Mechanism for site-dependent differences in the shape of the resetting response curve in fixed barrier reentry.

INTRODUCTION: We investigated whether the site of stimulation within a reentrant circuit affects the resetting response curve (RRC). RRCs are used to characterize the excitable gap of reentrant circuits, including the duration of the fully excitable gap and the presence of partially excitable tissue. METHODS AND RESULTS: We reset proximal and distal to a site of interval-dependent conduction (IDC) in canine in vitro atrial tricuspid rings. Adjustable reentry allowed changes in the cycle length and direction of reentry. In nine preparations we reset 26 tachycardias. In the 16 tachycardias with one site of IDC, RRCs were significantly different when stimulating distal and proximal to a site of interval-dependent conduction. For the distal curves, the duration of the flat portion was 42 +/- 26 msec greater (P < 0.001), the slope of the increasing portion was 0.20 +/- 0.17 less (P < 0.02), and the increase in the return cycle was 14 +/- 9 msec less (P < 0.001). These differences resulted from early activation of the site of IDC by the antidromic premature impulse when stimulating from distal sites. As a result, the coupling interval of the orthodromic impulse at the site of IDC was the same or greater than at the stimulation site. In 10 tachycardias with multiple sites of IDC, significant differences in the resetting responses did not occur even when the antidromic impulse penetrated one site of IDC. CONCLUSION: In a fixed anatomic barrier reentrant circuit with one site of IDC, resetting distal to this site misrepresents the properties of the excitable gap of the entire circuit.

Termination of reentry by lidocaine in the tricuspid ring in vitro. Role of cycle-length oscillation, fast use-dependent kinetics, and fixed block.

We hypothesized that drugs with rapid recovery kinetics from use-dependent sodium channel block could promote oscillatory termination of reentry by enhancing interval-dependent conduction. Mechanisms of termination were related to properties of the reentrant circuit. Nine adjustable reentrant preparations were used in which the canine atrial tricuspid ring was cut and then reconnected electronically by sensing activation on one side of the cut and pacing the other after an adjustable delay. The cycle length and diastolic interval during reentry were manipulated by changing this delay. Lidocaine (1.28 x 10(-5) mol/L) significantly increased refractoriness (94 +/- 39 ms) and the slope of the conduction curve (-0.12 +/- 0.07) at the site of block during pacing. Lidocaine terminated sustained reentry by two mechanisms. Early termination resulted from increased cycle length oscillation and refractoriness (reproducible in each experiment) but only at short delays with short initial diastolic intervals. The range of delays showing this mechanism of termination was 100 +/- 48 ms. Increased cycle-length oscillation resulted from an increased slope of the conduction curve. In eight experiments, lidocaine terminated reentry by causing fixed block after 50 minutes of drug superfusion, which prevented reentry at all delays. Fixed block occurred at one of two vulnerable sites and was transiently reversed by acetylcholine. Termination due to refractory block occurred only when the initial diastolic interval was short, and termination due to fixed block developed when there was a susceptible region with a low safety factor for propagation. Fast recovery from sodium channel block promotes oscillatory termination by increasing the slope of the conduction curve.

Lessons from animal models of atrial arrhythmias.

This article presents selected lessons from experimental studies of atrial fibrillation and atrial flutter that pertain to the mechanisms and predisposing factors for flutter and fibrillation and approaches to treatment by antiarrhythmic drugs. Experimental studies also provide lessons for the effects of ablation and surgical lesions on prevention or facilitation of atrial fibrillation and flutter.

Assessing the excitable gap in reentry by resetting. Implications for tachycardia termination by premature stimuli and antiarrhythmic drugs.

BACKGROUND: The shortest excitable gap during reentry may determine responses to pacing and antiarrhythmic drugs. The resetting response has been used clinically to assess the excitable gap, but it cannot directly indicate the shortest excitable gap. METHODS AND RESULTS: We studied resetting in the in vitro canine atrial tricuspid ring using an adjustable reentry preparation in which the ring was cut and reconnected electronically with an adjustable delay to vary the cycle length and excitable gap. We reset the tachycardias using 31 delays in 12 experiments. Tachycardias were terminated by premature stimuli in 16 delays. The reset window overestimated the shortest excitable gap by 25 +/- 14 ms, and the maximum degree of advancement of tachycardia underestimated the shortest excitable gap by 22 +/- 11 ms. The slope of the increasing portion of the resetting response curve was steeper in tachycardias terminated by premature stimuli than in those not terminated (-0.69 +/- 0.2 versus -0.37 +/- 0.2, P < .01). The effective refractory period difference between the sites of pacing and of block correlated with the slope of the resetting response curve. Damped cycle length oscillation after a long return cycle during resetting was always present when there was a partially excitable gap. CONCLUSIONS: The reset window during pacing within the circuit and the maximum degree of advancement provided equally good estimates bracketing the shortest excitable gap. The slope of the resetting response curve predicted the likelihood of termination by premature stimuli. Damped cycle length oscillation after resetting detected a partially excitable gap.

Reversal of reentry and acceleration due to double-wave reentry: two mechanisms for failure to terminate tachycardias by rapid pacing.

OBJECTIVES: We sought to demonstrate mechanisms by which rapid pacing can cause conduction block without terminating reentry. BACKGROUND: Rapid pacing can fail to terminate or can accelerate tachycardias in patients. Mechanisms for these responses are poorly understood. METHODS: We studied reentry in the canine atrial tricuspid ring and a left ventricular ring in vitro in 12 preparations. Activations were recorded from 10 sites around the ring, and monophasic action potentials were recorded from critical sites of block. Rapid pacing at cycle lengths that intermittently caused conduction block was performed at multiple sites. RESULTS: Action potential alternans contributed to block of an orthodromic impulse during rapid pacing. When pacing continued for two stimuli after orthodromic block, a second episode of block could reverse the direction of tachycardia. Continued pacing at this site was likely to produce block of an antidromic impulse, which may initiate double-wave reentry. Double-wave reentry could be sustained or nonsustained. Its cycle length was 56% to 77% of the single-wave cycle length. The ratio of double-wave cycle length to single-wave cycle length was inversely correlated with the relative excitable gap (p < 0.01). Double-wave reentry can be a mechanism for persistent cycle length alternation during tachycardia. CONCLUSIONS: Successful termination of reentry by rapid pacing required block of an othrodromic impulse and stopping pacing within one stimulus after orthodromic block. Reversal of reentry makes the circuit resistant to termination from this site of pacing. Antidromic block can cause acceleration due to double-wave reentry when there is a substantial excitable gap.

d-Sotalol terminates reentry by two mechanisms with different dependence on the duration of the excitable gap.

We used eight adjustable preparations in which the canine atrial tricuspid rings were cut and reconnected electronically by sensing activation on one side of the cut and pacing the other after an adjustable delay. A long delay resulted in a long cycle length (CL) and excitable gap (EG) during reentry. Decreasing delay decreased CL and EG. d-Sotalol (4 mg/l) significantly increased effective refractory period (ERP) and action potential duration with no effects on conduction time during constant 400-msec pacing. During reentry, d-sotalol increased action potential durations more than CLs, so it decreased diastolic intervals. It decreased EG by increasing ERP more than CL. Although d-sotalol increased action potential duration more at longer delays with longer CLs, showing reverse use-dependence, it terminated sustained tachycardias by increasing ERP only for the short delays when the initial EG was short. In 5 of 8 experiments, longer equilibration with d-sotalol produced fixed block at a vulnerable site, so reentry could not be induced at any delays. Fixed block could be transiently reversed by ACh and resolved after washout of d-sotalol. We conclude that d-sotalol terminated reentry by two mechanisms: 1) It terminated sustained reentry by increasing ERP when the initial EG was sufficiently short. 2) In some preparations, it caused fixed block at a vulnerable site, which prevented reentry regardless of the initial EG.

Proarrhythmic and antiarrhythmic effects of flecainide on nonsustained reentry around the canine atrial tricuspid ring in vitro.

The effect of flecainide, 0.3 mg/L and 1.0 mg/L, on inducible nonsustained reentry was studied, in vitro, in the canine tricuspid ring. Nonsustained reentry was engineered by cutting the ring and reconnecting it with an adjustable electronic delay. Delays were used that produced reentry lasting 1-3 beats (group A), 4-10 beats (group B), and 11-25 beats (group C). Reentry was initiated multiple times at each selected delay. A proarrhythmic effect, defined as a significant increase in the duration of reentry, was observed in all 14 trials at the low dose and in two of 15 trials at the high dose in seven experiments. In four more trials a transient proarrhythmic response was seen initially during exposure to the high dose. In five of seven experiments, reentry became sustained after at least one dose of flecainide. Proarrhythmic responses resulted when flecainide increased the tachycardia cycle length more than the effective refractory period and there was less cycle length oscillation after initiation. Antiarrhythmic responses resulted either from a marked increase in effective refractory period at the site of block or production of fixed block.

Spontaneous termination of reentry after one cycle or short nonsustained runs. Role of oscillations and excess dispersion of refractoriness.

This study describes factors that contribute to spontaneous termination of reentry lasting one to 10 cycles after induction by a single premature stimulus. Reentry was studied in vitro in rings of canine atrial tissue from around the tricuspid valve orifice. Activation was recorded from a circular array of 10 extracellular bipolar electrodes equally spaced around the ring. In some experiments, transmembrane or monophasic action potential recordings were made near critical sites. Termination of reentry within one cycle after induction was recorded 110 times in 11 of 35 experiments. Important factors contributing to termination were 1) an obligatory reversal of the activation sequence that resulted in a long coupling interval in the critical region beyond the site of unidirectional block after the premature stimulus and 2) much longer refractory periods limited to this critical region, which facilitated unidirectional block but contributed to termination when this region was first activated with a short coupling interval at the end of the first reentrant cycle. Termination of nonsustained reentry lasting longer than one cycle resulted from oscillations of conduction and refractoriness initiated by the abrupt shortening of cycle length after initiation of reentry. Oscillations of conduction resulted from interval-dependent conduction of reentrant impulses that encountered partially refractory tissue. For reentry to become sustained, the oscillations after induction of reentry must dampen. Thus, damped cycle length oscillations after induction may identify clinical tachycardias caused by reentry with a partially excitable gap.

A quantitative evaluation of refractoriness within a reentrant circuit during ventricular tachycardia. Relation to termination.

Programmed ventricular stimuli introduced during sustained monomorphic ventricular tachycardia frequently reset the tachycardia, resulting in a less than fully compensatory pause. A resetting response curve is generated when the set of return cycles is evaluated as the function of the coupling intervals of the extrastimuli delivered during the ventricular tachycardia. If the stimulated wave front encounters tissue within the tachycardia circuit that is not fully recovered, interval-dependent conduction changes should occur producing an increasing resetting response pattern. We quantified the magnitude of this interval-dependent conduction slowing in 17 morphologically distinct ventricular tachycardias. The slope of the increasing limb of the resetting response curve was determined by linear regression analysis and ranged from -0.30 to -1.14 (mean +/- SD, 0.70 +/- 0.25). Seven of the 17 ventricular tachycardias (41%) terminated during introduction of ventricular extrastimuli. The slope of the resetting response pattern in those ventricular tachycardias that terminated were significantly steeper than in those that did not terminate (-0.85 +/- 0.15 versus -0.61 +/- 0.21, respectively, p = 0.025). Six of the seven ventricular tachycardias terminated with programmed ventricular stimuli had a slope steeper than -0.75, whereas only one of 10 ventricular tachycardias that did not terminate exceeded this value. In conclusion, the slope of the increasing portion of the resetting response curve correlates with ability to terminate uniform sustained ventricular tachycardia by timed extrastimuli. This slope is the quantification of the magnitude of interval-dependent conduction slowing. Additionally, tissue within the reentrant circuit displaying greater degrees of interval-dependent conduction slowing may also have relatively longer effective refractory periods.

Ventricular reentry around a fixed barrier. Resetting with advancement in an in vitro model.

We studied an in vitro model of reentrant tachycardia in a ring of ventricular endocardial tissue surrounding the canine mitral and aortic valves to understand how the response of a reentrant tachycardia to premature impulses can provide insight into the underlying tachycardia mechanism, circuit characteristics, and nature of the central barrier. Reproducible regular reentrant tachycardias (cycle length range, 177-450 msec) were induced with programmed stimulation in 19 intact preparations studied at 34-38 degrees C. Tachycardias were sustained and stable until terminated by programmed stimulation in 95% of preparations. Reentry was reliably reinitiated during experiments lasting 2-15 hours. Data supporting reentry as the mechanism of these tachycardias included sequential activation around the ring that spanned the cycle length of the tachycardia, unidirectional block during initiation of the reentrant rhythm, and termination of the tachycardia after interruption of the circuit. Tachycardias in 13 preparations were systematically reset by premature stimuli. During reentry, each of these preparations had full recovery of excitability by the end of their excitable gap as evidenced by a flat portion along their resetting response curve (eight of 13) or by lack of faster conduction velocity during the second poststimulus beat after premature impulses that produced a long return cycle (13 of 13). From analysis of the conduction of premature impulses and their return cycles, we reached several conclusions useful for interpreting resetting response curves when the reentrant circuit is not fully accessible for study. The duration of a flat portion of the resetting response curve indicated the duration of the shortest fully recovered excitable gap in the reentrant circuit. The window of reset of the tachycardia reflected only the local excitable gap at the site of stimulation and did not define the shortest excitable gap within the circuit. The extent of advancement of the tachycardia provided a lower-limit estimate of the shortest excitable gap in the reentrant circuit. Advancement of a tachycardia in time by premature stimuli indicated advancement at each point in the circuit. Finally, for tachycardias advanced by premature impulses, the length of the reentrant path cannot be determined by the recovery of a refractory barrier.

Electrical properties of canine subendocardial Purkinje fibers surviving in 1-day-old experimental myocardial infarction.

The passive electrical properties of subendocardial Purkinje fibers surviving in infarcted regions of canine ventricle 24 hours after coronary ligation were studied by using microelectrode techniques and cable theory. In normal hearts, cells within the subendocardial Purkinje fiber strands were found to be well coupled to each other but electrically isolated from neighboring myocardium. Voltage response to intracellular current injection was consistent with one-dimensional cable behavior and yielded estimates of passive electrical properties in general agreement with previous work on free-running Purkinje strands (membrane length constant, 1.2 +/- 0.1 mm; membrane time constant, 7.3 +/- 0.8 msec; input resistance, 67.4 +/- 7.4 K omega; membrane resistance, 8.2 +/- 0.7 K omega.cm; axial resistance, 0.52 +/- 0.06 M omega/cm; membrane capacitance, 960 +/- 102 nF/cm) (n = 21). On the day after coronary ligation, subendocardial Purkinje fiber action potentials were prolonged and slightly depolarized. Significant increases were measured in input resistance (+40.5%), membrane resistance (+43.9%), and axial resistance (+47.5%), whereas membrane capacitance was found to be significantly decreased (-24.3%) (n = 19). Conduction velocity, membrane length constant, membrane time constant, and the time constant and capacitance for the foot of the action potential remained unchanged. These results are consistent with electrical uncoupling between adjacent cells, which will increase internal resistivity, accompanied by changes in cellular phospholipid content, which can increase membrane resistance and alter membrane capacitance. Alternatively, the results can be explained by a simple model in which the apparent electrical structure is altered by changes in electrical coupling alone, with specific electrical properties remaining constant. Although the mechanisms underlying the observed changes remain uncertain, the present study indicates that myocardial infarction is associated with alterations in the passive electrical structure of surviving subendocardial Purkinje fibers, which, together with changes in action potential configuration, may provide a substrate for the generation of ventricular arrhythmias 24 hours after coronary ligation.

Procainamide-induced slowing of ventricular tachycardia with insights from analysis of resetting response patterns.

To investigate the mechanism of slowing of the rate of ventricular tachycardias (VTs) by procainamide, resetting response patterns were characterized in 24 VTs in 22 patients. All patients had coronary artery disease and inducible sustained VT during procainamide therapy. Only tachycardias with the same surface QRS morphology before and after procainamide were studied: all were slowed by procainamide. The mean cycle length was 292 +/- 61 ms before and 374 +/- 61 ms after procainamide (p less than 0.05). The mean effective refractory period, measured at the right ventricle, was 241 +/- 21 ms before and 261 +/- 24 ms after procainamide (p less than 0.05). During procainamide therapy, single and double extrastimuli were delivered during VT and resetting response patterns identified. Patterns were characterized as flat, increasing or flat plus increasing. Resetting was seen in 17 (71%) of these VTs and resetting response patterns were identified in 16 (94%) of these. The resetting response pattern was flat in 7, flat plus increasing in 5 and increasing in 4. The finding of some flat portion at the end of resetting response patterns in 12 VTs after procainamide indicates that the reentrant impulse conducts through fully recovered tissue within the circuit. It suggests that procainamide slowed these VTs by slowing conduction velocity in fully recovered tissue due to sodium channel blockade and not by prolongation of action potentials and refractory periods.

The effect of chronic oral and acute intravenous amiodarone administration on ventricular defibrillation threshold using implanted electrodes in dogs.

The effect of acute intravenous administration and chronic oral loading of amiodarone on defibrillation threshold was evaluated in normal anesthetized dogs using implanted superior vena caval spring and left ventricular patch electrodes. The effect of oral loading with amiodarone was evaluated by comparing three groups of six dogs each that received either no drug, 200 mg/day for 9 days, or 400 mg/day for 9 days. Defibrillation threshold was evaluated by administering a fixed sequence of shocks with increasing energies until defibrillation was successful. Defibrillation was determined 13 times in each animal. The mean defibrillation threshold (plus or minus standard error of the mean) was 7.5 +/- 0.3 J in the control group, 15.4 +/- 0.6 J in the group receiving amiodarone 200 mg/day, and 17.9 +/- 0.8 J for the group receiving 400 mg/day. These values are significantly different using analysis of variance and Tukey's test. The acute effect of intravenous amiodarone, 5 mg/Kg was evaluated in five dogs using each dog as its own control. The mean defibrillation threshold during control period was 10.8 +/- 0.4 J, and during the first two hours after amiodarone administration was 10.8 +/- 0.4 J. There was no significant difference. Thus, in this study oral administration of a loading dose of amiodarone comparable to that used in patients produced a dose dependent increase in defibrillation threshold, whereas no change in defibrillation threshold was observed acutely after intravenous administration.

The human atrial strength-interval relation. Influence of cycle length and procainamide.

We defined the atrial strength-interval relation in 23 patients at cycle lengths of 600, 450, and 300 msec before and after procainamide. The atrial diastolic threshold was similar at cycle lengths of 600 and 450 msec, but the threshold at 300 msec was significantly higher than that determined at 600 and 450 msec both before and after procainamide. Procainamide significantly increased the diastolic threshold only at a cycle length of 300 msec. The strength-interval relation was nonlinear, showing progressively decreasing decrements in the measured refractory period as the stimulating current was increased. Progressive decreases in the drive cycle length from 600 to 450 to 300 msec caused similar decreases in refractory periods. The shape of the curves was similar at cycle lengths of 600 and 450 msex. However, at low current strengths, the slope of the curve determined at 300 msex was significantly more vertical than the slopes of the curves at the longer drive cycle lengths. Procainamide caused similar increases in apparent refractory periods at each paced cycle length. Procainamide did not alter the shape of the curves at any paced cycle length. These observations confirm the importance of stimulation frequency on atrial excitability. They suggest that the effects of procainamide on the effective refractory period of the atrium are not cycle length dependent, although the drug effects on threshold are dependent on the drive cycle length.

Activation mapping of reentry around an anatomic barrier in the canine atrium. Observations during entrainment and termination.

We determined total right atrial activation sequences during entrainment and termination of flutter induced in dogs with a surgically induced atrial lesion. This type of atrial flutter is due to circus movement of an impulse around the tricuspid valve orifice. We recorded simultaneously from 96 bipolar intracavity electrodes in the right atrium of the isolated, perfused heart. By constructing isochronal maps, we demonstrated the pattern of atrial activation during atrial pacing protocols that either entrained or entrained and then terminated the reentrant rhythm. We show that during pacing the antidromic wavefront from the paced impulse (An) collides with the orthodromic wavefront from the previous paced impulse (On-1). During entrainment, the site of collision of the orthodromic and antidromic wavefronts was constant during pacing at a fixed rate but shifted in the antidromic direction as the pacing rate increased. Furthermore, the last paced beat was entrained only up to the site of collision of the previous paced beat. During one period of entrainment, termination of the reentrant arrhythmia occurred because On-1 blocked in the reentrant pathway due to refractory tissue left by On-2. However, subsequent An did not collide directly with On as was expected, but rather On blocked by an interaction with tissue left refractory by An. Because On was blocked, no reentry occurred when pacing ended.

Oscillations of conduction, action potential duration, and refractoriness. A mechanism for spontaneous termination of reentrant tachycardias.

The mechanism of cycle length oscillation and its role in spontaneous termination of reentry was studied in an in vitro preparation of canine atrial tissue surrounding the tricuspid orifice. Reentry occurred around a fixed path with incomplete recovery of excitability. Among 18 experiments, there was complete concordance between the occurrence of spontaneous cycle length oscillation and spontaneous terminations; both were observed in 10 experiments and neither in the other eight (p less than 0.001). Local changes in conduction during oscillations resulted from the dependence of both conduction velocity and action potential duration on the preceding local diastolic interval. Interval-dependent changes in action potential duration contributed to the oscillation by altering the next diastolic interval. Because of changes in action potential duration, changes in cycle length were poorly correlated with changes in diastolic interval and, therefore, with local conduction velocity. Complex oscillations resulted from variations in conduction time at multiple sites in the circuit. Oscillations caused most spontaneous terminations. The critical event was an exceptionally long diastolic interval preceding the next-to-last cycle that accelerated local conduction (which tended to shorten the last cycle) and prolonged action potential duration and refractoriness at the site of block. Ninety-two of 99 recordings of spontaneous termination showed evidence of oscillation of conduction and refractoriness causing block.

Cardiac cryolesions: factors affecting their size and a means of monitoring their formation.

Twenty-seven endocardial cryolesions were created in mongrel dogs and analyzed to determine the effects on cryolesion size of both the initial myocardial temperature (37 degrees C versus 12 degrees C) and the pressure within the nitrous oxide delivery line (tank pressure of more than 700 pounds per square inch [psi] versus tank pressure of less than 700 psi). In addition, local myocardial temperatures were monitored to determine their utility in the intraoperative determination of the extent of cryothermic cell death. Cryolesion volume was significantly affected by both the initial myocardial temperature (p less than 0.001) and the line pressure (p = 0.014). In a 37 degrees C myocardium, the mean lesion volume ranged from 0.501 +/- 0.183 cc at line pressures lower than 700 psi to 0.839 +/- 0.258 cc at line pressures greater than 700 psi. In a 12 degrees C myocardium, the mean volume was 1.151 +/- 0.436 cc at line pressures lower than 700 psi and 1.361 +/- 0.288 cc at line pressures higher than 700 psi. A myocardial temperature of 0 degrees C occurs at the edge of the area of cell death. When analyzing the range from -5 degrees to +5 degrees C, the probability of a point at or lower than 0 degrees C falling inside the cryolesion is 84.2%. Monitoring intramyocardial temperature will predict the border of a cryolesion.

Effect of recainam on the energy required for ventricular defibrillation in dogs as assessed with implanted electrodes.

The effect of recainam (WY-42,362), a new class IC antiarrhythmic drug, on ventricular defibrillation was evaluated with the use of implanted superior vena cava and left ventricular patch electrodes in 17 normal dogs anesthetized with sodium pentobarbital. The energy required for a 50% probability of successful defibrillation (E50) was used as the index of ventricular defibrillation threshold. The dogs were classified into three groups: a saline group (n = 6), a low dose recainam group (n = 6) and a high dose recainam group (n = 5). The low dose infusion involved an intravenous loading dose of 3.75 mg/kg body weight over 20 min followed by a maintenance infusion of 0.0375 mg/kg per min. The high dose infusion was double those rates. The low dose recainam infusion produced a plasma recainam concentration of 3.1 +/- 0.3 micrograms/ml and significantly increased QRS duration by 11.3 +/- 3% during sinus rhythm. The high dose recainam infusion produced a plasma concentration of 7.7 +/- 0.9 microgram/ml and significantly increased QRS duration by 27 +/- 7% in sinus rhythm. Recainam did not change ventricular effective refractory period or sinus cycle length. The mean change in E50 between control and infusion periods was 1 +/- 5% in the saline group (8.5 +/- 1.4 versus 8.6 +/- 1.6 joules); 42 +/- 11% in the low dose recainam group (8.1 +/- 1.0 versus 11.3 +/- 1.3 joules) and 92 +/- 17% in the high dose recainam group (11.2 +/- 2.1 versus 20.5 +/- 2.5 joules).(ABSTRACT TRUNCATED AT 250 WORDS)

Circus movement in the canine atrium around the tricuspid ring during experimental atrial flutter and during reentry in vitro.

A Y-shaped lesion in the right atrium allows induction of atrial flutter in dogs. We recorded the activation sequence during this tachycardia from 96 endocardial bipolar electrodes using intracavitary electrode arrays during 12 separate episodes in three isolated perfused hearts. In each case a reentrant impulse circulated around the tricuspid valve orifice in either a clockwise or counter-clockwise direction. Cutting the pathway terminated the rhythm and prevented its reinduction. There was no discrete segment of markedly slow conduction in the reentrant circuit. The tachycardia cycle length was decreased by methacholine and increased by lidocaine. Reentry was also induced in atrial tissue around the tricuspid orifice when this structure was isolated and superfused in vitro. Tachycardia cycle lengths varied from 205 to 399 msec, depending on the circumference of the ring and temperature. Induction of tachycardia by premature stimulation depended on differences in the duration of the effective refractory period among parts of the ring. Conduction velocity was relatively uniform and was slower during tachycardias than during pacing at long cycle lengths. Analysis of the response to premature stimuli that reset the tachycardia provided evidence for incomplete recovery of excitability between depolarizations during the tachycardia. Fast-response action potentials were recorded throughout the pathway and up to six to eight cell layers deep. Histologic studies showed the supravalvular lamina, a circumferential band of fibers several cell layers below the endocardial surface, to be continuous around the tricuspid orifice. Propagation through this layer best explains the conduction velocities observed in the intact heart during flutter in this preparation.

Metabolism and electrophysiology in subendocardial Purkinje fibers after infarction.

Subendocardial Purkinje fibers (SEPF) have been implicated in the genesis of fatal arrhythmias that occur 24-48 h after infarction but little is known about the metabolic processes involved. Quantitative microchemical and electrophysiological studies were performed on normal and infarcted hearts removed 24 h after coronary artery occlusion. ATP, ADP, AMP, total adenine nucleotide content, phosphocreatine (PCr), and inorganic phosphate in superficial subendocardial Purkinje fibers from infarct preparations decreased approximately 30% compared with normal preparations. The phosphate potential decreased 45% in the infarct group. Similar changes were observed in adjacent contractile muscle between normals and infarcts. Action potentials of SEPF from infarct hearts had increased automaticity, markedly prolonged action potential durations at 50 and 90% repolarization (APD50 or APD90), but unchanged resting membrane potentials. The decrease in ATP, total adenine nucleotides, and the phosphate potential correlated linearly with APD50 and APD90. No correlation was found between PCr and APD90. This combined biochemical and electrophysiological approach provides a promising new way to further probe the biochemical basis of the abnormal electrical properties of subendocardial Purkinje fibers after myocardial infarction.