Ventricular Refractory Period Research Articles

Role of Sodium Channels in Ventricular Fibrillation: A Study in Nonischemic Isolated Hearts

Because the role of sodium channels in the initiation and maintenance of VF is not fully elucidated, we studied the significance of sodium channel activity in VF using sodium channel blockers. In nonischemic isolated feline hearts, the following electrophysiologic parameters were measured before and after application of tetrodotoxin (5 x 10(-7) M, n = 6) or lidocaine (1 x 10(-5) M, n = 8): (a) during pacing, epicardial conduction time; refractoriness; the fastest rate for 1:1 pacing/response capture, and all tissue resistivity, indirectly reflecting intercellular electrical resistance; (b) during 8 min of electrically induced tachyarrhythmias, all tissue resistivity; peak frequency (to measure average frequency based on fast-Fourier transformation analysis); and normalized entropy (to measure the degree of arrhythmia organization). In nonischemic isolated rabbit hearts (n = 4), three-dimensional mapping was performed before and after application of lidocaine (1 x 10(-5) M). In feline hearts, lidocaine and tetrodotoxin application resulted in: (a) more spontaneous arrhythmia termination (63-67%) than in nontreated hearts (7%); (b) transformation from mainly VF into ventricular tachycardia with increased organization; and (c) prolongation of conduction time (155-248%) (p < 0.01 for all parameters). The ventricular refractory period was slightly prolonged by tetrodotoxin in the right ventricle and exhibited rate-dependent shortening in control and with lidocaine. Tetrodotoxin and lidocaine reduced the pacing rate for 1:1 pacing/response capture, and all tissue resistivity was not significantly affected. Peak frequency was decreased by tetrodotoxin and lidocaine mainly in the left ventricle (p < 0.01). In nontreated left ventricles, peak frequency was increased over time but was attenuated by lidocaine. In isolated rabbit hearts, several simultaneous wave fronts were detected during VF in nontreated hearts and were reduced to only one or two major wavefronts after application of lidocaine. Suppression of sodium channel activity that primarily slowed conduction time and had little or no effect on ventricular refractory period and all tissue resistivity resulted in less stable and more organized arrhythmias and reduced tachyarrhythmia rate compared with nontreated hearts. These results suggest an active role for sodium channels in the maintenance of ventricular fibrillation.

QT-prolonging effects of sparfloxacin, a fluoroquinolone antibiotic, assessed in the in vivo canine model with monophasic action potential monitoring.

Sparfloxacin, a fluoroquinolone antibacterial agent, prolongs cardiac repolarization, which may predispose to torsades de pointes. This study was designed to assess simultaneously the hemodynamic and electrophysiologic effects of sparfloxacin using the halothane-anesthetized, closed-chest in vivo canine model (n = 6). Sparfloxacin was intravenously administered in the following two doses with a pause of 20 min, a clinically relevant dose of 3.0 mg/kg/10 min and a 10 times higher dose of 30 mg/kg/10 min. After the low dose of sparfloxacin, cardiac output increased, heart rate decreased, and ventricular repolarization and refractory periods were prolonged. After the high dose, cardiac output increased, whereas heart rate and mean blood pressure decreased, and ventricular repolarization and effective refractory periods were prolonged. The increment was greater in repolarization than in refractoriness, indicating an increase of electrical vulnerability. Because sparfloxacin prolonged repolarization in a reverse use-dependent manner, its negative chronotropic effect may have potentiated the QT prolongation. Left ventricle preload, left ventricular contraction, and AV nodal as well as intraventricular conduction were minimally affected. These results suggest that caution should be used when administering sparfloxacin to patients having risk factors for QT prolongation.

Reproducibility of Minimum, Maximum and Median QT Intervals in the 12‐Lead Resting ECG

Background: Heterogeneity in the recovery of ventricular refractory periods is an important factor in the development of ventricular arrhythmia. The QT dispersion (QTD) is increasingly used to measure this heterogeneity but its clinical value is limited due to methodological problems. QTD is defined as the maximum minus the minimum QT intervals that are suspected to be the least reproducible of the QT measurements.Objective: To analyze the reproducibility of the minimum, maximum and median QT intervals.Material: One database consisted of 356 subjects: 169 with diabetes and 187 nondiabetic control persons. The other database consisted of 110 subjects with remote myocardial infarction: 55 with no history of arrhythmia, and 55 with a recent history of ventricular tachycardia or fibrillation.Methods: 12‐lead surface ECGs were recorded with an amplification of 10 millimeters per millivolt at a paper speed of 50 mm/s. QT was measured manually by the tangent‐method. The reproducibility was calculated from measurements of QT in successive beats.Results: The standard deviation (SD) of QTs reproducibility was 9 ms for the arrhythmia data and 8 ms for the diabetes data. The reproducibility of QTmax and QTmin were on average 30% and 15% worse than for QTmedian. The SD of QTmax was significantly higher than for QTmedian in both database (P &lt; 0.001), whereas SD of QTmin was only significantly higher than for QTmedian for the diabetes data (P &lt; 0.001).Conclusions: The reproducibility of QTmin and in particular QTmax was significantly lower than for QTmedian. This indicates that the QT dispersion is based on the least reproducible of the QT measurements. A.N.E. 2000;5(4):354–357

Eccentricities of dual chamber implantable pacemakers.

The consequences of a short 160 ms postventricular atrial refractory period (PVARP) were studied in 27 patients with Medtronic Elite series of pacemakers (programmed to the unipolar mode) by using chest wall stimulation and myopotential interference. Because the ventricular refractory period is nonprogrammable at 230 ms, appropriately timed signals produced As-Vr combinations where As is an atrial sensed event and Vr is a ventricular event detected in the ventricular refractory period. The As-Vr combination inhibited the release of the atrial stimulus at the completion of the atrial escape interval in the DDI, DDIR, DDD, and DDDR modes. A paced ventricular beat (Vp) was documented to initiate automatic PVARP extension in circumstances where Vp was preceded by a Vr event and the pacemaker interpreted the Vr-Vp sequence as 2 ventricular events without an intervening atrial event and Vp as a ventricular premature beat. Knowledge of these eccentricities should facilitate the interpretation of complex pacemakers responses to interference.

Dose-dependence of 4-aminopyridine plasma concentrations and electrophysiological effects in dogs : potential relevance to ionic mechanisms in vivo.

Previous investigators have administered 4-aminopyridine (4AP) to dogs to evaluate the role of transient outward current (I(to)) in vivo; however, plasma concentrations of 4AP were not measured, and it is therefore uncertain which cardiac ion channels were blocked at the concentrations achieved. We applied high-performance liquid chromatography to measure 4AP concentrations produced by intravenous 4AP administration to dogs. A previously described dose regimen produced plasma concentrations that increased during the maintenance infusion but never exceeded 250 micromol/L and caused significant mortality. Whole-cell patch-clamp experiments on isolated canine myocytes showed that even the maximum 4AP concentrations achieved in vivo failed to alter ventricular I(to) and had very small effects on atrial I(to); however, concentrations achieved in vivo had a strong inhibitory effect on the dog ultrarapid delayed rectifier (I(Kur.d)), present only in atrial cells. We designed a loading and maintenance infusion regimen to produce stable 4AP plasma concentrations. At concentrations in the range of 25 and 50 micromol/L, 4AP had no effect on ventricular refractory period but increased atrial refractoriness significantly, consistent with the results of voltage clamp studies. The interpretation of previous studies using intravenous 4AP administration to inhibit I(to) in dogs in vivo needs to be reevaluated in light of the fact that the infusion regimens used produce plasma concentrations that are inadequate to affect ventricular I(to). Our findings also support the concept that selective inhibition of ultrarapid delayed rectifier current can prolong atrial refractory periods without affecting ventricular refractoriness.

Electrophysiological profile after inward rectifier K channel blockade by barium in isolated rabbit hearts. Altered repolarization and unmasked decremental conduction property.

The aims of this study were to define the changes of cardiac conduction properties after selective IK1 blockade in isolated hearts. Intracardiac recording and stimulation in Langendorff-perfused rabbit hearts were used to define cardiac conduction properties after Ba2+, a well known IK1 blocker. Ba2+ prolonged the corrected QT interval and decreased, or even abolished, the amplitude of the T wave. The conduction time through the sinoatrial (SA interval), the atrioventricular node (AH interval) and His-Purkinje system (HV interval) were not significantly changed. However, at higher atrial pacing rates the HV interval was lengthened by Ba2+ in a frequency-dependent manner. The recovery curve of the His-Purkinje system (the relationship of H2V2 to V1H2) was changed by Ba2+ to a prematurity-dependent pattern (AV nodal behaviour). Such a response was neither observed with 4-aminopyridine (Ito blocker) nor with d-sotalol (IK blocker). The atrial and ventricular refractory periods as well as the relative refractoriness (measured by the difference between relative refractory period and the absolute refractory period) of the ventricular tissue were increased by Ba2+. The electrophysiological profile of selective IK1 block in isolated hearts revealed altered repolarization of cardiac tissue. The decremental conduction properties, which are normally present in the atrioventricular node (with a paucity of IK1), were unmasked by IK1 block in the His-Purkinje system. The T wave, particularly its amplitude, is more closely related to IK1 than to Ito.

Effects of a Class III Antiarrhythmic Drug, Dofetilide, on the In Situ Canine Heart Assessed by the Simultaneous Monitoring of Hemodynamic and Electrophysiological Parameters

The cardiovascular profile of dofetilide was examined using halothane-anesthetized, closed-chest in vivo canine model (n=6). Dofetilide was administered at the dose of 1,10 or 100 μg/kg, i.v. over 10 min with a pause of 20 min. After the lowest infusion rate, no significant change was detected in any of the cardiovascular parameters. Infusion of 10 μg/kg dofetilide, which was close to the submaximal clinically effective antiarrhythmic dose, decreased the heart rate and prolonged the ventricular repolarization phase and refractory period. After the highest dose of dofetilide, the cardiac output and left ventricular contraction decreased during sinus rhythm, the latter of which was not changed during the constant heart rate of 150 beats/min, while the dose-related effects were observed on the heart rate, repolarization phase and refractory period. The afterload and preload to the left ventricle and AV nodal as well as intraventricular conductions were hardly affected even at 100 μg/kg, i.v. These results obtained in the in vivo canine model support the previous reports describing that dofetilide possesses a highly selective blocking property for IKr. Moreover, the absence of effects on the afterload and preload to the left ventricle and the cardiac conduction makes dofetilide favorable as an antiarrhythmic drug because it is often used for patients with moderate to severe left ventricular dysfunction.

Fast Fourier transform analysis of ventricular fibrillation intervals to predict ventricular refractoriness and its spatial dispersion.

A technique of fast Fourier transform analysis has been used to derive mean ventricular fibrillation (VF) intervals, and to confirm that these VF intervals predict ventricular refractory periods. Twenty episodes of VF were induced by a rapid ventricular pacing in 12 sheep. VF activations in a 10-second period were simultaneously acquired from 64 epicardial sites with an electrode sock. The VF electrograms were analyzed by a fast Fourier transform analysis. The dominant peak frequency of the VF spectrum in each epicardial site was converted into milliseconds and served as a mean VF interval. The dominant peak frequency of VF electrograms ranged from 8.1 to 11.5 Hz, and the corresponding mean VF intervals were 87 to 124 ms. In five sheep, the mean VF intervals and the effective refractory periods were determined by the extrastimulus technique obtained from 29 epicardial sites. There was a very good correlation between the two parameters when the effective refractory periods were determined at a basic cycle length of 300 ms (r = 0.89, P < 0.001) and 400 ms (r = 0.87, P < 0.001), respectively. VF was induced twice in eight sheep. The maximum difference in the mean VF intervals between the two VF episodes in the same sheep was 3 ms (P > 0.05). In conclusion, mean VF intervals determined by the fast Fourier transform analysis have a good reproducibility and a good correlation with ventricular refractory periods measured by the classic extrastimulus technique. The mean VF intervals could serve as an index of ventricular refractoriness.

Importance of pacemaker noise reversion as a potential mechanism of pacemaker-ICD interactions.

Numerous types of interactions between pacemakers and implantable cardioverter defibrillators (ICDs) have been described. Pacemaker outputs preventing appropriate detection of ventricular tachycardia or ventricular fibrillation by the ICD is one of the more serious. Asynchronous pacemaker activity during ventricular arrhythmias may be caused by either nonsensing of the arrhythmia or by noise reversion, which is an algorithm that causes the pacemaker to switch to asynchronous pacing when repetitive sensing at a high rate occurs. We analyzed the mechanisms underlying asynchronous pacemaker activity in ventricular arrhythmias using pacemaker telemetry during the arrhythmia. Thirty-nine induced arrhythmias from 26 different procedures in 19 patients with both pacemakers and ICDs were analyzed. Of the 39 arrhythmias, asynchronous pacemaker activity occurred in 16. The underlying mechanism was nonsensing in 4 episodes and noise reversion in 12 episodes. Clinically significant interference with detection arose on three occasions. Conditions favoring the occurrence of noise reversion include specific pacemaker models, arrhythmia cycle lengths in the range causing noise reversion of the individual pacemaker model, long noise sampling periods, and VVI pacing mode. Noise reversion can be diagnosed by telemetering the pacemaker marker channel during ventricular arrhythmias as a part of routine pacemaker-ICD interaction evaluation. It can be prevented or minimized by programming short ventricular refractory periods or using pacemakers with short retriggerable refractory periods.

Electrophysiologic assessment of calcium channel blockers in transplanted hearts: An experimental study

The effects of calcium channel blockers on automaticity, conduction, and refractoriness were studied in a model of heterotopic heart transplantation in dogs, which combined an innervated heart (recipient) and a denervated one (donor). Following the surgical procedure, 0.2 mg/kg verapamil (n = 10), 0.15 mg/kg diltiazem (n = 10), or 5 μg/kg + 30 μg/kg/h nifedipine (n = 10) was administered intravenously. In basal situation and after drug administration, each heart was assessed for AV interval, cycle length, sinoatrial conduction time, atrioventricular node antegrade block point, and atrioventricular node and ventricular refractory periods; electrocardiographic PR and QT intervals and QRS complexes; systemic arterial, pulmonary artery, central venous, and pulmonary capillary wedge pressures; and cardiac output. The depressor effects of these calcium channel blockers on automaticity, refractoriness, and conduction were more intense in the transplanted hearts, very possibly because of the absence of adrenergic reflexes mediated by the autonomic nervous system; in particular, verapamil produced a great depression of sinus automaticity in a large number of cases.

Mechanism of endothelin-induced malignant ventricular arrhythmias in dogs.

The development of ventricular tachyarrhythmias caused by low-dose intracoronary infusion of endothelin-1 (ET-1) has recently been observed in dogs. The aim of the present study was to investigate the pathomechanism of ET-1-induced ventricular arrhythmias in 32 anesthetized, open-chest mongrel dogs in group A (n = 14) without, in group B (n = 14), and in group C (n = 4 control) with atrioventricular node ablation. The coronary blood flow (CBF) was measured in the left anterior descending (LAD) coronary artery by an electromagnetic flowmeter. Standard ECG, atrial and ventricular electrograms, and in groups B and C endocardial and epicardial monophasic action potentials (MAPs) were recorded. ET-1 was administered into the LAD at a low dose (30-60 pmol/min). At the time of the appearance of premature beats, CBF was only slightly decreased. The effective ventricular refractory period did not change significantly. Onset of spontaneous polymorphic and monomorphic sustained ventricular tachycardia (sVT) was observed in five dogs without bradycardia and in nine dogs with bradycardia. VTs in dogs with complete AV block were longer and slower. In most of the cases, ventricular fibrillation occurred. ET-1 treatment resulted in a significant increase in MAP 90% duration (255 +/- 9 vs. 290 +/- 8 ms endocardial, 244 +/- 10 vs. 292 +/- 12 epicardial; p < 0.05) at 70 beats/min ventricular pacing. In eight cases (group B), third-phase early afterdepolarization could be recorded. According to our results, the mechanism of ET-1-induced arrhythmias appears to be based on prolongation of MAP duration and development of afterdepolarizations.

Modification of ventricular tachycardia by carotid sinus massage

A case of ventricular tachycardia (VT) was aggravated by carotid sinus massage in a woman with an old myocardial infarction. The patient presented with a wide QRS complex tachycardia with a rate of 143 beats/min, which fulfilled the classic and newer electrocardiographic criteria for the diagnosis of VT. Carotid sinus massage performed during the tachycardia resulted in its conversion to another, wide QRS complex tachycardia, with different morphology and a faster rate resembling ventricular flutter. This latter tachycardia was converted to sinus rhythm by a thump on the patient's chest. The initial tachycardia was proved to be of ventricular origin by electrophysiologic study at a later stage during a recurrence. Vagal stimulation probably resulted in inhomogeneous increase of the ventricular refractory period, creating conditions for a reentrant circuit other than the preexisting one and for the emergence of VT with a different QRS morphology and rate. Although termination and/or initiation of VT by carotid sinus massage has been reported in the past, modification of VT by carotid sinus massage has not been described previously.

Differential Effects of Changes in Local Myocardial Refractoriness on Atrialand Ventricular Latency

Assessment of myocardial refractoriness and conduction properties, critical to development and propagation of reentrant arrhythmias, is an integral part of the investigation of atrial and ventricular tachycardias through the use of programmed electrical stimulation. Local conduction itself, however, may be affected by myocardial refractoriness. We studied the effects of changes in myocardial refractoriness on local conduction in right atrial and ventricular myocardium in 19 patients. Changes in effective, functional, and relative refractoriness were accomplished with the use of four pacing protocols, including drive train pacing cycle lengths (PCLs) of 600 and 400 milliseconds (ms) and drive train durations (DTDs) of 8 and 50 stimuli. Unipolar cathodal stimulation was performed from the distal electrode, and unipolar electrograms were recorded from the proximal three poles of quadripolar catheters with 5-mm interelectrode spaces. Atrial and ventricular effective and relative refractory periods (ERPs and RRPs) were significantly shortened by both the reduction in PCL and the increase in DTD. The reduction in the PCL shortened atrial and ventricular refractory periods significantly more than did the increase in the DTD. Changes in ventricular refractory periods were significantly greater compared with atrial refractory periods. The ratio of RRP to ERP was reduced in the atrium but significantly increased in the ventricle with reduction in PCL and increase in DTD. For all premature intervals, the conduction interval from stimulus to the first recording electrode pole was significantly greater than conduction intervals measured between subsequent electrode poles. The greatest increase in conduction interval with closely coupled premature complexes occurred between the stimulus artifact and the first recording electrode pole. Reduction in ventricular but not atrial ERP was associated with significantly increased local conduction interval. First, most of the conduction delay after the stimulus artifact occurs within 5 mm from the pacing site. Second, closely coupled premature complexes delay conduction primarily by prolonging latency in the first 5 mm from the pacing site. Third, fundamental differences occur between the atrium and ventricle regarding changes in local conduction as a function of changes in ERP, suggesting that factors involved in sudden changes in refractoriness (eg, heart rate acceleration) could produce divergent effects on atrial and ventricular arrhythmogenesis.

THE DEVELOPMENTAL ELECTROPHYSIOLOGY OF VENTRICULOATRIAL CONDUCTION IN THE RABBIT. † 129

This study investigates developmental differences in ventriculoatrial conduction during incremental ventricular pacing in the perfused rabbit heart. In 16 adult and 13 neonatal perfused preparations, ventricular prematures S2 were introduced after a train of 10 S1 stimuli. S2 was progressively shortened until the ventricular refractory period was reached. Parameters of retrograde conduction and refractoriness were then compared.

Electrophysiologic profile and efficacy of intravenous dofetilide (UK-68,798), a new class III antiarrhythmic drug, in patients with sustained monomorphic ventricular tachycardia

There is increasing evidence that class III antiarrhythmic agents may be superior to class I agents for the long-term treatment of life-threatening ventricular tachyarrhythmias. This open study evaluated the acute electrophysiologic effects, antiarmythmic efficacy, and safety of different doses of intravenous dofetilide, a new class III drug, in 50 patients with sustained monomorphic ventricular tachycardia inducible by programmed electrical stimulation who had previously been unsuccessfully treated with 0 to 7 (median 3) other drugs. Intravenous dofetilide was administered over 60 minutes at the following dose levels: 1.5, 3.0, 6.0, 9.0, and 15.0 μg/kg. Significant class III activity was apparent at doses of 3.0 to 15.0 μg/kg, as evidenced by dose-related prolongation of the QTc interval by 13.4% to 14.2%, ventricular effective refractory period by 7.9% to 20.6%, and ventricular functional refractory period by 7.3% to 25.0%. The corresponding mean ± SD plasma dofetilide concentrations ranged from 1.45 ± 0.52 to 6.48 ± 1.31 ng/ml. There was no evidence of reverse use-dependence. At these electrophysiologically active dose levels, intravenous dofetilide suppressed (complete response) or slowed (partial response) inducible ventricular tachycardia in 17 of 41 patients (41%) compared with 0 of 9 patients receiving only 1.5 μg/kg. The response rate was fairly uniform among the groups receiving 3.0, 6.0, 9.0, and 15.0 μg/kg. Intravenous dofetilide was hemodynamically well tolerated. Torsades de pointes (which was self-limiting) developed in only 1 patient, who was allocated to receive 15.0 μg/kg. There were no other proarrhythmic episodes or serious adverse effects. Further evaluation of the therapeutic potential of dofetilide in the management of life-threatening ventricular arrhythmias is justified.

Use of Double Ventricular Extrastimulation to Determine the Preexcitation Index in Atrioventricular Nodal Reentrant Tachycardia

The ability of single paced ventricular beats during tachycardia to penetrate the tachycardia circuit and reset the subsequent atrial depolarization (atrial preexcitation), enabling calculation of the "preexcitation index," can be helpful in analyzing supraventricular tachycardias. However, the ventricular refractory period often prevents ventricular capture of beats with the necessary prematurity to demonstrate atrial preexcitation, particularly in atrioventricular nodal reentrant tachycardia (AVNRT). We hypothesized that the use of double premature stimuli could overcome this limitation. In 25 consecutive patients with either AVNRT or atrioventricular reciprocating tachycardia (AVRT) we attempted to demonstrate atrial preexcitation with single and double ventricular extrastimuli. Whereas atrial preexcitation with a single extrastimulus could only be achieved in 3 of 11 patients with AVNRT, all but 1 patient demonstrated atrial preexcitation with the use of double ventricular extrastimuli. On the other hand, in all but 1 patient with AVRT, atrial preexcitation could be achieved with single and double extrastimuli. A formula was derived for obtaining a preexcitation index with double extrastimuli and shown to correspond closely with the preexcitation index obtained with a single extrastimulus in the 16 patients in whom atrial preexcitation could be achieved with single and double extrastimuli. Thus, this technique significantly enhances the ability to achieve atrial preexcitation and to calculate the preexcitation index in patients with AVNRT, and thus may be useful in deciphering tachycardia mechanism in some patients, as well as being a useful technique in studying the electrophysiological properties of the antegrade and retrograde limbs of AVNRT.

Circadian Variation in Human Ventricular Refractoriness

The incidence of sudden cardiac death is highest in the morning hours. Although a circadian variation in myocardial ischemia may be responsible in part for this observation, other factors also may be contributory. It is not known whether a circadian variation in ventricular refractoriness exists that may be related to the increased morning incidence of sudden cardiac death. Nine subjects with primary conduction system disease, no evidence of structural heart disease, and permanent pacemakers were studied. Autonomic nervous system function as assessed by tilt table and baroreflex sensitivity testing was normal in all subjects. Using noninvasive programmed stimulation, ventricular effective refractory periods were measured hourly for 24 hours. Potassium, epinephrine, and norepinephrine levels also were measured hourly. In a subset of five subjects, ventricular refractory periods were again measured hourly over 24 hours during beta-blockade. A significant circadian variation in ventricular refractoriness was noted, with a mean difference between the shortest and longest refractory periods in individual subjects of 23 ms and 21 ms at drive cycle lengths of 600 ms and 400 ms, respectively. In eight subjects, the shortest refractory periods observed over 24 hours occurred within 2 hours of waking (random probability < 10(-8)). Adjustment of refractory period data according to the hour of waking resulted in a better correlation between ventricular refractory periods and time. Although a significant circadian variation was observed in potassium and catecholamine levels, neither was an independent predictor of refractory periods after adjustment for the hour of waking. The adjusted time of day was the only significant (P < .0001) independent predictor of refractory periods. beta-Blockade abolished the circadian variation in ventricular refractory periods. A significant circadian variation in ventricular refractory periods exists. Maximal shortening between hourly refractory periods as well as the shortest refractory periods occur in the early morning hours when the incidence of sudden cardiac death is greatest. Fluctuations in beta-adrenergic tone appear to be largely responsible for this phenomenon.

Electrophysiologic Consequences of Hyperkalemic Cardioplegia during Surgical Ischemia

Abstract Myocardial protection strategics use cardioplegic solutions to reduce the injury induced by surgical ischemia and reperfusion. However, there is a high incidence of electrophysiotogic abnormalities after cardioplegic arrest. A computerized epicardial mapping system in a porcine cardiopulmonary bypass model was used to measure the electrophysiologic consequences of different myocardial protection techniques. Both warm and cold, crystalloid and blood cardioplegic solutions were compared. The effects of hypothermia and prolonged cardiopulmonary bypass were examined in a control group that underwent a 2-hour period of hypothermia without cardioplegia or aortic cross-clamping, followed by 2 hours of normothermic reperfusion. Isochronous activation maps, unipolar electrograms, ventricular refractory periods, and pacing thresholds were measured before cardioplegic arrest and during reperfusion. Compared with the control group, crystalloid cardioplegia, but not blood cardioplegia, was accompanied by large changes in the pattern of ventricular activation and by persistent (> 2 hours) and significant slowing of the time required for complete ventricular activation. This was not the result of hypoxia. Moreover, the effective refractory period and the pacing threshold were unchanged by any cardioplegia. Our data suggest that crystalloid cardioplegia increases myocardial resistance to current flow leading to a derangement of electrical impulse propagation that may underlie arrhythmogenesis.

Electrophysiologic consequences of hyperkalemic cardioplegia during surgical ischemia

Myocardial protection strategics use cardioplegic solutions to reduce the injury induced by surgical ischemia and reperfusion. However, there is a high incidence of electrophysiotogic abnormalities after cardioplegic arrest. A computerized epicardial mapping system in a porcine cardiopulmonary bypass model was used to measure the electrophysiologic consequences of different myocardial protection techniques. Both warm and cold, crystalloid and blood cardioplegic solutions were compared. The effects of hypothermia and prolonged cardiopulmonary bypass were examined in a control group that underwent a 2-hour period of hypothermia without cardioplegia or aortic cross-clamping, followed by 2 hours of normothermic reperfusion. Isochronous activation maps, unipolar electrograms, ventricular refractory periods, and pacing thresholds were measured before cardioplegic arrest and during reperfusion. Compared with the control group, crystalloid cardioplegia, but not blood cardioplegia, was accompanied by large changes in the pattern of ventricular activation and by persistent (> 2 hours) and significant slowing of the time required for complete ventricular activation. This was not the result of hypoxia. Moreover, the effective refractory period and the pacing threshold were unchanged by any cardioplegia. Our data suggest that crystalloid cardioplegia increases myocardial resistance to current flow leading to a derangement of electrical impulse propagation that may underlie arrhythmogenesis.

Benzopyran Class III anti-arrhythmic agents

Patent SummaryNovel benzopyran Class III anti-arrhythmic agents are disclosed which may have utility for the treatment of cardiac arrythmias.In vitro experiments utilizing the isolated right ventricular papillary muscle of guinea-pigs were carried out to determine the anti-arrhythmic activity. Measurement of the ventricular refractory period produced changes in the range 35-125 msec at 3±10-6M. D-sotalol produced a change of 40 msec at 3±10-5M.Synthesis was by standard methods. Sixteen compounds are exemplified by synthesis. Twenty-seven compounds are specifically claimed. N-(3,4-dihydro-2H-1-benzopyran-4-yl)methyl]-4-piperidinyl]-4-pyridi-necarboxamide dihydrochloride is typical of the claim.