Sustained symptomatic sinus node reentrant tachycardia: incidence, clinical significance, electrophysiologic observations and the effects of antiarrhythmic agents.

The clinical, electrocardiographic and electrophysiologic determinants and effects of antiarrhythmic agents on sustained sinus node reentrant tachycardia remain poorly defined. Of 65 consecutive men undergoing electrophysiologic studies for symptomatic paroxysmal supraventricular tachycardia over a 4 year period, 11 (16.9%), who ranged in age from 39 to 76 years, demonstrated sustained sinus node reentrant tachycardia. On the surface electrocardiogram, before electrophysiologic studies, the following diagnoses were considered in the 11 patients: sinus node reentrant tachycardia on the basis of an RP'/P'R ratio of greater than 1 and P wave configuration similar to that of sinus P waves (7 patients); atrioventricular (AV) nodal reentrant tachycardia on the basis of an RP'/P'R ratio of less than 1 (3 patients); and paroxysmal atrial tachycardia with AV block (1 patient). All 11 patients had a history of recurrent palpitation, 4 had syncope, 2 had dizzy spells and 9 had organic heart disease. Sustained sinus node reentrant tachycardia could be reproducibly induced in all 11 patients during atrial pacing or premature atrial stimulation, or both, over a wide echo zone. The tachycardia could be terminated by carotid sinus massage, atrial pacing and premature atrial stimulation. Characteristics of tachycardia included: high-low activation sequence; cycle lengths of 250 to 590 ms with wide fluctuations of 20 to 180 ms in individual patients; RP'/P'R ratio of greater than 1 in 8 (73%) of the 11 patients and a ratio of less than 1 in 3 (27%). Induction of sustained sinus node reentrant tachycardia was prevented by intravenous ouabain (0.01 mg/kg body weight) in two of two patients, by intravenous verapamil (10 mg) in two of two patients and by intravenous amiodarone (5 mg/kg body weight) in four of four patients. In contrast, intravenous propranolol (0.1 mg/kg body weight) did not affect induction of sustained sinus node reentrant tachycardia in two of two patients. It is concluded that sustained sinus node reentrant tachycardia, seen in 16.9% of the study patients with paroxysmal supraventricular tachycardia, is not as benign as previously believed; it is frequently associated with organic heart disease; it demonstrates wide variations in cycle length, unlike other forms of paroxysmal supraventricular tachycardia; it can masquerade as AV nodal reentrant tachycardia and paroxysmal atrial tachycardia with AV block on the surface electrocardiogram in 36% of patients; and it is responsive to intravenous administration of ouabain, verapamil or amiodarone.

Enhancement of triggered activity in ischemic Purkinje fibers by ouabain: a mechanism of increased susceptibility to digitalis toxicity in myocardial infarction.

Enhanced susceptibility to toxic arrhythmias by digitalis administration has been reported in clinical and experimental myocardial infarction. To investigate the mechanism responsible for this phenomenon, the effects of superfusion with normal Tyrode's solution and superfusion with Tyrode's solution containing 4 X 10(-8)M of ouabain in ischemic Purkinje fibers were compared. Ischemic Purkinje fibers of small endocardial preparations from 1 day old myocardial infarcts in 18 dogs were used for the study. During control conditions, these endocardial preparations demonstrated delayed afterdepolarizations and triggered activity. Superfusion with normal Tyrode's solution resulted in a gradual increase in maximal diastolic potential and action potential amplitude, a decrease in delayed afterdepolarizations amplitude and slowing and termination of triggered activity. Superfusion for 90 minutes with Tyrode's solution containing ouabain resulted in: 1) an increase in the magnitude of delayed afterdepolarizations in preparations demonstrating subthreshold delayed afterdepolarizations, 2) sustainment of triggered activity in preparations showing nonsustained triggered activity, and 3) shortening of cycle lengths of the triggered activity in preparations demonstrating sustained triggered activity before superfusion with ouabain. These effects occurred despite the gradual increase in maximal diastolic potential and action potential amplitude. Superfusion of normal Purkinje fibers with Tyrode's solution containing 4 X 10(-8)M of ouabain for 90 minutes did not result in delayed afterdepolarizations or triggered activity. Thus, ouabain at a concentration that has no toxic effect on normal Purkinje fibers may enhance arrhythmias in ischemic Purkinje fibers by increasing the magnitude of delayed afterdepolarizations and enhancing triggered activity.

The predictive value of electrophysiologic studies in untreated patients with Wolff-Parkinson-White syndrome.

The ability of invasive electrophysiologic studies to predict future arrhythmic events in patients with minimally symptomatic Wolff-Parkinson-White syndrome is not known. To assess this ability, 42 patients with evidence of atrioventricular (AV) pre-excitation on the surface electrocardiogram underwent electrophysiologic studies and were then followed up as outpatients taking no medications. The patients were classified into three groups on the basis of prestudy symptoms: group I, 15 asymptomatic patients; group II, 10 patients with infrequent symptoms but no documented arrhythmias; and group III, 17 patients with one documented episode of supraventricular tachycardia or atrial fibrillation, or both. At electrophysiologic study, the number of patients with short anterograde accessory pathway effective refractory periods and rapid ventricular responses during induced atrial fibrillation did not differ statistically among the three groups. During a mean follow-up period of 7.5 +/- 4.9 years, 11 of the 42 patients had documented arrhythmias: 2 patients from group II and 2 patients from group III had supraventricular tachycardia and 7 patients from group III had atrial fibrillation. All nine patients from group III with subsequent arrhythmias had had clinical atrial fibrillation before study. No patient from group I had an arrhythmia during follow-up. There were no episodes of ventricular fibrillation or sudden cardiac death during follow-up in any of the patients. The only predischarge variables that correlated with the subsequent occurrence of arrhythmias were a history of documented arrhythmias before electrophysiologic study (p less than 0.01) and inducible supraventricular tachycardia at electrophysiologic study (p less than 0.05).(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.

Regional changes in blood flow, extracellular potassium and conduction during myocardial ischemia and reperfusion.

OBJECTIVES: We postulated that ventricular arrhythmias may arise from the heterogeneous washout of ischemic metabolites. Our objective was to investigate the distribution of extracellular potassium concentration ([K+]o) during myocardial ischemia and reperfusion and to correlate this distribution with regional differences in myocardial blood flow. BACKGROUND: Our previous study showed that reperfusion after a brief period of ischemia resulted in heterogeneous reflow of the ischemic myocardium. METHODS: The changes in regional myocardial blood flow, midmyocardial [K+]o and electrogram duration were quantitated in 14 dogs undergoing 20 min of left anterior descending coronary artery occlusion and 1 min of reperfusion. Regional myocardial blood flow was measured by using 15-microns radioactive microspheres in 1- to 1.5-g full thickness myocardial samples. The [K+]o was measured with intramyocardial K(+)-sensitive electrodes. RESULTS: During coronary occlusion, the ischemic zone exhibited a reduction in regional blood flow to 0.13 +/- 0.06 ml/g per min and increases in [K+]o to 9.3 +/- 2.6 mmol/liter and electrogram duration to 131.8 +/- 38.6% of control. Heterogeneous reduction in regional blood flow at various sites in the ischemic zone had fair correlations with variable increases in [K+]o (r = -0.70) and electrogram duration (r = -0.75). During min 1 of reperfusion, regional blood flow ranged from two to more than seven times baseline, resulting in a disorganized spatial distribution of perfusion with islands of high and low blood flows. Associated with the heterogeneous early reperfusion regional myocardial blood flow, [K+]o and electrogram duration changed at different rates toward normal. Whereas correlation between regional blood flow and [K+]o or standardized electrogram duration was fair during ischemia, this correlation was poor during early reperfusion. CONCLUSIONS: Spatial heterogeneity in regional myocardial blood flow during myocardial ischemia and early reperfusion is associated with heterogeneity in [K+]o and electrophysiologic characteristics, which in turn may play an important role in the genesis of arrhythmias arising from the ischemic and reperfused myocardium.

"Stunning" of the left atrium after spontaneous conversion of atrial fibrillation to sinus rhythm: demonstration by transesophageal Doppler techniques in a canine model.

OBJECTIVES: This study compared left atrial and left atrial appendage contraction velocities in sinus rhythm before and after a brief period of atrial fibrillation in a canine model. BACKGROUND: In patients, left atrial appendage contraction velocities measured during sinus rhythm after cardioversion from atrial fibrillation are depressed relative to left atrial appendage emptying velocities measured during atrial fibrillation, suggesting that the left atrial appendage is mechanically "stunned." METHODS: This phenomenon was studied in a canine model of acute (60 min) pacing-induced atrial fibrillation followed by spontaneous reversion to sinus rhythm using epicardial and transesophageal pulsed wave Doppler. Unique features of the model include: 1) comparison of left atrial function postconversion to baseline sinus rhythm rather than to measurements during atrial fibrillation, 2) control of the duration of atrial fibrillation and 3) elimination of the extraneous influences of direct current shock and antiarrhythmic agents, which may independently depress left atrial function. RESULTS: Hemodynamic conditions (heart rate, mean arterial pressure, cardiac output, mean pulmonary artery pressure, mean right atrial pressure and mean left atrial pressure) at baseline, during 60 min of atrial fibrillation and after reversion to sinus rhythm were constant throughout the study period. Peak left atrial contraction velocities (measured from the transmitral flow velocity profile) were significantly (p < 0.02) reduced to 64+/-22% of baseline values upon spontaneous conversion of atrial fibrillation to sinus rhythm and recovered to basal values by 20 min after resumption of sinus rhythm. Peak left atrial appendage contraction velocities were significantly (p < 0.001) reduced to 49+/-24% of baseline values upon spontaneous conversion of atrial fibrillation to sinus rhythm and recovered to basal values by 40 min after reversion to sinus rhythm. CONCLUSIONS: Even brief (60 min) periods of atrial fibrillation in normal canine hearts result in marked depression of global left atrial systolic function and regional left atrial (left atrial appendage) systolic function upon resumption of sinus rhythm. This "mechanical stunning" of left atrial systolic function appears to be more profound and of longer duration for the left atrial appendage compared with the left atrium as a whole, which may predispose the appendage to blood stasis and thrombus formation. Chronic models of atrial fibrillation need to be developed to examine the impact of longer periods of atrial fibrillation upon the magnitude and duration of postconversion left atrial "stunning."

Effects of hyperkalaemia on sinus nodal function in dogs: sino-ventricular conduction.

The effects of hyperkalaemia on electrograms recorded from the sinus node, crista terminalis, Bachmann bundle, right and left atria and His bundle were studied in anaesthetised dogs. Increasing hyperkalaemia up to about 8.5 mol X litre-1 produced: 1) a gradual prolongation of the sino-crista terminalis interval, and 2) a shift in sinus pacemaker location. Hyperkalaemia between 8.5 and 10.0 mmol X litre-1 produced arrest of most of the atria but persistence of electrical activity of the sinus node, crista terminalis, Bachmann bundle, His bundle and ventricles and sustained sino-ventricular conduction. During the course of increasing hyperkalaemia, right atrial electrograms from sites closer to the crista terminalis disappeared later than those from sites more remote from the crista terminalis. Decremental conduction through sites progressively remote from the axis of the crista terminalis (and possibly also other "preferential pathways") seemed to be the basis of hyperkalaemic atrial arrest.

Quantitative assessment of aortic regurgitation by colour flow Doppler in an open chest canine model.

Colour flow Doppler maps the extent of the flow velocity disturbance of aortic regurgitation onto the two dimensional echocardiographic image of the left ventricular cavity. The spatial extent of this flow velocity disturbance expressed as a percentage of end diastolic left ventricular cavity area (CD%) was compared to regurgitant fraction (RF), measured volumetrically, in nine open chest dogs with varying degrees of surgically created aortic regurgitation (RF 0-85%). Right heart bypass controlled venous return to the left atrium and hence net left ventricular output, while total left ventricular output was measured with an aortic electromagnetic flow probe under various loading conditions, achieving mean diastolic transvalvular pressure gradients of 23-114 mm Hg, net left ventricular outputs of 750-3000 ml.min-1 and diastolic filling periods of 162-320 ms. A linear correlation between CD% and RF (r = 0.89) was demonstrated over this wide range of loading conditions. At a given transvalvular diastolic pressure gradient [68(SD9) mm Hg] CD% was linearly proportional to regurgitant aortic orifice area (r = 0.87). Thus CD% is proportional to the volumetric severity of aortic regurgitation under a wide range of haemodynamic conditions and varies appropriately with regurgitant aortic orifice area when diastolic transvalvular pressure gradient is held constant. The application of these principles to the non-invasive quantitation of valvular regurgitation by colour Doppler appears feasible.

Cryothermal mapping of the sinus node in dogs: a simple method of localising dominant and latent pacemakers.

To investigate the potential use of cryothermal mapping to localise the sites of the dominant and latent pacemakers of the sinus node, we compared the results of cryothermal and electrical mapping of the sinus node in 16 dogs. In all dogs, cooling (-5 to +5 degrees C) of a localised epicardial area of about 3 X 3 mm2 close to the sulcus terminalis (area 1) resulted in a decrease in heart rate and a change in the P wave configuration. Cooling of an additional area of up to 15 X 3 mm2 (area 2) while cooling of area 1 was maintained resulted in a further decrease in heart rate and a further change in P wave configuration until junctional rhythm occurred. In all dogs areas 1 and 2 could be identified within 5 min. The heart rate and P wave configuration returned to control following cooling suggesting no adverse effect of cooling on the sinus node in this temperature range. In dogs with sufficiently slow heart rates, recording from area 1 showed diastolic and upstroke slopes followed by primary negativity, indicating that area 1 was the area of the dominant pacemaker. Recording from area 2 showed only diastolic slopes indicating that area 2 was the area of the latent pacemaker. Compared to electrical mapping for identifying diastolic slope, upstroke slope and primary negativity or earliest atrial activation, cryothermal mapping is a simple, quick and safe procedure for localisation of the sinus pacemakers. Unlike recording of sinus nodal electrograms, cryothermal mapping can be performed in the presence of rapid heart rates.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrograms from the canine sinoatrial pacemaker recorded in vitro and in situ.

We have identified extracell potential changes associated with the electrical activity of the canine sinoatrial pacemaker. Small nonpolarizable electrodes and low frequency high gain amplification were used to record unipolar electrograms from both the epicardial and the endocardial surfaces of the canine sinus node. Initially in vitro studies were performed so that transmembrane action potential changes could be recorded simultaneously with the extracell potentials. The sinus nodal electrogram showed two characteristic potentials when the electrode was in immediate proximity to pacemaking cells: (1) During phase 4 there was a steady slope of about -30 to -100 muv/sec, and (2) during the transition from phase 4 to phase 0 of the transmembrane action potential the slope of the electrogram increased smoothly to approximately -400 to -1,000 muv/sec. These potentials were followed by high frequency deflections as cells in the surrounding atrium depolarized. Tetrodotoxin (5 mg/liter) rendered the atrial muscle inexcitable and delayed and then abolished the high frequency activity in the sinus electrogram, which then appeared as a continuous smooth tracing similar to the sinus pacemaker action potential but reversed in polarity. We then recorded these small localized potentials from the in situ canine heart. Sinus nodal electrograms could be obtained from beating hearts with hand held probes on the epicardial surface and with conventional recording catheters on the endocardial surface. The results demonstrate that the canine sinus node gives rise to detectable and characteristic changes in extracell potential and suggest that similar potentials can be recorded from man to evaluate sinus nodal function.

Impact of food on the pharmacokinetics and electrocardiographic effects of sustained release verapamil in normal subjects.

To evaluate the impact of food on the pharmacokinetics and electrocardiographic effects of sustained release (SR) verapamil tablets, 9 healthy men each received 3 single doses of verapamil in a randomized, crossover manner: 10 mg of intravenous verapamil, 240 mg SR verapamil on an empty stomach, and 240 mg SR verapamil with a standardized meal. PR intervals and racemic verapamil serum concentrations were measured serially over 30 hours after administration. The time to peak concentration was longer (7.5 +/- 3.0 vs 4.4 +/- 2.3 hours), resulting in a lower peak verapamil serum concentration (118 +/- 43 vs 175 +/- 50 ng/ml) when SR verapamil was administered with food (p < 0.05). Food tended to decrease the bioavailability of SR verapamil (34 +/- 12 vs 49 +/- 14%), although this difference did not reach statistical significance (p = 0.065). Precipitous or exaggerated release of verapamil from the SR tablet was not observed in any subject during the fasting state. Prolongation of the PR interval paralleled these alterations in serum concentration. The maximal change in the PR interval was greater (21 +/- 8 vs 14 +/- 5%; p < 0.05) when SR verapamil was given in the fasting state. Although an exaggerated verapamil release or effect was not observed, food significantly altered the absorption and electrocardiographic effects of a single dose of SR verapamil. Manipulation of the administration condition may be helpful in achieving desired outcomes.

Autonomic dependence of ventriculoatrial conduction.

To evaluate the effects of isoproterenol and atropine on patients with poor ventriculoatrial (VA) conduction, 17 patients were studied who did not have 1-to-1 VA conduction during ventricular pacing at a rate slightly faster than sinus rate (group I) and 11 patients were studied who had 1-to-1 VA conduction, but only at constant ventricular pacing cycle lengths longer than 600 ms (group II). Isoproterenol infusion at a rate causing a 20 to 30% increase in sinus rate or up to 4 micrograms/min shortened the ventricular pacing cycle lengths that induced VA block in all group II patients. Atropine administration at a dose causing a 20 to 30% increase in sinus rate or up to a total dose of 2 mg also shortened the ventricular pacing cycle lengths that induced VA block in all group II patients. At similar pacing cycle lengths, isoproterenol and atropine induced shorter VA intervals than control. Nine of 17 group I patients had demonstrable 1-to-1 VA conduction either during isoproterenol infusion or after atropine administration. Of these 9 patients, 1-to-1 VA conduction could be found only during isoproterenol infusion in 3 patients and only after atropine administration in 4 patients. The improvement of VA conduction by these drugs was related to their effects on the atrioventricular node. The change in VA conduction mediated by autonomic changes induced by these drugs may explain why some patients without demonstrable VA conduction during rest may have, under certain circumstances, "endless-loop" tachycardia or paroxysmal supraventricular tachycardia using atrioventricular nodal conduction as the retrograde limb.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term follow-up in patients with incessant ventricular tachycardia.

Seventeen patients with coronary artery disease, idiopathic dilated cardiomyopathy or no organic heart disease who presented with incessant ventricular tachycardia (VT) were studied and followed for a mean period of 51 +/- 35 months. In these patients the incessant VT included greater than or equal to 3 episodes of sustained VT at a rate of greater than or equal to 120 beats/min and frequent episodes of nonsustained VT over a 24-hour period. No patient had electrolyte disorder, prolonged QT interval, drug-induced arrhythmia or myocardial infarction less than 2 weeks old. Six patients died within 27 months of follow-up; 4 from sudden death and 2 from acute myocardial infarction. Three of the 11 surviving patients had remission of their VT within 1 week after the diagnosis of incessant VT. In 3 other patients in whom antiarrhythmic drugs were discontinued during follow-up because of adverse effects of the drugs or other medical reasons, 2 were found in remission. In the remaining 5 alive patients, deliberate attempts were made to discontinue the antiarrhythmic drugs; 4 of these patients were found in remission when the drugs were discontinued. Thus, 9 of these patients (53%) with incessant VT had remission over a mean follow-up of 55 +/- 34 months after discontinuation of the antiarrhythmic drugs. The probability of remission in patients surviving incessant VT warrants trials of discontinuation of antiarrhythmic drugs in these patients.

Electrophysiologic drug testing in symptomatic ventricular arrhythmias after repair of tetralogy of Fallot.

Nine patients with symptomatic ventricular arrhythmias were evaluated a mean interval of 16 years after surgical repair of tetralogy of Fallot. The clinical arrhythmia was sustained ventricular tachycardia (VT) in 4 patients (group I) and premature ventricular contractions in 5 (group II). All patients underwent cardiac catheterization and electrophysiologic studies. Ventricular tachycardia was induced at electrophysiologic study in all patients in group I and in 3 patients in group II. Six patients with inducible sustained monomorphic VT underwent chronic drug testing based on electrophysiologic study. A mean of 3.3 drugs per patient was tested. Patients with right ventricular systolic hypertension did not respond to any drug tested, and underwent surgery. Five patients received drug treatment based on the results of electrophysiologic study. During a mean follow-up period of 2.2 years, no patient in either group had recurrent episodes of VT or syncope. In the postoperative patient with tetralogy of Fallot with symptomatic ventricular arrhythmias, it is concluded that electrophysiologic study is useful in reproducing clinical episodes of VT and in selecting effective antiarrhythmic medication; a small number of patients with ventricular premature complexes alone will have inducible sustained VT during electrophysiologic study; prognosis of these patients may be improved by treatment that results in prevention of VT induction; and in patients with right ventricular hypertension, VT is likely to be refractory to drug treatment.

Evaluation of the pharmacokinetics and electrocardiographic effects of intravenous verapamil with intravenous calcium chloride pretreatment in normal subjects.

To evaluate the effects of calcium pretreatment on the disposition and electrocardiographic effects of verapamil, 8 healthy male volunteers received treatment in each of 3 phases in a randomized, double-blind, crossover manner. Phase I denoted 10 ml of 0.9% intravenous sodium chloride followed by 10 mg of intravenous verapamil; phase II denoted 10 ml of 10% intravenous calcium chloride followed by 4 ml of 0.9% intravenous sodium chloride; and phase III denoted 10 ml of 10% intravenous calcium chloride followed by 10 mg of intravenous verapamil. Blood samples for the determination of verapamil concentrations were drawn at 5, 10, 15, 20, 30, 45, 60 and 90 minutes, and at 2, 4, 6, 10 and 24 hours. Blood pressure, heart rate and PR intervals were also measured at these times. Pretreatment of verapamil with intravenous calcium did not alter the disposition of intravenous verapamil. Blood pressure was not significantly altered in any treatment phase, although calcium tended to increase mean arterial pressure and verapamil abolished this effect. Calcium had no significant affect on verapamil-induced PR prolongation (maximum percent change in PR interval: phase I = 19 +/- 11%, phase III = 18 +/- 7%; time to maximal prolongation: phase I = 0.38 +/- 0.21 hours, phase III = 0.37 +/- 0.26 hours; and area under the percent change in PR vs time curve: phase I = 15.5 +/- 10, phase III = 21 +/- 9). Verapamil caused a reflex increase in heart rate of similar magnitude in both phases I and III (24 +/- 10% and 21 +/- 7%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Method for recording electrical activity of the sinoatrial node and automatic atrial foci during cardiac catheterization in human subjects.

A method for recording electrical activity of the sinoatrial (S-A) node and automatic atrial foci in human subjects is described. To record S-A nodal electrograms, an electrode catheter was inserted percutaneously into the femoral vein and advanced under fluoroscopic control to the superior vena caval-right atrial junction. The distal terminal of the catheter was placed in the area of the S-A node and the proximal terminal on the free right atrial wall or in the right atrial lumen. Polarity was reversed from the conventional electrocardiographic recording; high amplification (about 100 microV/cm) and selective filters (0.1 to 20 hertz) were used. S-A nodal electrograms recorded with this method in human subjects were similar to electrograms obtained previously from the dog and rabbit and revealed negatively directed diastolic and upstroke slopes preceding the P wave of the electrocardiogram. Sinoatrial conduction time measured from the S-A nodal electrograms in 15 cases was 34.9 +/- 2.1 ms(mean +/- standard error of the mean) for a sinus cycle length of 736.4 +/- 38.6 ms. The coronary sinus electrograms in a patient with coronary sinus rhythm were recorded by the same technique except that the distal terminal of the catheter was placed at the coronary sinus ostium. A negatively directed diastolic slope preceding the P wave was consistently recorded. This method for recording electrograms of the S-A node and ectopic automatic atrial foci should prove useful in (1) assessment of both normal and abnormal S-A nodal function, (2) direct determination of conduction time from the S-A nodal pacemaker to the atrium, and (3) localization of automatic atrial foci.

Flecainide-induced sustained ventricular tachycardia successfully treated with lidocaine.

A 69-year-old man had new sustained ventricular tachycardia caused by flecainide which promptly responded to intravenous lidocaine therapy. Discontinuation of the lidocaine infusion resulted in the reappearance of ventricular tachycardia which again immediately terminated after lidocaine was given. In this case, lidocaine effectively reversed the proarrhythmic effects of flecainide.

Effects of contrast media on coronary hemodynamics and myocardial metabolism.

RATIONALE AND OBJECTIVES: This study was designed to compare the effects of ionic contrast medium (CM), Renografin-76 (R76), and nonionic CM, Omnipaque-350 (OM350), on coronary hemodynamics and myocardial metabolism. METHODS: In 10 open-chest, atrial-paced dogs, 4 mL of R76 and OM350 were injected into the left anterior descending coronary artery. Coronary blood flow (CBF), myocardial oxygen consumption (MVO2), lactate extraction (LE), left ventricular (LV) dp/dt, and aortic systolic pressure (AOP) were measured. RESULTS: The maximal CBF changes caused by OM350 and R76 were 23.7 +/- 3.3 mL/minute and 18.3 +/- 3.3 mL/minute (NS), respectively. OM350 produced an increase in LV dp/dt by 378 +/- 85 mm Hg/second, which was different from -244 +/- 65 mm Hg/second by R76 (P < .05). The changes in MVO2 and LE after OM350 injection were 2.6 +/- 0.6 mL/minute and 10.2 +/- 5 microM/minute, respectively; those were different from -0.1 +/- 0.4 mL/minute, and -7.7 +/- 5.1 microM/minute after R76 injection (P < .05). CONCLUSION: Although both agents increased CBF, they appeared to act by different mechanisms. That a direct coronary vasodilator effect is the main action of R76 on coronary vascular response is suggested by decreasing myocardial contractility and oxygen consumption. However, OM350, by enhancing both parameters, may augment CBF at least in part by autoregulation.

Cocaine-related sudden cardiac death: a hypothesis correlating basic science and clinical observations.

Sudden, unexpected death due to cocaine in young otherwise healthy individuals occurs in an idiosyncratic manner and is commonly felt to be arrhythmogenic in nature, although the exact cause of death is rarely documented. In addition to indirect sympathomimetic actions, cocaine is a potent sodium channel blocking drug and, in this regard, most closely resembles agents such as flecainide. We suggest that sudden death due to cocaine is proarrhythmic in nature, occurring under similar circumstances as that due to specific antiarrhythmic drugs.

Reversal of the electrocardiographic effects of cocaine by lidocaine. Part 2. Concentration-effect relationships.

Ventricular arrhythmias due to cocaine may be related to its ability to slow ventricular conduction or prolong repolarization. We previously showed that lidocaine reversed QRS prolongation due to cocaine. The purposes of these experiments were to characterize cocaine's concentration-effect relationship on both ventricular conduction and repolarization, and to determine the effects of lidocaine on these relationships. The effects of lidocaine on cocaine-induced electrocardiographic changes were studied in 20 isolated, Tyrode-perfused guinea pig hearts. Variables at cocaine concentrations ranging from 3-195 microM were measured and repeated in the presence of a fixed concentration of lidocaine 30 microM. Using nonlinear regression analysis, the sigmoid Emax and simple Emax models were fit to cocaine concentration versus percentage change in QRS plots. Measures of best fit indicated that this relationship was best described by the sigmoid Emax model. Compared with cocaine alone, the curve for cocaine with lidocaine showed a greater EC50 (concentration at 50% of maximum effect) (59 vs 100 microM) but similar Emax (371 vs 367%), consistent with competition. Similar values were obtained from the linear transformation of the data. Cocaine concentration versus percentage change in the JTc interval showed a biphasic effect: concentrations below 65 microM prolonged JTc, but those above 65 microM had no effect or decreased JTc. In contrast to changes in QRS, addition of lidocaine increased the effects of cocaine on JTc: area under the concentration-effect curve for cocaine alone was 720 versus 859 microM% for cocaine with lidocaine. Lidocaine reverses cocaine-induced slowed ventricular conduction through competition for binding, but it appeared to increase cocaine-induced prolongation of repolarization.(ABSTRACT TRUNCATED AT 250 WORDS)