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Biomedical subjects

S Motoyoshi

Publications and source records attributed to S Motoyoshi.

At least 37 records · Page 2Linked to original sources

The effect of indomethacin on liver blood flow and oxygen supply-uptake relationship in the dog.

The effects of indomethacin on liver blood flow and oxygen supply-uptake relationship were investigated using a right heart bypass technique. Portal venous blood flow was decreased by the mesenteric vascular effects of indomethacin, which produce intense mesenteric vasoconstriction. Hepatic arterial blood flow was increased and therefore, total liver blood flow was not significantly changed after indomethacin administration. Portal venous oxygen delivery was significantly decreased by reductions in both portal venous blood flow and portal venous oxygen content. Total liver oxygen delivery, however, was not changed after indomethacin administration. This response was caused by a large increase in hepatic arterial oxygen delivery. Liver oxygen uptake and liver oxygen extraction ratio were not changed after indomethacin administration. We conclude, therefore, that total liver blood flow and oxygen delivery were well maintained, even if the mesenteric vascular effects of indomethacin decreased both portal venous blood flow and portal venous oxygen delivery.

Animals↗

The effects of dopamine and dobutamine on liver oxygen supply-uptake relationship in the dog.

The effects of dopamine and dobutamine in various doses on liver oxygen supply-uptake relationship were studied in 12 mongrel dogs. Dopamine 3 and 7 micrograms/kg/min infusion rates and dobutamine 5 micrograms/kg/min infusion rate did not produce any changes in total liver oxygen delivery. On the contrary, total liver oxygen delivery was increased at the 15 micrograms/kg/min dopamine in fusion rate and dobutamine 10 and 15 micrograms/kg/min infusion rates. The ratio of total liver oxygen delivery to the systemic oxygen delivery was increased at the 15 micrograms/kg/min dopamine infusion rate. Liver oxygen extraction ratio was decreased at the 15 micrograms/kg/min dopamine infusion rate and at the same rate of dobutamine. These decreases were due to the increases in oxygen delivery while both oxygen uptakes were avariant from control levels. The results of this study demonstrated that high dose of dopamine (15 micrograms/kg/min) and medium and high doses of dobutamine (10 and 15 micrograms/kg/min) should be useful to increase the liver oxygen delivery. However, these increases in liver oxygen delivery during dopamine and dobutamine infusion were not associated with an improvement in liver oxygen metabolism, since liver oxygen uptake was not changed.

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The selective effects of dopamine and dobutamine on liver circulation in the dog.

The selective effects od dopamine and dobutamine in various doses on liver circulation were studied in 12 mongrel dogs. Dopamine increased portal flow but decreased hepatic arterial flow markedly as infusion rate of dopamine increased. Dopamine 3 micrograms/kg/min infusion rate produced vasodilation in mesenteric vascular bed and the portal flow ratio to cardiac output was significantly increased. Dobutamine increased both portal and hepatic arterial flows at the 5 and 10 micrograms/kg/min dobutamine infusion rates, and decreased hepatic arterial flow at the 15 micrograms/kg/min dobutamine infusion rate. Both dopamine and dobutamine increased total liver flows, however, total liver flow ratio to cardiac output was not increased. Pressure gradient of portal system was not changed during dopamine and dobutamine infusion, since both portal venous pressure and hepatic venous pressure were avariant from control values. These findings suggest that congestive hyperemia was not occurred in intrahepatic portal vascular system when portal flows were increased during dopamine and dobutamine infusion. The results of this study demonstrate that both dopamine and dobutamine did not produce selective increases in total liver blood flow. In addition, both agents should be safe to use to the normal liver patient; total liver blood flow did not decrease and intrahepatic congestive hyperemia was not occurred when portal flow was increased.

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Effect of food on liver circulation in conscious dog.

Hepatic hemodynamics and the liver oxygen supply-uptake relationship, in response to eating, were investigated in a chronically catheterized conscious dog method. Portal venous pressure was significantly increased after eating, however was within the normal range reported previously. Hepatic venous pressure correlated well with portal venous pressure throughout the experiment, therefore, the pressure gradient of the portal system was unchanged. Hepatic venous oxygen content, correlated well with liver oxygen extraction, was unchanged after eating. Therefore, it is possible to assume that liver oxygen supply-uptake relationship is well maintained during digestion of food.

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The effect of hypovolemic shock and reperfusion on the hepatic oxygen supply-uptake relationship in the dog.

The hepatic oxygen supply-uptake relationship was investigated during hypovolemic shock using a right heart bypass technique. The results were dissimilar to those previously reported in that the ratio of liver oxygen delivery to systemic oxygen delivery was significantly decreased during shock. The decreased ratio was due to a significant decrease in the portal venous oxygen delivery when compared to the decrease in the systemic oxygen delivery. The decrease in portal venous oxygen delivery was caused not only by the decrease in portal venous blood flow, but also by the decrease in oxygen content of portal blood. The ratio of hepatic arterial oxygen delivery, on the other hand, was significantly increased during shock. Hypovolemic shock increased the liver oxygen extraction ratio to nearly 100% of the pre-shock value. These findings suggest a hepatic protective mechanism for matching oxygen uptake to rising hepatic oxygen requirements. Liver oxygen delivery returned to pre-shock value after correction of hypovolemia primarily due to a significant increase in hepatic arterial oxygen delivery. A significant negative correlation between the liver oxygen extraction ratio and the oxygen content of hepatic venous blood was observed. The hepatic venous oxygen content appears to be a simple and appropriate index of liver oxygenation in clinical medicine because it is difficult to evaluate the liver oxygen extraction ratio directly.

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Effects of hypovolemic shock and reperfusion on liver blood flow in the dog.

Liver blood flow was investigated in hypovolemic shock using a modified right heart bypass technique which can obtain accurate portal blood flow. Findings were similar to those previously reported: hepatic blood flow accounted for 34% of cardiac output in this study; 76% of hepatic blood flow was delivered from the portal vein and 24% from the hepatic artery. Hypovolemic shock markedly decreased total liver blood flow by a reduction in portal venous blood flow. The findings of this study provide evidence that mesenteric blood flow is a peripheral circulation circuit where blood flow is restricted during reduced circulatory volume. Development of a hepatic arterial buffer response during hypovolemic shock was confirmed by an increased ratio of hepatic arterial flow to cardiac output. Reduced total hepatic blood flow during hypovolemic shock returned to control flow by an increase in hepatic arterial flow after reperfusion. The results of this study demonstrate that compensated reactions for maintaining liver blood flow mainly due to the hepatic arterial buffer response were functioned both during hypovolemic shock and after elimination of shock.

Animals↗

Glucose transport and glycolytic enzyme activities in erythrocytes of two-year-old thoroughbreds undergoing training exercise.

D-Glucose transport and cytosolic enzyme activities were measured in erythrocytes from 2-year-old thoroughbreds under continuous training exercise (race horses) and compared with those from untrained horses of various ages (sires, mares and untrained 2-year-old thoroughbreds). The activities of the glucose transport and glycolytic enzymes, hexokinase and pyruvate kinase, in the race horses' erythrocytes were elevated to 2-3.5 times above those of untrained horses. There were no significant differences in plasma glucose, triglyceride or IRI concentrations between the horses in training and untrained horses. The increases in glucose transport and glycolytic enzyme activities in their erythrocytes are considered to reflect an increased metabolic activity in the race horses resulting from the training exercises.

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Plasma atrial natriuretic peptide in normal calves during the first 10 days of life.

The concentration and molecular form of the plasma atrial natriuretic peptide (ANP) in normal calves during the first 10 days of life were investigated. The mean (SEM) ANP concentration on the day of birth was 62.7 (5.52) pmol litre-1, and thereafter it decreased progressively and significantly (P < 0.001). After 10 days, the plasma ANP concentration had decreased to normal adult values (11.3 [3.87] pmol litre-1). On the day of birth and 10 days later a single peak corresponding to alpha-ANP alone was detected in the plasma of the calves.

Aging↗

Inhibition of leukotriene production by N-[4-[4-(diphenylmethyl)-1- piperazinyl]butyl]-3-(6-methyl-3-pyridyl) acrylamide (AL-3264), a new antiallergic agent.

The effects of AL-3264, which exhibits a 5-lipoxygenase (5-LO) inhibiting property by blocking histamine H1-receptors and inhibition of histamine release, were examined on leukotriene (LT) production and LT-mediated responses. AL-3264 (1-30 microM) inhibited the A23,187-induced LT production from human leukocytes with almost the same potency as that of nordihydroguaiaretic acid. AL-3264 (30-100 mg/kg, p.o.) inhibited the antigen-induced LT production in the abdominal cavity of passively sensitized rats; its effect was as potent as that of AA-861, a 5-LO inhibitor. AL-3264 (30 microM) suppressed both the initial and sustained phases of the antigen-induced contractions in isolated trachea from actively sensitized guinea pig. Phenidone (3 microM), a dual inhibitor of 5-LO and cyclooxygenase (CO), suppressed the sustained phase, while indomethacin was without effect on either phase. AL-3264 (40-160 mg/kg, p.o.) suppressed the arachidonic acid-induced ear edema in mice, for which 5-LO inhibitors were effective but antihistamines were not. The anti-edematous effect of AL-3264 (160 mg/kg) was reduced by intradermal administration of LTC4 (0.1 microgram). These results suggest that AL-3264 suppresses LT production in vivo and in vitro by inhibiting 5-LO activity, and this property may contribute to the antiallergic effect of AL-3264.

Acrylamides↗

A useful method for differential evaluation of anti-inflammatory effects due to cyclooxygenase and 5-lipoxygenase inhibitions in mice.

This study was performed to establish a useful method for monitoring the effects of inhibitors of 5-lipoxygenase (5-LO) and/or cyclooxygenase (CO) and for differential evaluation of these inhibitors. After oral dosing, CO inhibitors such as indomethacin (20-40 mg/kg) and ketoprofen (40-80 mg/kg), zileuton (5-LO inhibitor, 20-80 mg/kg) and MK886 (5-LO-activating-protein inhibitor, 640 mg/kg) potently suppressed arachidonic acid (AA, 0.25 mg)-induced ear edema in mice. Methysergide (serotonin antagonist, 20 mg/kg) showed a slight anti-edematous effect, while mepyramine (160 mg/kg) and bromelain (320 mg/kg) had no effect. The anti-edematous effects of indomethacin and ketoprofen were reduced by concomitant topical application of prostaglandin E2 (PGE2, 1 micrograms/ear), but not by concomitant intradermal application of leukotriene C4 (LTC4, 0.1 micrograms/ear). On the contrary, the anti-edematous effects of zileuton and MK886 were reduced by LTC4, but not by PGE2. Dual (5-LO and CO) inhibitors such as phenidone (80-160 mg/kg) and BW755C (40-80 mg/kg), which inhibited the biosynthesis of LTB4 13-15 times more potently than that of PGE2 in rat peritoneal exudate cells, also showed anti-edematous effects that were reduced by LTC4, but not by PGE2. These results suggest that the AA (0.25 mg)-induced ear edema in mice is mainly mediated by LTs and PGs and is suitable for evaluating inhibitors of 5-LO and/or CO, and that an application of LTC4 or PGE2 with AA is a useful method for differential evaluation of these inhibitors.

Animals↗

Analysis of longitudinal distribution of pulmonary vascular resistance by use of a five element lumped model.

To analyze longitudinal distribution of pulmonary vascular resistance, we proposed a five element lumped model which partitioned pulmonary circulation into pulmonary arterial, middle and pulmonary venous segment. The validity and anatomical correlation of the model were tested in an isolated, perfused, canine lung lobe preparation with inflow/outflow occlusion techniques. With arterial occlusion, pulmonary arterial pressure fell rapidly and then exponentially. With venous occlusion, pulmonary venous pressure rose suddenly and then exponentially. Theoretical pressure profiles produced by computer simulation of the model well approximated the general characteristics of the experimental traces. Serotonin increased the pressure gradient across the pulmonary arterial segment (delta Pa), whereas histamine increased the gradient across the pulmonary venous segment (delta Pv). Neither drug altered the gradient across the middle segment (delta Pm). The results suggest that the lumped model is a useful concept to understand the longitudinal distribution of pulmonary vascular resistance, and that delta Pa, delta Pm and delta Pv reflect the resistance distribution of anatomical pulmonary arteries, alveolar vessels and pulmonary veins, respectively.

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Cardiovascular effects of dibutyryl cyclic AMP and milrinone under right heart bypass in anesthetized dogs.

To compare the cardiovascular effects of dibutyryl cyclic AMP (DBcAMP) and milrinone, we used the right heart bypass method in intact anesthetized dogs. The preload of the left ventricle was maintained constant throughout the experiment. Therefore, the effects of DBcAMP and milrinone on cardiac contractility and afterload of the left ventricle were investigated respectively without preload influence. DBcAMP and milrinone exhibited marked positive chronotropic-, positive inotropic-, vasodilative- and diuretic-activity. DBcAMP expressed these effects gradually and continuously, whereas milrinone expressed its pharmacological actions rapidly, but for a short duration of time. Both the afterload-reducing and the cardiac contractile force-enhancing activities of DBcAMP were longer lasting than those of milrinone. Mean arterial pressure was not altered by DBcAMP infusion, whereas it was increased significantly (p < 0.05) by milrinone infusion. The results of this study suggested that DBcAMP appeared to be indicated when there is a need to increase cardiac output by reducing afterload and increasing cardiac contractile force gradually and continuously. On the other hand, milrinone would seem to be indicated when the goal is to raise blood pressure rapidly and to increase cardiac output simultaneously.

Animals↗

Changes of plasma osmotic pressure during lactation in rats.

It is known that blood and plasma volume increase during lactation. The present paper examines whether an increase in plasma volume is accompanied by the change in plasma composition or attributed to hydro-dilution. Six dam-nursed pups and six dam-removed pups housed individually were designated as lactating rats and control rats, respectively. The plasma osmotic pressure and hematocrit value (Ht) were measured in the rats on days 3, 5, 7, 10, 13 and 18 of lactation. The total plasma protein (TP) and serum sodium concentration were also measured as they are factors affecting the plasma osmotic pressure. In addition, milk yield was estimated by the Morag technique. On day 5 and after day 10, the osmotic pressure of the lactating rats was found to be significantly lower than that of the control rats. The serum sodium concentration (days 5 and after day 10) and Tp values (days 3, 10 and 18) of the lactating rats were significantly lower than those of the control rats. Except on day 5, the Ht values of the lactating rats were significantly lower than those of the controls. During the period between days 3 and 10, milk yield was increased and it become steady (18 g/12 hr) on days 10 and 18. On and after day 10 when rats secreted a large amount of milk, it is considered that a decrease in the plasma osmotic pressure was mainly attributed to the reduction of sodium concentration by hydro-dilution. The Ht values indicate that an increase in blood volume is mainly through plasma volume rather than blood cell volume in lactating rats.

Animals↗

Changes in reticuloendothelial function in dogs with endotoxin-induced shock.

A shock model was experimentally produced by intravenous injection of a lethal dose (3 mg/kg) of endotoxin under general anesthesia induced by pentobarbital sodium using 7 beagles. The effect of this endotoxic shock on the reticuloendothelial function was investigated. The blood endotoxin concentration peaked immediately after administration and decreased subsequently. However, the value still remained on an increased level (1,051 pg/ml) even at 360 min after endotoxin treatment. The lipid emulsion test as an index of reticuloendothelial phagocytotic activity and the arterial ketone body ratio as an index of the energy charge in the liver decreased after endotoxin treatment and failed to recover during the experiment. Fibronectin, one of opsonic proteins, tended to decrease after injection of the endotoxin and was significantly (p < 0.01) low at 180 and 360 min compared with the value before injection of the endotoxin. These results suggested the depression of the reticuloendothelial function during endotoxin-induced shock.

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Evaluation of extravascular thermal volume in the lung in dogs with endotoxin-induced shock by double indicator dilution method using heat and sodium ions.

Accuracy assessment was undertaken under varying hemodynamic conditions for a lung water volume measurement device which is based on the principle of a double indicator dilution method using heat and sodium ions. Changes in extravascular thermal volume were investigated in dogs with endotoxin-induced shock. The isoproterenol- or propranolol-induced changes in hemodynamics had no effect on the measurement. This confirmed the high accuracy of this measuring method. The measurement revealed a tendency for the extravascular thermal volume to gradually increase (p < 0.05) during endotoxin shock. This confirmed the gradual progression of pulmonary edema during endotoxin shock.

Animals↗

D-glucose transport activities in erythrocytes and hepatocytes of dogs, cats and cattle.

1. The activities of D-glucose transport and hexokinase were investigated in erythrocytes or hepatocytes of dogs, cats and cattle. 2. The mean D-glucose transport activity in erythrocytes of dogs was 6.0 nmol/min/mg protein, half the value of hepatocytes. 3. The activities of D-glucose transport in erythrocytes and hepatocytes or hepatic hexokinase of cats were about one-third of those of dogs. 4. Cattle with low blood glucose concentrations showed considerably low activities of D-glucose transport and hexokinase, about one-third of those of dogs.

Animals↗

[Effect of shikonin and its derivatives, pentaacetylated shikonin (MDS-004) on granuloma formation and delayed-type allergy in experimental animals].

Of twelve reduced and acetylated derivatives of shikonin, a chemical constituent of Shikon, the accelerating activity on granuloma formation and the inhibitory activity on delayed-type allergy were investigated in order to find a compound having more characteristic effect than shikonin on wound healing in experimental animals. As a result, it was found that a reduced and pentaacetylated derivative of shikonin, MDS-004, has more excellent pharmacological activity. MDS-004 (0.1-1 mg/pellet) accelerated dose-dependently felt-pellet-induced granuloma formation when given topically together with felt-pellets in rats. It also produced strong inhibition against delayed-type allergies (ear edema) caused by oxazolone and dinitrofluorobenzene by topical application of up to 1 mg/ear to the ear skin of mice; its potency was far superior to that of shikonin. Orally administered MDS-004, unlike shikonin, inhibited carrageenan-induced hind paw edema, and exhibited tendency to heal acetic acid-induced gastric ulcer in rats. However, MDS-004, as well as commercial wound healing drugs tested and shikonin, did not show any healing action in the incised and open wound models in rats, if applied topically to the wound as 5 and 10% powders. On the other hand, MDS-004 did not produce irritative action on the ear skin at a topical dose of 1 mg/ear different from shikonin, and any behavioral changes after oral administration of 100 mg/kg in mice. These results suggest that a white powder MDS-004, different from deep purple shikonin, has accelerating action on granuloma formation without irritative action and stronger inhibitory action on delayed-type allergy by topical application than shikonin.

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