Biomedical subjects

M Aomine

Publications and source records attributed to M Aomine.

At least 37 records · Page 2Linked to original sources

PubMed1989

Effects of amiodarone on barium-induced automatic activity in guinea pig ventricular muscle.

1. The electrophysiological effects of a potent antiarrhythmic agent, amiodarone, on BaCl2-induced automaticity of guinea pig ventricular papillary muscle were studied by means of conventional microelectrode techniques. 2. BaCl2 (5 x 10(-4) M) depolarized the maximum diastolic potential of muscle preparation to about -62 mV and induced the spontaneous activity at rate of about 62 beats/min. 3. The application of amiodarone (4.4 x 10(-5) M to 1.1 x 10(-3) M) to the BaCl2-induced automatic muscle fibers decreased the spontaneous rate and slope of slow diastolic depolarization in a dose-dependent manner, associated with insignificant changes in action potential duration. 4. Amiodarone may exert the inhibitory effects of BaCl2-induced automaticity by decreasing steady-state conductance for the Na+ and Ca2+, probably thereby permitting the manifestation of antiarrhythmic properties in combination of its other actions.

Action Potentials↗

PubMed1989

Electrophysiological effects of lidocaine on isolated guinea pig Purkinje fibers: comparison with its effects on papillary muscle.

1. The effects of lidocaine on action potentials of isolated guinea pig Purkinje fibers were examined and compared with those on the papillary muscle, by use of conventional microelectrode techniques. 2. Lidocaine 2.1 x 10(-4) M significantly depressed the resting membrane potential, amplitude, overshoot, maximum upstroke velocity, and duration of action potential of the Purkinje fibers stimulated at cycle length (CL) 1 sec, while the lower concentration (2.1 x 10(-5) M) produced no significant effect. 3. Various parameters of action potentials from the papillary muscle at CL = 1 sec were also depressed by lidocaine 2.1 x 10(-4) M, but the extent of the depression was less marked than in Purkinje fibers. 4. When the Purkinje fibers were stimulated at various CLs (0.3-10 sec), the shortening of action potential duration induced by lidocaine was more evident at slower stimulus rate.

Action Potentials↗

PubMed1989

Comparative effects of tetrodotoxin, lidocaine, and amiodarone on Vmax in guinea pig cardiac Purkinje and papillary muscle fibers.

1. Electrophysiological effects of three drugs (tetrodotoxin, lidocaine, and amiodarone), which are known to depress Na channels in cardiac tissues, were studied on isolated guinea pig Purkinje fibers, by means of microelectrode techniques, and compared the findings with their effects on the ventricular papillary muscle. 2. Special attention was paid with regard to their effects on the maximum upstroke velocity (Vmax) of action potentials. 3. In Purkinje fibers, tetrodotoxin was the most inhibitory for Vmax, then in descending order, amiodarone, and lidocaine. 4. That is, half maximal inhibition (IC50) of Vmax by tetrodotoxin, lidocaine and amiodarone was approximately 1.7 x 10(-5) M, 1.5 x 10(-4) M and 2.8 x 10(-4) M, respectively. 5. As for papillary muscle, higher concentrations of the three drugs were needed to get similar potency. 6. The relationships between the depression in the Vmax and action potential duration are discussed in conjunction with their antiarrhythmic activities.

Action Potentials↗

PubMed1989

Inhibition of tetrodotoxin-sensitive plateau sodium current by amiodarone in guinea pig cardiac muscles.

1. The acute effects of amiodarone (AM), a potent antiarrhythmic drug, on tetrodotoxin (TTX)-sensitive component of action potentials of Purkinje fibers from guinea pig were studied by use of conventional microelectrode techniques, and compared the findings with the results obtained in the papillary muscle. 2. The present study showed that the action potentials of Purkinje fibers (PF) were more sensitive to AM, compared to those of papillary muscle. 3. Acute exposure (30 min) to 4.4 x 10(-5) M AM led to a depression of plateau potential of PF action potential, but the drug did not affect the total action potential duration. 4. TTX (2-4 x 10(-6) M) shortened the PF action potential duration at all levels of repolarization. 5. The depression of PF plateau potential in the presence of AM was, at least in part, involved in a decrease in TTX-sensitive plateau sodium current, because no further depression of the plateau potential was observed by addition of TTX in the presence of AM.

Action Potentials↗

PubMed1989

Suggestive evidence for inhibitory action of amiodarone on Na+, K+-pump activity in guinea pig heart.

1. Effects of amiodarone, a powerful antiarrhythmic agent, on Na+, K+-pump activity were examined on ventricular papillary muscle of guinea pig, by means of conventional microelectrode technique. 2. The activity of Na+, K+-pump was measured by two methods. One of them was to measure the amplitudes of depolarization observed during overdrive stimulation (3.3 Hz) and of hyperpolarization observed after the overdrive stimulation (post-overdrive hyperpolarization), and the other, to measure the hyperpolarization observed following introduction of 10 mM K+, after exposure to K+ free solution for a certain duration. 3. Amiodarone significantly decreased the amplitude of depolarization during overdrive stimulation and the amplitude of post-overdrive hyperpolarization. 4. In the latter method, the deactivation process of hyperpolarization recorded by the introduction of 10 mM K+ following K+ depletion slowed down by amiodarone. 5. These findings suggest that amiodarone may inhibit, at least in part, the Na+, K+-pump activity in the ventricular muscle of guinea pig.

Action Potentials↗

PubMed1989

Differential electrophysiological effects of amiodarone on ventricular muscle and Purkinje fibers in canine one-day-old myocardial infarction.

1. We examined the electrophysiological effects of acute exposure to amiodarone (AM) on ischemic myocardium. 2. Regional myocardial ischemia was performed by occlusion on left anterior descending coronary artery in dog heart. 3. Conventional glass microelectrode techniques were used for electrophysiological investigation of regional ischemia. 4. The effects of AM on action potentials of subendocardial Purkinje fibers and ventricular muscle excised from ischemic area were studied and compared the findings with those obtained from non-ischemic area. 5. Acute exposure to AM, 4.4 x 10(-5) M, prolonged the total duration of action potential in the ischemic ventricular muscle and decreased the maximum upstroke velocity of action potentials significantly. 6. On the other hand, in the ischemic Purkinje fibers, AM produced no significant actions. 7. These findings suggest that AM's antiarrhythmic activity is, at least in part, due to its differential effects on repolarization of ischemic Purkinje fibers and ventricular muscle.

Action Potentials↗

PubMed1989

Tetrodotoxin-sensitive component in action potential plateau of guinea pig Purkinje fibers: comparison with the papillary muscle.

1. The effects of tetrodotoxin on action potentials of isolated guinea pig purkinje fibers were examined and compared the findings with those obtained in the ventricular papillary muscle, by use of conventional microelectrode techniques. 2. Tetrodotoxin (5 x 10(-7)-10(-5) M) decreased the amplitude, overshoot, and maximum upstroke velocity of action potentials of the Purkinje fibers, and shortened the duration of action potential at all levels of repolarization concentration- and stimulus cycle length-dependently. 3. The longer the stimulus cycle length, the greater the shortening by the drug of the action potential duration. 4. In particular, the plateau potential of the Purkinje fibers exposed to tetrodotoxin was remarkably depressed, and which occurred even in case of blockade of K+ conductance, using tetraethylammonium. 5. On the other hand, a high concentration (10(-5) M) of tetrodotoxin did not significantly affect the papillary muscle action potentials. 6. These findings suggest that there is a tetrodotoxin-sensitive component of Na+ current in plateau voltage range of the Purkinje fibers, but little in the papillary muscle, and that the component plays an important role to maintain the plateau of Purkinje fibers action potential.

Action Potentials↗

PubMed1989

Electrophysiologic effects of a short-chain acyl carnitine, L-propionylcarnitine, on isolated canine Purkinje fibers.

The effects of L-propionylcarnitine (PC), a derivative of L-carnitine, on action potentials of canine Purkinje fibers in vitro, were studied under acidic conditions (pH 6.9), using conventional microelectrode techniques. The concentrations of 10(-5) M to 3 X 10(-3) M had no significant effect on action potential amplitude, maximal upstroke velocity of phase 0, and resting potential. However, higher concentrations of PC (10(-2) M and 3 X 10(-2) M) decreased some of these action potential parameters and such high concentrations of PC consistently prolonged the action potential duration (APD), most of which was attributed to the lengthening of phase 3. Under hypoxic conditions (PO2 less than or equal to 40 mm Hg) the drug (10(-2) M) also lengthened the APD with eventual cancellation of the hypoxia-induced shortening in the APD. The drug also prolonged the APD of slow response with a slight decrease in Vmax. In addition, PC significantly (p less than 0.05) depolarized the maximal diastolic potential of the fibers only at low [K+]o (less than or equal to 2.7 mM) and not at high [K+]o (greater than or equal to 5.4 mM). These observations suggest that the PC-induced prolongation of APD is, at least in part, due to a decrease in membrane K+ conductance, an effect partly shared with other amphiphilic intermediates of lipid metabolism, such as palmitylcarnitine or lysophosphatidylcholine.

Action Potentials↗

PubMed1988

Multiple electrophysiological actions of amiodarone on guinea pig heart.

The cellular electrophysiologic effects of acute exposure to amiodarone (AM) on guinea pig papillary muscle (PM) and Purkinje fibres (PF) were investigated by means of conventional microelectrode techniques. Superfusion with AM less than 1.1 x 10(-4) mol/l reduced the maximum rate of rise (Vmax) of the action potential (AP) upstroke phase 0 of both PM and PF stimulated at 1 Hz, without changing resting membrane potential (RMP) or action potential duration (APD). AM greater than 1.1 x 10(-4) mol/l decreased APD at all levels, accompanied by decreases in Vmax and RMP. PF AP's were much more sensitive to AM than PM. In contrast, chronic exposure (20 mg/kg/day, 3 1/2 weeks) prolonged PM APD at all levels and decreased Vmax. In addition, acute exposure shifted steady state inactivation of Vmax by 4-7 mV to more negative potentials. The decrease of Vmax was frequency- and concentration-dependent. Half-maximal inhibition (IC50) of Vmax by AM was affected by K+-induced membrane depolarization (in 4 mmol/l K+, IC50 congruent to 2.3 x 10(-4) mol/l; in 8 mmol/l K+, IC50 congruent to 9 x 10(-5) mol/l). Frequency-dependent inhibition of closed Na+ channels by AM was demonstrated and AM increased the time constant for recovery from Na+ channel blockade. Depression of PF plateau by AM was similar to the effects of tetrodotoxin (TTX). Finally, AM depolarized RMP of PM exposed to low K+. The multiplicity of changes suggests that AM exerts inhibitory effects on a number of ionic current components, including at least fast Na+ current, slow inward current, TTX-sensitive plateau and outward K+ currents. Possible implications with respect to the broad spectrum of antiarrhythmic activity exhibited by AM are considered.

Action Potentials↗

PubMed1988

Effects of L-propionylcarnitine on electrical and mechanical alterations induced by amphiphilic lipids in isolated guinea pig ventricular muscle.

We examined the effects of L-propionylcarnitine (Prop. C), a short-chain acylcarnitine, on amphiphile (L-lysophosphatidylcholine or L-palmitoylcarnitine)-induced electrophysiological and ultrastructural changes in isolated guinea pig ventricular papillary muscles, under acidic conditions (pH 6.9). Conventional microelectrode, tension-recording, and electron microscope techniques were used. Both amphiphiles, at a concentration of 10(-4) M, significantly decreased the resting membrane potential, action potential amplitude, and action potential duration, but increased the developed and resting tension. Such amphiphile-induced electrical changes were not observed in muscles pretreated with the beta-blocker, atenolol, although the mechanical changes remained unaffected. The application of Prop. C (10(-2) M), in the continued presence of the amphiphiles caused a return of the action potential duration and the developed tension to the control level. However, the resting potential and action potential amplitude remained unaffected; in fact, the maximum upstroke velocity (Vmax) of the action potential tended to decrease further. Pretreatment with Prop. C prevented all the amphiphile-induced electrophysiological and mechanical changes, except for Vmax. Electron microscopic studies revealed that amphiphile-induced ultrastructural changes were prevented, at least in part, in the presence of Prop. C. Thus, Prop. C antagonizes some of deleterious effects of amphiphiles, such as lysophosphatidylcholine and palmitoylcarnitine, upon the electrical and mechanical activities of the ventricular muscle, under acidic conditions.

Animals↗

PubMed1988

Acute effects of amiodarone on action potentials of isolated canine Purkinje fibers: comparison with tetrodotoxin effects.

1. We compared the acute electrophysiological effects of amiodarone (AM) and tetrodotoxin (TTX) on action potentials of isolated canine Purkinje fibers. All two drugs suppressed action potential amplitude, overshoot, and maximum rate of upstroke of action potential, and shortened action potential duration (APD). 2. However, higher concentrations (4.4 x 10(-4) M) of AM showed differential effects on APD, compared with TTX. 3. These differences between effects of AM and TTX suggest that in case of high concentration of AM the APD-shortening by AM might be masked by AM's other action(s), while in low concentration the APD-shortening effect of AM, probably due to decrease in Na+ and slow Ca2+ current, was predominant.

Action Potentials↗

PubMed1988

Acute effects of amiodarone on action potentials of isolated guinea-pig ventricular muscle exposed to simulated ischemic solution and metabolic inhibitors.

1. Acute effects of an antiarrhythmic agent, amiodarone (AM), on action potentials from isolated guinea-pig ventricular papillary muscles exposed to simulated ischemic solution and Tyrode's solution containing NaCN or dinitrophenol (DNP) were examined. 2. In the papillary muscles exposed to simulated solution (K+ = 6 mM, glucose = 2.3 mM, pH = 7.1, PO2 less than 40 mmHg) or metabolic inhibitors (10(-3) M NaCN or 10(-4) M DNP), resting membrane potential (RMP) and maximum upstroke velocity (Vmax) of action potential were decreased with increasing time to the exposure, and action potential duration (APD) was shortened. In these conditions, addition of 4.4 x 10(-5) M AM produced transient and small increase in the APD and Vmax, followed by progressive APD-shortening and decrease in Vmax and RMP. 3. These results suggest that acute AM's antiarrhythmic effects reported are not due to APD prolonging action (Vaughan Williams Class III) of the drug, but mainly due to its local anesthetic action (Class I).

2,4-Dinitrophenol↗

PubMed1988

Does acute exposure to amiodarone prolong cardiac action potential duration?

1. The acute effects of a potent antiarrhythmic agent, amiodarone (AM), were studied in isolated guinea pig ventricular muscle. Transmembrane action potentials were recorded by conventional microelectrode techniques, and isometric contractile tension, by a strain gauge. 2. Short-term (30 min) exposure to 4.4 x 10(-5) M AM did not significantly effect action potential characteristics, whereas the peak developed tension was significantly depressed. 3. On the other hand, long-term (3-5 hr) exposure to the same concentration of AM led to a significant decrease in the resting membrane potential, amplitude of action potential, overshoot of action potential, maximum upstroke velocity of action potential, and the peak developed tension. However, the duration of action potential at all levels of repolarization was not significantly effected by 4.4 x 10(-5) M AM during the entire duration of the experiment. 4. These results suggest that the acute AM's antiarrhythmic actions reported may be not due to APD-lengthening action, but probably due to other actions (mainly, inhibition of Na+ channels, Ca2+ channels).

Action Potentials↗

PubMed1988

Inhibition by amiodarone of slow response action potentials and contraction in guinea pig ventricular muscle.

1. Effects of an antiarrhythmic agent, amiodarone (AM), on slow response action potentials and contraction of guinea pig ventricular muscle were examined. 2. AM (4.4 x 10(-5) M, 1.1 x 10(-4) M) significantly inhibited the maximum upstroke velocity of slow response action potentials and contraction. 3. As for action potential duration (APD), higher concentration (1.1 x 10(-4) M) of AM significantly shortened the APD, while low concentration (4.4 x 10(-5) M) had little effect on it. 4. These findings strongly suggest that AM blocks slow inward current inflow via Ca2+ channels in the ventricular muscle.

Action Potentials↗

PubMed1987

Differential effects of L-propionylcarnitine on the electrical and mechanical properties of guinea pig ventricular muscle in normal and acidic conditions.

We studied the effects of L-propionylcarnitine (PC) on transmembrane action potentials and isometric contractile tension in isolated guinea pig ventricular papillary muscles. The effects of 5 concentrations of PC (10(-5), 10(-4), 10(-3), 10(-2) and 3 X 10(-2)M) were examined in both normal (pH 7.4) and acidic (pH 6.9) conditions. The concentrations of 10(-5) to 10(-2)M had no significant effect on action potential amplitude, maximum upstroke velocity of phase 0 and resting potential, in either condition. At pH 7.4, action potential duration (ADP) was significantly (P less than 0.05) or insignificantly shortened by the drug depending upon the concentration used. At pH 6.9, however, the APD was prolonged by moderate PC concentrations (10(-3) and 10(-2)M), in which the effective refractory period (ERP) was also lengthened, associated with an increased ERP/APD ratio. In both pH conditions, the highest concentration (3 X 10(-2)M) significantly (P less than 0.05) decreased all these action potential parameters. PC had a biphasic effect on the developed tension. In both pH conditions, low PC concentrations (10(-5) to 10(-3)M) produced an initial augmentation of the contraction, followed by subsequent reduction. The initial augmentation disappeared by pretreatment with reserpine or propranolol, suggesting the involvement of beta-adrenoceptors. In the steady state, all PC concentrations produced a negative inotropic effect at pH 7.4, while at pH 6.9 only high concentrations (10(-2)M and 3 X 10(-2)M) had this effect. These results suggest that the effects of PC in an acidic condition differ considerably from those in a normal pH condition and that limited concentrations of PC (10(-3) to 10(-2)M) may prevent re-entrant arrhythmias from developing under acidic conditions via lengthening of the ERP, without deleterious effects on the contractile force.

Action Potentials↗

PubMed1987

Amiodarone-induced block of sodium current in isolated cardiac cells.

Sodium current (INa) block by amiodarone (AMI) was investigated in isolated single Purkinje and ventricular myocardial cells using the single suction-pipette voltage-clamp technique. AMI produced marked resting block that was enhanced at low holding potentials, findings consistent with a shift in the steady-state INa availability curve to more negative potentials (-16 +/- 3 mV). Resting block was not associated with any change in the time course of INa decay during a depolarizing clamp step. AMI also produced use-dependent block in conjunction with increases in rate (0.5-5.0 Hz) and pulse duration (2-200 msec). These changes are consistent with a slowing of the recovery from inactivation of the sodium channel. Brief depolarizing pulses produced little use-dependent block, suggesting that the onset of drug-induced block is slow. Thus, AMI blocks INa and shifts the availability curve in isolated myocytes, both of which contribute to the net tonic block. The results suggest that both rested state and inactivated state sodium channel block are factors in AMI's antiarrhythmic efficacy.

Amiodarone↗

PubMed1986

Na,K-ATPase activity and repolarization of ventricular action potentials in simian hearts.

We measured Na,K-ATPase activity and ATP content of 4 different areas of the left ventricular muscle of Japanese monkeys (Mucaca fuscata): The apex, base, and epicardium (Epi) and endocardium (Endo) of the free wall. We compared those values with electrical parameters such as action potential duration (APD) and the level of resing potentials. APDs of base and Endo were significantly longer than those of apex and Epi, respectively. There was no significant difference in ATP contents among the four tissues while Na,K-ATPase activity in Epi was significantly higher, thereby indicating that the maximum capacity of the Na,K-pump activity is greater in Epi than in Endo. This observation serves to explain the following differences in electrophysiology characteristics found between Epi and Endo: greater shortening of APD in Endo when the cycle length of stimulation was shortened (from 2,000 to 200 ms) or when ouabain (0.5-1 microM) was applied; larger amplitude of post-overdrive hyperpolarization in Epi; and marked ouabain-induced depolarization of the resting potential in Endo, as compared to Epi. We conclude that the difference in Na,K-ATPase activity accounts for the different electrical behavior observed in Epi and Endo of the simian ventricle.

Action Potentials↗

PubMed1985

Pretreatment with coenzyme Q10 protects guinea pig ventricular muscle from hypoxia-induced deterioration of action potentials and contraction.

Effects of coenzyme Q10 (CoQ10) on hypoxia-induced changes in transmembrane action potentials and isometric tension were studied in isolated guinea pig ventricular papillary muscles. Guinea pigs were pretreated with CoQ10 (60 mg/kg/day i.p., n = 4) or the solvent (n = 4) for 3 consecutive days before the study. The hypoxia for 30 min (Po2 = 40 mmHg) was induced to the preparation twice with a 20 min normoxic perfusion (Po2 = 300 mmHg) intervention. The hypoxia markedly shortened action potential duration (APD) and decreased the developed tension, the effects being more pronounced during the second than the first-induced hypoxia. Pretreatment with CoQ10 or the solvent did not affect the membrane potentials and contractile tension under normoxic conditions. The decreases in APD and the developed tension produced by hypoxia were partially but significantly suppressed in the preparation obtained from CoQ10-pretreated animals. The results suggest that the pretreatment with CoQ10 partially protects the isolated ventricular muscle subjected to hypoxia from the deterioration of action potentials and contraction.

Action Potentials↗