Indications for modification of coexisting dual atrioventricular node pathways in patients undergoing surgical ablation of accessory atrioventricular connections.

Concomitant susceptibility to atrioventricular (AV) node reentrant tachycardia has been demonstrated in certain patients having reentrant tachycardia utilizing accessory AV connections. For those patients undergoing accessory connection ablation, AV node surgical modification may be warranted during the same operative procedure. To assess indications for a combined operative procedure, this study evaluated potential predictors of subsequent spontaneous AV node reentrant tachycardia in patients undergoing ablation of accessory AV connections. Among 62 consecutive patients undergoing surgical ablation of an accessory AV connection, 13 (21%) manifested dual AV node pathways. The latter were identified preoperatively in five patients (four with concealed and one with bidirectional accessory connections) and postoperatively in seven (all seven with bidirectional accessory connections). In one patient with a bidirectional accessory connection, dual AV node pathways could not be demonstrated preoperatively, but AV node reentrant tachycardia was induced. Operative ablation of an accessory connection was successful in all patients. However, postoperatively, 2 of the 13 patients had inducible AV node reentrant tachycardia, 5 had AV node "echo" beats and 6 had no inducible arrhythmia. During 26 +/- 7 months of follow-up study, the two patients with inducible AV node reentrant tachycardia postoperatively had symptomatic AV node reentrant tachycardia. In addition, the one patient with inducible AV node reentrant tachycardia preoperatively had recurrence of this tachycardia 4 months after attempted surgical modification of the AV node. Consequently, although dual AV node pathways appear to be common in patients undergoing surgical ablation of an accessory AV connection (21%), only a small group (3 of 13) of these patients are at risk for subsequent clinical AV node reentrant tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of the ventricular response during atrial fibrillation in patients with enhanced atrioventricular node conduction and Wolff-Parkinson-White syndrome.

Although ventricular fibrillation is a well known sequel to atrial fibrillation in the Wolff-Parkinson-White syndrome, ventricular fibrillation is not generally associated with supraventricular tachycardia in the presence of enhanced atrioventricular (AV) node conduction without pre-excitation. It was hypothesized that the ventricular response during atrial fibrillation may be less in patients with enhanced AV node conduction than in their counterparts with Wolff-Parkinson-White syndrome matched for anterograde effective refractory period. Slower ventricular rates during atrial fibrillation would suggest an increased propensity for concealed conduction in the enhanced AV node conduction group than in the group with an accessory pathway. Three groups of patients aged 16 to 65 years underwent electrophysiologic testing for supraventricular tachycardia or after surgical correction of Wolff-Parkinson-White syndrome. Sixteen patients had enhanced AV node conduction, 16 had Wolff-Parkinson-White syndrome and 16 had normal AV node conduction. Patients with enhanced AV node conduction and Wolff-Parkinson-White syndrome were well matched for anterograde effective refractory period (245 +/- 22 versus 258 +/- 25 ms) and minimal cycle length, maintaining 1:1 anterograde conduction (261 +/- 21 versus 260 +/- 40). There was no difference in intervals during atrial fibrillation (average RR interval = 372 +/- 37 versus 346 +/- 66) or shortest RR interval (266 +/- 27 versus 243 +/- 51). Thus, patients with Wolff-Parkinson-White syndrome and those with enhanced AV node conduction matched for anterograde refractory period exhibit similar ventricular rates during atrial fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)

Intravenous diltiazem for termination of reentrant supraventricular tachycardia: a placebo-controlled, randomized, double-blind, multicenter study.

To assess the efficacy and safety of intravenous diltiazem, 54 patients with inducible sustained supraventricular tachycardia received diltiazem, 0.25 mg/kg or 0.25 mg/kg, followed by 0.35 mg/kg body weight, or placebo in a double-blind, randomized study. Twenty patients had atrioventricular (AV) node reentrant tachycardia, whereas 34 had orthodromic AV reciprocating tachycardia associated with the Wolff-Parkinson-White syndrome. Supraventricular tachycardia was terminated in 24 (86%) of 28 patients given intravenous diltiazem compared with 5 (19%) of 26 given placebo (p = 0.0000014). Nineteen (95%) of 20 patients initially given placebo had termination of supraventricular tachycardia after receiving diltiazem. Overall, 43 (90%) of 48 patients receiving intravenous diltiazem had conversion of supraventricular tachycardia to sinus rhythm; the median time to tachycardia termination was 2 min after initiation of a 2 min diltiazem infusion. All 20 patients (100%) with AV node reentrant tachycardia treated with diltiazem had conversion of tachycardia to sinus rhythm as did 26 (81%) of 30 patients with AV reciprocating tachycardia treated with diltiazem. Diltiazem prolonged refractoriness and slowed conduction of the AV node and thereby provided antiarrhythmic action to cause tachycardia termination. Diltiazem had no effect on the electrophysiologic properties of accessory AV connections. Adverse effects were seen in 3 (6%) of the 48 patients given diltiazem. For paroxysmal supraventricular tachycardia initiated in the electrophysiology laboratory, it is concluded that intravenous diltiazem is safe and very effective for acute tachycardia termination when the AV node is part of the reentrant circuit.

Cardiac asystole: a manifestation of neurally mediated hypotension-bradycardia.

It has been proposed that prolonged cardiac asystole mimicking an episode of sudden cardiac death may occur as a manifestation of neurally mediated hypotension-bradycardia syndrome. To assess this possibility, electrocardiographic and hemodynamic findings during upright tilt testing were evaluated in six survivors of suspected asystolic sudden cardiac arrest with normal conventional electrophysiologic evaluation (Group I). These observations were compared with findings in two control groups: six patients with syncope but without evident asystole and with normal conventional electrophysiologic evaluation but demonstrable neurally mediated hypotension-bradycardia (Group II), and six patients with syncope in whom conventional electrophysiologic evaluation provided a presumptive diagnosis (Group III). Patients in all three groups ranged in age from 16 to 59 years. During head-up tilt testing (either alone or with isoproterenol infusion), patients in both Groups I and II developed syncope in less than or equal to 5 min, whereas patients in Group III remained asymptomatic. Patients in Groups I and II exhibited a similar tilt-induced decrease in mean arterial pressure (-46 +/- 9 and -40 +/- 9 mm Hg, respectively, p = NS) and heart rate (-44 +/- 28 and -49 +/- 12 beats/min, respectively, p = NS). In contrast, patients in Group III manifested only a moderate decrease in mean arterial pressure (-14 +/- 5 mm Hg) and had an increase in heart rate (+14 +/- 8 beats/min). Both mean arterial pressure and heart rate changes in Group I and Group II patients differed significantly (p less than 0.001) from values in Group III patients.(ABSTRACT TRUNCATED AT 250 WORDS)

The conformational equilibrium of human growth hormone.

The structural stability of recombinant human growth hormone (rhGH) has been studied by differential scanning calorimetry, circular dichroism and by following the tyrosine and histidine chemical shifts in the 1H NMR spectrum. These studies demonstrate that the folding/unfolding equilibrium of rhGH involves a partially folded dimeric intermediate. The formation of this dimeric intermediate is a reversible process. At acid pH (pH 3) the conformational equilibrium is reversible even at high protein concentrations (10 mg/ml). At neutral pH reversibility is observed only at low protein concentrations (<0.5 mg/ml). The free energy of this intermediate conformation is only approximately 3 kcal/mol apart from the native state indicating that the conformational equilibrium can be effectively modulated by changes in solvent composition or physical conditions. According to the spectroscopic and thermodynamic results, the formation of the dimeric intermediate occurs without a major loss in helical content and is driven by the formation of substantial hydrophobic contacts between two partially folded molecules. A thermodynamic model that accounts quantitatively for the experimental data has been developed. These studies demonstrate that partially folded conformations of certain proteins are able to form stoichiometric complexes, and that the formation of these complexes provide a significant source of stabilizing Gibbs energy for conformational states that, otherwise, will be characterized by extremely unfavorable free energies.

Thermodynamic characterization of an intermediate state of human growth hormone.

The thermal denaturation of recombinant human growth hormone (rhGH) was studied by differential scanning calorimetry and circular dichroism spectroscopy (CD). The thermal unfolding is reversible only below pH 3.5, and under these conditions a single two-state transition was observed between 0 and 100 degrees C. The magnitudes of the deltaH and deltaCp of this transition indicate that it corresponds to a partial unfolding of rhGH. This is also supported by CD data, which show that significant secondary structure remains after the unfolding. Above pH 3.5 the thermal denaturation is irreversible due to the aggregation of rhGH upon unfolding. This aggregation is prevented in aqueous solutions of alcohols such as n-propanol, 2-propanol, or 1,2-propanediol (propylene glycol), which suggests that the self-association of rhGH is caused by hydrophobic interactions. In addition, it was found that the native state of rhGH is stable in relatively high concentrations of propylene glycol (up to 45% v/v at pH 7-8 or 30% at pH 3) and that under these conditions the thermal unfolding is cooperative and corresponds to a transition from the native state to a partially folded state, as observed at acidic pH in the absence of alcohols. In higher concentrations of propylene glycol, the tertiary structure of rhGH is disrupted and the cooperativity of the unfolding decreases. Moreover, the CD and DSC data indicate that a partially folded intermediate with essentially native secondary structure and disordered tertiary structure becomes significantly populated in 70-80% propylene glycol.

Comparative analysis of the cytotoxicity of substituted (phenylglyoxal bis(4-methyl-3-thiosemicarbazone)) copper (II) chelates.

Seven para-substituted [phenylglyoxal bis(4-methyl-3-thiosemicarbazone)]copper (II) chelates (12-18) have been designed, synthesized, and tested for their ability to inhibit the respiration of rat liver slices as a normal cell model and Ehrlich ascites cells as a tumor cell model. Relationships between chemical structure and respiratory inhibition are described on a quantitative basis using substituent contants (pi, Es, and sigmap) by computerized multiparameter regression analyses. The correlations indicate that changes in Es have the largest effect on liver slice toxicity of chelates while pi and sigmap account for most of the variation in toxicity to ascites cells. A comparative analysis strongly suggests that electron-donating substituents with greater water solubility should increase cytotoxicity to ascites cells at the expense of cytotoxicity to the rat liver cells. The predictions of the equations were checked by synthesizing and testing an additional derivative. The results strengthen the initial predictions.

Comparative analysis of the cytotoxicity of substituted [phenylglyoxal bis(4-methyl-3-thiosemicarbazone)] copper(II) chelates. 2. Parabolic correlations and their implications for selective toxicity.

The synthesis of an extended series of para-substituted [phenylglyoxal bis(4-methyl-3-thiosemicarbazone)] copper(II) chelates is reported. Subsequent biological evaluation and regression analysis have been performed, correlating pI50 with extrathermodynamic substituent parameters. Parabolic correlations with pi have resulted which predict optimum lipophilic character of the para substituent with respect to Ehrlich ascites cytotoxicity (pi0 = -2.13) and with respect to ascites vs. liver slice cytotoxicity (pi0 = -1.31). Results indicated clearly that the chelate most toxic to the tumor cell model may not be the most selective.

Antitumor 1-(X-aryl)-3,3-dialkyltriazenes. 1. Quantitative structure-activity relationships vs. L1210 leukemia in mice.

Quantitative structure-activity relationships (QSAR) have been formulated for phenyl-, pyrazolyl-, and imidazolyltriazenes acting L1210 leukemia in mice. All three sets of congeners have the same ideal lipophilicity (log Po approximately 1). Electron releasing substituents increase potency; ortho substitution decreases activity. The synthesis of a number of new triazenes and some of their partition coefficients are reported.

4-hydroxyquinoline-3-carboxylic acids as inhibitors of cell respiration. 2. Quantitative structure-activity relationship of dehydrogenase enzyme and Ehrlich ascites tumor cell inhibitions.

Studies on dehydrogenase enzyme inhibition have been extended with the design, synthesis, and correlation analysis of 7-[(substituted-benzyl)oxy]-, 7-[(substituted-phenethyl)oxy]-, and 7([substituted-phenoxy)ethoxy]-4-hydroxyquinoline-3-carboxylic acids. Sixteen new congeners and the fifteen molecules previously synthesized have been tested against cytoplasmic malate dehydrogenase and lactate dehydrogenase, as well as against mitochondrial malate dehydrogenase. The lipophilic congeners show a clear specificity for inhibition of the mitochondrial enzyme. Correlation analysis of the data on the three enzymes allows a comparison of the binding sites in quantitative terms, while examination of the data on inhibition of ascites tumor cell respiration affords an indication of membrane transport. A newly developed high-pressure liquid chromatography based retention index is compared to the octanol-water pi constant as a model for hydrophobic interactions.

4-[4-[(2-Hydroxybenzoyl)amino]phenyl]butyric acid as a novel oral delivery agent for recombinant human growth hormone.

A series of N-acetylated, non-alpha, aromatic amino acids was prepared and shown to promote the absorption of recombinant human growth hormone (rhGH) from the gastrointestinal tract. Seventy compounds in this family were tested in vivo in rats. Of the compounds tested, 4-[4-[(2-hydroxybenzoyl)amino]phenyl]butyric acid was identified as a preclinical candidate and was used to demonstrate the oral delivery of rhGH in primates. A significant positive correlation was found between the relative log k' of the delivery agents, as determined by HPLC on an immobilized artificial membrane (IAM) column, and serum rhGH concentrations following oral or colonic dosing in rats. Structure-activity relationships have also been developed on the basis of electronic effects and hydrogen-bonding characteristics of the aromatic amide substituents.

Electrophysiologic profile of asymptomatic Wolff-Parkinson-White pattern.

Electrophysiologic testing in patients with asymptomatic Wolff-Parkinson-White syndrome (WPW) may be useful in defining arrhythmic substrates and predictors of fatality. Forty-two patients with asymptomatic WPW, mean age 36 years, underwent electrophysiologic studies and were followed prospectively. They were compared with a matched control group of patients studied within the same period for documented tachycardia associated with the WPW syndrome. Asymptomatic patients had longer anterograde effective refractory periods of the accessory pathway, longer minimum cycle lengths maintaining 1:1 conduction over the accessory pathway, longer minimum RR intervals between consecutive preexcited beats during atrial fibrillation (AF) and longer mean RR intervals during AF than their symptomatic counterparts. Sustained reciprocating tachycardia could not be induced in most patients and induction of AF required rapid atrial pacing in all patients. Nine patients had an anterograde effective refractory period of less than 270 ms and 17% had minimum cycle length less than 250 ms during induced AF. Over a follow-up of 29 +/- 18 months, 1 patient died of noncardiac causes and the rest remained asymptomatic. Thus, patients with asymptomatic WPW have deficient electrophysiologic substrates to maintain orthodromic reciprocating tachycardia under baseline conditions and do not have atrial vulnerability. Seventeen percent of patients had potentially lethal ventricular rates during induced AF.

Demonstration of macroreentry and feasibility of operative therapy in the common type of atrial flutter.

Two patients are described who had recurrent and long-standing atrial flutter of the common type and were referred for electrophysiologic testing and surgical management. In both patients, atrial flutter could be initiated and terminated by programmed stimulation. Atrial endocardial mapping showed earliest activation during flutter at the orifice of the coronary sinus, with activity proceeding to the low atrial septum, high lateral right atrium and low right atrium, respectively. Programmed atrial extrasystoles from the high right atrium at a time when the atrial septal region was refractory advanced atrial flutter in proportion to prematurity of the extrastimulus, while maintaining the low to high activation sequence. Intraoperatively, epicardial atrial mapping revealed a large right atrial reentrant circuit beginning in the posteroseptal region and proceeding superiorly and laterally through the right atrial free wall before returning to its starting point. The narrowest part of the circuit and that showing relatively slow conduction during atrial flutter was observed in the low right atrial tissue between the tricuspid valve ring and the orifices of the inferior vena cava and proximal coronary sinus, respectively. Cryosurgical ablation around the orifice of the coronary sinus and surrounding atrial wall has prevented recurrent atrial flutter over short term follow-up in both patients, although 1 of the patients has required antiarrhythmic therapy for postoperative atrial fibrillation.

Bundle branch block during orthodromic reciprocating tachycardia onset in infants.

Transesophageal electrophysiologic studies were performed in 58 infants (age less than or equal to 1 year, median 10 days) with electrocardiographically documented orthodromic reciprocating tachycardia (ORT). The aim was to evaluate the occurrence, type and electrophysiologic effects of bundle branch block (BBB) during ORT onset. Of the 58 infants, 25 (43%) had BBB with pacing-induced tachycardia onset. BBB was initiated by single or double premature atrial extrastimuli and by burst atrial pacing; 4 infants also demonstrated BBB with spontaneous ORT onset during transesophageal study. Two of 25 infants had BBB only after intravenous procainamide. Comparison of the 25 infants exhibiting BBB at ORT onset with the 33 infants not demonstrating BBB revealed that age was not statistically different in the 2 groups, but that severity of illness (based on a 1 to 3 scale) was greater (p less than 0.05) and normal QRS ORT cycle length was shorter (p less than 0.02) in the infants with BBB. Of the 25 infants with BBB at ORT onset, 17 had left BBB, 3 had right BBB and 5 had both left and right BBB. Ventriculoatrial interval or cycle length increases during ORT with BBB in 16 of 25 (64%) infants suggested left free wall-accessory atrioventricular connections.(ABSTRACT TRUNCATED AT 250 WORDS)

Therapeutic and diagnostic utility of adenosine during tachycardia evaluation in children.

Adenosine has become the drug of choice for termination of regular, normal QRS tachycardia. Initial studies in adult and pediatric patients have shown that the drug is effective for tachycardias using the atrioventricular (AV) node as an integral part of the tachycardia circuit and has few serious side effects. Experience with adenosine administration in children was reviewed to examine the diagnostic and therapeutic usefulness, effective dose, and adverse effects of adenosine. Adenosine was administered to 38 children during 50 separate electrophysiologic evaluations. Eleven patients had structural or acquired heart disease. Tachycardia mechanisms included orthodromic-reciprocating tachycardia using an accessory AV connection (23 patients), primary atrial tachycardia (6 patients), AV node reentrant tachycardia (3 patients), ventricular tachycardia (2 patients), postoperative junctional tachycardia (1 patient), and antidromic-reciprocating tachycardia (1 patient). Adenosine successfully terminated 51 of 53 episodes (96%) of tachycardia using the AV node, 5 of 10 primary atrial tachycardias, 1 of 1 junctional tachycardia, and 1 of 3 ventricular tachycardias. Reinitiation of tachycardia was seen after 16 of 58 successful terminations (28%), reducing the effectiveness to 39 of 53 (74%) for tachycardia requiring the AV node. Average effective dose was 132 micrograms/kg, range 50 to 250 micrograms/kg, and was slightly higher for peripheral (147 micrograms/kg) than for central (120 micrograms/kg) administration. Significant complications occurred in 4 of 38 patients, including atrial fibrillation, accelerated ventricular tachycardia, apnea, and 1 minute of asystole. Although adenosine is useful therapeutically and diagnostically in children with tachycardia, its effectiveness is limited by tachycardia reinitiation and adverse effects. Higher doses may be required for peripheral intravenous administration.

Relation between clinical presentation and induced arrhythmias in the Wolff-Parkinson-White syndrome.

Electrophysiologic testing is warranted in patients with the Wolff-Parkinson-White (WPW) syndrome presenting with rapid atrial fibrillation (AF) or ventricular fibrillation. Indications are less clear in patients presenting only with atrioventricular reentrant tachycardia (ART). A knowledge of propensity of this latter group to show a rapid ventricular response in the event of AF and the ability of electrophysiologic testing to reproduce the type and rate of clinical arrhythmias are relevant to this decision. The records of 126 symptomatic patients with manifest WPW syndrome were reviewed and separated into 4 groups according to presentation: group 1--AF; group 2--ART; group 3--palpitations suggesting ART; and group 4--AF and ART. All patients except those in group 3 had electrocardiographically documented clinical arrhythmias, and these arrhythmias were compared with those induced during electrophysiologic testing. The shortest RR interval during induced AF and the cycle length of induced ART correlated well with those occurring clinically (r = 0.72, p less than 0.00001), as did the cycle length of induced ART (r = 0.79, p less than 0.00001). Patients presenting with AF (65%) had a higher incidence of atrial vulnerability (48%) and sustained AF at electrophysiologic testing than those presenting with ART (16% and 5%) or undocumented palpitations (27% and 21%). Forty-one percent of patients with ART and 51% with undocumented palpitations had potentially lethal rates (shortest RR interval less than 250 ms) during induced AF. The ability to reproduce clinical arrhythmias and the frequency of rapid rates during AF induced in patients presenting with only ART or undocumented palpitations supports the recommendation for electrophysiologic testing in symptomatic patients with WPW.

Usefulness of combined propranolol and verapamil for evaluation of surgical ablation of accessory atrioventricular connections in patients without structural heart disease.

Successful surgical ablation of atrioventricular (AV) accessory connections may be confirmed during postoperative electrophysiologic testing by the absence of accessory connection conduction in both the anterograde and retrograde directions. Whereas the former may be readily apparent by examination of the surface electrocardiogram during sinus rhythm or atrial pacing, assessment of the latter may be complicated by the frequent presence of enhanced retrograde AV nodal conduction in the postoperative period. Consequently, availability of interventions that selectively affect AV nodal conduction and refractoriness without concomitant effects on accessory connections may be helpful for assessing the success of the surgical procedure. In this study the effects of combined propranolol and verapamil administration on electrophysiologic properties of the AV node and the accessory AV connection were assessed both pre- and postoperatively in 17 patients (12 men and 5 women, mean age 33 years) undergoing surgical ablation of accessory connections. Preoperatively, electrophysiologic characteristics of all but 1 of the accessory AV connections were unaffected by propranolol and verapamil administration. Postoperatively, on the other hand, propranolol and verapamil significantly prolonged both the retrograde AV node effective refractory period (baseline: 272 +/- 34 ms vs after drugs: 384 +/- 70 ms [p less than 0.0001]) and the shortest cycle length maintaining 1:1 ventriculoatrial conduction (baseline: 357 +/- 99 ms vs after drugs: 485 +/- 64 ms [p less than 0.0001]). Late postoperative electrophysiologic evaluation (7 +/- 3 weeks) revealed no evidence of residual accessory AV connection conduction, and all patients remain asymptomatic at 21 +/- 10 months follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Usefulness of disopyramide for prevention of upright tilt-induced hypotension-bradycardia.

Susceptibility to transient hypotension-bradycardia of neurally mediated origin has been attributed in part to accentuated afferent neural traffic arising from cardiopulmonary mechanoreceptors, and consequently, may be diminished by agents with anticholinergic and negative inotropic effects, such as disopyramide phosphate. This study assessed electrocardiographic and hemodynamic responses to upright tilt testing (alone or during isoproterenol infusion) before and after disopyramide therapy in 10 patients (age range 16 to 74 years) with recurrent syncopal episodes of neurally mediated origin. Untreated, syncope occurred at less than or equal to 7 minutes of tilt alone (6 patients) or tilt plus isoproterenol at less than or equal to 3 micrograms/min (4 patients) and was associated with hypotension (mean arterial pressure, 40 +/- 16 mm Hg vs baseline 76 +/- 10 mm Hg, p less than 0.001) and inappropriate heart rate slowing (mean heart rate, 59 +/- 39 beats/min vs baseline 88 +/- 18 beats/min, p less than 0.005). After oral disopyramide 150 mg 3 times daily (mean plasma level, 3.0 +/- 0.64 micrograms/ml), all patients tolerated 10 minutes of both tilt and tilt plus isoproterenol (maximum dose, 3 micrograms/min) without symptoms, hypotension (mean arterial pressure; tilt 1 min, 79 +/- 7 mm Hg vs tilt 10 min, 77 +/- 8 mm Hg, difference not significant) or bradycardia (mean heart rate; tilt 1 min, 81 +/- 12 beats/min vs tilt 10 min, 83 +/- 11 beats/min, difference not significant). Furthermore, during subsequent 20 +/- 5 months of disopyramide therapy, all but 1 patient remain asymptomatic. Thus, oral disopyramide may be effective for preventing inducible and spontaneous neurally mediated syncope.

Usefulness of isoproterenol during atrial fibrillation in evaluation of asymptomatic Wolff-Parkinson-White pattern.

The asymptomatic individual with a Wolff-Parkinson-White (WPW) pattern is considered at risk for ventricular fibrillation if a rapid ventricular response (shortest RR interval less than or equal to 250 ms) is observed during induced atrial fibrillation (AF) in the laboratory. It has been suggested that isoproterenol administration during AF may more accurately define the patient at risk. Consequently, the effect of isoproterenol on ventricular response during AF was studied in 21 asymptomatic individuals with WPW pattern to assess the potential of isoproterenol to identify patients at risk for sudden death. An electrophysiologic study that included elective induction of AF was performed. The shortest and mean RR intervals between 2 consecutive preexcited and normal QRS complexes, the average RR interval and the proportion of preexcited QRS complexes were measured in the control state and after bolus injections of isoproterenol (0.5, 1.0, 2.0 and 4.0 micrograms) during AF. Both atrioventricular nodal and accessory pathway conductions were enhanced proportional to isoproterenol dose. Isoproterenol had a greater effect on the atrioventricular node, as reflected by significantly greater changes in the shortest RR between normal complexes (339 +/- 70 vs 255 +/- 21 ms, mean +/- standard deviation, p less than 0.001) than the shortest RR between preexcited complexes (264 +/- 39 vs 219 +/- 34 ms, p less than 0.001) and a decrease in percentage of preexcited complexes (65 +/- 37 vs 50 +/- 33%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Reproducibility of head-up tilt-table testing for eliciting susceptibility to neurally mediated syncope in patients without structural heart disease.

Head-up tilt testing has gained acceptance as a tool for assessing susceptibility to neurally mediated syncopal syndromes (e.g., vasovagal syncope), and is currently being evaluated as a means of testing therapeutic interventions in these conditions. To assess reproducibility of head-up tilt testing and thereby assess the potential of such testing for immediate evaluation of a planned treatment, findings during 2 sequential 80 degrees head-up tilt tests were compared in 23 patients (age range 6.5 to 74 years) undergoing evaluation of syncope of unknown origin. Upright tilt was performed initially in the absence of drugs, and repeated if necessary during pharmacologic provocation by means of isoproterenol infusions of 1 and 3 micrograms/min (tilt 1). End points were syncope, maximal tolerated isoproterenol dose, or a tilt duration of 10 minutes. The second tilt test (tilt 2) was conducted after approximately 30 minutes of supine rest using the maximal provocative conditions used in tilt 1. Fifteen of 23 patients (65%) developed syncope in either tilt 1 or 2, while 8 of 23 (35%) remained asymptomatic. Tilt testing results were concordant (i.e., positive in both tests, or negative in both tests) in 20 of 23 (87%) patients. Concordance was, however, less among tilt-positive patients (12 of 15, 80%) since 3 patients were tilt-positive in tilt 1 only.(ABSTRACT TRUNCATED AT 250 WORDS)