Biomedical subjects

S G Kim

Publications and source records attributed to S G Kim.

At least 19 recordsLinked to original sources

PubMed1992

Solution structure of the TnAn DNA duplex GCCGTTAACGCG containing the HpaI restriction site.

The solution structure of the self-complementary DNA duplex [d(GCCGTTAACGGC)]2, which contains the HpaI restriction site GTTAAC, has been elucidated by two-dimensional NMR, distance geometry (DG), and NOE back-calculation methods. Initial distance constraints were determined by polynomial fitting the two-spin initial NOE rates; backbone constraints from NOE and J-coupling observations (Kim et al., 1992) were included. RMSDs between initial-distance-refined structures derived from random-embedded DG, A-DNA, and B-DNA starting structures were all in the range 0.5-1.0 A, indicating good convergence properties of the algorithm, regardless of the starting structure. A semiautomatic back-calculation refinement procedure was developed and used to generate more refined structures for which the BKCALC-simulated NOE volumes matched the experimental data. The six final structures refined from various starting structures exhibit very good agreement with the experimental data (R values = 0.18) and converge well to within 0.8-A RMSD differences for the central 8 base pairs. The torsion and pseudorotation phase angles were found to be well determined by the data, and the local helical parameters for each base step converged quite well. The final structures show that the central T6-A7 step is somewhat underwound (twist angle ca. 29 degrees), with a large negative cup and a normal (wide) minor groove width, while the T5-T6 and A7-A8 steps have a partially narrowed minor groove.

Base Sequence↗

PubMed1992

The influence of oligodeoxyribonucleotide phosphorothioate pyrimidine strands on triplex formation.

Analogues of the homopyrimidine oligonucleotide dT15 that contained phosphorothioate bonds of a mixture of diastereoisomers or one of the two stereoisomers (either Rp or Sp) were synthesized. The analogues were mixed under conditions conducive to the formation of triple-stranded assemblies. The mixtures were characterized by their thermal stabilities (Tm values), CD spectra, and gel electrophoresis pattern. The 34-mer duplexes containing 15 central purines on one strand and 15 complementary pyrimidines on the other strand gave no detectable triple helix upon combination with dT15S14. On the other hand, 34-bp duplexes with dT15S1, having Rp or Sp, formed triple helixes. This suggests that a steric factor plays an important role in triple helix formation.

Base Sequence↗

PubMed1992

Rapid suppression of spontaneous ventricular arrhythmias during oral amiodarone loading.

OBJECTIVE: To determine the time course of effects of amiodarone during an oral loading period. DESIGN: A prospective, nonrandomized study. SETTING: Arrhythmia referral center at a university hospital. PATIENTS: Fifty patients with refractory sustained ventricular tachycardia (n = 44) or ventricular fibrillation (n = 6) and frequent (greater than or equal to 30/h) ventricular premature complexes. INTERVENTION: Oral amiodarone, 1200 mg/d for 14 days and 400 mg/d thereafter. MEASUREMENTS: Ambulatory electrocardiographic monitorings, 12-lead electrocardiograms, and amiodarone blood levels on days 3, 5, 7, 9, 11, 13, and 28. RESULTS: Dramatic reductions of ventricular arrhythmias were noted during the first 72 hours of the therapy. Average ventricular premature complexes/h, couplets/h, and nonsustained ventricular tachycardias/24 h were 524 +/- 1224/h, 16 +/- 61/h, and 167 +/- 611/24 h, respectively, at baseline, and reduced to 140 +/- 243/h, 11 +/- 50/h, and 33 +/- 117/24 h, respectively, on day 3 (P less than 0.05 for all). Subsequent reductions of ventricular arrhythmias from day 3 to day 13 were more gradual but were still significant (P less than 0.05). A significant reduction of ventricular arrhythmias (greater than or equal to 70% reduction of ventricular premature complexes and greater than or equal to 90% reduction of nonsustained ventricular tachycardias) was noted in 50% of patients on day 3, in 65% on day 7, and in 83% on day 13. Prolongation of the QT interval exhibited a similar time course. There were no further differences in reduction of ventricular premature complexes or QT intervals between day 13 and day 28. CONCLUSIONS: Oral amiodarone given in loading doses produces rapid and dramatic reductions in spontaneous ventricular arrhythmias within 72 hours. Subsequent reductions of spontaneous arrhythmia were gradual and less dramatic.

Administration, Oral↗

PubMed1992

Evidence for elevation of cytochrome P4502E1 (alcohol-inducible form) mRNA levels in rat kidney following pyridine administration.

The effects of pyridine on renal cytochrome P4502E1 (CYP2E1) expression in rat have been examined by immunoblot and Northern blot analyses. Immunoblot analyses revealed that 2E1 protein levels were elevated from 1.4- to 4.6-fold following pyridine administration in a dose- and time-dependent manner. Northern blot analyses revealed that renal 2E1 poly(A)+ RNA levels increased from 1.4- to 3.8-fold following pyridine treatment and that these increases in 2E1 mRNA paralleled the dose- and time-dependent increases in 2E1 protein content. In contrast, hepatic 2E1 poly(A)+ RNA levels failed to increase following these same dosing regimens, suggesting that metabolic alterations, such as those associated with starvation, were not etiologic factors in renal 2E1 induction. These results show that pyridine induced CYP2E1 in kidney and that elevation of renal 2E1 protein levels accompanying pyridine administration occurred at least partly as a consequence of increased 2E1 poly(A)+ RNA levels. The results of this research reveal that regulatory mechanisms governing CYP2E1 expression may differ in hepatic and renal tissues.

Animals↗

PubMed1992

Intrinsic signal changes accompanying sensory stimulation: functional brain mapping with magnetic resonance imaging.

We report that visual stimulation produces an easily detectable (5-20%) transient increase in the intensity of water proton magnetic resonance signals in human primary visual cortex in gradient echo images at 4-T magnetic-field strength. The observed changes predominantly occur in areas containing gray matter and can be used to produce high-spatial-resolution functional brain maps in humans. Reducing the image-acquisition echo time from 40 msec to 8 msec reduces the amplitude of the fractional signal change, suggesting that it is produced by a change in apparent transverse relaxation time T*2. The amplitude, sign, and echo-time dependence of these intrinsic signal changes are consistent with the idea that neural activation increases regional cerebral blood flow and concomitantly increases venous-blood oxygenation.

Brain Chemistry↗

PubMed1992

Reproducibility of electrophysiologic testing during antiarrhythmic therapy for ventricular arrhythmias secondary to coronary artery disease.

Although electrophysiologic studies are often used to assess antiarrhythmic drug efficacy in patients with ventricular tachycardia (VT), the reproducibility of these studies during therapy has not been definitively established. Confirmation studies were performed during drug therapy in 64 patients (51 men, mean age 63 years) with sustained ventricular arrhythmias induced during initial study to assess the reproducibility of drug effect. All patients had coronary artery disease. The stimulation protocol used included the serial introduction of up to 3 premature ventricular stimuli during sinus rhythm and with ventricular pacing at 2 pacing rates. Rapid ventricular pacing techniques were also used. Antiarrhythmic drug efficacy was confirmed in 77% of patients. Sustained VT was induced at repeat electrophysiologic study in 19% of patients during antiarrhythmic therapy that was previously thought to be effective. In summary, electrophysiologic study results during antiarrhythmic therapy exhibit significant day-to-day variability. Sustained VT can be induced during antiarrhythmic therapy that was previously defined as effective by programmed stimulation in a substantial number of patients.

Adult↗

PubMed1992

Errors in RNA NOESY distance measurements in chimeric and hybrid duplexes: differences in RNA and DNA proton relaxation.

Nuclear magnetic resonance experiments reveal that the base H8/H6 protons of oligoribonucleotides (RNA) have T1 relaxation times that are distinctly longer than those of oligodeoxyribonucleotides (DNA). Similarly, the T1 values for the RNA H1' protons are approximately twice those of the corresponding DNA H1' protons. These relaxation differences persist in single duplexes containing covalently linked RNA and DNA segments and cause serious overestimation of distances involving RNA protons in typical NOESY spectra collected with a duty cycle of 2-3 s. NMR and circular dichroism experiments indicate that the segments of RNA maintain their A-form geometry even in the interior of DNA-RNA-DNA chimeric duplexes, suggesting that the relaxation times are correlated with the type of helix topology. The difference in local proton density is the major cause of the longer nonselective T1s of RNA compared to DNA, although small differences in internal motion cannot be completely ruled out. Fortunately, any internal motion differences that might exist are shown to be too small to affect cross-relaxation rates, and therefore reliable distance data can be obtained from time-dependent NOESY data sets provided an adequately long relaxation delay is used. In hybrid or chimeric RNA-DNA duplexes, if the longer RNA relaxation times are not taken into account in the recycle delay of NOESY pulse sequences, serious errors in measuring RNA proton distances are introduced.

Base Sequence↗

PubMed1992

Determination of nucleic acid backbone conformation by 1H NMR.

In DNA or RNA duplexes, the six-bond C3'-O3'-P-O5'-C5'-C4'-C3' backbone linkage connecting adjacent residues contains six torsion angles (epsilon, zeta, alpha, beta, gamma, delta) but only four protons. This seriously limits the ability to define the backbone conformation by NMR using purely 1H-1H distance geometry (DG) methods. The problem is further compounded by the inability to assign two of the four backbone protons, namely the poorly resolved H5' and H5'' protons, and invariably leads to DG structures with poorly defined backbone conformations. We have developed and tested a reliable method to constrain the beta, gamma, and epsilon (and indirectly alpha and zeta) backbone torsion angles by lower-bound NOE distances to unassigned H5'/H5'' resonances combined with either 1H line widths or the conservative use of sigma J measurements; the method relies only on 1H 2-D NMR data, does not involve any structural assumptions, and leads to much improved backbone convergence among DG structures. The C4'-C5' torsion angle gamma is constrained by lower-bound NOE distances from H2' and from H6/H8 to any H5'/H5'', as well as by sigma JH4, coupling measurements in the 3.9-4.4 ppm region; delta is constrained by H1'-H4' NOE distances and by H3'-H4' and H3'-H2'' J couplings in COSY data; epsilon is partially constrained by H3' line width and/or further constrained by subtracting the minimum possible sigma JH3'-H from the observed sigma JH3' (COSY) to arrive at the maximum possible JH3'-P, which is then converted to H3'-P distance bounds. The angle beta is partially constrained via H5'-P and H5''-P distance bounds consistent with the maximum H5'-P and H5''-P J couplings derived from the observed H5' and H5'' line widths, while alpha and zeta are indirectly constrained by lower distance bounds on the observed (n)H1' to (n + 1)H5'/H5'' NOEs combined with the prior partial constraints on beta, gamma, delta, and epsilon. The combined effects of these additional constraints in determining distance geometry structures have been demonstrated using a 12-base duplex, [d(GCCGTTAACGGC)]2. Coordinate RMSDs per atom between structures refined with these constraints from random-embedded DG structures, from ideal A-DNA, and from B-DNA starting structures were less than 0.4 A for the central 8 base pairs indicating good convergence. All backbone angles for the central 8 base pairs are very well constrained with less than 10 degrees variation in any of the 48 torsion angles.

Base Sequence↗

PubMed1992

Nonglycolytic acidification of murine radiation-induced fibrosarcoma 1 tumor via 3-O-methyl-D-glucose monitored by 1H, 2H, 13C, and 31P nuclear magnetic resonance spectroscopy.

The effects of 3-O-methyl-D-glucose (3-OMG) on subcutaneously implanted murine radiation-induced fibrosarcoma 1 tumor were examined with 2H, 13C, and 31P nuclear magnetic resonance (NMR) in situ. Using 31P NMR, changes in tumor high-energy phosphate metabolism were monitored for 2.5 h after i.p. administration of 3-OMG (8.1 g/kg body weight); tumor pH decreased by a mean maximum of 0.52 +/- 0.05 (SE) (n = 10), [PCr] decreased by 54%, [NTP] decreased by 35%, and [Pi] increased by 36%. Tumor blood flow, as measured by 2H NMR monitoring of D2O washout kinetics, decreased by 40% at 1 h and by 47% at 2 h after 3-OMG injection (n = 4). This substantial tumor acidification (pH decrease much greater than 0.1), expected to require a glycolytic substrate (Hwang et al., Cancer Res., 51: 3108-3118, 1991), is surprising in light of the previously documented metabolically inert nature of 3-OMG. In situ 13C NMR spectroscopy, following [6-13C]3-OMG i.p. injection, examined the possibility of the glycolytic metabolism of 3-OMG. However, only the C-6 resonance of 3-OMG was detected (n = 6); no resonances from [6-13C]3-OMG-6-phosphate or [3-13C]lactate were observed. These results confirmed that 3-OMG was not metabolized in radiation-induced fibrosarcoma 1 tumor. At the completion of the in situ 13C NMR experiments, tumors were freeze clamped, and perchloric acid extraction was performed. High-resolution 1H NMR measurement of lactate concentrations showed no statistically significant difference in control tumor extracts (from mice not receiving i.p. injection; n = 5) and in tumor extracts from mice administered i.p. [6-13C]3-OMG (n = 5), indicating that there was no significant increase in lactate level in the tumor extracts from mice administered i.p. 3-OMG due to increased plasma glucose concentration. The results of these 1H and 13C NMR studies indicated that the radiation-induced fibrosarcoma 1 tumor acidification caused by i.p. administration of 3-OMG was not due to a direct (3-OMG----lactate) or an indirect (systemic glucose----lactate) increase in tumor lactic acid levels.

3-O-Methylglucose↗

PubMed1992

Use of antisense RNA to confer bacteriophage resistance in dairy starter cultures.

The strategy and implementation of a unique system for engineering bacteriophage resistant starter cultures of Lactococcus lactis employing antisense RNA is reviewed. As a necessary prerequisite for developing this system, we have cloned and sequenced a number of bacteriophage genes coding for minor and major structural proteins. In addition, we have also identified a series of genes whose function(s) is not known but their sequences appear to be conserved in a vast number of isolates. One of these latter sequences, designated gp51C, codes for a 51-kDa protein which is extremely charged and shares some homology with yeast translation initiation factor. Resistance to a broad class of isometric bacteriophages has been achieved by expression of an antisense RNA targeted against, for example, gp51C. In the best case, expression of the antisense gp51C RNA results is a greater than 99% reduction in the total number of plaque forming units. Additional antisense RNA constructs directed against other bacteriophage genes, including the major capsid protein, also appear effective at inhibiting infection from 40-55% suggesting that this approach may prove useful for engineering a set of truly isogenic strains to be used in a starter culture rotation plan.

Bacteriophages↗

PubMed1992

Combined maze procedure and septal myectomy in a septuagenarian.

A 75-year-old woman with refractory paroxysmal atrial fibrillation and hypertrophic obstructive cardiomyopathy underwent a successful combined maze procedure and septal myectomy. Postoperative episodes of atrial fibrillation and flutter occurred only during periods of bradyarrhythmia and did not recur with atrial inhibited pacing.

Aged↗

PubMed1992

Differences between rats and rabbits in hepatic cytosolic glutathione S-transferase expression in response to nitrogen heterocycle and other inducers.

Glutathione S-transferase (GST) expression was examined in hepatic cytosol from rats and rabbits treated with 4-picoline, pyrrole, pyridine, pyrazine, imidazole, or piperidine using enzymatic activity, SDS-PAGE, and immunoblot analyses and the results were compared to those obtained with phenobarbital and 3-methylcholanthrene. SDS-PAGE and immunoblot analyses of hepatic cytosol prepared from rats treated with pyrazine revealed the induction of class alpha (Ya and Yc) and mu (Yb) bands with a corresponding 2.4-fold increase in metabolic activity using 1-chloro-2,4-dinitrobenzene as substrate. A new class alpha band migrating in the region of the Yc band was observed in the SDS-PAGE and detected in the immunoblot of cytosol from pyrrole-treated rats, whereas treatment with 4-picoline, imidazole, or piperidine failed to alter the expression of the major classes of GST isozymes in this species. SDS-PAGE and immunoblot analyses of rabbit hepatic cytosol revealed a unique species-dependent difference in the expression of GSTs. While phenobarbital and 3-methylcholanthrene induce class alpha and mu GST expression in rat hepatic cytosol, one of the most interesting observations was that neither of these agents stimulated GST expression in the rabbit. Immunoblot analysis of cytosol isolated from 4-picoline-treated rabbits using GST class alpha-specific IgG showed the appearance of a novel class alpha 28-kDa GST band and the concomitant disappearance of a class alpha 29-kDa GST band. In addition, SDS-PAGE and immunoblot analyses showed that treatment of rabbits with pyrrole, pyrazine, imidazole, or piperidine resulted in the disappearance of this class alpha 29-kDa GST band with no detectable expression of the class alpha 28-kDa GST band; the level of the class alpha 29-kDa band was unaffected by pyridine treatment. In contrast, immunoblot analyses of hepatic cytosol revealed that a 25.5-kDa class mu GST band disappeared following treatment with pyridine, but was unaffected by treatment with other nitrogen heterocycles. The Vmax of glutathione conjugation to the substrate 1-chloro-2,4-dinitrobenzene decreased by 52, 36, 59, 41, 37, and 32% in hepatic cytosol isolated from 4-picoline-, pyrrole-, pyridine-, pyrazine-, imidazole-, and piperidine-treated rabbits, respectively. The results suggest that nitrogen heterocycles differ in their ability to modulate glutathione S-transferase isozyme expression in rat and rabbit hepatic tissue and that rabbit hepatic GSTs are refractory to induction by agents such as pyrazine, phenobarbital, or 3-methylcholanthrene and hence these xenobiotics do not appear to be bifunctional inducers in this species.

Animals↗

PubMed1992

Implementation of a new DDDR algorithm for tachycardia prevention and treatment utilizing an implantable RAM-based software-controlled pacemaker.

Reentry within the atrioventricular node or over accessory pathways are common causes of symptomatic tachycardia. These arrhythmias are frequently initiated by a spontaneous atrial or ventricular premature beat. Appropriately timed atrial or ventricular extrastimuli can, in some patients, render one limb of the reentrant circuit refractory and prevent induction of tachycardia. Currently available implantable devices are not suitable for this application. The authors have implemented a new implantable pacing algorithm capable of extremely short atrial and ventricular refractory periods, rapid triggered ventricular pacing rates, protection against encroachment on the ventricular vulnerable period, protection against tachycardia induction by ventricular premature beats, automated antitachycardia pacing in either atrium and ventricle, as well as an extensive event storage capability. This application has been made possible by a new, RAM-based microprocessor controlled dual chamber pacemaker (Medtronic Prometheus Model 6100). Its use in intraatrial tachycardia with atrioventricular block as well as Wolff-Parkinson-White syndrome is demonstrated. This device is capable of prevention of tachycardia induction in some patients. Where prevention is not feasible or fails, it is backed up by automated or manually activated antitachycardia pacing. The great flexibility of a completely reprogrammable software based pacemaker has enabled the implementation of a very complex experimental pacemaker that will permit evaluation in the implanted setting of this new pacing strategy.

Algorithms↗

PubMed1992

Functional brain mapping using magnetic resonance imaging. Signal changes accompanying visual stimulation.

Easily detectable (5%-20%) transient increases in the intensity of water proton magnetic resonance (MR) signals in human primary visual cortex were observed during visual stimulation in gradient echo images at 4-T field strength. The signal intensity increases were predominantly restricted to areas containing gray matter and were used to produce high-spatial-resolution human functional brain maps. Time dependence of the functional brain maps also was monitored during visual stimulation using images acquired every approximately 5 seconds; these images with high spatial and temporal resolution demonstrated that photic stimulation first resulted in signal increases in a large area of the visual cortex followed by a reduction in the size of the area, and that signal intensity increases in the gray matter were time dependent. Reducing the image acquisition echo times reduced the amplitude of the fractional signal change, suggesting that it is produced by a change in T2 or T2*. The amplitude, sign, and echo time dependence of these intrinsic signal changes are consistent with the idea that neural activation increases regional cerebral with the idea that neural activation increases regional cerebral blood flow (rCBF) with a concomitant increase in venous blood oxygenation.

Brain Mapping↗

PubMed1992

Programmed electrical stimulation protocols: variations on a theme.

A series of prospective protocols were designed to determine the yield ratio (true positives vs. false positives = nonclinical) in various patient groups using a variety of programmed electrical stimulation (PES) variables. First, a PES protocol was used in 772 patients. Single, double, and triple extrastimuli were delivered in sequence (leaving each successive extrastimulus just beyond its refractory period before moving to the next extrastimulus) during sinus rhythm and two ventricular paced rates at the RV apex, before moving to the outflow tract and repeating the sequence and then moving on to isoproterenol infusion with the PES sequence repeated at the apex. This protocol met NASPE standards for induction of VT in patients with coronary artery disease and a history of VT, while failing to induce monomorphic VT in any control patient. The best yield ratios combined with the greatest likelihood of inducing clinical tachycardia were achieved with sinus rhythm and three extrastimuli, and pacing at the lower rate and three extrastimuli. Pacing at the faster rate and triple extrastimuli was highly inductive of clinical arrhythmias, but had a low yield ratio due to induction of more nonclinical arrhythmias than other steps. The next protocol was performed in 61 patients with inducible ventricular tachycardia. In each case, the protocol described above was completed at the RV apex, even if tachycardia was also induced at an earlier point in the protocol. This allowed for more accurate yield ratios to be established for each step in the protocol, since each patient was exposed to each of these steps.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗

PubMed1992

Clinical evaluation of the safety of repetitive intraoperative defibrillation threshold testing.

One goal of the initial implantation procedure for a cardioverter defibrillator is determination of the configuration and patch location with the lowest defibrillation threshold (DFT). To determine the safety of multiple defibrillation tests, an analysis of the intraoperative defibrillation threshold tests (DFTT) in our patients was performed. In 84 patients, the mean number of DFT trials was 5.27; the mean number of joules received was 275.0. The maximum number of shocks in one implant procedure was 50 for a total of 4,895 joules without complications. Four patients received 30 or more DFT shocks without complication. There were two complications related directly to the DFTT: one patient with severe noninflammatory cardiomyopathy developed electromechanical dissociation and was subsequently resuscitated and survived; the second patient with severe triple vessel coronary artery disease suffered an intraoperative myocardial infarction during testing and eventually died 22 days postoperatively. All patients received an ICD unit; six patients had DFTs of greater than 20 joules. Based on our experience, we followed the clinical status (heart rate, blood pressure, ECG changes, fluid status, total anesthesia time) during the DFTT to determine the extent and duration of our testing protocol. Multiple shocks due to repositioning of the leads in a stable patient should not prohibit extensive testing as adverse consequences do not appear to be cumulative.

Electric Countershock↗

PubMed1992

Programmed electrical stimulation of the ventricle: an efficient, sensitive, and specific protocol.

A relatively simple and efficient ventricular programmed electrical stimulation (PES) protocol was developed, capable of achieving high degrees of sensitivity and specificity. In a series of 481 subjects, 1, 2, and 3 extrastimuli (ES) were used successively during sinus rhythm and ventricular pacing at two drive cycle lengths, at one or more ventricular sites, together with rapid ventricular pacing, and other maneuvers such as isoproterenol infusion. Three ES were used immediately after two ES at each drive rate, rather than returning after completion of the protocol with two ES. Using the protocol, appropriate arrhythmias could be induced in 88% of all patients with ventricular fibrillation, 84% of all patients with sustained ventricular tachycardia (91% with underlying coronary disease), and 58% of patients with severe nonsustained ventricular tachycardia. There were significant differences in inducibility between patients whose ventricular arrhythmias were due to coronary artery disease and other causes. In contrast, sustained ventricular arrhythmias (all ventricular fibrillation) could be induced in only 5% of a control group of control patients, for a specificity of 95%. The protocol described is simpler and more efficient than those that use exhaustive testing of two ES before going to three ES. Three ES during sinus rhythm proved to be the most productive step, with a higher yield ratio (true: false-positives) than two ES or three ES during pacing, especially at faster rates. Greater efficiency is also achieved by leaving the timing of an extrastimulus just beyond its effective refractory period when an additional extrastimulus is to be added, compared to protocols in which the extrastimulus is moved later in the cycle and then decremented in tandem with the additional extrastimulus. Coupling intervals less than 200 msec produced some false-positives, but fewer overall than intervals greater than or equal to 200 msec, and with yield ratios comparable to other protocol steps. The protocol described meets NASPE standards for ventricular programmed stimulation protocols, and with its demonstrated specificity and relative simplicity and efficiency may be useful as a model for groups not yet committed to an alternative protocol.

Cardiac Pacing, Artificial↗

PubMed1992

Stimulation hierarchy: optimal sequence for double and triple extrastimuli during electrophysiological studies.

To determine the optimal ventricular stimulation sequence, an 11-step programmed electrical stimulation (PES) protocol was completed, even if a ventricular arrhythmia (VA) was induced with earlier steps. The protocol consisted of one, two, and three extrastimuli during sinus rhythm (SR), and at two drive pacing rates (VP1 and VP2) plus rapid burst and ramp pacing. By analyzing the 79 completed protocols that induced the clinical arrhythmia, the following were determined: (1) the frequency of induced clinical and nonclinical VA with each stimulation step; (2) the yield ratio (YR) of each step, defined as the probability of inducing clinical versus nonclinical arrhythmia; (3) the cumulative yield of induced clinical and nonclinical arrhythmia with two widely used stimulation sequences, i.e., triple extrastimuli delivered early in the stimulation protocol (MMC sequence) and triple extrastimuli delayed until after double extrastimuli failed to induce the clinical arrhythmia (B sequence); (4) the relative efficiency of these sequences were determined. The percentage of induced clinical and nonclinical arrhythmia with SR + 3 extrastimuli, VP1 + 2 extrastimuli, and VP2 + 2 extrastimuli were (53%, 5%), (36%, 5%), and (41%, 9%), respectively. The cumulative yield of induced clinical VA with the MMC-type sequence reached 55% by the third step of the protocol, whereas 50% was attained only at the eighth step of the B-type sequence. The cumulative percentage of induced nonclinical VA with either sequence was similar during the early steps of the protocol. The MMC sequence was more efficient, requiring overall 36% of potential steps for clinical arrhythmia induction, compared with 48% for the B sequence (P less than 0.001). For questionable arrhythmia states, e.g., syncope of unknown origin and nonsustained VT, a modified sequence is proposed that may further reduce the induction of uninterpretable arrhythmias.

Anti-Arrhythmia Agents↗