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Biomedical subjects

H Toda

Publications and source records attributed to H Toda.

At least 199 records · Page 11Linked to original sources

Cardiac electrophysiologic effects of etafenone hydrochloride (Dialicor), a new antiarrhythmic agent.

The electrophysiologic effects of etafenone hydrochloride (Dialicor) were studied in isolated rabbit hearts and canine or rabbit cardiac tissues with intracellular microelectrode techniques. The concentration range used was 0.25-10 mg/L, except in experiments with direct addition of etafenone into the tissue bath. Etafenone depressed automaticity in the sinus node, atrioventricular junction and Purkinje fibers at concentrations not affecting the action potential contour. In both atrial and ventricular fibers, etafenone prolonged the action potential duration and total refractory period. The action potential upstroke was slowed and conduction time increased. Higher concentrations reduced the resting potential, causing incomplete depolarization. Atrial action potentials were affected at lower concentrations than ventricular and Purkinje action potentials. Occasi-nally, etafenone produced localized conduction block within the atria, usually sparing internodal conduction. In electrically driven hearts, direct recording of His bundle potential as well as surface electrograms revealed marked prolongation of intraatrial and intranodal conduction times, with some increase in His-Purkinje and ventricular conduction times. Depression of atrioventricular conduction was insignificant under sinus rhythm. Possible therapeutic implications of these electrophysiologic effects are discussed.

Action Potentials↗

Characterization of phospholipase A activity of beta1-bungarotoxin from Bungarus multicinctus venom. II. Identification of the histidine residue of beta1-bungarotoxin modified by p-bromophenacyl bromide.

beta1-Bungarotoxin modified with p-bromophenacyl bromide (BPB) was reduced and carboxymethylated, and the resulting two constituent RCM-polypeptide chains (the RCM-A and B chains) were separated. The RCM-A chain was found to be modified by BPB by measuring its UV absorption spectrum and was shown to have lost one histidine residue by analyzing its amino acid composition. To determine the location of the modified histidine residue in the A chain of the toxin, the RCM-A chain was digested with TPCK-trypsin, and the resulting peptides were fractionated by gel filtration followed by DEAE-cellulose chromatography. The modified residue was finally identified as histidine-48 in the A chain by Edman degradation and from the amino acid composition of the BPB-modified peptide. The amino acid sequence around the modified histidine residue in the A chain is highly homologous with those of porcine pancreas phospholipase A2 and presynaptic toxin, notexin. We conclude that histidine-48 in the A chain participates in the phospholipase A activity of beta1-bungarotoxin.

Acetophenones↗

Cardiac electrophysiologic action of carteolol hydrochloride (OPC-1085), a new beta-adrenergic blocking agent.

Cardiac electrophysiologic action of a new beta-adrenergic blocking agent carteolol hydrochloride, or OPC-1085, was studied in either isolated, perfused rabbit hearts or in atrial, ventricular or Purkinje fibers of dogs and rabbits superfused in the tissue bath. Transmembrane potentials were recorded with intracellular microelectrodes and atrioventricular conduction was studied by recording a His bundle electrogram. OPC-1085 at a concentration of 0.1 mg/L shortened the sinus node recovery time, while propranolol at a comparable concentration prolonged it. Isoproterenol-enhanced canine Purkinje automaticity was more markedly depressed by OPC-1085 than by propranolol. In rabbit atrial and ventricular muscle, OPC-1085 up to the concentration of 2 mg/L did not alter the action potential characteristics but tended to shorten the conduction time. At 20 mg/L, OPC-1085 significantly decreased the maximal rate of depolarization and maximal following frequency, and prolonged the action potential duration and conduction time in non-reserpinized as well as reserpinized preparations. On atrioventricular conduction, 0.1 mg/l to 5mg/L of this drug prolonged the St-A and H-V intervals but tended to shorten the A-H interval. All these intervals were prolonged at 20 mg/L. The action potential duration of canine Purkinje-ventricular block developed at higher frequencies of stimulation. In view of the clinical dosage levels, it is sugg ested that the antiarrhythmic effects of OPC-1085 depend predominantly on its beta blocking action. At higher concentrations, OPC-1085 may exert some beta stimulating action, whereas still higher and possibly toxic concentrations could depress conduction through a direct membrane effect.

Action Potentials↗