Biomedical subjects

T Sawanobori

Publications and source records attributed to T Sawanobori.

At least 37 records · Page 2Linked to original sources

PubMed1998

Non-dipolarity of heart potentials estimated by magnetocardiography in normal subjects.

We studied non-dipolarity characteristics during ventricular excitation in normal adults and children by magnetocardiography (MCG) by recording magnetic field on the thorax. The source and currents of the electrical dipole from the onset up to 60 ms of ventricular excitation were analyzed in 16 adults and 5 children. A single equivalent current dipole (ECD) was estimated by Sarvas' formula for the sphere model at 1 ms intervals. The non-dipole value (NDV) was calculated from the magnetic field strength at each recording point and theoretically estimated by ECD, representing an index for the non-dipolarity. At 32-34 ms from the beginning of QRS, the mean NDV was a minimum in all subjects suggesting at least a non-dipole component during this period. High NDV (over 5%) were present in most subjects in both the early and late phase compared to this period. Thirteen of 16 adults had a high NDV in the early phase (9.3 +/- 3.0%, mean +/- SD) and all 16 subjects had a high NDV in the late phase (21.5 +/- 10.5%). All 5 children had high NDV in both the early (10.5 +/- 5.4%) and late phases (16.8 +/- 7.9%). A single ECD estimation by MCG showed a relatively low non dipolar component and MCG could be applied to the clinical evaluation of cardiac excitation in both normal and pathological conditions.

Adult↗

PubMed1998

[Differences in exercise blood pressure response between dipper and non-dipper elderly patients with essential hypertension].

We evaluated the circadian variation and exercise stress response patterns of blood pressure (BP) in elderly patients with essential hypertension. Ambulatory BP monitoring for 48 hours every 30 minutes, and treadmill exercise test using a Bruce protocol at PM 3 to 5 were performed in 49 untreated patients with hypertension. Mean daytime (awake), and night-time (sleeping) systolic BP (SBP) and diastolic BP (DBP) values were analyzed by reviewing the patients' diaries, and the nocturnal reduction rate (NRR) of SBP and DBP were calculated according to the following formula. NRR (%) = [(daytime mean-nighttime mean)/daytime mean] x 100. The patients were divided into two groups according to the presence (dipper, n = 25) or absence (non-dipper, n = 24) of a reduction in both SBP and DBP during the night by an average of more than 10% of the daytime BP. Mean values of SBP and DBP measured over 48 hours in the dipper and non-dipper groups were similar. Responses of SBP to dynamic exercise at 2 to 5 minutes in the non-dipper group were significantly smaller than those in the dipper group (p < 0.05). Non-dipper patients with hypertension responded to dynamic exercise stress with smaller increases in SBP than did those in the dipper group. The differences in BP responses to exercise may affect the circadian blood pressure profile in dipper and non-dipper elderly patients with essential hypertension.

Aged↗

PubMed1997

Precordial leads QRST time integrals for evaluation of right ventricular overload in children with congenital heart diseases.

It was previously shown that body surface QRST isointegral maps of the anterior chest were abnormal in patients with right ventricular overload and that the abnormalities varied with hemodynamic status. The QRST isointegral maps were first characterized by using a departure index map for normal controls. The study group consisted of 14 patients with pulmonary stenosis (PS), 20 with tetralogy of Fallot, (TOF) and 43 with atrial septal defect (ASD). The QRST isointegral maps of these three groups were compared with the data on 23 to 65 age-matched normal children. In mean departure index maps, the patients with right ventricular pressure overload (PS or TOF) showed an increase in departure index on the anterior midchest, while those of right ventricular volume overload (ASD) showed two maxima on the anterior and left lateral chest, with a trough-like negative area between them. Since the abnormal findings were seen on the anterior chest, we evaluated the diagnostic usefulness of QRST time integral values for precordial leads of the routine electrocardiogram (ECG) in a second part of this study. The precordial QRST time integral values from 9 patients with PS and 11 with TOF (0-2 years of age, mean 1.1 years) and 22 ASD patients (6-15 years, mean 10.1 years) were compared with those of the age-matched control children. The QRST time integral values of the precordial leads in right ventricular pressure overload were significantly increased in the right precordial leads (V1, V2). In right ventricular volume overload, the QRST time integral values of the V1, V2, V4, and V6 leads demonstrated a significant deviation from those of the control group. Therefore, a discrimination formula was constructed by using the values of these leads, and the criteria derived from this formula revealed good (98%) diagnostic accuracy. In detection of right ventricular overload, the QRST time integral values of the precordial lead ECG, if confirmed in a larger data set, may be useful as a simple screening method.

Adolescent↗

PubMed1997

Multiple modulations of action potential duration by different calcium channel blocking agents in guinea pig ventricular myocytes.

Effects of extracellular applications of different types of Ca2+ channel blocking agents (Mn2+, verapamil, and nisoldipine) on action-potential duration and membrane currents were studied by the whole-cell patch-clamp technique in guinea pig ventricular myocytes. Low concentrations of Mn2+ (1 mM) and verapamil (1 microM) prolonged action-potential duration at 90% repolarization (APD90) with a suppressed plateau phase. Increases in Mn2+ (5 mM) and verapamil (5 microM) shortened APD90 with a further depression of the plateau. Nisoldipine (0.2-1 microM) shortened APD90 without lengthening it. Applications of Mn2+ and verapamil suppressed amplitudes of the L-type Ca2+ current (ICa), the delayed outward K+ current (IK), and the inward rectifier K+ current (IK1). Furthermore, the ratios of ICa:IK inhibition were similar by low and high concentrations of Mn2+ and verapamil. Nisoldipine selectively suppressed ICa without effect on IK and IK1. A low concentration (1 mM) of Mn2+ not only decreased the peak amplitude of ICa but also delayed its decay time course, which caused an increase in late ICa amplitude at the end of a 200-ms depolarizing pulse. Both verapamil and nisoldipine suppressed peak ICa without affecting its decay. Whereas Mn2+ suppressed IBa without changing its decay time course, verapamil and nisoldipine speeded up the IBa decay with suppressed amplitude of IBa. We conclude that different types of Ca2+ channel blocking agents (Mn2+, verapamil, and nisoldipine) diversely modulate APD because of their multiple modes of actions on ICa and IK.

Action Potentials↗

PubMed1996

Electrophysiological effects of clentiazem, a new Ca2+ antagonist, on rabbit hearts.

Electrophysiological effects of clentiazem, a new 1,5-benzothiazepine type Ca(2+) antagonist, were examined in comparison with those of diltiazem in excised rabbit heart preparations. In Langendorff-perfused hearts electrically driven at basic cycle lengths of 400-500 ms, clentiazem (10(-8)-10(-6)M) and diltiazem (10(-8)-10(-6)M) caused a concentration-dependent prolongation of the atrio-His bundle conduction time (A-H interval) without affecting the His bundle-ventricular conduction time (H-V interval). The effects of clentiazem were equivalent to those of diltiazem. In isolated rabbit atrioventricular (A-V) node preparations electrically driven at 400- to 500-ms intervals, clentiazem and diltiazem at >10(-6)M concentrations produced concentration-dependent decreases in action potential amplitude (APA), maximum rate of depolarization (V max), and shortened action potential duration at 20 and 50% repolarization (APD(20) and APD(50)), whereas APD(90) was little affected. Application of 10(-6)M clentiazem prolonged effective refractory period (ERP) of the A-V node by approximately 7% of the control, an effect similar to that of diltiazem. In spontaneously beating sinoatrial (S-A) node preparations, clentiazem l0(-6)M or the higher concentration significantly decreased APA, V(max), and slope of slow diastolic depolarization, while reducing the maximum diastolic potential. The inhibitory effects of clentiazem showed strong suppression of APA and V(max) by 31.1 and 47.2% of the control, respectively, whereas both clentiazem (10(-7)-10(-5)M) and diltiazem (10(-7)-10(-5)M) had no effects on parameters of ventricular APs. These results suggest that dentiazem, like diltiazem, has a preferential inhibitory action on cardiac slow Ca(2+) channels.

Action Potentials↗

PubMed1996

Functions of cardiac ion channels under normal and pathological conditions.

Using the patch clamp technique, normal and abnormal functions of cardiac ion channels were studied. The transient outward K+ current contributes to the early repolarization phase of the action potential as well as to the plateau height and total duration. The latter role is observed in at premature excitations due to slow recovery from inactivation of this current compared to that of the Ca2+ current. Early and delayed afterdepolarizations are produced by multiple components of ionic currents, especially in the former case. Transient inward current is mainly involved in the formation of delayed afterdepolarizations, but the activities can be produced by a different ionic mechanism in rare occasions. Barium-induced automaticity can be brought about by blocking and unblocking of the inward rectifier K+ channels. The ATP-sensitive K+ channels are assumed to play important roles in myocardial ischemia and related conditions. The channels are a target of the K+ channel openers and their functions are modulated by various intracellular factors. While the channel activity is strongly inhibited by intracellular ATP, ATP is necessary for the channel in an operative state. The former effect by ATP is produced by its ligand action, but the latter may be brought about by hydrolysis of MgATP, which may be regulated by the assembly and disassembly of the actin cytoskeleton.

Action Potentials↗

PubMed1996

Effects of antiarrhythmic agents and Mg2+ on aconitine-induced arrhythmias.

The effects of antiarrhythmic agents, including Classes I and IV and 3-10 mM Mg2+ on aconitine-induced arrhythmias were examined using a conventional microelectrode and patch clamp method in Langendorff-perfused rabbit hearts and isolated guinea-pig ventricular myocytes. Intracoronary application of 0.1 microM aconitine induced polymorphic ventricular tachycardia (PVT) which continued for more than 60 minutes. Application of aconitine to ventricular myocytes caused a prolonged action potential duration (APD) and the appearance of early afterdepolarization (EAD) together with the occurrence of an inward hump of the I-V curve around -60 to -40 mV and increased outward current at positive voltages. Application of 10 microM TTX and 5 mM or higher Mg2+ restored aconitine-induced PVT to sinus rhythm in Langendorff-perfused preparations and also shortened the prolonged APD, demonstrating the abolishment of EAD by aconitine in ventricular myocytes. However, antiarrhythmic agents did not exert such effects. In conclusion, the antiarrhythmic actions of Mg2+ and TTX in aconitine-induced arrhythmia are to abolish EAD and shorten the prolonged APD by suppression of the inward Na+ current around -60 to -40 mV.

Aconitine↗

PubMed1996

[A case report of multiple pseudoaneurysms of the left ventricle following acute myocardial infarction].

Multiple pseudoaneurysms of the left ventricle following acute myocardial infarction were successfully repaired in a 50-year-old man. Three days after onset of acute myocardial infarction, we electively performed PTCA on the right coronary artery which was completely occluded at the proximal segment. One month after PTCA, the left ventriculogram revealed multiple pseudoaneurysms of the left ventricle. Primary closure of orifices of the pseudoaneurysms was performed using pledgeted mattress sutures under cardiopulmonary bypass. Histology of aneurysm confirmed the diagnosis of pseudoaneurysm.

Aneurysm, False↗

PubMed1995

Diagnosis of right ventricular overload by body surface QRST isointegral maps in children with postoperative right bundle branch block.

The utility of body surface QRST isointegral maps (QRST-Imaps) for the detection of right ventricular (RV) overload was examined in children with postoperative development of right bundle branch block. In healthy children with no evidence of bundle branch block (n = 31), the QRST-Imap demonstrated a maximum at the left anterior chest and a minimum near the right shoulder with a single dipole distribution. The positive areas extended from the left anterior chest to the left back, and negative areas extended from the right anterior chest to the right back. Children with complete right bundle branch block but without heart disease demonstrated a QRST-Imap that was similar to that seen in normal children. In patients with RV overload (n = 15; 8 with ventricular septal defect and complicated anomaly and 7 with tetralogy of Fallot), the QRST-Imaps were abnormal and demonstrated double maxima, a rightward shift of the maximum, and extension of positive areas to the right chest. In the 10 patients who developed postoperative complete right bundle branch block, 4 had no evidence of RV overload by hemodynamic or echocardiographic assessment and demonstrated a normal QRST-Imap. In the six children who had residual RV overload during hemodynamic assessment, the QRST-Imap was abnormal. These results suggest that the QRST-Imap is a useful method for the detection of RV overload in pediatric patients complicated with conduction disturbances.

Adolescent↗

PubMed1995

QRST isointegral map reflects the sudden reduction of right ventricular pressure after balloon pulmonary valvuloplasty.

To elucidate the mechanism of electrocardiographic changes due to right ventricular pressure overload, serial changes on body surface maps recorded in two children with valvular pulmonary stenosis before and after successful reduction of right ventricular pressure by balloon valvuloplasty (BVP) were studied. Body surface maps and 12-lead electrocardiograms were simultaneously recorded before and 1-1.5 hours, 8 hours, and 5 days after BVP. Before BVP, QRST isointegral maps showed either two maxima or an expanded single maximum on the right anterior chest. These abnormal characteristics become normal or near normal 1-1.5 hours after BVP. Electrocardiographic waveforms and QRS and ST-T isointegral maps showed minimal changes. Changes in QRST isointegral maps were observed near the center of the midanterior chest. These results suggest that increased right ventricular pressure caused a primary repolarization abnormality in the mid-anterior chest that was easily detected by body surface QRST isointegral maps.

Body Surface Potential Mapping↗

PubMed1995

Role for ATP-sensitive K+ channel in the development of A-V block during hypoxia.

The role of the ATP-sensitive K+ channel (IK,ATP) in the development of A-V block during hypoxic interventions was studied using Langendorff perfused rabbit hearts, multicellular rabbit A-V nodal preparations and single guinea-pig ventricular myocytes. With the Langendorff perfused hearts, hypoxic perfusion (PO2 not equal to 40 mmHg) for 30 min caused slowing of the sinus rate and prolongation of the A-H interval without the appearance of blocked beats. Substrate-free hypoxic perfusion induced second or third degree A-V block in 8/10 hearts and substrate-free hypoxic perfusion plus 2-deoxyglucose (5 mM) produced third degree A-V block in 6/6 preparations. Addition of 50 mM glucose in the perfusate restored A-V conduction during hypoxic intervention. Application of glibenclamide, a specific blocker of IK,ATP, prevented the development of second or third degree A-V block during substrate-free hypoxia (n = 6), whereas pinacidil, an opener of IK,ATP, caused development of third degree A-V block during hypoxia (n = 9). Application of theophylline (100 microM) or 8-phenyl-theophylline (10 microM) did not prevent the development of advanced degrees of A-V block during hypoxic interventions. In multicellular A-V nodal preparations, 10 microM glibenclamide prevented the shortening of action potential duration and block development without marked effects on the maximum upstroke velocity of action potentials during hypoxic intervention. In isolated ventricular myocytes studied by the patchclamp method, the substrate-free hypoxia plus 2-deoxyglucose induced the openings of IK,ATP in 9/25 preparations with cell-attached patches, while 2/20 patches exhibited sporadic channel openings in the normoxic condition during comparable observation period. These results suggest that openings of the ATP-sensitive K+ channels play a role in the development and aggravation of advanced A-V block during hypoxic interventions.

Action Potentials↗

PubMed1995

Dual effects of external magnesium on action potential duration in guinea pig ventricular myocytes.

Effects of extracellular magnesium (Mg2+) on action potential duration (APD) and underlying membrane currents in guinea pig ventricular myocytes were studied by using the whole cell patch-clamp method. Increasing external Mg2+ concentration [Mg2+]o) from 0.5 to 3 mM produced a prolongation of APD at 90% repolarization (APD90), whereas 5 and 10 mM Mg2+ shortened it. [Mg2+]o, at 3 mM or higher, suppressed the delayed outward K+ current and the inward rectifier K+ current. Increases in [Mg2+]o depressed the peak amplitude and delayed the decay time course of the Ca2+ current (ICa), the latter effect is probably due to the decrease in Ca(2+)-induced inactivation. Thus 3 mM Mg2+ suppressed the peak ICa but increased the late ICa amplitude at the end of a 200-ms depolarization pulse, whereas 10 mM Mg2+ suppressed both components. Application of 10 mM Mg2+ shifted the voltage-dependent activation and inactivation by approximately 10 mV to more positive voltage due to screening the membrane surface charges. Application of manganese (1-5 mM) also caused dual effects on APD90, similar to those of Mg2+, and suppressed the peak ICa with slowed decay. These results suggest that the dual effects of Mg2+ on APD in guinea pig ventricular myocytes can be, at least in part, explained by its action on ICa with slowed decay time course in addition to suppressive effects on K+ currents.

Action Potentials↗

PubMed1994

Mechanism for reactivation of the ATP-sensitive K+ channel by MgATP complexes in guinea-pig ventricular myocytes.

1. A mechanism underlying reactivation of the adenosine 5'-triphosphate-sensitive K+ (K+ATP) channels by MgATP complexes after run-down was examined in guinea-pig ventricular myocytes using the patch-clamp technique with inside-out patch configuration. 2. After run-down was induced by exposure of the intracellular side of the membrane patch to Ca2+ (1 mM), channel activity was reactivated by exposure and subsequent wash-out of MgATP (2 mM). Addition of inhibitors of various serine/threonine protein kinases to the MgATP solution did not suppress reactivation of the run-down channels. 3. Non- or poorly hydrolysable ATP analogues were unable to reactivate run-down channels. 4. The degree of channel recovery was dependent upon the duration of MgATP exposure. The apparent half-activation value (K1/2) of MgATP for reactivation was decreased with increasing exposure time. 5. Various products of ATP hydrolysis were unable to reactivate run-down channels except a relatively low concentration (100 microM) of ADP exposure. 6. Other nucleotide triphosphates, in the presence of Mg2+, were unable to reactivate rundown channels. 7. Fluorescein 5-isothiocyanate (50 microM), which interacts with lysine residues of the nucleotide-binding site on various ATPases, inhibited K+ATP channel activity. After wash-out, channel activity recovered only slightly. 8. These data suggest that the hydrolysis of ATP is important for reactivation of run-down K+ATP channels but that protein phosphorylation by serine/threonine protein kinases may not be involved. Since no products of ATP hydrolysis could reproduce MgATP-induced channel reactivation and since the degree of channel recovery was dependent upon the duration of MgATP application, the hydrolysis energy appears to be utilized for channel reactivation.

Adenosine Diphosphate↗

PubMed1994

Properties of single potassium channels in guinea pig hepatocytes.

The patch-clamp technique of cell-attached and inside-out configurations was used to study the single potassium channels in isolated guinea pig hepatocytes. The single potassium channels in isolated guinea pig hepatocytes were recorded at different K+ concentrations. A linear single-channel current-voltage relationship was obtained at the voltage range of -80 to -20 mV with slope conductance of 70 +/- 6 pS (n = 10). Under symmetrical high K+ concentration of 148 mM in the cell-attached patch membrane, the I-V curve exhibited a mild inward rectification at potentials positive to + 20 mV. The values of reversal potential was +5 +/- 2 mV (n = 10). When the external potassium concentration ([K+]o) was decreased to 74 mM and 20 mM, the slope conductance was decreased to 48 +/- 2 pS (n = 4) and 24 +/- 3 pS (n = 3), respectively. The reversal potential was changed by 58 mV for a tenfold change in [K+]o, indicating that this channel was highly selective for K+. Open probabilities (Po) of the channel were 73-93% without apparent voltage dependence. The distributions of open time of the channels were fitted to two exponentials, while those of closed time were fitted to three exponentials, exhibiting no voltage dependence. The success rate of K+ channel activity to be recorded was 28% at room temperature, and there were no increases in the success rate nor in the channel opening probabilities at a temperature of 34-36 degrees C. Po in inside-out patches was not changed by application of 1 microM Ca2+ nor 1 mM Mg2+ to the internal side of patch membranes. It is concluded that a novel type of the K+ channels in guinea pig hepatocytes had different properties of slope conductance, channel kinetics, and sensitivity to [Ca2+]i, from those in other species.

Animals↗

PubMed1994

External pH modifies sodium channel block by mexiletine in guinea pig ventricular myocytes.

OBJECTIVE: The aim was to examine the kinetics and the degree of Na+ channel block by mexiletine under different values of external pH to produce a fractional variation of charged and uncharged forms of mexiletine. METHODS: The Na+ current (INa) was recorded using the patch clamp technique of whole cell configuration in guinea pig ventricular myocytes. RESULTS: In the presence of 20 microM mexiletine, INa block developed with a single exponential when depolarising pulse trains of 5 ms were applied to -30 mV from a holding potential of -100 mV at a diastolic interval of 500 ms. At the 30th pulse, the degree of use dependent block of INa was 12.3(SEM 0.41)% (n = 4) of the 1st pulse. When the duration of pulses was prolonged to 200 ms, the degree of use dependent block was increased to 25.6(4.7)%, which had the block development of two exponentials with fast and slow rate constants. The slow component at the 200 ms pulses was comparable to the single exponential component at the 5 ms pulses. Drug binding to the inactivated channel was increased by external alkalinisation, which increased the uncharged form of mexiletine, whereas the block at the 5 ms pulses was not affected by the change of external pH. CONCLUSIONS: Uncharged mexiletine caused use dependent block with a fast rate constant having affinity for the inactivated state of the Na+ channel, while the charged form produced a slow component of the block having affinity for the activated state. Therefore the fraction of the uncharged to the charged form of mexiletine could be one of the important determinants in the development and mechanism of INa block.

Animals↗

PubMed1994

Effects of magnesium on polymorphic ventricular tachycardias induced by aconitine.

We examined the effects of Mg2+ on aconitine-induced polymorphic ventricular tachycardias (PVT) in excised rabbit hearts under Langendorff perfusion and in Purkinje-muscle preparations. Local electrograms using bipolar electrodes and transmembrane potentials with the microelectrode technique were recorded from Langendorff hearts and Purkinje-muscle preparations, respectively. In Langendorff preparations, intracoronary application of 0.1 microM aconitine induced PVT 28.8 +/- 3.4 min after development of regular monomorphic ventricular tachycardias (MVT) in all 18 preparations. Application of 5 and 10 mM Mg2+ restored aconitine-induced PVT to sinus rhythm after 26.8 +/- 3.4 min (n = 9), but < 3 mM Mg2+ was not effective in restoring of sinus rhythm. Increased Mg2+ concentrations < or = 5 mM in the coronary perfusate prevented development of PVT by aconitine. Intracoronary application of 10 microM tetrodotoxin (TTX) also restored aconitine-induced PVT to sinus rhythm after 3.2 +/- 0.8 min (n = 4). Although applications of 50 microM lidocaine, 10 microM flecainide, or 1 microM verapamil could change PVT to MVT, they were not effective in restoring sinus rhythm. In Purkinje-muscle preparations, spontaneous action potentials (AP) from slow diastolic depolarization appeared after aconitine at the maximum diastolic potential of -75.0 +/- 3.7 mV in Purkinje fibers and were conducted to ventricular muscles (n = 5). Spontaneous activity gradually increased in rate and then developed triggered activity arising from early after depolarization (EAD). EAD induced by aconitine always appeared first in Purkinje fibers and later in muscle fibers. Once triggered activities started from EAD, rate, rhythm and amplitudes of APs became fast and variable.(ABSTRACT TRUNCATED AT 250 WORDS)

Aconitine↗

PubMed1994

Subcellular mechanism for Ca(2+)-dependent enhancement of delayed rectifier K+ current in isolated membrane patches of guinea pig ventricular myocytes.

Intracellular Ca2+ augments delayed rectifier K+ current (IK) in cardiac myocytes, which may play a major modulatory role in repolarization of action potentials. We investigated subcellular mechanisms for Ca(2+)-induced enhancement of IK in large-pipette inside-out membrane patches excised from isolated guinea pig ventricular myocytes. When [Ca2+]i was raised from 10(-8) to 10(-6) mol/L, the amplitude of IK measured at +80 mV was increased from 12.0 +/- 2.2 to 19.5 +/- 3.3 pA (P < .01). The enhancement of IK by Ca2+ was dose dependent, with an EC50 of 3.8 x 10(-8) mol/L. A calmodulin antagonist, W7 (50 mumol/L), calmidazolium (100 mumol/L), or HT-74 (20 mumol/L), added to the intracellular solution abolished enhancement of IK by Ca2+, whereas the inactive form of the W7 analogue, W5, had no effect on IK. In the presence of a protein kinase inhibitor with a relatively high specificity for protein kinase C (H7), for protein kinase A (H8 or peptide-type inhibitor PKI), or for calmodulin kinase II (KN-62) or a nonspecific inhibitor of serine/threonine protein kinases (staurosporine), increases in [Ca2+]i still enhanced IK. Ca(2+)-induced enhancement of IK was also observed when Mg2+ and ATP were omitted from the intracellular solution to delete exogenous phosphate donors and when adenylylimidodiphosphate was added to preclude trapped cytoplasmic substrates. Thus, cardiac IK was enhanced by increases in [Ca2+]i at a physiological range via a calmodulin-dependent pathway, which did not involve a phosphorylation process.

Animals↗

PubMed1994

Effects of NS-2, a new class 1 antiarrhythmic agent, and AFD-19, its active metabolite, on ventricular arrhythmias induced by coronary artery occlusion and reperfusion in anesthetized rats: comparison with disopyramide and mexiletine.

We studied the antiarrhythmic effects of NS-2 (4-diisobutylamino-1,1-diphenyl-1-butanol maleate) and AFD-19 (active metabolite of NS-2) on early stage ventricular arrhythmias induced by coronary artery occlusion and reperfusion in anesthetized male rats. These effects were compared with those of disopyramide and mexiletine. Drugs were intravenously administered either before or after coronary occlusion. When administered 5 min before occlusion, 3 mg/kg of NS-2 and AFD-19 exhibited equivalent anti-arrhythmic activity to that of 5 mg/kg of disopyramide and mexiletine, as assessed by reductions in the number of premature ventricular complexes and in the incidences of ventricular tachycardia and ventricular fibrillation. In a dose of 5 mg/kg, the antiarrhythmic effects of NS-2 and AFD-19 were more pronounced. When administered 5 min after coronary artery occlusion, only NS-2 and AFD-19 (in doses of 5 mg/kg) had significant antiarrhythmic effects. None of the drugs influenced the severe ventricular arrhythmias induced by reperfusion when administered 1 min before reperfusion. In conclusion, NS-2 might be effective in reducing the severity of the life-threatening ventricular arrhythmias that occur during acute myocardial infarction.

Amino Alcohols↗