Relationship between use-dependent effects of antiarrhythmic drugs on conduction and Vmax in canine cardiac Purkinje fibers

The purpose of these experiments was to evaluate the relationship between interval dependent effects of antiarrhythmic drugs on conduction time and Vmax in canine cardiac Purkinje fibers. Standard microelectrode techniques were used to monitor action potential characteristics at two sites along a canine cardiac false tendon and to measure interelectrode conduction time. The maximum rate of voltage rise during phase 0 (Vmax) and conduction time were independent of diastolic interval under control conditions. In the presence of local anesthetic drugs, recovery from drug-induced depression of Vmax and conduction were first order processes with recovery time constants (mean +/- S.D. in seconds) of 0.14 +/- 0.02 (for Vmax) and 0.15 +/- 0.04 (for conduction time) for lidocaine; 0.17 +/- 0.04 and 0.18 +/- 0.05, respectively, for mexiletine; 0.26 +/- 0.05 and 0.27 +/- 0.07 for amitriptyline; and 1.01 +/- 0.31 and 1.00 +/- 0.32 for procainamide. The kinetics of onset of block were studied using a 30-sec pause, followed by a pacing cycle length of 300 msec (for procainamide) or 1 sec (for quinidine). The onset time constants averaged 2.66 +/- 0.53 pulses (for Vmax) and 2.49 +/- 0.42 pulses (for conduction time) in the presence of procainamide; and 4.02 +/- 1.33 pulses (for Vmax) and 3.86 +/- 1.22 pulses (for conduction time) in the presence of quinidine. These experiments show that local anesthetic drugs produce use dependent changes in conduction time in vitro with time constants comparable to simultaneously measured time constants for effects on Vmax. They imply that the use dependence of drug effects on cardiac conduction can be studied quantitatively in vivo by studying the response to changes in activation frequency.     

Effect of antiarrhythmic drugs on the premature action potential duration in canine cardiac Purkinje fibers

We studied the effect of six class I antiarrhythmic drugs, i.e., quinidine (5 micrograms/ml), disopyramide (10 micrograms/ml), procainamide (30 micrograms/ml), flecainide (4 micrograms/ml), lidocaine (4 micrograms/ml) and mexiletine (4 micrograms/ml), on the durations of the basic action potential (APDb) at a cycle length of 500 ms and on the premature APD (APDt) elicited at progressively increasing diastolic intervals (DI) in canine Purkinje fibers. The difference between APDt elicited at diastolic intervals of 100 msec and the earliest APDt elicited at the onset of effective refractory period was defined as the range of APDt. In control this range was 98 +/- 1.8 ms (n = 59). Disopyramide and procainamide did not change the range significantly but the other four drugs decreased it significantly (P less than .01) as follows: quinidine by 50.2%, lidocaine by 60.2%, mexiletine by 61.6% and flecainide by 61.4%. The following four factors contributed to this decrease in range of APDt: shorter duration of APDb, increased effective refractory period/APD ratio, slower kinetics of APD restitution, and shift of normalized restitution curve toward longer APDt values. The magnitude of the contribution made by each of the above factors varied with different drugs. The greatest contributing factor for quinidine was an increased effective refractory period/APD ratio, for lidocaine a slower restitution and for flecainide and mexiletine the shift of the restitution curve. We concluded that antiarrhythmic drugs belonging to the same class have different effects on the range of premature APD and that these effects cannot be predicted from the effect of the drug on APDb alone.     

Reduction of Vmax by QX-314 and benzocaine in neonatal and adult canine cardiac Purkinje fibers

The authors have previously shown that the use-dependent action of lidocaine on the Vmax of canine Purkinje fibers and on intraventricular conduction in the in situ heart undergoes significant developmental changes. In this study, they use standard microelectrode techniques to test whether these age-related differences are due to the charged, more hydrophilic form or to the uncharged, more lipophilic form of a local anesthetic. QX-314, a permanently charged lidocaine derivative, depressed Vmax to a significantly greater extent in adult than in neonatal Purkinje fibers. This difference was due to its use-dependent blocking action and not to its tonic blocking action. The kinetic time constant (tau on) for the development of use dependence was shorter in adults (90 +/- 9 vs. 134 +/- 15 beats; P less than .05), whereas the time constant for recovery from use dependence (tau off) was shorter in neonates (53 +/- 4 vs. 106 +/- 10 sec; P less than .05). QX-314 (3 X 10(-5) M) shifted the curve of Vmax vs. activation voltage in a hyperpolarizing direction by 16.2 +/- 2.4 mV in adults and 5.1 +/- 1.1 mV in neonates (P less than .05). In contrast, the uncharged tertiary amine benzocaine (1 X 10(-5)-5 X 10(-4) M) showed no developmental differences in its effects on Vmax. Adult and neonatal fibers showed comparable tonic block and no use-dependent block. These results extend those of the authors' previous studies and suggest that developmental differences in the action of local anesthetics depend primarily on the use-dependent action of the charged molecular form.     

Determining the effects of memory and action potential duration alternans on cardiac restitution using a constant-memory restitution protocol

Restitution, the dependence of action potential duration (APD) on diastolic interval, may be causally linked to the vulnerability of cardiac tissue to certain types of arrhythmias. While a number of pacing protocols are commonly used to quantify the restitution relation, one of these, the dynamic protocol, may result in the occurrence of APD alternans. However, the effects of APD alternans, and the concomitant alternation in cardiac memory, on the restitution curve are currently not well understood. Alternans preceding a given action potential may cause that action potential to have a different duration from one preceded by action potentials of identical duration. This interaction of alternans and memory can result in a dynamic restitution curve that is not unique. To address this, we have developed a constant-memory restitution protocol that enables the experimenter or modeller to obtain unique, constant-memory restitution curves at all diastolic intervals. Using this protocol, we obtained unique restitution curves for two ionic models of the cardiac action potential in the absence of alternans at all diastolic intervals. A comparison of the unique constant-memory and non-unique dynamic restitution curves for the two models shows that the presence of alternans can significantly alter the shape of the restitution curve compared to when alternans is absent.     

Phospholipase C modulates automaticity of canine cardiac Purkinje fibers

Alpha-1 adrenergic agonists increase cardiac Purkinje fiber automaticity and elevate D-myo-inositol-trisphosphate (IP3) levels. To learn about the relationship between phosphoinositide metabolism and the modulation of cardiac rhythm, we used phospholipase C to activate phosphoinositide hydrolysis in an alpha-1 receptor-independent fashion and determined whether this intervention modulated automaticity. We used standard microelectrode techniques to study automaticity in adult Purkinje fiber bundles, fluorescence microscopy to study fura-2 fluorescence in isolated Purkinje and ventricular myocytes and standard biochemical techniques to measure inositol phosphate production in ventricular myocytes. Phospholipase C increased Purkinje fiber automaticity, a process that was enhanced by 10 mM lithium (which had no effect alone) and suppressed by verapamil or ryanodine (both 10 microM). Superfusion with 12-O-tetradecanoyl-phorbol-13-acetate phorbol ester, phospholipase D and A2, as well as L-alpha-phosphatidic acid, trypsin and D-myo-inositol-1-phosphate, D-myo-inositol-1,4-bisphosphate, IP3 and D-myo-inositol-1,4,5,6-tetrakisphosphate did not affect automatic rate or transmembrane potentials. Biochemical studies of ventricular myocytes demonstrated a phospholipase C-induced increase in intracellular and extracellular IP3, D-myo-inositol-1,4-bisphosphate and D-myo-inositol-1-phosphate at 3 min, with the extracellular increase persisting thereafter. Fluorescence microscopy with fura-2 revealed that phospholipase C increased systolic-free calcium.(ABSTRACT TRUNCATED AT 250 WORDS)     

Characterization of concentration- and use-dependent effects of quinidine from conduction delay and declining conduction velocity in canine Purkinje fibers.

The dynamic response of squared conduction velocity, theta 2, to repetitive stimulation in canine Purkinje fibers with quinidine was studied using a double-microelectrode technique. With stimulation, a frequency-dependent monoexponential increase in conduction delay (CD) and a decline in theta 2 were observed. The exponential rates and changes in steady-state CD and theta 2 were frequency- and concentration-dependent. The overall drug uptake rates describing blockade and the interpulse recovery interval were linearly related and steady-state values of theta 2 were linearly related to an exponential function of the stimulus intervals. Based on first-order binding, the frequency- and concentration-dependent properties of quinidine were characterized by the apparent binding and unbinding rates of 14.2 +/- 5.7 X 10(6) mol-1.s-1 and 63 +/- 12 s-1 for activated and 14.8 +/- 1.0 X 10(2) mol-1.s-1 and 0.16 +/- 0.03 s-1 for resting states. The recovery time constant extracted from the pulse train interpulse interval was 5.8 +/- 1.5 s compared with 5.1 +/- 0.6 s determined from a posttrain test pulse protocol. This study demonstrates that the kinetics of drug action can be derived from measures of impulse propagation. This provides a basis for characterizing frequency-dependent properties of antiarrhythmic agents in vivo and suggests the plausibility of a quantitative assessment of drug binding and recovery rates in man.     

Electrophysiological effects of cesium and tetraethylammonium in canine cardiac Purkinje fibers

Cesium (Cs) and tetraethylammonium (TEA) have been shown to increase action potential duration. However, action potential duration is known to be influenced by the rate of stimulation. In this study, the effect of stimulation rate on action potential characteristics was studied in Cs-treated and TEA-loaded canine Purkinje fiber preparations. Action potentials of Purkinje fibers from Cs-treated and TEA-loaded preparations had longer durations than action potentials of Purkinje fibers from normal preparations. Greater prolongation of action potential duration was observed when the rate of stimulation was reduced in Purkinje fibers from Cs-treated and TEA-loaded preparations than those from normal preparations. Whereas the increase in action potential duration of Purkinje fibers from Cs-treated preparations was accompanied by a significant membrane depolarization, no change in membrane potential was observed in Purkinje fibers from TEA-loaded preparations. In some Cs-treated and TEA-loaded preparations, the prolonged duration observed at slow stimulation rates was associated with the appearance of early afterdepolarizations. Lidocaine and cromakalim, agents known to reduce action potential duration in normal Purkinje fibers, also shortened action potential duration in Purkinje fibers from both Cs-treated and TEA-loaded preparations. However, lidocaine and cromakalim caused a significant membrane depolarization in Cs-treated Purkinje fibers but not in TEA-loaded Purkinje fibers. Our results suggested that although Cs and TEA are capable of producing rate-dependent prolongation of action potential duration and the occurrence of bradycardia-dependent early afterdepolarization, differences exist in Cs-treated Purkinje fibers in terms of the appearance of membrane depolarization at reduced stimulation rate and in the presence of lidocaine and cromakalim.     

Effects of amiloride on pH regulation in canine cardiac Purkinje fibers

Myocardial cells utilize membrane transport systems for proton extrusion as well as internal buffers to preserve pH homeostasis. Our laboratory had shown previously that amiloride (0.01-1.0 mM) causes a time- and dose-dependent increase in action potential duration, early after depolarizations and enhanced automaticity. Ion-selective microelectrode technique was used to evaluate whether the observed electrophysiologic effects of amiloride are linked to inhibition of Na/H exchange and subsequent inability of the myocardial cell to maintain steady-state intracellular pH (pHi), either under normal physiological conditions or in the presence of an imposed acid load. We analyzed different components of intracellular pH transients that occur in response to NH4Cl exposure and washout, which allowed us to quantitatively describe the effects of Na/H exchange inhibition in a multicellular preparation. Amiloride (0.01-1.0 mM) did not change the steady-state pHi, but did cause a dose-dependent increase in both the time for the pHi to reach a minimum value (time-to-peak) during washout of NH4Cl as well as in the absolute minimum value of pHi (peak acid). The effects of amiloride on pHi transients are rapidly reversible and antagonized by physiologic values of extracellular sodium activity. We conclude that Na/H exchange inhibition by amiloride does not cause intracellular acidosis under normal physiologic conditions, despite the dramatic changes in action potential characteristics. However, amiloride affected the time-to-peak and the peak acid value of the pHi transient during NH4Cl washout at concentrations that had no discernible effect on the overall time course of pHi recovery.     

Effects of lidocaine and on slow response and depressed fast response action potentials of canine cardiac Purkinje fibers

Disease may decrease resting potential of cardiac fibers, thereby depressing the upstroke velocity of the action potential, causing slow conduction and reentry. A decrease in resting potential may also cause automaticity. We studied the effects of lidocaine (5 and 20 mg/l) on canine Purkinje fibers with reduced membrane potentials with either depressed Na+-dependent upstrokes (depressed fast responses) or with slow inward (Ca++) current-dependent upstrokes (slow responses). Depressed fast responses were produced by elevating [K+]0 in the perfusate, reducing membrane potential to around -60 mV, without abolishing excitability. Slow responses were produced by either perfusing fibers with a Na+-free, Ca++-rich solution, or by perfusing them with a high [K+]0 Tyrode's solution containing norepinephrine. Lidocaine had a marked depressant effect on depressed fast response action potentials. The drug markedly decreased Vmax and conduction velocity. It sometimes decreased action potential amplitude and caused conduction block. Resting potential was not changed. On the other hand, lidocaine had little effect on slow response action potentials. Resting potential, Vmax and action potential amplitude were not altered nor was conduction changed. The rate of spontaneous impulse initiation was slightly reduced by 5 mg/l of lidocaine but not by 20 mg/l. We conclude that lidocaine does not exert its antiarrhythmic effect by directly depressing the slow inward current but may be antiarrhythmic because it depresses an already depressed fast inward current and can cause conduction block.     

Lubeluzole-induced prolongation of cardiac action potential in rabbit Purkinje fibres

Lubeluzole, a novel neuroprotective compound, has been associated with cases of QT interval prolongation but its effects on the cardiac action potential have not been described to date. Thus, the electrophysiological effects of lubeluzole were studied in rabbit isolated Purkinje fibres. The results demonstrate that lubeluzole (0.001-1 microM) concentration-dependently lengthened action potential duration at 50% and 90% of repolarization (APD50 and APD90) without significantly modifying other parameters. Furthermore, APD lengthening induced by lubeluzole was not significantly decreased by reducing the basic cycle length (from 3,000 to 1,000 ms). The results demonstrate that lubeluzole potently and concentration-dependently increases APD from 0.01 microM, consistent with class III-type antiarrhythmic actions, which is likely to underlie QT interval prolongation induced by the drug.     

Adenosine attenuation of the electrophysiological effects of isoproterenol on canine cardiac Purkinje fibers

Adenosine is known to have effects on electrophysiologic parameters of the sinus node, AV node and atrium and to antagonize isoproterenol-induced increased inotropy in the ventricle. However, the effects on cardiac Purkinje fibers are not well established. Therefore, the purpose of the present experiments was to examine the effects of adenosine alone and adenosine on isoproterenol-treated canine cardiac Purkinje fibers. Microelectrode techniques were used to record transmembrane action potentials. Adenosine alone (10(-7) to 10(-4) M) produced no effects on action potential characteristics of paced fibers. Adenosine in concentrations of 10(-7), 10(-6), 10(-5) and 10(-4) M produced a 15, 24, 44* and 72*% attenuation of isoproterenol (10(-6) M)-induced action potential duration shortening, respectively (*P less than .001). In 7 of 7 fibers depolarized with 22 mM K+, adenosine (10(-4) M) ablated calcium-dependent action potentials restored with isoproterenol (10(-6) M). These effects were antagonized by theophylline (5 X 10(-5) M) and adenosine deaminase (1 U/ml). Action potential shortening due to superfusion of high calcium Tyrode's solution and calcium-dependent action potentials generated in Na+ free-high Ca++ Tyrode's solution were not antagonized by adenosine. Adenosine (10(-5) M) produced a negative chronotropic effect, increasing escape intervals from 2669 +/- 647 to 3702 +/- 717** msec in control fibers and from 1864 +/- 329 to 2658 +/- 399** msec in tyramine (10(-4) M)-treated fibers (**P less than .05), but failed to produce a negative chronotropic response in fibers pretreated with propranolol (10(-7) M).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of aprindine HCl on slow channel action potentials and transient depolarizations in canine Purkinje fibers

The electrophysiologic effects of aprindine hydrochloride were studied on normal Purkinje fibers, on Purkinje fibers superfused with Tyrode's solution containing 22 mM KCl and isoproterenol (1 X 10(-5) M) and on transient depolarizations induced by exposure to acetylstrophanthidin (1.7--2 X 10(-7) M). Aprindine (3 X 10(-6) M) significantly reduces the action potential amplitude and dV/dtmax and shortens the action potential duration but does not alter the resting membrane potential. Transient depolarizations were suppressed by aprindine at a dose of 2 X 10(-6) M. Isoproterenol (1 X 10(-5) M) failed to restore the transient depolarizations after suppression with aprindine. Slow responses induced in K-depolarized, isoproterenol-treated fibers were unchanged by aprindine (3 X 10(-6)-1 X 10(-5) M) in the presence as well as in the absence of acetylstrophanthidin. These experiments suggest that aprindine does not have slow channel blocking properties and that an inward current through the slow channel cannot be considered as the sole basis of the digitalis-induced transient depolarization.     

Effects of quinidine on the transmembrane potentials of young and adult canine cardiac Purkinje fibers

We used standard microelectrode techniques to study developmental changes in the actions of quinidine on the transmembrane potentials of Purkinje fibers obtained from the hearts of adult dogs and of dogs less than 1 month old. Quinidine had no major effect on resting membrane potential and action potential overshoot at either age. It reduced Vmax significantly at a basic cycle length of 500 msec, the magnitude of effect not differing with age. When frequency-dependent effects on Vmax were studied at basic cycle lengths of 1500 and 500 msec, the magnitude of the effect was not age-related nor were the time or number of beats to steady state effect and the recovery from quinidine effect. However, in its actions on repolarization, quinidine did demonstrate age dependence: the magnitude of change was greater in young than in adult fibers. Our results with quinidine are different from those of previous studies in which we showed age dependence of the effects of lidocaine on Vmax and repolarization, with greater effects occurring in the adult than in the neonate. This difference in the ability of lidocaine and of quinidine to modify transmembrane potential characteristics with age emphasizes the differences that exist in the effects of individual antiarrhythmic drugs on the determinants of cardiac electric activity.     

Adenosine and prostacyclin independent electrophysiological effects of dipyridamole in guinea-pig papillary muscles and canine cardiac Purkinje fibers

Dipyridamole was initially introduced as a coronary vasodilator. The exact mechanism of action of dipyridamole on the coronary vasculature is unknown, but proposed mechanisms of action include inhibition of adenosine uptake, increased myocardial prostacyclin production and inhibition of phosphodiesterase activity. The purpose of our study was to examine the electrophysiological effects of dipyridamole on guinea-pig papillary muscles and canine cardiac Purkinje fibers to determine whether similar mechanisms might account for the electrophysiological effects of this compound. Conventional microelectrode techniques were used to record transmembrane action potentials from either guinea-pig papillary muscles or canine cardiac Purkinje fibers. Dipyridamole produces a dose-dependent prolongation of action potential duration with a threshold concentration of approximately 5 X 10(-7) M in tissues from either species. Dipyridamole (10(-5) M) increases action potential amplitude (124 +/- 1 to 127 +/- 1 mV), increases action potential duration (119 +/- 6 to 146 +/- 5 msec) and produces hyperpolarization of the resting potential (-85 +/- 1 to -87 +/- 1 mV) in guinea-pig papillary muscles (n = 27, P less than .05). Dipyridamole (10(-5) M) increases action potential duration (276 +/- 5 to 293 +/- 5 msec) in canine cardiac Purkinje fibers (n = 21, P less than .05). The effects of dipyridamole (5 X 10(-7) M) are neither accentuated by adenosine (10(-4) M) nor attenuated by adenosine deaminase (1 U/ml) Pretreatment with indomethacin (10(-5) M) does not block these effects. Dipyridamole (10(-5) M) produces a negative chronotropic response in canine Purkinje fibers, increases mean escape intervals from 4.9 +/- 0.9 to 7.8 +/- 1.4 sec (n = 8, P less than .05) and fails to suppress slow response action potentials in 22 mM K+ depolarized tissues.(ABSTRACT TRUNCATED AT 250 WORDS)     

Interval-dependent effects of lidocaine on conduction in canine cardiac Purkinje fibers: experimental observations and theoretical analysis

Whereas the interval-dependence of antiarrhythmic drug effects on Vmax is known, the corresponding time-dependence of drug-induced changes in cardiac conduction is not established. The purpose of these experiments was to study the relationship between the time-dependence of lidocaine-induced changes in Vmax and in conduction time. Standard microelectrode techniques were used to monitor conduction and action potential characteristics of Purkinje fibers within free-running canine false tendons. Lidocaine-induced alterations in conduction and Vmax were related to drug concentration and to the preceding diastolic recovery time. At concentrations of 18 to 74 microM, changes in both Vmax and conduction time were an exponential function of diastolic interval, with recovery time constants averaging 123 to 150 msec for conduction time and 138 to 150 msec for Vmax. With higher lidocaine concentrations, changes in Vmax continued to be an exponential function of recovery interval, whereas changes in conduction time consistently deviated from the terminal exponential relationship at short diastolic intervals. These observations are consistent with the predictions of a model based on linear cable theory. Calculations using this model suggest that recovery from moderate drug-induced conduction slowing should proceed with a time course similar to changes in Vmax, whereas recovery from more severe conduction slowing should occur more rapidly than changes in Vmax. These observations suggest that the time dependence of drug effects on conduction in vivo can be analyzed quantitatively in relationship to observations on Vmax in vitro.     

Frequency-dependent actions of phenytoin in adult and young canine Purkinje fibers

Phenytoin has been reported to be particularly effective in the treatment of postoperative ventricular arrhythmias in children. The authors used standard microelectrode techniques to examine the developmental changes in the action of phenytoin on the transmembrane action potential of neonatal and adult canine Purkinje fibers. Their goals were to test whether developmental differences in phenytoin action on the action potential might explain the clinical observations and to evaluate the contribution of use-dependent reduction of Vmax and effects on slow responses to the antiarrhythmic action of phenytoin. In Tyrode's solution with [K+]0 = 4 mM, phenytoin at 5 and 10 micrograms/ml (concentrations comparable to therapeutic plasma levels) had no major effects on action potential characteristics or use dependence at either age. At [K+]0 = 6 mM, on decreasing the drive cycle length from 1300 to 300 msec, phenytoin reduced Vmax significantly and in a concentration-dependent manner. The magnitude of this action was similar at both ages. Conduction times were also significantly prolonged. The time constants for onset of (tau o) and recovery from (tau r) use-dependent block were similar in neonates and adults. The effects of phenytoin on slow responses were significant, although modest, at both ages, but there was no significant effect on conduction. This study indicates that in K+-depolarized Purkinje fibers, use-dependent reduction of the fast Na+ current is a major determinant of the antiarrhythmic action of phenytoin. In contrast to lidocaine and quinidine, no age-related changes in phenytoin action were found, underscoring the different developmental effects of individual antiarrhythmic drugs.     

Developmental changes in the muscarinic stimulation of canine Purkinje fibers

Acetylcholine (ACh) hyperpolarizes adult canine Purkinje fibers and induces a decrease in their automaticity. In Purkinje fibers from young dogs, there is a biphasic effect on automaticity, which increases at low and decreases at high ACh concentrations. We used standard microelectrode techniques to study these actions of ACh. In fibers from young dogs, 10(-10) to 10(-9) M ACh increased automaticity and 10(-5) M ACh decreased automaticity. The decrease was blocked by the M2 muscarinic blocker AFDX-116, whereas the increase was blocked by the predominant M1 blocker pirenzepine. The M2 agonist oxotremorine never increased automaticity. Rather, it decreased automaticity and hyperpolarized adult and young fibers, the former more than the latter. The hyperpolarization and biphasic effect on automaticity of ACh in fibers from young dogs failed to occur after treatment with pertussis toxin, suggesting that these effects are dependent on a pertussis toxin-sensitive G protein. These electrophysiologic studies suggest that postsynaptic M1 and M2 muscarinic processes modulate the automatic response of Purkinje fibers from young dogs and that the postsynaptic M1 pathway is no longer seen in the adult.     

动作电位恢复性质与室颤机制研究

目的 探讨心肌动作电位动态变化在室颤机制中的作用.方法 37只健康雄性3月龄大约克猪随机分为两组:22只猪结扎冠状动脉左前降支第一分支制备心肌梗死模型,15只同家系同月龄大约克猪入选对照组.4周后右室程序刺激猪的在体心肌,三层心肌针式复合电极记录刺激过程中陈旧性梗死心脏和正常结构心脏左室前壁心肌跨壁复极离散度(TDR),动作电位时程(APD)与舒张间期(DI)的动态变化等电生理参数.采用方差分析及q检验.结果 心肌梗死4周后,陈旧性心梗组存活18只,其中12只诱发室颤,刺激周期为(190±5)ms;对照组全部存活,其中5只诱发室颤,刺激周期为(175±5)ms.两组间的差异有统计学意义[(190±5)ms vs (175±5)ms,P=0.001].与正常心脏相比,陈旧性心梗组TDR显著增大[(15.66±4.45)ms vs(25.72±6.70)ms,P=0.001].但是诱发室颤组与未诱发室颤组比较,两组TDR的差异无统计学意义[(20.43±7.01)ms vs(22.32±7.53)ms,P=0.45].心肌APD恢复斜率最大值以及斜率大于1所占的比例从高到低依次为:陈旧性心梗诱发室颤组[MI+VF(+)组],假手术诱发颤动组[SO+VF(+)组],假手术未能诱发颤动组[SO+VF(-)组],陈旧性心梗未能诱发颤动组[MI+VF(-)组].结论 APD恢复性质在室颤的维持机制中占有重要地位.APD恢复曲线越陡峭越容易发生室颤.TDR是心脏固有异质性的表现之一,对室颤的发生不具有明确的预测性.