PubMed Health⌕ Search

Biomedical subjects

M Akima

Publications and source records attributed to M Akima.

87 records · Page 5Linked to original sources
PubMed1975

Positive and negative chronotropic response of the S-A node to oxyfedrine.

Direct perfusion of the sinus node artery under a constant pressure of 100 mmHg was carried out in vagotomized dogs. "Selective" injection of L-3-methoxy-omega-(1-hydroxy-1-phenylisopropylamino) propiophenone hydrochloride (oxyfedrine) into the sinus node artery induced three types of chronotropic response; a pronounced sinus tachycardia, an initial bradycardia followed by sustained tachycarcia, or a definite sinus bradcardia alone. The paradoxical sinus bradycardia induced by oxyfedrine was more pronounced at higher doses of the compound, whereas it was nver produced by the injection of isoproterenol. The oxyfedrine-induced sinus tachycardia, which occurred even in reserpinized preparations, was not suppressed by the treatment with tetrodotoxin, hexamethonium or bretylium, but it was selectively inhibited by propranolol. Atropine, tetrodotoxin or hexamethonium did not prevent the occurrence of sinus bradycardia induced by oxyfedrine, and physostigmine failed to enhance the response. The present study indicates that the oxyfedrine-induced tachycardia is mediated mainly by a direct stimulating action on adrenergic beta-receptors, while the bradycardia appears to be induced by a direct depressant action on the S-A node.

Animals↗
PubMedDate not supplied

Methylmercury poisoning in common marmosets--a study of selective vulnerability within the cerebral cortex.

Neuropathological lesions found in chronic human Minamata disease tend to be localized in the calcarine cortex of occipital lobes, the pre- and postcentral lobuli, and the temporal gyri. The mechanism for the selective vulnerability is still not clear, though several hypotheses have been proposed. One hypothesis is vascular and postulates that the lesions are the result of ischemia secondary to compression of sulcal arteries from methylmercury-induced cerebral edema. To test this hypothesis, we studied common marmosets because the cerebrum of marmosets has 2 distinct deep sulci, the calcarine and Sylvian fissures. MRI analysis, mercury assays of tissue specimens, histologic and histochemical studies of the brain are reported and discussed. Brains sacrificed early after exposure to methylmercury showed high contents of methylmercury and edema of the cerebral white matter. These results may explain the selective cortical degeneration along the deep cerebral fissures or sulci.

Animals↗
PubMedDate not supplied

Pharmacological features of the coronary, renal, mesenteric, and femoral vascular beds of rats revealed by intra-arterial administration of drugs.

We investigated the effects of 42 drugs on the circulation in the isolated, blood-perfused heart, kidney, small intestine, and hindlimb of rats and compared them with previously reported results in dogs. Single intra-arterial injections of drugs were made into the perfusion system of the coronary, renal, mesenteric, or femoral vascular bed. The most striking qualitative differences between rats and dogs were observed in vascular responses to nicotine, dipyridamole, 5-hydroxytryptamine (5-HT), lobeline, tetraethylammonium (TEA), and procaine. Nicotine constricted all vascular beds except the coronary bed in dogs, but dilated all four vascular beds in rats. Dipyridamole produced a dilatation in all vascular beds of rats, while it specifically constricted the renal vasculature of dogs. 5-HT constricted all vascular beds of rats, but dilated the coronary vasculature of dogs. Lobeline, TEA, and procaine constricted only the renal vascular bed in dogs, but elicited constriction of all vascular beds of rats.

Animals↗
PubMedDate not supplied

Cardiohaemodynamic effects of long-term intravenous administration of N-(2-hydroxyethyl)nicotinamide nitrate (SG-75), a potent coronary vasodilator: comparison with glyceryl trinitrate.

1. Cardiohaemodynamic changes have been studied in beagle dogs treated with intravenous injections of either 300 micrograms/kg of N-(2-hydroxyethyl)nicotinamide nitrate (SG-75) or 30 micrograms/kg of glyceryl trinitrate three times a day for 1-2 months. Throughout the experimental period, no significant changes in general behaviour, body weights and plasma levels of enzymes and substrates were observed in either the SG-75-or glyceryl-trinitrate-treated groups. 2. At 1 and 2 months after the start of chronic drug administrations, the dogs were anaesthetized and measurements were made of resting systemic blood pressure, pulse pressure, heart rate, right atrial pressure, coronary blood flow, aortic blood flow, left ventricular (LV) pressure and LVdP/dt: there were no significant differences between non-treated dogs and dogs treated chronically with SG-75 or glyceryl trinitrate. 3. The effects of the acute intravenous administration of SG-75 and glyceryl trinitrate were examined in dogs pretreated intravenously with SG-75 (300 micrograms/kg) and glyceryl trinitrate (30 micrograms/kg), respectively, three times a day for 1-2 months. The depressor and coronary vasodilator responses to the two drugs remained unchanged in comparison with those in non-treated dogs. 4. These results indicated that, with the doses used, neigher SG-75 nor glyceryl trinitrate produced changes in sensitivity or tolerance after long-term intravenous administration.

Animals↗
PubMedDate not supplied

Influence of nicorandil, an antianginal agent, on the therapeutic and toxic cardiovascular actions of ouabain in the anaesthetized dog.

The effects of nicorandil were investigated on ouabain-induced cardiovascular actions in pentobarbitone-anaesthetized dogs. Nicorandil (500 micrograms/kg per h) and ouabain (100 micrograms/kg per h), alone and in combination, were infused intravenously to three groups of dogs. Nicorandil gradually decreased systemic blood pressure, pressure-rate product, left ventricular systolic pressure, and coronary vascular resistance, but did not significantly affect heart rate, left ventricular dP/dt max, coronary blood flow, plasma electrolyte concentrations and ECG patterns. The lethal dose of ouabain was 122 micrograms/kg (s.e.m. = 3, n = 6) and the dose required to elicit ventricular premature beats was 63 micrograms/kg (s.e.m. = 3, n = 6). When nicorandil and ouabain were simultaneously infused intravenously, nicorandil did not affect either the lethal dose of ouabain or the dose required to produce ventricular premature beats, but it significantly inhibited the marked increases in coronary vascular resistance and systemic blood pressure induced by ouabain alone. Even in combination with nicorandil, ouabain maintained its own positive inotropic effect. The results indicate that the combination of ouabain with nicorandil may be beneficial in some conditions of angina pectoris.

Angina Pectoris↗
PubMedDate not supplied

Alpha-adrenoceptor antagonistic effects and antihypertensive activity of SGB-1534 in conscious normotensive and deoxycorticosterone acetate (DOCA)-salt hypertensive dogs: comparison with prazosin.

In conscious normotensive and deoxycorticosterone acetate (DOCA)-salt hypertensive dogs, alpha-adrenoceptor antagonistic and antihypertensive actions of SGB-1534, given orally, were compared with those of prazosin. SGB-1534 and prazosin did not markedly influence systemic blood pressure (SBP) and heart rate (HR) in normotensive dogs. These alpha 1-adrenoceptor antagonists inhibited SBP and HR increases induced by i.v. adrenaline in a dose-dependent manner. In DOCA-salt hypertensive dogs, persistent hypotension, accompanied by a reflex tachycardia, occurred after oral administration of SGB-1534 and prazosin. The hypotensive activity of SGB-1534 was much more potent in magnitude and duration than that of prazosin. In isolated canine mesenteric and femoral arteries, SGB-1534, compared to prazosin, elicited a more potent inhibition on the contractile response to a relatively selective alpha 1-adrenoceptor agonist, phenylephrine. It appears that the antihypertensive activity of SGB-1534, like prazosin, is nearly in parallel with its alpha 1-adrenoceptor antagonistic effect.

Adrenergic alpha-Antagonists↗
PubMedDate not supplied

Tissue angiotensin-converting enzyme blockade by MC-838 (altiopril calcium) infused intravenously to miniature pigs: comparison with captopril.

The effect of a new orally active angiotensin-converting enzyme (ACE) inhibitor, calcium(-)-N-[(S)-3-[(N-cyclohexyl-carbonyl-D-alanyl)thio]-2-methyl- prolinate (MC-838, altiopril calcium), on cardiohemodynamics and tissue ACE activity was compared with that of captopril in the anesthetized miniature pig. MC-838 and captopril were infused i.v. for 1 or 3 hr at an equimolar rate of 20 and 10 micrograms/kg.hr-1, respectively. When MC-838 was infused i.v., captopril appeared in approximately 40% of MC-838 in serum, indicating that the amount of serum captopril during the equimolar concentration treatment with MC-838 corresponds to half of serum captopril after the dosing of captopril. During the infusion, the drugs did not significantly affect systemic blood pressure (SBP), heart rate (HR), renal blood flow (RBF) and renal vascular resistance (RVR). MC-838 and captopril, in a similar degree, attenuated the vasoconstrictor response to angiotensin-I (A-I) injected into the renal artery (i.a.), and enhanced the vasodilator one to i.a. bradykinin, 3 hr after the onset of the drug infusion. The animals were sacrificed at 1 and 3 hr after the onset of the infusion of MC-838 or captopril, and the ACE activity in serum and some target organs (lung, kidney, heart, brain and aorta) was determined. Effective activities of MC-838 and captopril occurred in the lung and kidney (only at 3 hr for captopril) where higher ACE activity in a variety of tissues was found, to a lesser degree in the serum (only by captopril) and not at all in the brain, heart and aorta.

Angiotensin-Converting Enzyme Inhibitors↗
PubMedDate not supplied

Comparative cardiovascular effects of a novel angiotensin converting enzyme inhibitor altiopril calcium (MC-838) and captopril in spontaneously hypertensive rats.

The cardiovascular effects of a newly developed angiotensin converting enzyme (ACE) inhibitor, calcium(-)-N-[(S)-3-[(N-cyclohexylcarbonyl-D-alanyl)thio]-2- methylpropionyl]-L-prolinate (MC-838, altiopril calcium), were examined in anesthetized spontaneously hypertensive rats and isolated donor-perfused, rat heart preparations, and compared with those of captopril. Equidepressor doses of MC-838 (0.3 and 3 mg/kg) and captopril (0.03 and 0.3 mg/kg) given i.v. induced dose-dependent decreases in systemic blood pressure, left ventricular systolic pressure (LVSP), LVdP/dT max, and femoral, renal and mesenteric vascular resistance. MC-838 as well as captopril had no significant effects on femoral blood flow (except for 3 mg/kg MC-838) and heart rate (HR). Marked and sustained increases in renal blood flow were observed with the ACE inhibitors. These agents caused two-phase changes in mesenteric blood flow: initial increase followed by decrease. In isolated, donor-perfused rat heart preparations, MC-838 (0.01-1 mg) injected locally into the coronary artery resulted in positive inotropic effects, as indicated by dose-dependent increases in LVSP and LVdP/dT max, with no significant changes in HR, while captopril (0.01-1 mg) had negative inotropic effects. The positive inotropic response to MC-838 appears to be due to Ca++ in the MC-838 solution.

Angiotensin-Converting Enzyme Inhibitors↗
PubMedDate not supplied

Adult adrenal neuroblastoma with extension into inferior vena cava.

An adult left adrenal neuroblastoma that extended into the left renal vein and inferior vena cava is reported. To the best of our knowledge, venous involvement of adrenal tumors has been reported in adrenal cortical carcinomas, but not in neuroblastomas. Differentiation of renal and adrenal tumors is also discussed.

Adrenal Gland Neoplasms↗
PubMedDate not supplied

Chronic liver failure induced by long-term administration of tegafur: a case report.

A 55 year-old man was admitted with massive ascites. Although the laboratory data on admission were compatible with hepatic cirrhosis and remarkable esophageal varices were observed during endoscopy, the imaging findings such as computed tomography and ultrasonographic examination did not confirm hepatic cirrhosis. The patient had no history of alcohol abuse, blood transfusions or acute hepatitis. Serological markers related to viral and autoimmune hepatitis were all negative. Seven years ago, the patient had undergone an operation for colon cancer and has been taking tegafur since then for a total of 55 months. Tegafur was suspected as the causative agent for the liver dysfunction of this patient and the administration of tegafur was stopped. His laboratory data improved gradually and the ascites vanished. The first liver biopsy performed 6 months after discontinuation of tegafur still revealed chronic active hepatitis. However, at the liver biopsy performed 18 months after withdrawal of tegafur, inflammatory activity had subsided and the third liver biopsy, performed 34 months thereafter, revealed further improvement of the pathological changes that had occurred in the liver. We therefore conclude that the administration of tegafur may have caused chronic active liver injury with portal hypertension manifested as ascites and esophageal varices.

Antimetabolites, Antineoplastic↗