Nobuko Tsushima

Effects of elastase on the stiffness and elastic properties of arterial walls in cholesterol-fed rabbits

The effect of cholesterol feeding and elastase administration on the arterial stiffness and elastic properties was investigated in rabbits by pressure-diameter tests on excised thoracic aortas, common carotid and femoral arteries. Rabbits in groups RA and RB were fed 1% cholesterol diet for 14 weeks. Groups RC and RD were fed the cholesterol diet for the first 7 weeks, and then given regular chow for the last 7 weeks. In addition, rabbits in groups RB and RC were administered elastase daily for the last 7 weeks. Rabbits in group RE were fed the regular chow for 14 weeks and served as the control group. The arterial stiffness and the elastic modulus of wall material in the RA rabbits were generally higher than those in the control rabbits. Administration of elastase and/or feeding of the regression diet decreased the wall stiffness and elastic modulus significantly, although the effect of elastase did not appear clearly when used in combination with the regression diet. The cholesterol feeding decreased the ratio of thickness to wall radius, whereas the ratio was more or less increased by the elastase administration and/or the regression diet.

Mechanical properties of aortas and pulmonary arteries of calves implanted with cardiac prostheses

Abstract Left ventricular assist devices (LVAD) were implanted in calves of 3-months old between the natural left ventricular apices and middle descending aortas, while total artificial hearts (TAH) were implanted to replace the natural heart ventricles. The stiffness and strength of upper and lower descending aortas obtained from the calves implanted with the LVADs for 1–2 months were significantly lower than those of non-pumped control calves, accompanied by local detachment and damage of endothelial surfaces, while the mechanical properties of the aortas from TAH-implanted calves were very similar to those of the control calves. However, the decreased stiffness and strength of the aortas in the LVAD-implanted calves were recovered to the control levels by pumping for another 1 month or by the pump removal. These characteristic changes in aortic mechanics and structures by the LVAD pumping for an intermediary duration were ascribed to the distortion of blood flow produced around the anastomosis of the pump outflow conduit to the descending aorta.

Change of hematocrit and blood viscosity in cholesterol-fed rabbits

In the cholesterol-fed rabbits, we observed that the whole blood viscosity was maintained at the normal level in spite of the decrease in hematocrit. This phenomenon suggests that there exists some visco-regulatory mechanism, and we could simulate it by a simple integration type model.

Blood rheology in the endotoxin-administered rabbits

The effects of endotoxin on blood rheology were studied in rabbits. Non-treated six rabbits (Group A) were used to obtain control data. Thirteen rabbits who were administered 0.1 mg of endotoxin three times at intervals of 3 days were divided into two groups; seven rabbits (Group B) were injected with 1 ml saline solution as the vehicle for endotoxin at 7 days after the final administration of endotoxin, while the remaining six rabbits (Group C) were administered endotoxin at 0.2 mg/kg on the same day. Blood was sampled from the femoral artery 120 min after the final treatment. Blood viscosity was measured at a shear rate of 150 s-1 at 37 degrees C using a cone-plate viscometer. The passage time for a 5% red blood cell suspension and that for plasma were determined by filtration; the former represents erythrocyte deformability while the latter is related to plasma fluidity. The hematocrit, whole blood viscosity and erythrocyte deformability did not show significant differences among these three groups. The ratio of hematocrit to whole blood viscosity is considered to be an index of oxygen delivery from the hemorheologic point. This index did not show significant difference either. A good correlation was observed between whole blood viscosity and hematocrit in Group A, but not in the endotoxin-treated groups. The plasma fluidity was lower in Groups B and C than in Group A. These data indicate that plasma fluidity and the hematocrit-viscosity relationship are affected in endotoxin-treated rabbits, although blood viscosity, erythrocyte deformability and oxygen delivery hardly changed.

Changes in blood rheologic factors following coronary artery surgery

Blood rheologic parameters were examined in 16 patients without multiple organ failure 2 weeks after coronary artery surgery. The whole blood viscosity (shear rate = 94.5 sec-1) was unchanged (4.59 +/- 0.53 to 4.56 +/- 0.58 mPa.s) despite a significant decrease in hematocrit (39.8 +/- 4.3 to 37.1 +/- 3.8%, P less than 0.05). The oxygen delivery index (the ratio of hematocrit to whole blood viscosity) was significantly decreased (8.67 +/- 0.35 to 8.18 +/- 0.59%/mPa.s, P less than 0.05). Plasma viscosity (shear rate = 94.5 sec-1) increased significantly (1.60 +/- 0.13 to 1.72 +/- 0.10 mPa.s, P less than 0.01), as did serum levels of globulin (2.8 +/- 0.4 to 3.0 +/- 0.4 g/dl, P less than 0.01), alpha 1-antitrypsin (232 +/- 41 to 308 +/- 60 mg/dl, P less than 0.001), and fibrinogen (381 +/- 81 to 479 +/- 117 mg/dl, P less than 0.001). Total protein and globulin levels showed a good correlation with plasma viscosity, but the fibrinogen concentration demonstrated no correlation. The passage time of a 40% red blood cell suspension (0.5 ml) was shortened significantly from 10.2 +/- 1.1 to 9.2 +/- 1.0 sec (P less than 0.05). These results indicate that an increase in plasma viscosity is important in determining blood rheologic properties 2 weeks after coronary artery surgery.

A selective thromboxane synthetase inhibitor, OKY-046, fails to improve blood rheology in endotoxin-shocked rabbits

Effects of a selective thromboxane synthetase inhibitor, (E)-3-[4-(1-imidazolylmethyl) phenyl]-2-propenoic acid hydrochloride monohydrate (OKY-046), were studied hemorheologically in endotoxin shocked-rabbits. The animals were intravenously administrated with 0.1 mg of endotoxin 3 times at intervals of 3 days. At 7 days after the last endotoxin injection, endotoxin (0.2 mg·kg−1) was intravenously administrated to induce a shock. OKY-046 (30 mg·kg−1) was administrated after hypotension was developed by the endotoxin treatment and, then, it was continuously injected at 0.03 mg·kg−1·min−1. Blood pressure remained unchanged and hypotensive was maintained during the treatment with OKY-046. Blood was sampled from the femoral artery 15 (before the administration of OKY-046), 45, and 120 minutes after the final administration of endotoxin. Pao2 increased, and PaCO2, arterial pH, and base excess (BE) decreased during the endotoxin shock. The decrease of pH and BE was prevented by the administration of OKY-046. In the endotoxin-shocked animals, hematocrit, whole blood viscosity, erythrocyte deformability, plasma fluidity, and the ratio of hematocrit to whole blood viscosity showed no significant differences between the OKY-046 treated animals and non-treated ones. These data show that a selective thromboxane synthetase inhibitor (OKY-046) does not improve the blood rheology during endotoxin shock, although it seems to prevent the acidosis in some extent.