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Biomedical subjects

R S Sheldon

Publications and source records attributed to R S Sheldon.

At least 37 records · Page 2Linked to original sources
PubMed1997

Divergence of endocardial QT interval components during programmed electrical stimulation including observations during induction of sustained ventricular tachyarrhythmias.

Measurements were made in 12 normal subjects and during induction of sustained ventricular tachyarrhythmias in 31 patients with remote myocardial infarction. QT interval measurements were made semiautomatically with computer assistance and the total QT interval was divided into early (QT1) and late (QT2) components. QT intervals and QT interval dispersion between two right ventricular endocardial sites were plotted against the degree of prematurity of the last extrastimulus (S2, S3, or S4). In the control group, total QT and QT1 intervals shortened with increasing prematurity of the last extrastimulus (p < 0.001). Slopes (positive) were steeper with faster pacing rates (600, 500, or 400 ms) and more extrastimuli (1 to 3). The relationship between QT2 intervals and prematurity of the last extrastimulus was flat, but the slope was slightly negative (p = 0.05 to < 0.001) and did not vary with changes in pacing cycle length or number of extrastimuli. QT interval dispersion in the control group was minor (95% CI 0-40 ms). During induction of sustained ventricular tachyarrhythmias, total QT and QT1 intervals were longer (y intercepts) than in the control group (p < 0.05 at 400-ms pacing cycle length) and their dispersion was increased (p < 0.05). Generally, QT2 intervals were shorter (p < 0.05 at 600-ms pacing cycle length) during induction of ventricular arrhythmias in comparison with the control group but dispersion was increased (p < 0.05 at 400-ms pacing cycle length). QT intervals and QT interval dispersion show an orderly and predictable relationship with prematurity of the last extrastimulus in normal subjects. These patterns differ during induction of sustained ventricular tachyarrhythmias. Such differences may be exploited to derive clinically predictive and useful measurements.

Aged↗
PubMed1997

North American Vasovagal Pacemaker Study: study design and organization.

The North American Vasovagal Pacemaker Study is an ongoing multicenter randomized, clinical trial that assesses the efficacy of dual chamber pacing utilizing rate drop sensing in patients with frequent syncopal spells. Patients are eligible if they have had at least six syncopal spells and a positive tilt table test, or a recurrence of syncope within 6 months of a positive tilt test. The tilt table test must have provoked a relative bradycardia. Patients are randomized to receive a Medtronic Thera DR with rate drop sensing, or to continue on their usual therapy. All patients complete a log of their presyncopal and syncopal spells daily, and are contacted every 2 months. The primary outcome measure is the time to the first recurrence of syncope. The goal of the main study is to recruit 284 patients in 3 years with a final fourth year of follow-up; this will result in an 80% chance of detecting a 30% reduction in the risk of syncope. A pilot study is under way with the aim to recruit 60 patients over a period of 2 years with a final third year of follow-up. Recruitment began in July 1995 and 47 patients have been enrolled to date.

Bradycardia↗
PubMed1996

[3H]dofetilide binding: biological models that manifest solely the high or the low affinity binding site.

Dofetilide is a Class III antiarrhythmic agent known to selectively block the rapid component of the delayed rectifier K+ current (IKr). [3H]Dofetilide binds to a low and a high affinity sites on guinea-pig myocytes. The purposes of this study were: (1) to find biological models which express solely the high or the low [3H]dofetilide binding sites; (2) to characterize the single binding site models; and (3) to establish which of the high or the low affinity binding sites is associated with IKr. We compared and characterized the [3H]dofetilide binding on guinea-pig myocytes, neonatal mouse ventricular homogenate and untransfected CHO cells. These tissue preparations were selected since the neonatal mouse tissue expresses IKr while this current is absent from CHO cells. We compared the IC50 concentrations of dofetilide and two other known IKr blockers E-4031 and sotalol, on [3H]dofetilide binding to these three preparations. Using steady-state and kinetic binding techniques, we characterized the interaction of E-4031 and sotalol with the high and the low [3H]dofetilide binding sites. We found that neonatal mouse ventricle manifest solely the high affinity site (Kd 20 +/- 4 nmol/l, Bmax 18 +/- 4 fmol/mg) while CHO cells manifest solely the low affinity binding site (Kd 1.6 +/- 0.1 mumol/l, Bmax 5.8 +/- 0.8 pmol/mg). We demonstrated that the high and low affinity binding sites present on guinea-pig myocytes show characteristics similar to the single high affinity site expressed on neonatal mouse homogenate and to the single low affinity site expressed on CHO cells, respectively. Class III antiarrhythmic drugs inhibited binding to the high affinity site at concentrations similar to those required to inhibit 50% of IKr current in electrophysiologic studies. In contrast, dofetilide and E-4031 inhibited [3H]dofetilide binding to the low affinity site only at supra-pharmacologic concentrations. We next demonstrated that Class III drugs interact in a competitive manner with the high affinity site on neonatal mouse tissue while they interact with a site allosterically coupled to the low binding site on CHO cells. These data suggest that dofetilide interacts with the high and low affinity sites in a fundamentally different manner. We defined biological models which express solely the high or low [3H]dofetilide binding sites. Only the high affinity site is related to IKr.

Animals↗
PubMed1996

Abnormal reflex venous function in patients with neuromediated syncope.

OBJECTIVES: We sought to compare the forearm reflex venous response to mental arithmetic stress in patients with neuromediated syncope and in normal subjects. BACKGROUND: Patients with neuromediated syncope have a paradoxic arterial vasodilation in response to stressors that usually provoke vasoconstriction. Given the postulated role of diminished preload in provoking the reflex responses resulting in syncope, we hypothesized that mental stress might provoke paradoxic reflex venodilation in patients with neuromediated syncope. METHODS: Twelve normal subjects (mean age [+/-SD] 47 +/- 9 years) and 27 patients with neuromediated syncope (mean age 42 +/- 13 years) were studied before and during a mental arithmetic stress test. Forearm venous pressure-volume relations were determined by using radionuclide plethysmography. RESULTS: During mental arithmetic stress, heart rate and systolic and diastolic blood pressure increased significantly and similarly both in normal subjects and in patients with neuromediated syncope. The heart rate and blood pressure changes were qualitatively similar in both groups. However, with mental arithmetic stress, forearm venoconstriction of 13 +/- 2% (mean +/- SEM) was noted in normal subjects (p < 0.001) but not in patients with neuromediated syncope (mean 2%, p = NS). This group response of patients with neuromediated syncope did not result from a lack of individual responses but occurred because these patients had a wide range of responses. The normal physiologic and methodologic variability of the method was +/- 4%. Thirteen of the 27 patients with neuromediated syncope had forearm venoconstriction of 14.5 +/- 6.8% during mental arithmetic stress, whereas 7 had paradoxic forearm venodilation of 14.6 +/- 8.8%, and 7 were considered nonresponders (-1.3 +/- 3.4%). Thus, 14 (52%) of the 27 patients with syncope did not have normal vasoconstriction in response to mental stress. CONCLUSIONS: Patients with neuromediated syncope have an abnormal range of forearm venomotor responses to mental arithmetic stress. Reflex control of the veins may play an important role in the pathogenesis of neuromediated syncope.

Adult↗
PubMed1996

Developmental changes in the delayed rectifier K+ channels in mouse heart.

Expression of cardiac transient outward current and inwardly rectifying K+ current is age dependent. However, little is known about age-related changes in cardiac delayed rectifier K+ current (IK, with rapidly and slowly activating components, IKr and IKs, respectively). Accordingly, the purpose of the present study was to assess developmental changes in IK channels in fetal, neonatal, and adult mouse ventricles. Three techniques were used: conventional microelectrode to measure the action potential, voltage clamp to record macroscopic currents of IK, and radioligand assay to examine [3H]dofetilide binding sites. The extent of prolongation of action potential duration at 95% repolarization (APD95) by a selective IKr blocker, dofetilide (1 mumol/L), dramatically decreased from fetal (137% +/- 18%) to day-1 (75% +/- 29%) and day-3 (20% +/- 15%) neonatal mouse ventricular tissues (P < .01). Dofetilide did not prolong APD95 in adult myocardium. IKr is the sole component of IK in day-18 fetal mouse ventricular myocytes. However, both IKr and IKs were observed in day-1 neonatal ventricular myocytes. With further development, IKs became the dominant component of IK in day-3 neonates. In adult mouse ventricular myocytes, neither IKr nor IKs was observed. Correspondingly, a high-affinity binding site for [3H]dofetilide was present in fetal mouse ventricles but was absent in adult ventricles. The complementary data from microelectrode, voltage-clamp, and [3H]dofetilide binding studies demonstrate that expression of the IK channel is developmentally regulated in the mouse heart.

Action Potentials↗
PubMed1995

Effects of pericardial constraint on left ventricular mechanoreceptor activity in cats.

BACKGROUND: The purpose of this study was to assess the effect of pericardial constraint on the activity of left ventricular (LV) mechanoreceptors with nonmyelinated vagal afferents. METHODS AND RESULTS: Single-unit activity of cervical vagal afferents (conduction velocity, 1.6 +/- 0.5 m/s) was recorded in six cats anesthetized with alpha-chloralose. Discharge frequency during diastole (DFdiastole) and systole (DFsystole) was determined after correction for conduction delay of the nerve action potential. When the pericardium was closed and LV end-diastolic pressure (LVEDP) was approximately 5 mm Hg, DFdiastole and DFsystole were 1.3 +/- 1.0 and 0.3 +/- 0.1 impulses per second, respectively. Volume expansion increased LVEDP, LV transmural LVEDP, and segment length and was associated with a significant increase in DFdiastole. At a given LVEDP, DFdiastole was significantly greater in the absence of the pericardium than with the pericardium closed. Removal of the pericardium increased the slope of the relation between DFdiastole and intracavitary LVEDP but did not alter the slope of the relations between DFdiastole and transmural LVEDP and LV segment length. CONCLUSIONS: These results suggest that, rather than the absolute value of intracavitary LVEDP, transmural LVEDP and distension appear to be more important determinants of diastolic LV mechanoreceptor activity and that pericardial constraint may attenuate mechanoreceptor activity by limiting cardiac distension.

Animals↗
PubMed1995

Long-term reproducibility of ventricular tachycardia induction in patients with implantable cardioverter/defibrillators. Serial noninvasive studies.

BACKGROUND: Noninvasive electrophysiological studies (EPSs) can be performed in current implantable antitachycardia pacemaker/cardioverter/defibrillators (ICDs). Thus, these devices may be used as tools to study changes in the electrophysiological substrate and ventricular tachycardia characteristics over time. METHODS AND RESULTS: Fifty-five patients receiving an ICD for treatment of sustained ventricular tachyarrhythmias underwent serial EPSs after implantation of the ICD. Studies were performed before hospital discharge and 1, 3, 5, 9, 12, 18, 24, and 36 months after ICD implantation. Sustained monomorphic ventricular tachycardia (VT) was induced in 37 patients (group 1) at the predischarge EPS, whereas no sustained arrhythmia could be induced in 18 patients (group 2) at baseline. Group 1 patients underwent 165 noninvasive EPSs after discharge. Sustained monomorphic VT was induced during 72% of the follow-up EPSs, ventricular fibrillation (VF) was induced during 11% of follow-up EPSs, and no sustained VT or VF was induced during 17% of follow-up visits. Sustained VT was induced at every follow-up EPS in 23 patients (62%), whereas no sustained VT/VF could be induced at least once during follow-up in 14 patients (38%). Clinical or electrophysiological variables did not predict noninducibility during follow-up. However, the probability that a patient would experience spontaneous VT decreased significantly over time in patients in whom VT was not inducible during at least 1 follow-up EPS (P = .05). Group 2 patients underwent 86 noninvasive EPSs after discharge. Sustained monomorphic VT was induced during 22% of follow-up EPSs, VF was induced during 19% of follow-up EPSs, and no sustained VT/VF could be induced during 68% of follow-up EPSs. No sustained VT/VF could be induced during every follow-up EPS in 9 patients (50%), whereas sustained monomorphic VT was induced at least once during follow-up in 7 patients (34%). Persistent noninducibility of VT during follow-up was associated with low probability of occurrence of spontaneous VT (11%), whereas inducibility of VT at least once during follow-up was associated with the occurrence of spontaneous VT (89%, P = .003). CONCLUSIONS: Considerable variability of VT induction is observed over a lengthy period in patients presenting with sustained VT/VF. Persistent noninducibility of VT is associated with a reduced probability of spontaneous VT. These observations suggest that the substrates for inducible and spontaneous VT change in parallel over time.

Aged↗
PubMed1995

High- and low-affinity sites for [3H]dofetilide binding to guinea pig myocytes.

Dofetilide specifically blocks the rapid component of the delayed rectifier current (IKr) at nanomolar concentrations in a saturable manner, suggesting the presence of a receptor. We characterized two [3H]dofetilide binding sites to ventricular myocytes from adult guinea pigs by using a conventional filter assay. Scatchard analysis revealed two binding sites with different affinities: a high-affinity site (Kd, 2.8 +/- 0.3 x 10(-8) mol/L; Bmax, 76 +/- 15 fmol/10(6) myocytes) and a low-affinity site (Kd, 1.64 +/- 0.4 x 10(-6) mol/L; Bmax, 1620 +/- 260 fmol/10(6) myocytes) (n = 11). Kinetic studies showed that there were two dissociation rate constants for [3H]dofetilide (0.02 +/- 0.005 min-1 [high-affinity site] and 0.22 +/- 0.064 min-1 [low-affinity site], n = 4), although the observed association rate constant is equally well fit to a single- or two-site model. The ability of known IKr blockers to compete with [3H]dofetilide binding to both sites was assessed. E4031, clofilium, quinidine, and sotalol competed for binding at both sites. Disopyramide and NAPA only competed for a single binding site. The mean IC50 values for inhibition of binding to both the high- and low-affinity binding sites correlated with their concentrations required to inhibit IKr in electrophysiological studies. However, inhibition of [3H]dofetilide binding to the high-affinity site by class III antiarrhythmic drugs occurred at pharmacological concentrations, whereas suprapharmacological concentrations were required to inhibit binding to the low-affinity site.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Ring and link requirements for tocainide binding to the class I antiarrhythmic drug receptor on rat cardiac myocytes.

Our purpose was to assess the structural and physicochemical determinants of the binding of tocainide and several of its homologs to the class I antiarrhythmic drug receptor associated with rat cardiac sodium channels. The homologs were chosen to assess the contributions of substituents of the aryl ring and the arylamine link on drug binding. Drug affinity was measured with a radioligand binding assay using [3H]Batrachotoxin A 20 alpha-Benzoate and freshly isolated cardiac myocytes. The affinities of the homologs were compared to determine the relationship between the affinity for the receptor and the physicochemical and structural properties of the parent drug. The contributions to the free energy of binding were determined with the Gibb's equation delta G = -RT In (1/Ki). Hydrophobic interactions are important at most sites. Meta substituents on the aryl ring and substituents on the link each interact hydrophobically with the receptor and contribute about 0.3 kcal/mol of carbon. The hydrophobic pocket near the link binding site accommodates at least six carbons. A para methoxy substituent reduces the free energy of tocainide binding by 43%. This profound reduction in the free energy of binding might be due to anomolously high aqueous solubility of alkyl aryl ethers. Longer alkoxy chains contribute 1.09 kcal/mol of carbon to the binding energy. Ortho substituents contribute little to binding specificity. These findings support a notion of a complex drug receptor with hydrophilic and hydrophobic domains that recognize specific moieties on class I antiarrhythmic drugs.

Animals↗
PubMed1994

Amiloride-quinidine interaction: adverse outcomes.

OBJECTIVES: Previous studies have reported beneficial antiarrhythmic effects when selected drugs were combined. The purpose of this study was to assess whether a favorable interaction would occur with amiloride and quinidine. DESIGN: The antiarrhythmic and electrophysiologic effects of quinidine alone and in combination with amiloride were assessed in 10 patients with inducible sustained ventricular tachycardia. Parallel electrophysiologic studies assessed this drug combination in guinea pig papillary muscle. RESULTS: None of the patients had adverse effects during quinidine monotherapy. However, seven of 10 patients had adverse responses to the combination treatment: three patients had suppression of inducible ventricular tachycardia during quinidine monotherapy but had sustained ventricular tachycardia induced during combination treatment; three other patients had somatic side effects that resulted in discontinuation of the combination therapy but were absent during quinidine monotherapy; and one patient had 12 episodes of sustained ventricular tachycardia during this combination therapy. The patient had no such response during monotherapy. Surface QRS duration was significantly more prolonged during combination therapy than during monotherapy. Parallel electrophysiologic effects assessed this drug combination in guinea pig papillary muscle. The combination of amiloride (1 mumol/L) and quinidine (10 mumol/L) synergistically decreased the maximum rate of rise of phase 0 of the action potential (Vmax) (43 +/- 12 V/sec) compared with quinidine alone (24 +/- 9 V/sec) because of a greater degree of tonic block of Vmax (14% +/- 6%) as compared to quinidine alone (3% +/- 3%) with no significant change in action potential duration. CONCLUSIONS: Amiloride exaggerates the effects of quinidine on QRS duration in patients and on Vmax during in vitro study, which implies that the proarrhythmic effect of the combination of amiloride and quinidine may be associated with synergistic increase in sodium channel blockade.

Action Potentials↗
PubMed1994

Class I antiarrhythmic drugs: allosteric inhibitors of [3H] batrachotoxinin binding to rat cardiac sodium channels.

This study assessed whether class I antiarrhythmic drugs allosterically inhibit [3H]batrachotoxinin A 20-alpha-benzoate ([3H]BTXB) binding to sodium channels on freshly isolated rat cardiac myocytes. All class I drugs tested inhibited equilibrium [3H]BTXB binding in a concentration-dependent manner. Scatchard analysis showed that disopyramide, flecainide, transcainide, lidocaine and amiodarone reduced [3H]BTXB maximum binding (Bmax) whereas procainamide, mexiletine, quinidine, quinine, tocainide, propafenone, encainide and O-demethylencainide increased [3H]BTXB KD but had little effect on Bmax. Kinetic [3H]BTXB binding assays were used to assess the mechanism by which class I drugs inhibit [3H]BTXB binding. Drugs that increase the unidirectional dissociation rate constant (k-1) of [3H]BTXB probably bind to sodium channels to which [3H]BTXB is already bound. Although all class I drugs increased the k-1 of [3H]BTXB, they did so weakly and at concentrations above the IC50 values of the drugs. Thus, drug binding to [3H]BTXB-bound channels does not appear to be the predominant mechanism underlying their ability to inhibit [3H]BTXB binding. Conversely, drugs which allosterically decrease the unidirectional association rate constant (K+1) of [3H]BTXB probably bind to channels to which [3H]BTXB is not already bound. All class I drugs decreased the k+1 of [3H]BTXB, indicating drug binding to [3H]BTXB-free channels. The estimated affinities of drugs for [3H]BTXB-free channels correlated closely with the IC50 values of these drugs (r = 0.94, P < .001), suggesting that this effect is a common and major determinant in their ability to inhibit [3H]BTXB binding. The results are discussed in light of electrophysiologic theories of class I antiarrhythmic drug action.

Allosteric Regulation↗
PubMed1993

Canadian Implantable Defibrillator Study (CIDS): study design and organization. CIDS Co-Investigators.

The Canadian Implantable Defibrillator Study (CIDS) is an on-going randomized multicenter clinical trial that compares implantable cardioverter-defibrillator (ICD) therapy against amiodarone in patients with prior cardiac arrest or hemodynamically unstable ventricular tachycardia. Eligible patients are equally randomized to receive or not receive an ICD as initial management. Those not receiving an ICD receive amiodarone. All patients are seen in follow-up every 6 months. The primary outcome event cluster is arrhythmic death or any other death occurring within 30 days of therapy initiation. Secondary outcomes are all-cause mortality and nonfatal occurrences of ventricular tachycardia or fibrillation. The goal of the study is to recruit 400 patients over 4 years. All patients will be followed to the end of the year. This will result in an 80% chance of detecting a reduction in arrhythmic death of 58% by ICD if such a difference in truth exists. Recruitment began in October 1990 and 184 patients have been enrolled to date.

Amiodarone↗
PubMed1993

A prospective randomized comparison of autodecremental pacing to burst pacing in device therapy for chronic ventricular tachycardia secondary to coronary artery disease.

A number of modes of antitachycardia pacing therapies are available in the newer generations of implantable cardioverter/defibrillators. The efficacy of synchronized burst overdrive pacing for the termination of induced and spontaneous monomorphic ventricular tachycardia (VT) was compared with synchronized autodecremental (ramp) pacing in 21 patients who received an implantable antitachycardia pacemaker/cardioverter/defibrillator for treatment of recurrent sustained monomorphic VT. Patients undergoing serial noninvasive VT induction studies after device implantation were prospectively randomized to receive trials of burst or ramp pacing therapies in a crossover study design. Antitachycardia pacing therapies were equally efficacious in treating induced VT (68% for ramp, 76% for burst pacing trials). The efficacy of ramp (93%) and burst (96%) pacing therapies was significantly higher in terminating spontaneously occurring episodes of VT than in terminating induced episodes (p = 0.001). The incidence of tachycardia acceleration was similar for both modes of pacing. The incidence of VT acceleration was lower for spontaneously occurring episodes of VT (0.01%) than for induced episodes of VT (6%, p < 0.01). Thus, antitachycardia pacing is an effective therapy for episodes of monomorphic VT, and the risk of accelerating VT to a hemodynamically unstable form is low. Antitachycardia pacing therapies are more effective against spontaneously occurring episodes than induced episodes of VT. Differences in tachycardia cycle length and duration may contribute to these effects.

Adult↗
PubMed1993

Characteristics of patients with nonfatal cardiac arrest 3 to 180 days after acute myocardial infarction.

Patients who survive a tachyarrhythmic cardiac arrest in the first 6 months after acute myocardial infarction (AMI) are at risk for recurrent arrests, but the magnitude, timing and characteristics of this phenomenon are unknown. This study characterizes the nature of recurrent tachyarrhythmic cardiac arrests in the absence of reversible factors or new myocardial necrosis in patients between 3 and 180 days after AMI. We retrospectively assessed 28 patients (mean age 61 +/- 12 years) who survived an initial cardiac arrest a median of 10 days after AMI. Mean left ventricular ejection fraction was 36 +/- 9%. Fourteen patients (50%) had at least 1 recurrence of cardiac arrest, and 10 had > 2 arrests. Almost all (92%) recurrent cardiac arrests occurred within 5 days of the preceding arrest, and the high-risk periods were similar after the first, second or third cardiac arrest. Very fast ventricular tachycardia (mean cycle length 212 +/- 30 ms) was the documented responsible arrhythmia in 44 of 51 cardiac arrests. The morphology was either polymorphic, monomorphic or sinusoidal. No clinical or laboratory values could be found that predicted whether a patient would have a recurrent arrest. Nineteen patients (68%) survived to leave the hospital and have been followed for up to 96 months. For these, actuarial 5-year overall survival was 76% and actuarial 5-year arrhythmia-free probability was 80%. Thus, patients who survive a cardiac arrest in the first 6 months after AMI are at high risk of recurrent cardiac arrest for a further 5 days, and the arrests are due to characteristically fast ventricular tachycardias.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗
PubMed1993

Risks of developing supraventricular and ventricular tachyarrhythmias after implantation of a cardioverter-defibrillator, and timing the activation of arrhythmia termination therapies.

The clinical courses of 39 consecutive recipients (mean age 61 +/- 12 years, and mean left ventricular ejection fraction 0.32 +/- 0.15) of an automatic implantable cardioverter-defibrillator (ICD) were examined to determine the risks of developing ventricular tachycardia (VT) and supraventricular tachyarrhythmias (SVT) after surgery, with ventricular response rates fulfilling ICD detection criteria. ICD system leads were implanted by thoracotomy in 25 patients and by using nonthoracotomy lead systems in 14. Six patients (18%) developed SVT after surgery, whereas 14 (36%) developed sustained VT. The median times to the development of both SVT and VT were 2 days. By actuarial analysis, the probability of developing VT after surgery was significantly greater than that of SVT during hospitalization (p = 0.04). This significant excess of postoperative VT over SVT was most marked in patients aged < or = 61 years, those who received nonthoracotomy rather than epicardial lead systems, those who presented with VT rather than ventricular fibrillation, and those who received > 20 intraoperative defibrillation shocks. These observations recommend the activation of ICD therapies immediately after implantation.

Age Factors↗
PubMed1993

Comparison of biphasic and monophasic shocks for defibrillation using a nonthoracotomy system.

A comparison of defibrillation thresholds was made using biphasic and monophasic shocks delivered by a nonthoracotomy lead system in 2 clinically distinct groups of patients. The first group were patients receiving an implantable cardioverter-defibrillator who were studied before surgery with their chests closed. The second group were patients undergoing coronary artery bypass grafting (CABG) who were studied before surgery with their chests open but reapproximated. Biphasic defibrillation thresholds (stored energy) were significantly (p < 0.001) less than monophasic ones in subjects with the implantable cardioverter-defibrillator (12.3 +/- 5.3 vs 21.1 +/- 9.3 J) or CABG (14.6 +/- 7.1 vs 24.2 +/- 12.6 J). These values are less than were previously reported with a similar nonthoracotomy lead configuration. There were no significant differences between the 2 groups in all measurements derived from corresponding shock waveforms, although impedance tended to be greater in patients with CABG. However, subjects with CABG had greater left ventricular ejection fractions and did not have history of potentially lethal ventricular arrhythmias. Despite these differences, the conclusion that biphasic shocks are more effective would have been made in a study of either group alone. It is concluded that patients with CABG who have not had preceding potentially lethal ventricular arrhythmias may be a potential source of surrogate subjects for defibrillation research such as epicardial mapping, which requires that the chest be open.

Coronary Artery Bypass↗
PubMed1993

Electrocardiographic correlates of spontaneous termination of ventricular tachycardia in patients with coronary artery disease.

BACKGROUND: In vitro studies have reported that beat-to-beat variance in tachycardia cycle length and in conduction and repolarization properties can result in spontaneous termination of reentrant arrhythmias. The purpose of this study was to define the ECG patterns associated with spontaneous termination of ventricular tachycardia in humans late after myocardial infarction. METHODS AND RESULTS: The QRS durations, QT intervals, and cycle lengths were measured on a beat-to-beat basis during episodes of sustained and spontaneously terminating ventricular tachycardias (VT) induced at antiarrhythmic drug-free and drug-assessment electrophysiological studies. Twenty-six patients were studied. Four categories of inducible ventricular tachycardia were studied: inducible sustained ventricular tachycardia in an antiarrhythmic drug-free state, spontaneously terminating ventricular tachycardia in an antiarrhythmic drug-free state, sustained ventricular tachycardia on antiarrhythmic therapy, and spontaneously terminating ventricular tachycardia on antiarrhythmic therapy. The ECG patterns that were statistically related to spontaneous termination of ventricular tachycardia included impingement of the QTP interval on the tachycardia cycle length (P < .001) both in the presence and absence of drugs, transient shortening of QRS just before termination, and paradoxical prolongation of QTP after abrupt shortening of ventricular tachycardia cycle length. In addition, greater beat-to-beat variances in tachycardia cycle lengths, QT intervals, and QRS durations were statistically associated with spontaneously terminating ventricular tachycardia. These ECG patterns did not occur during sustained episodes of ventricular tachycardia during the antiarrhythmic drug-free state or during ineffective antiarrhythmic drug therapy. CONCLUSIONS: A dynamic interplay between QRS duration, QT interval, and cycle length of tachycardia and their variances are associated with spontaneous termination of ventricular tachycardia in humans late after infarction. This study of ECG changes associated with spontaneous termination of ventricular tachycardia provides insight into potential mechanisms of antiarrhythmic drug efficacy.

Anti-Arrhythmia Agents↗