular stroke work went from 3.0 +/- 0.6 gm-m/m2 to 6.4 +/- 0.9 gm-m/m2 (p less than 0.0005). Right ventricular performance was also significantly related to the timing of right ventricular free wall contraction. Thus, the right ventricular free wall played an important role in the maintenance of normal cardiac hemodynamics.     

Mitral valve replacement with preservation of chordae tendineae and papillary muscles

An operative technique for mitral valve replacement (MVR) with preservation of the chordae tendineae to the anterior leaflet as well as the posterior leaflet is reported. This technique consists of the division of the anterior leaflet into anterior and posterior segments, the shifting and reattachment of the divided segments to the mitral ring of the respective commissural areas, and the use of a low-profile bileaflet prosthetic valve. A comparison of left ventricular function data between patients having operation with this technique and those having operation with the conventional method of MVR revealed significantly better improvement in cardiac index (p less than 0.06), left ventricular end-systolic volume index (p less than 0.05), and left ventricular ejection fraction (p less than 0.10) in the former group. Left ventricular wall motion improved in the anterolateral (p less than 0.01) and apical areas (p less than 0.02) in patients operated on with our technique. Maintenance of continuity between the mitral annulus and papillary muscles is expected to have a beneficial effect on postoperative left ventricular performance in spite of increased afterload.