PubMed Health⌕ Search

Biomedical subjects

H Sada

Publications and source records attributed to H Sada.

At least 37 records · Page 2Linked to original sources
PubMed1986

Depressant action of Ca-antagonists on slow action potentials in guinea pig ventricular muscles.

The depressant action of four Ca antagonists, including a novel drug, tiapamil, on Ca channels was investigated using a conventional microelectrode technique. "All or none" slow action potentials were recorded in K+-depolarized guinea-pig papillary muscles. Verapamil and diltiazem decreased the amplitude and maximum rate of rise (Vmax) of the slow action potentials at concentrations up to 2 microM. The depressant effect of a novel Ca-antagonist, tiapamil, on the slow action potentials was as marked as that of verapamil and diltiazem. However, prenylamine was less potent than the other 3 drugs. In addition, the action of all drugs on the slow action potentials was enhanced as the frequency of stimulation was increased between 0.0083 and 1 Hz. It was concluded that tiapamil, as verapamil and diltiazem, produced a frequency-dependent blockade of the slow Ca channel.

Action Potentials↗
PubMed1985

Effects of diacetyl monoxime (DAM) on slow and fast action potentials of young and old embryonic chick hearts and rabbit hearts.

The effects of the negative inotropic agent, diacetyl monoxime (DAM), were studied on cardiac action potentials in young (3 day old) and old (13-18 day old) embryonic chick hearts and in rabbit papillary muscles. DAM (5-10 mM) decreased the action potential (AP) amplitude, the maximum rate of rise (Vmax), and AP duration of slow and fast APs in both young and old embryonic chick hearts. Concomitantly with these changes, the spontaneous beating rate was increased in young hearts. At 20 mM DAM, the maximum diastolic potential (MDP) was decreased. In fast APs of old embryonic chick hearts, the most prominent effect of DAM was a shortening of AP duration, the effects on AP amplitude, Vmax, and resting potential being less. In rabbit papillary muscles, DAM had little effect on the slow AP parameters except for shortening of AP duration. The onset of the DAM effects was rapid, the peak effect being attained by 5 min in all preparations. Reversal of the effects of DAM upon washout were fast, complete recovery being attained within 10 min. We conclude that DAM suppressed the slow Na+ current present in young chick embryonic hearts. The effects of DAM, up to 10 mM, on Vmax of the fast Na+-dependent APs in old embryonic chick hearts was less, and there was no effect on rabbit hearts. DAM suppressed the slow Ca2+-dependent APs in old embryonic chick hearts but not in rabbit papillary muscles, suggesting that the effect of DAM on the Ca2+ slow channels depends on the species.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1985

Effects of para-substituted beta-adrenoceptor blocking agents and methyl-substituted phenoxypropanolamine derivatives on maximum upstroke velocity of action potential in guinea-pig papillary muscles.

The effects of atenolol (2-5 mmol/l), sotalol (1-2 mmol/l) and pamatolol (0.1-1 mmol/l), together with N-tertiary butyl phenoxypropanolamines with o-methyl (D-2T: 50-100 mumol/l) m-methyl (D-3T: 50-100 mumol/l) and p-methyl (D-4T: 100-200 mumol/l) group as well as with o,p-methyl groups (D-24T) (50-100 mumol/l) on action potentials (APs) were investigated in isolated guinea-pig papillary muscles. All the drugs in these concentrations produced a concentration-dependent reduction of the maximum upstroke velocity (Vmax). The reduction of Vmax in premature APs induced by stimuli interpolated between the basic driving rate of 0.25, 0.1 or 0.027 Hz decayed exponentially during diastolic intervals. The time constants of these decay processes tau for atenolol, pamatolol and sotalol ranged between 260-541 ms, those for D-3T and D-4T between 655-1,166 ms, and D-2T and D-24T between 1,565-1,931 ms. A drug which provided larger tau values caused the reduction of Vmax in a wider range of the frequency.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1985

The calcium channel agonist, Bay K-8644, antagonizes effects of diacetyl monoxime on cardiac tissues.

Effects of a novel slow channel activator, Bay K-8644 (Bay K), were studied on slow action potential (APs) in young and old embryonic chick hearts, and on its antagonism of the effects of diacetyl monoxime (DAM). The slow APs of young hearts are mediated by slow Na+ channels, whereas those of old hearts are mediated by slow Ca2+ channels. In slow APs of old (13-18 days old) embryonic chick hearts superfused with a high (22 mM) K+ solution, Bay K (10-6 M) gradually increased the amplitude, maximum rate of rise (Vmax), and duration of the slow APs. The actions of Bay K persisted for a long time (greater than 30 min) after washout of the drug. DAM (10 mM) depressed the Vmax, duration and amplitude of the slow APs. Some of the changes in slow AP parameters produced by DAM, e.g., Vmax decrease, were antagonized by the addition of Bay K (10(-6) M). In 3-day-old embryonic chick hearts. Bay K potentiated the slow APs and DAM depressed them; Bay K antagonized these effects of DAM. Thus, the actions of Bay K and DAM are likely to be produced, respectively, via the activation and depression of slow Ca2+ channels in old embryonic chick hearts. In addition, the drugs seem to influence slow Na+ channels found in young embryonic chick hearts.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1983

Effects of beta-adrenoceptor blocking agents of N-tertiary butyl derivatives on maximum upstroke velocity of action potential in guinea-pig papillary muscles.

The effects of bufetolol (27.8-138.9 mumol/l), bunitrolol (70.2-351.1 mumol/l), bupranolol (16.2-100 mumol/l), carteolol (60.7-607 mumol/l), D32 (17.3-100 mumol/l), penbutolol (1.5-29.4 mumol/l) and timolol (115.5 and 231.2 mumol/l) on action potentials were investigated in isolated guinea-pig papillary muscles. All these beta-adrenoceptor blocking agents of teritary butyl aminopropranol derivatives produced a concentration-dependent reduction of Vmax at driving rates of 1 Hz, 0.027 Hz and 4 Hz. The reduction was frequency-dependent but at all the rates penbutolol was highest in potency, as estimated by ED30 (0.027 Hz) and ED 50 values (1 and 4 Hz), followed by bupranolol, D-32, bufetolol and bunitrolol. These were followed in turn by timolol and carteolol in ED30 at 0.027 Hz and ED50 at 1 Hz, but by carteolol and timolol in ED50 at 4 Hz. Each log (1/ED) value is a linear function of log n-octanol/water partition coefficient (log P). The slope and intercept (the value at log P = 0) of the line of log (1/ED50) at 4 Hz are steeper and higher, respectively, than those of the lines at the other frequencies. The time course of recovery of Vmax during diastole was studied by assessing Vmax in premature responses at 0.027 Hz, being approximated by a single exponential function. The time constants of recovery (tau) and intercepts (Ao: the value extrapolated to the time of APD90 of the conditioning responses) at the level of ED50 and at 100 mumol/l of the drugs were thus estimated.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1982

Negative inotropic effects of tiapamil (Ro11-1781) and verapamil in rabbit myocardium.

The effects of tiapamil (Ro11-1781) and verapamil on contractility were studied at 1 Hz in isolated rabbit left atrium and right ventricular papillary muscle. The ED50 of tiapamil for the depression of contractility was 33 and 18 times higher than that of verapamil in the former and latter tissue, respectively. In the presence of 100 microM of tiapamil or 10 microM verapamil, the positive staircase phenomenon in papillary muscle was reversed to a negative one. Also, the depression of contractility tended to be less in the first and second responses after a longer interruption of driving stimuli. Both drugs antagonized the inotropic effects of Ca2+ competitively and the pA2 for tiapamil was less than that for verapamil by 1.01. The potency ratios of tiapamil to verapamil for the contractility in this study correspond roughly with those found in clinical use.

Animals↗
PubMed1982

Effects of disopyramide on the maximum rate of rise of action potential (Vmax) in guinea-pig papillary muscles.

The correlation between the steady state and non-steady state depression of Vmax by 50 microM disopyramide was investigated in 2.7, 5.4 and 8.1 mM [K+]o using isolated guinea-pig papillary muscles. An elevation of [K+]o from 2.7 to 8.1 mM strengthened the depressant action of the drug on Vmax (steady state) at 1 to 5 Hz, but attenuated this action at 0.05 and 0.1 Hz. The Vmax-membrane potential (Vm) relationship (steady state) was examined at stimulation rates of 0.1 and 1 Hz by increasing [K+]o from 2.7 to 19 mM. The drug shifted the normalized Vmax-Vm curve at 1 Hz in a hyperpolarizing direction, but shifted the curve at 0.1 Hz upward at Vm between -90 and -65 mV without a shift along the Vm axis. The recovery process of Vmax (non-steady state) was examined by introducing premature stimuli or by interrupting the basic stimulus of 1 Hz for a certain period. The control recovery processes in three [K+]o were approximated by a triple exponential function (the earliest, intermediate and latest components). The drug slowed the intermediate component, but accelerated the latest one (the earliest component was situated within the refractory period) of [K+]o attenuated the depressant action of disopyramide on the Vmax at 0.05 and 0.1 Hz and accelerated the recovery process of Vmax at long diastolic intervals of more than 10 sec was quite unique.

Action Potentials↗
PubMed1981

Phalangeal microgeodic syndrome in childhood: report of seven cases and review of the literature.

Seven cases of phalangeal microgeodic syndrome in childhood are reported. Reviewing the literature, we have found a total of thirty Japanese cases, including the cases of our own. On the other hand, only ten cases have been reported outside Japan. The mean age of onset of the Japanese was six and a half years, which is older than that in the initial description. Of further interest is the fact all the cases in Japan occurred sporadically and exclusively in winter, and regressed spontaneously and fairly rapidly within six months. Furthermore, most of the cases reported in Europe also occurred in the winter months. These facts imply an etiological relationship between the lowered temperature and the bone lesions.

Bone Diseases↗
PubMed1981

Effects of various structurally related beta-adrenoceptor blocking agents on maximum upstroke velocity of action potential in guinea-pig papillary muscles.

The effects of indenolol (7.0-100 mumol/l), befunolol (15.3-250 mumol/l), metoprolol (58.4-1000 mumol/l), Kö707 (7.3-100 mumol/l), D-25 (3.7-100 mumol/l) and Kö1313 (73.9-1000 mumol/l) on action potentials were investigated in isolated guinea-pig papillary muscles. All these aryloxyisopropylaminopropanol derivatives produced a concentration-dependent reduction of V max at a basic rate of 1 Hz. The reduction was less prominent when interstimulus intervals were prolonged. The time course of recovery of V max during diastole was studied by assessing V max in premature responses at 0.25, 0.1 and 0.027 Hz and in responses after interrupting driving stimuli of 1 Hz. The recovery process was approximated by a single exponential function prominent when interstimulus intervals were prolonged. The time course of recovery of V max during diastole was studied by assessing V max in premature responses at 0.25, 0.1 and 0.027 Hz and in responses after interrupting driving stimuli of 1 Hz. The recovery process was approximated by a single exponential function prominent when interstimulus intervals were prolonged. The time course of recovery of V max during diastole was studied by assessing V max in premature responses at 0.25, 0.1 and 0.027 Hz and in responses after interrupting driving stimuli of 1 Hz. The recovery process was approximated by a single exponential function. The results, together with those reported previously (Sada and Ban 1980, 1981), revealed: (1) a significant correlation between potencies of these derivatives for depression of V max at 0.027, 0.25, 1 and 5 Hz and their log n-octanol/water partition coefficients (log P): (2) The time constants of recovery were relatively concentration independent and correlated significantly with the molecular weights. The results suggest that the potency of these drugs for the depression of V max was mainly determined by log P, being modified secondarily by the time constants of recovery which are intimately associated with the molecular weights.

Action Potentials↗
PubMed1981

Frequency-dependent block of nerve conduction by beta-adrenergic blocking agents.

We investigated frequency-dependent effects of 12 beta-adrenergic blocking agents, all 1-aryloxy-3-isopropylaminopropane-2-ol derivatives, on the height of the compound action potential of frog sciatic nerves, using sucrose gap techniques. The order of 1/ED50 of these agents at 0.1 Hz for the reduction of the height was: indenolol greater than D-25 greater than propranolol greater than alprenolol greater than pindolol greater than toliprolol greater than oxprenolol greater than befunolol greater than Kö1313 greater than acebutolol greater than metoprolol greater than atenolol. The order was similar also at 100 Hz. Logarithms of n-octanol/buffer partition coefficients (log P) correlated well with log (1/ED50) at either 0.1, 1, 10 or 100 Hz (p less than 0.01). The order of log [(ED50)0.1 Hz/(ED50)100 Hz] was oxprenolol greater than befunolol greater than propranolol greater than alprenolol greater than toliprolol greater than indenolol greater than Kö1313 greater than pindolol greater than D-25. Molecular weight of these drugs correlated well with the difference of log (ED50)100 Hz and log (ED50)10 Hz from log (ED50)0.1 Hz (P less than 0.05). The results indicate that the local anesthetic potency of these beta-blockers is mainly determined by the lipid solubility of the drugs, being modified by the frequency-dependent component of action which is related to the molecular weight.

Action Potentials↗
PubMed1980

Effects of tocainide and lidocaine on the transmembrane action potentials as related to external potassium and calcium concentrations in guinea-pig papillary muscles.

Effects of lidocaine and tocainide on transmembrane potentials were studied in isolated guinea-pig papillary muscles, superfused with modified Tyrode's solution containing either 5.4, 2.7, 10.0 or 8.1 mmol/l potassium concentration, [K]0. The last solution applied contained either 1.8 (normal [Ca]0) or 7.2 mmol/l [Ca]0 (high [Ca]0. The concentrations of lidocaine and tocainide used were 18.5, 36.9 and 73.9 mumol/l and 43.7, 87.5 and 174.9 mumol/l in 5.4 mmol/l [K]0 solution and 36.9 and 87.5 mumol/l in the other solutions, respectively. At the driving rate of 1 Hz in 5.4 mmol/l "K]0 solution, both drugs produced dose-dependently a reduction of maximum rate of rise of action potential (Vmax), together with a prolongation of the relative refractory period. Vmax decreased progressively as the driving rate was increased from 1 Hz (for lidocaine) and from 0.25 Hz (for tocainide) to 5 Hz. This action was accentuated dose-dependently. A slow component (time constant tau = 232 ms for lidocaine, 281--303 ms for tocainide) and slower component (tau = 2.1--3.8 s for tocainide) of the recovery (reactivation) of Vmax were observed in premature responses at 0.25 Hz and in the first response after interruption of the basic driving rate at 1 Hz. All these effects were accentuated with rising [K]0 and attenuated in the high [Ca]0 solution. Both drugs abbreviated the action potential duration at 50% (APD50) and 90% (APD90) levels at 5.4, 8.1 and 10.0 mmol/l [K]0 but not at 2.7 mmol/l [K]0 nor a high [Ca]0 at 1 Hz. These [K]0-dependent effects of lidocaine on Vmax were successfully simulated by the model proposed by Hondeghem and Katzung (1977), with a slight change in parameter values. The mode of interaction of lidocaine with sodium channels in the open, closed and rested states was deduced from these results.

Action Potentials↗
PubMed1980

Effects of mexiletine on transmembrane action potentials as affected by external potassium concentration and by rate of stimulation in guinea-pig papillary muscles.

1. The effects of mexiletine and quinidine were compared on transmembrane potentials in guinea-pig papillary muscles, using conventional microelectrode techniques. 2. Mexiletine (23.1 mumol/l) decreased the maximum rate of rise of the action potential (Vmax) and increased the ratio of the effective refractory period to the action potential duration at 90% repolarization level (ERP/APD90); these effects were prominent with elevation of the external potassium concentration ([K]o) from 2.7 to 5.4, 8.1 and 10.0 mmol/l. 3. The percentage decrease in Vmax induced by 5 and 10 mumol/l of quinidine was approximately constant in 2.7, 5.4 and 10.0 mmol/l [K]o solutions. 4. The decrease in Vmax produced by mexiletine was progressively increased as the driving rate was raised from 0.25 to 5Hz. This rate-dependent change was pronounced when the concentration was raised from 23.1 to 46.2 and 92.4 mumol/l. 5. Mexiletine in concentrations of 23.1 and 92.4 mumol/l delayed the recovery of Vmax in a premature action potential to the level of Vmax in the conditioning action potentials at the driving rate of 0.25 Hz. 6. It appears that mexiletine exerts its anti-arrhythmic action by a selective depressant effect on depolarized cells (high [K]0) and cells with high frequency discharges, as is the case with lignocaine.

Action Potentials↗
PubMed1980

Effects of acebutolol and other structurally related beta adrenergic blockers on transmembrane action potential in guinea-pig papillary muscles.

The effects of acebutolol (13-134 microM), pindolol (10-50 microM), oxprenolol (16-66 microM) and (+) and (-)-Kö592 (39-193 microM) on action potentials were investigated in isolated guinea-pig papillary muscles. All the drugs reduced Vmax at 1 Hz, dose-dependently. The reduction was less prominent with prolongation of the interstimulus interval until there was virtually no reduction. The time course of recovery of Vmax during diastole was studied by assessing Vmax in premature responses at 0.1 Hz or in responses after interrupting driving stimuli at 1 Hz. Time constants of recovery thus estimated were 12 to 14 sec for acebutolol and pindolol, 3 to 6 sec for oxprenolol and 0.7 to 1 sec for (-)-Kö592. The reduction of Vmax was rate dependent for all the drugs, and at 5 Hz, the order of potency was oxprenolol > pindolol > acebutolol congruent to (-)- and (+)-Kö592. The most potent was alprenolol (3.5-17.5 microM), which we have already studied in detail. At 1 Hz or lower, the action potential duration was shortened by application of all the compounds mentioned except acebutolol, but tended to be longer than in control, at higher rates for all the drugs. We conclude that molecular bulkiness and dimension may be associated with the time constant of recovery, whereas the potency at high driving rates may be correlated roughly linearly with the lipid solubility of the agents.

Acebutolol↗
PubMed1979

Effect of procainamide on transmembrane action potentials in guinea-pig papillary muscles as affected by external potassium concentration.

Effects of procainamide (PA), 0.18, 0.37 and 0.74 mmol/l, on the transmembrane potential were studied in isolated guinea-pig papillary muscles, superfused with modified Tyrode's solution (external K concentration, [K]0 = 5.4 mmol/l) at the basic driving rate of 1 Hz. PA, at 0.37 mmol/l, significantly reduced the maximum rate of rise of action potential (Vmax) with no change in the resting potential. When 2.7 mmol/l [K]0 of the superfusate was exchanged for 15 mmol/l [K]0 solution a decrease in Vmax induced by 0.37 mmol/l PA became more prominent with decrease in resting potential. The reduction of Vmax at steady state was less at lower driving rates (0.25 and 0.5 Hz) and more at higher driving rates (2-5 Hz) than at 1 Hz in 2.7, 5.4 and 10.0 mmol/l [K]0 solution. Such changes were enhanced concentration-dependently by PA at 5.4 mmol/l [K]0. Also, the changes became more significant with an increase in [K]0 from 2.7 mmol/l to 5.4 mmol/l and then to 10.0 mmol/l. The recovery process of Vmax proceeded with two components. The time course of the slow component seen in the Vmax of the first response after interruption of basic driving stimulation at 1 Hz, followed an approximate monoexponential function. The time constants were 6.3, 4.4 and 5.8 s in the presence of 0.18, 0.37 and 0.74 mmol/l PA at 5.4 mmol/l [K]0 and 3.4 and 3.7 s both in the presence of 0.37 mmol/l PA at 2.7 and 10.0 mmol/l [K]0. Vmax values after 30 or 60 s interruption of stimulation were 80-92% of the predrug Vmax value at 1 Hz. The time constants of the first component, estimated by the peeling-off methods at the driving rate of 0.1 Hz, were 11, 31 and 5-22 ms in the presence of 0.37 mmol/l at 5.4, 10.0 and 2.7 mmol/l [K]0 and did not differ significantly from the time constants in control preparations. The results were found to be consistent, to a certain extent, with the model proposed by Hondeghem and Katzung (1977).

Action Potentials↗
PubMed1978

Effect of phentolamine, alprenolol and prenylamine on maximum rate of rise of action potential in guinea-pig papillary muscles.

Effects of phentolamine (13.3, 26.5 and 53.0 micron), alprenolol (3.5, 7.0 and 17.5 micron) and prenylamine (2.4, 4.8 and 11.9 micron) on the transmembrane potential were studied in isolated guinea-pig papillary muscles, superfused with Tyrode's solution. 1. Phentolamine, alprenolol and prenylamine reduced the maximum rate of rise of action potential (.Vmax) dose-dependently. Higher concentrations of phentolamine and prenylamine caused a loss of plateau in a majority of the preparations. Resting potential was not altered by any of the drugs. Readmittance of drug-free Tyrode's solution reversed these changes induced by 13.3 micron of phentolamine and all conconcentrations of alprenolol almost completely but those induced by higher concentrations of phentolamine and all concentrations of prenylamine only slightly. 2. .Vmax at steady state was increased with decreasing driving frequencies (0.5 and 0.25 Hz) and was decreased with increasing ones (2--5 Hz) in comparison with that at 1 Hz. Such changes were all exaggerated by the above drugs, particularly by prenylamine. 3. Prenylamine and, to a lesser degree, phentolamine and alprenolol delayed dose-dependently the recovery process of .Vmax in premature responses. 4. .Vmax in the first response after interruption of stimulation recovered toward the predrug value in the presence of the above three drugs. The time constants of recovery process ranged between 10.5 and 15.0s for phentolamine, between 4.5 and 15.5s for alprenolol. The time constant of the main component was estimated to be approximately 2s for the recovery process with prenylamine. 5. On the basis of the model recently proposed by Hondeghem and Katzung (1977), it is suggested that the drug molecules associate with the open sodium channels and dissociated slowly from the closed channels and that the inactivation parameter in the drug-associated channels is shifted in the hyperpolarizing direction.

Action Potentials↗