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Biomedical subjects

M Akima

Publications and source records attributed to M Akima.

At least 73 records · Page 4Linked to original sources
PubMed1981

Effects of N-(2-hydroxyethyl)nicotinamide nitrate (SG-75) on methacholine-induced ECG changes in intact anesthetized rats.

The effects of a newly developed nicotinamide derivative, N-(2-hydroxyethyl)nicotinamide nitrate (SG-75, Nicorandil), were examined in an experimental model of angina pectoris, utilizing methacholine-induced ECG changes as main parameter in intact anesthetized rats. The right carotid artery was exposed and through it a special cannula was inserted to a point near the right and left coronary ostium. Such a device made it possible to inject drugs more selectively into the coronary artery. Single intra-aortic injections of 4 to 8 micrograms of methacholine caused a transient elevation of the ST segment and T wave of the electrocardiogram (ECG). SG-75 (3 mg/kg i.v. or 10 mg/kg p.o.) prevented these changes in the ECG, while a potent vasodilator, papaverine, failed to do so. In the isolated, donor-perfused rat heart, SG-75 (1-30 micrograms) injected into the coronary perfusion system caused dose-dependent vasodilation, while 0.1-0.8 micrograms acetylcholine as well as methacholine produced marked vasoconstriction. SG-75 (10 mg/kg) administered orally to the donor rat inhibited the coronary vasoconstriction produced by the cholinomimetic drugs, whereas papaverine (30 micrograms i.a.) failed to prevent it. The inhibitory effects of SG-75 on methacholine-induced ECG changes in intact rats seemed to be due to its spasmolytic action.

Acetylcholine↗
PubMed1981

The hypotensive mechanisms of the new anti-anginal drug, N-(2-hydroxyethyl)nicotinamide nitrate (SG-75) in beagle dogs.

The hypotensive mechanisms of N-(2-hydroxyethyl) nicotinamide nitrate (SG-75, Nicorandil) were studied in anesthetized dogs. Intravenous injections of SG-75 (0.03-1 mg/kg) decreased systemic blood pressure (SBP) and increased peripheral (coronary, renal, mesenteric and femoral) blood flow (PBF) dose-dependently. The duration of the PBF increase, however, was much shorter than that of the SBP decrease. When peripheral vascular beds were perfused by means of a pump under a constant perfusion pressure near the SBP, the duration and magnitude of the SBP decrease and the PBF increase were equal. In doses of 0.03-0.3 mg/kg i.v., SG-75 did not significantly affect pulse pressure, heart rate, aortic blood flow, left ventricular pressure (LVP) and LVdP/dt max. Intra-arterial injections of SG-75 (0.003-1 mg) increased coronary, renal, mesenteric and femoral blood flow dose-dependently, without affecting SBP and cardiac function. In heart-lung preparations the drug (0.1-2 mg) did not cause cardiodepression. No hypotensive effect was observed following the administration of SG-75 (3 mg) into the cisterna magna. The results indicate that the hypotensive effect of SG-75 may be due mainly to its peripheral mechanisms, relating to vasodilation.

Animals↗
PubMed1980

Vascularly perfused rat small intestine: a research model for drug absorption.

Rat isolated small intestine was perfused at a fixed flow rate through the superior mesenteric artery with whole rat blood recycled from a devised oxygenator-reservoir. As indicated by perfusion pressure, tissue glucose and oxygen consumption, and histological studies, the perfused intestine remained in a viable state over the perfusion period of 2 hr. Rapid absorption of glucose from the intestinal tract was observed after the intraduodenal injection. When single doses of acetaminophen were injected into the duodenal lumen or poured over the perfused intestine, the absorption was rapid and dose-dependent. Shortly after single intraduodenal injections of salicylamide, salicylamide in free and conjugated forms (sulfate and glucuronide) appeared in the circulating blood. These results indicate that the vascularly perfused intestinal preparation has wide applications in biochemical experimental fields.

Acetaminophen↗
PubMed1980

Pharmacodynamic and metabolism studies on a new coronary vasodilator, N-(2-hydroxyethyl) nicotinamide nitrate (SG-75).

Pharmacodynamics and metabolism of N-(2-hydroxyethyl) nicotinamide nitrate (SG-75) were investigated in rats in relation to its main metabolic product. When SG-75 was orally administered, SG-75 and SG-86, a denitrate compound of SG-75, appeared in the blood. Within 7 yr, approximately 60% of the administered SG-75 were recovered in the urine as SG-86. When administered intraduodenally, SG-75 was rapidly absorbed and transferred in an unaltered form into the portal vein. SG-75 possessed hypotensive and coronary vasodilating actions, while SG-86 had little effect on the cardiovascular system. The coronary vasodilating effects of SG-75 k(0.3-20 micrograms i.a.) were unaffected by the continuous infusion of SG-86 into the coronary perfusion system, even in large doses (50 micrograms/min, or 500 micrograms/min).

Animals↗
PubMed1979

Analysis of the contractile responses of the ileal segment of the isolated blood-perfused small intestine of rats to adenosine triphosphate and related compounds.

For close-arterial injection the isolated small intestine of the rat was perfused by a cross-circulation technique at a fixed flow rate through the superior mesenteric artery with arterial blood from a donor. Single intra-arterial injections of purine derivatives elicited a monophasic fast contraction of the ileum. In order to elucidate the mechanism of the fast contraction, adenosine triphosphate (ATP) was chosen for further investigations. The ileal response to ATP was abolished by tetrodotoxin, hexamethonium or morphine, but was resistant to blockade by atropine, methysergide or mepyramine. These results definitely indicate that ATP causes the fast contraction of the ileum by a stimulation of neuronal elements in the myenteric plexus involving cholinergic interneurons.

Adenine Nucleotides↗
PubMed1979

An analysis of the stimulant effects of 5-hydroxytryptamine on isolated, blood-perfused rat heart.

In rat isolated hearts perfused at a fixed low rate, single injections of 5-hydroxytryptamine (5-HT) (0.1--3 microgram) into the coronary perfusion produced dose-dependent increases in left ventricular (LV) dP/dt max and perfusion pressure (PP), but no clear changes in heart rate. The increases in the LVdP/dt max and PP were not significantly affected by treatment with propranolol, while they were abolished by methysergide. The present study indicates that the positive inotropic and vasoconstrictor responses of the rat heart to 5-HT are not mediated by endogenous catecholamine release, but are induced by a direct action on 5-HT receptors.

Animals↗
PubMed1979

Comparative studies with 5-hydroxytryptamine and its derivatives in isolated, blood-perfused small intestine and ileum strip of the rat.

The mode of actions of 5-hydroxytryptamine (5-HT) and its derivatives, tryptophan (TP), 5-hydroxytryptophan (5-HTP) and 5-hydroxyindole acetic acid (5-HIAA) was studied on the isolated, blood-perfused small intestine and isolated ileum strip of rats. In the isolated, blood-perfused intestinal preparations, 5-HT and 5-HTP injected into the superior mesenteric artery caused a monophasic fast contraction, while TP and 5-HIAA had no effects on the intestine. The contractile responses to 5-HT and 5-HTP were abolished by tetrodotoxin (TTX), hexamethonium (C6) and morphine, but were resistant to blockade of either atropine, methysergide or phentolamine. On the other hand, in the ileum strip preparations, 5-HT contracted the ileum, but its derivatives had no effects on the ileum. TTX, C6, morphine and atropine failed to prevent the contractile response to 5-HT, whereas methysergide effectively antagonized the response. The present results indicate that 5-HT acts by exciting intramural neuronal elements or by directly contracting the smooth muscle of the intestine. 5-HTP seems to act in the same manner as 5-HT.

Animals↗
PubMed1979

A possible purinergic mechanism for reactive ischemia in isolated, cross-circulated rat kidney.

The isolated kidney of the recipient rat was perfused at a fixed flow rate with blood from a donor by a cross-circulation technique. The renal vasculature responded to the release of arterial occlusion with vasoconstriction, the magnitude of which was increased with increase in the duration of occlusion. ATP, ADP, AMP, adenosine, noradrenaline and 5-HT injected into the renal artery induced a prominent vasoconstriction; IMP and inosine had only a weak vasoconstrictor effect even in large doses. Theophylline reduced the vasoconstriction in response to arterial occlusion and to ATP and adenosine but did not affect that produced by noradrenaline or 5-HT. This suggests that adenine compounds, particularly adenosine, may play a role in the genesis of reactive vasoconstriction after arterial occlusion in the isolated rat kidney.

Animals↗
PubMed1979

Femoral vascular responses to purine and pyrimidine derivatives: release of 5-hydroxytryptamine by purine derivatives in isolated, cross-circulated rat hindlimb.

The mode of actions of the purines, adenosine, adenosine-5'-triphosphate (ATP), guanosine and guanosine-5'-triphosphate (GTP), and the pyrimidines, cytidine, cytidine-5'-triphosphate (CTP), thymidine, thymidine-5'-triphosphate (TTP), uridine and uridine-5'-triphosphate (UTP) was investigated in the isolated hindlimb preparation of the rat. A single injection of adenosine, ATP, GTP or UTP into the femoral artery induced a biphasic response, a prominent vasoconstriction preceded by a transient vasodilatation, whereas guanosine and uridine caused only a vasoconstriction. Cytidine, CTP, thymidine and TTP were almost ineffective on the vascular bed. The vasoconstrictor responses to adenosine, ATP, guanosine and GTP were effectively antagonized by either methysergide or reserpine, whereas those to uridine and UTP were not modified by either methysergide or phentolamine. Adenine, D-(-)-ribose and hypoxanthine had no effect on the vascular bed. The 5-hydroxytryptamine (5-HT) release from the hindlimb was fluorometrically determined. The present results provide direct evidence that the vasoconstriction caused by ATP, adenosine, GTP and guanosine is attributed to the release of 5-HT from their stores and that purine nucleotides and nucleosides are capable of releasing 5-HT.

Animals↗
PubMed1978

Vasoconstriction after adenosine and inosine in the rat isolated hindlimb abolished by blockade of tryptaminergic mechanisms.

The isolated right hindlimb of the rat was perfused at a fixed flow rate through the femoral artery with heparinized blood from the carotid artery of a donor. Single injections of adenosine (1--300 microgram) induced a biphasic response, a long-lasting vasoconstriction preceded by a transient vasodilatation. Inosine (1--300 microgram) produced only vasoconstriction. After repeated administration of 300 microgram of these substances, the vasoconstriction became less prominent, and finally reverted to vasodilatation. The vasoconstrictor response to these substances (300 microgram) was also diminished or reverted to vasodilatation after pretreatment with reserpine or methysergide. From these results, it is concluded that vasoconstriction after adenosine or inosine may be mediated by 5-hydroxytryptamine released from the peripheral stores and that the intrinsic direct action of these substances on the femoral vascular bed is vasodilator.

Adenosine↗
PubMed1978

Diffuse infantile fibromatosis.

A boy 15 months old with diffuse infantile fibromatosis in the thigh is reported. A rapidly growing tumor in the right thigh was the only clinical manifestation, suggesting a malignant soft tissue tumor. Macroscopically, the lesion in the medial vastus muscle with an illdefined border gave a pepper and salt appearance. Histologically, the lesion was characterized by an abnormal proliferation of fibroblasts accompanied by some fibrosis, infiltration of chronic inflammatory cells, formation of lymphoid follicles, proliferation of capillaries and the presence of a small number of mature fat cells. No evidence of recurrence is found at present one and half years after operation.

Fibroma↗
PubMed1977

Craniometaphysial dysplasia with leukoencephalopathy. A case report.

A case of craniometaphysial dysplasia with extensive degeneration of the cerebral white matter is presented. The cortex of the swollen part of the long bones was quite thin and there was striking trabecular atrophy. Both the vault and base of the skull showed marked thickening and sclerosis, leaving no interlaminal zone. It is probable that the diffuse degenerative change of the cerebral white matter with gliosis bears some resemblance to that produced by a circulatory disturbance of the great vein of Galen. Due to the narrowed foramen magnum, deformed atlase and axis, and the surrounding postoperative scar, the upper cervical cord was compressed, markedly atrophic and degenerated. Other segments of the cervical and thoracic cord displayed secondary wallerian degeneration and focal neurolytic lesions in the white matter. At the level of Th11 there was a pencil-like malacic lesion, suggesting an apparent interference of circulatory disturbance due possibly to the deformed vertebral column.

Adult↗