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Biomedical subjects

M Nakashima

Publications and source records attributed to M Nakashima.

At least 559 records · Page 31Linked to original sources

Enhancement of avoidance-suppressing effect after repeated administration of haloperidol and serum haloperidol in rats.

Adult male rats of the Wistar strain, which were trained under a discriminated lever-press avoidance schedule (intertrial interval; 25 sec. presentation of conditioned stimuli; 5 sec), were given SC 0.025-0.05 mg/kg of haloperidol at fixed intervals of 1, 3-4 and 7 days. The avoidance-suppressing effect of haloperidol was enhanced in parallel to the number of drug administrations until it attained a maximum level. The intensity of the maximum effect tended to be stronger, and the number of administrations necessary to attain it was smaller, when a higher dose was given. When the administration interval exceeded one day, the enhanced effect remained irreversible one month after withdrawal of drug administration. The enhancement of the effect was produced after repeated administrations in an experimental chamber, but not in a home cage. Temporal changes in serum haloperidol concentration were determined 30-90 min after 0.035 mg/kg given SC to the haloperidol-pretreated and saline-pretreated groups. No significant difference in the pharmacokinetic change was detected between the two groups. These results suggest that learning during the drug effect under repeated exposure to a fixed experimental situation influences the enhancing effect.

Animals↗

Association of stroke and myocardial infarction in children.

A 9-year-old boy with cerebrovascular accident (CVA) and old myocardial infarction with mural thrombi is reported. The cause of the myocardial infarction was congenital coronary artery fistula originating from the left coronary artery and emptying into the right atrium. Although a common cause of strokes in adults, myocardial infarction has infrequently been reported as the source of emboli in children.

Brain↗

Hen egg white ovomacroglobulin has a protease inhibitory activity.

Hen egg white ovomacroglobulin purified by Miller and Feeney without reference to its activity was shown to have a protease inhibitory activity towards trypsin, papain, and thermolysin. It has four subunits of equal molecular weight (175,000 by SDS-PAGE) and each two of which are disulfide bonded. Upon incubation with trypsin it yields a fragment of Mr = 80,000 plus smaller ones. The subunit composition, amino acid composition and a newly found protease inhibitory activity place ovomacroglobulin as a closely related protein to human serum alpha 2-macroglobulin.

Amino Acids↗

Influence of hypothyroid status on dopamine-induced positive chronotropic and inotropic effects on isolated rat atria.

The involvement of alpha- and beta-adrenoceptors in dopamine (DA)-induced positive chronotropic and inotropic effects was investigated in isolated atria from euthyroid and hypothyroid rats. Propranolol at 3 x 10(-7) M remarkably inhibited the positive chronotropic effect of DA in both euthyroid and hypothyroid rats, and 1 x 10(-6) M phentolamine inhibited the effects of DA in the presence of propranolol in hypothyroid rats. Propranolol remarkably inhibited the positive inotropic effect of DA in both euthyroid and hypothyroid rats, while phentolamine was effective only in hypothyroid rats. In atria from reserpinized rats, the pD2-values for DA in both chronotropic and inotropic effects were reduced, but effectiveness of propranolol or phentolamine on DA-induced positive chronotropic and inotropic effects in euthyroid and hypothyroid rats was similar to that in non-reserpinized rats. In hypothyroid rats, DA increased the maximal rate of tension development, which was inhibited by both phentolamine and propranolol. DA shortened the duration of contraction. DA in the presence of phentolamine significantly shortened the duration of contraction but did not in the presence of propranolol. In conclusion the DA-induced positive chronotropic effect is mainly produced by beta-adrenoceptor stimulation in both euthyroid and hypothyroid rats, and also by a alpha-adrenoceptors to some extent in hypothyroid rats. The DA-induced positive inotropic effect is produced by alpha- as well as beta-adrenoceptor stimulation in both groups. However, alpha-adrenoceptors were involved to a greater extent in hypothyroid rats than in euthyroid rats. The stimulation of alpha-adrenoceptors by DA causes an increase in the maximal rate of tension development without a significant change in the duration of contraction, and the stimulation of beta-adrenoceptors by DA causes an increase in the maximal rate of tension development and shortening of the duration of contraction.

Animals↗

Effects of thymoxamine on ouabain-induced arrhythmias in dogs.

The effect of thymoxamine, a pure alpha-adrenoceptor blocking agent, on ouabain-induced arrhythmias was investigated in dogs to clarify whether thymoxamine has an arrhythmogenic or an anti-arrhythmic action. Thymoxamine. 1 mg/kg i.v., inhibited the manifestation of ventricular arrhythmias (VA) and the pressor effect produced by ouabain infusion (1 microgram/kg/min i.v.) as 5 mg/kg i.v. of phentolamine did. Low doses of these drugs did not affect the VA. Simultaneous infusion of phenylephrine (5 micrograms/kg/min i.v.) with ouabain enhanced the manifestation of VA accompanying pressor effects, which were inhibited by thymoxamine (1 mg/kg) in a parallel manner. Infusion of isoprenaline (0.2 microgram/kg min i.v.) with ouabain enhanced the manifestation of VA, but the enhancement was to a lesser extent than with phenylephrine. Thymoxamine, 1 mg/kg, did not affect the VA. The infusion of CaCl2 (20 mg/kg/min i.v.) with ouabain enhanced the manifestation of VA, which was not inhibited by thymoxamine. These results show the possibility that the protective effect of thymoxamine on the manifestation of VA may be mainly associated with inhibitions of pressor effects mediated through vascular alpha-adrenoceptors.

Animals↗

Pharmacological effects of several drugs on the myoepithelium and the vascular smooth muscle of the lactating mammary gland in goats.

The present experiments were performed to investigate whether the responses of the myoepithelium to several drugs would be of a parallel nature with those of the vascular smooth muscle in the lactating mammary gland of goats. The drugs were injected into the mammary artery. Kallikrein, bradykinin, oxytocin, and acetylcholine caused marked milk-ejection with vasodilation in a dose-dependent manner. Marked milk-ejections with high doses of oxytocin were observed despite of accompanying vasoconstriction. The relative order of their potency in milk-ejection activity was kallikrein greater than bradykinin greater than oxytocin greater than acetylcholine: 1 greater than 1/100 greater than 3/1000 greater than 5/1000000. As for the vasodilator activity, the relative potency of the drugs was in the same order: 1 greater than 1/10 greater than 1/1000 greater than 1/10000. Catecholamines, histamine, serotonin, angiotensin-II, vasopressin and high doses of prostaglandin E2 caused dose-dependent vasoconstriction. Isoprenaline, pilocarpine, adenosine, PGI2 and low doses of PGE2 caused dose-dependent vasodilation. But these drugs did not affect milk-ejection. PGE1 decreased milk-ejection and was accompanied by vasodilation. From these experiments it is suggested that the relative order of the potency of secretagogues in milk-ejection activity and in vasodilator activity is nearly equal. It is also suggested that some drugs are different in their effects on the myoepithelium and on the vascular smooth muscle of the lactating mammary gland.

Acetylcholine↗

Effects of calcium antagonists on the alternation of the ST-T complex and associated conduction abnormalities during coronary occlusion in dogs.

1 The effects of Ca2+ -antagonists on the relationships between alternate changes in the ST-T complex in the epicardial electrogram, ST-T alternans, and associated excitation-conduction abnormalities during coronary occlusion were examined in anaesthetized dogs. 2 Epicardial unipolar electrograms, bipolar electrograms (BPEG) and monophasic action potentials (MAP) were recorded with unipolar, composite and suction electrodes, respectively. 3 ST-T alternans was associated with serious conduction delay. During the period of ST-T alternans, the amplitude of MAP changed alternately and the negative deflection of the ST-T complex was associated with a larger MAP. A depression of the TQ level and decrease in the resting potential of MAP were marked. 4 Verapamil (0.2 mg/kg) and diltiazem (0.5 mg/kg) inhibited ST-T alternans, conduction abnormalities, TQ depression and changes in MAP. However, after these drugs, the TQ depression and the decrease in the resting potential were evident after a longer period of occlusion at a time when ST-T alternans, conduction abnormalities and alternate changes in MAP were still inhibited. Dipyridamole (0.5 mg/kg) had no effect on either ST-T alternans or the conduction abnormalities. 5 Verapamil and diltiazem inhibited ST-T alternans and the associated excitation and conduction abnormalities. The effects of these two drugs cannot be explained on the basis of attenuation of the decrease in the resting potential.

Action Potentials↗

Application of pulsatile cardiopulmonary bypass for profound hypothermia in cardiac surgery.

Profound hypothermia with core cooling has been considered unsafe as compared with surface cooling because of the induced metabolic acidosis. We carried out studies on mongrel dogs to determine whether or nor conventional cardiopulmonary bypass with pulsatile blood flow for core cooling could replace the bypass with non-pulsatile flow. The recovery time from anoxic damage of the brain due to circulatory arrest was also studied. Cerebral excess lactate (delta XL) (Huckabee) was determined throughout the course of hypothermia. During the cooling period from 30 degrees C down to 20 degrees C, the mean value of delta XL in the pulsatile group was significantly lower than that in the non-pulsatile group (p less than 0.01). After forty minutes of the first total arrest at 20 degrees C, thirty minutes of pulsatile perfusion tended to eliminate the anaerobic metabolism of the brain caused by the first total circulatory arrest (p less than 0.1). Thus, the anaerobic metabolism in the brain appears to be highly suppressed with pulsatile cardiopulmonary bypass during the cooling period. Correction of congenital heart disease in infancy can probably be more safely performed if pulsatile cardiopulmonary bypass for cooling and rewarming is employed instead of the non-pulsatile bypass.

Animals↗

Effect of calcium antagonists on the electrical alternans of the ST segment during acute coronary occlusion in dogs.

Effects of antagonists on the ST alternans during acute coronary occlusion were examined in dogs. The intravenous administration of verapamil at doses of 0.1 mg/Kg and 0.2 mg/Kg prominently attenuated the degree of alternans. Diltiazem at dose of 0.2 mg/Kg also attenuated the degree of alternans. Dipyridamole at dose of 0.5 mg/Kg did not significantly attenuate the degree of alternans. Verapamil significantly inhibited the ST-segment elevation. After verapamil, ST alternans did not occur even after a longer period of occlusion when changes in QRS complex and the ST-segment elevation were remarkable. It is possible that verapamil inhibits ST alternans by both the protecting effect against ischemic injury and a direct effect on the electrical activity of the myocardial cell membrane.

Acute Disease↗