Procainamide Infusion Research Articles

Preexcited tachycardia due to atrioventricular node reentry with a bystander accessory pathway diagnosed after procainamide infusion

Preexcited tachycardia due to atrioventricular node reentry with a bystander accessory pathway diagnosed after procainamide infusion

Cycle-length response of ventricular tachycardia associated with coronary artery disease to procainamide and amiodarone

We undertook this study to determine if the cycle-length response of ventricular tachycardia (VT) to procainamide and amiodarone is similar in the individual patient. We enrolled 40 patients with uniform, monomorphic VT at a baseline, drug-free electrophysiologic study, after procainamide infusion and during oral amiodarone therapy. We found a significant correlation (p < 0.01) between VT cycle-lengths on the 2 agents as well as the percent change in cycle length from baseline. Only 60% of the patients exhibited VT rates within 10% between the 2 agents. Importantly, < 20% of patients had further slowing of the VT rate (>10% slowing) during amiodarone therapy as compared to procainamide. Thus, although the cycle-length response of VT to procainamide correlates with the cycle-length response to amiodarone, 40% of patients have a disparate response (>10% difference in cycle length) to the 2 agents; additional slowing of VT rates in response to amiodarone beyond that seen with procainamide is unlikely. These results have important implications regarding the institution of amiodarone therapy and the need for repeat electrophysiologic testing during amiodarone therapy.

Evaluation of antifibrillatory effects of drugs

Several electrical stimulation techniques have been used to measure ventricular fibrillation (VF) threshold such as single pulse stimulation, train of pulses stimulation, continuous 50-Hz stimulation and sequential pulse stimulation. This study was undertaken to clarify the difference in VF threshold values obtained by each method. The development of VF was classified into 4 stages. Stage 1 is the phase in which fragmented activities are generated at the stimulated area of the ventricular muscle. In stage 2, the local activities propagate to surrounding ventricular muscle, causing ventricular excitation. Stage 3 is characterized by repetitive ventricular excitations. In stage 4, repetitive ventricular responses in a form of accelerating tachycardia induce disorganized excitations that finally degenerate into fibrillation. Based on this classification of stages between local excitation and fibrillation, single pulse stimulation is considered to measure VF threshold for stages 1 to 4, continuous SO-Hz stimulation for stages 2 to 4 and sequential pulse stimulation for stages 3 and 4. Thus, the antifibrillatory effect of drugs can be interpreted with some significance by using different stimulation methods. The sequential pulse stimulation method revealed that some antiarrhythmic agents caused a dissociation between repetitive nonstimulated excitation (RE) threshold and VF threshold. Procainamide and disopyramide increased RE threshold while decreasing VF threshold. Mexiletine and lidocaine elevated both RE and VF thresholds. Local infusion of procainamide at the site of test stimulation reduced both thresholds. However, after the application of procainamide to the whole heart, RE threshold remained decreased but VF threshold was elevated. It is likely that the antifibrillatory effect of the drug includes 2 different processes: antireentrant and antimultiple reentrant effects.

Preferential effect of procainamide on the reentrant circuit of ventricular tachycardia

Transient entrainment was used to test the hypotheses that 1) procainamide prolongs the cycle length of ventricular tachycardia in patients with coronary artery disease because it has a preferential effect on the reentrant tachycardia circuit, and 2) regions of slow conduction in the reentrant circuit are more susceptible to the effect of procainamide than are other areas of the ventricles. In five patients with prior myocardial infarction, sustained ventricular tachycardia with identical QRS configuration was inducible before and after intravenous infusion of procainamide. Transient entrainment of ventricular tachycardia was demonstrated at two or more cycle lengths by rapid pacing in the baseline state and after procainamide. Rapid pacing was performed from the same site during sinus rhythm at the cycle lengths that demonstrated transient entrainment of ventricular tachycardia. The conduction interval to the transiently entrained site during ventricular tachycardia (orthodromic interval) was compared with the conduction interval to the same site during pacing in sinus rhythm (antidromic interval).The mean tachycardia cycle length increased by 27% after procainamide administration (p = 0.002). The antidromic conduction intervals were prolonged by 9 % (p = 0.06) compared with a 28% increase in the mean orthodromic conduction interval (p = 0.002). The difference between the orthodromic and antidromic conduction intervals increased by 40% (p = 0.003). Prolongation of the tachycardia cycle length after procainamide administration correlated positively with increases in the orthodromic conduction intervals (r = 0.94, p = 0.02) but not with changes in the antidromic intervals (r = −0.08, p = NS). The effect of procainamide on the difference between orthodromic and antidromic conduction intervals correlated strongly with changes in the cycle length of venetricular tachycardia (r = 0.97 p = 0.006).Thus, procainamide has a preferential effect on the reentrant circuit of ventricular tachycardia compared with other areas of ventricular myocardium. In addition, these results are compatible with the hypothesis that the effect of procainamide is more marked in regions of conduction delay in the reentrant circuit.

Utility of introducing ventricular premature complexes during reciprocating tachycardia in specifying the location of left free wall accessory pathways

The usefulness of the response to single and double ventricular premature complexes (VPCs) introduced during reciprocating tachycardia (RT) in predicting the location of a left free wall accessory pathway was studied in 55 patients with the Wolff-Parkinson-White syndrome. One VPC introduced from the right ventricle into narrow QRS RT when the His bundle was refractory resulted in retrograde atrial preexcitation in 25 of 55 (45%) patients, while 30 (55%) showed no preexcitation. Double VPCs produced retrograde atrial preexcitation in 9 of 26 patients not responding to a single VPC. No difference in RT cycle length, AH, HV or ventriculoatrial intervals was found between those patients who did or did not show retrograde atrial preexcitation. The response to single and double VPCs during RT was related to the location of the AP. The average distance of the AP from the crux determined by intraoperative epicardial mapping in the 41 patients who underwent surgery was 2.7 ± 0.7 mapping units (left posterolateral region) in patients showing retrograde atrial preexcitation with a single VPC, 3.6 ± 0.7 units (at the lateral left ventricular margin) in those responding to double VPCs and 4.3 ± 0.8 units (beyond the LV margin) in those showing no response. Left bundle branch block (LBBB) aberrancy during RT resulted in an average 60 ± 14 ms prolongation of the ventriculoatrial interval in 40 patients, including 5 in whom LBBB was seen only after procainamide infusion. VPCs introduced into LBBB RT resulted in significant retrograde atrial preexcitation in 6 additional patients in whom no response during normal QRS RT was observed. It is concluded that the response to single and double VPCs during normal QRS RT is useful in predicting the location of a left free wall accessory pathway. This observation may be particularly helpful in those patients in whom the endocardial catheter cannot be fully advanced into the coronary sinus to overlay the accessory pathway. Furthermore, the introduction of double VPCs into normal QRS RT and VPCs into LBBB RT may facilitate the demonstration of retrograde atrial preexcitation without the need for a left ventricular stimulation site.

Rapid Assessment of Rate and Antiarrhythmic Drug Effect on the Myocardium Using Asymmetric Biphasic Pulse Stimulation

An asymmetric biphasic pulse which stimulates the heart and neutralizes the poststimulation polarization at the electrode-myocardial interface permitting the recording of the evoked endocardial response (EER) up to approximately 1 ms poststimulation with the same electrode used for stimulation is described. Using this mode of cardiac stimulation in 20 dogs the effects on the EER of increasing heart rate and antiarrhythmic drugs, procainamide (PA) and N-acetylprocainamide (NAPA), were studied. EERs were recorded during bipolar and unipolar pacing rates of 120, 150, and 200/min before and during a five step PA or NAPA infusion which resulted in progressively increasing PA and NAPA plasma concentrations (Cps), 1.7-32.5 mg/l for PA and 8.1-116.1 mg/l for NAPA. The effects of progressively increasing heart rates were: The T wave amplitude and QS area increased with increases in rate; during pacing at 120, 150, and 200/min, the T wave amplitudes were 7.6 +/- 2.3, 8.2 +/- 2.1, and 9.8 +/- 2.5 mV and the QS areas were 905 +/- 204, 995 +/- 199, and 1101 +/- 231 mVms. The QT interval and QST area decreased with increases in rate; during pacing at 120, 150, and 200/min, the QT intervals were 265 +/- 61, 249 +/- 57, and 226 +/- 52 ms and the QST areas were 288 +/- 198, 221 +/- 154, and 154 +/- 52 mVms. The effects of the antiarrhythmic drugs, PA and NAPA, on the EER were: PA prolonged both the QS duration and QT interval at low Cp (type Ia antiarrhythmic drug property); at a therapeutic PA Cp of 15.0 +/- 0.2 mg/l and a heart rate of 120/min the percent increase of the QS duration was 12 +/- 4% (P = 0.001) and that of the QT interval was 20 +/- 6% (P less than 0.001). The prolongation of the QS duration by PA was rate dependent, the faster the rate the greater the prolongation. NAPA prolonged the QT interval at low Cp, while the QS duration was not significantly effected at low or therapeutic Cps (type III antiarrhythmic drug property); at a therapeutic NAPA Cp of 15.9 +/- 1.6 mg/l and a heart rate of 120/min the percent increase of the QS duration was 1 +/- 1% (NS) and that of the QT interval was 13 +/- 9% (P = 0.018). Our results show that the use of an asymmetric biphasic pulse allows for pacing and recording of an EER, QS and T waves, with a single electrode.(ABSTRACT TRUNCATED AT 400 WORDS)

Prediction of successful suppression of sustained ventricular tachyarrhythmias by serial drug testing from data derived at the initial electrophysiologic study

This study investigated whether data available after the initial electrophysiologic study in patients with sustained ventricular tachyarrhythmia could identify those patients in whom serial drug testing is likely to be efficacious. One hundred six patients with inducible sustained ventricular tachyarrhythmia, whose initial study included short-term drug testing with intravenous procainamide, were evaluated. The baseline arrhythmia induced (in the absence of all antiarrhythmic drugs) was monomorphic tachycardia with a cycle length >200 ms in 81 patients and ventricular flutter or fibrillation in the remaining 25 patients. After intravenous infusion of procainamide (1,250 ± 300 mg), a ventricular tachyarrhythmia could still be induced in 80 patients during testing with up to three extrastimuli. Serial drug testing with one to four trials of oral conventional and investigational agents was then undertaken.Evaluation of 15 clinical, hemodynamic and electrophys-iologic variables by stepwise logistic regression identified two independent predictors of successful response to oral antiarrhythmic drugs: 1) noninducibility of ventricular tachycardia after intravenous procainamide (p < 0.001), and 2) left ventricular ejection fraction ≥40% (p < 0.05). Subgroup analysis combining each of these variables identified patients with a high, intermediate or low probability of finding a successful oral drug regimen. Patents whose arrhythmia was suppressed by intravenous procainamide had a 100% likelihood (if left ventricular ejection fraction was ≥40%) or an 87% likelihood (if ejection fraction was <40%) of responding to an oral regimen. Patients whose arrhythmia was still inducible after intravenous procainamide and had an ejection fraction ≥40% had an intermediate likelihood (46%) of oral drug response. Patients with persistent ventricular tachycardia after intravenous procainamide and an ejection fraction < 40% had a low probability (19%) of successful response to an oral antiarrhythmic regimen.Hence, patients who are unlikely to benefit from serial drug testing can be identified with use of a simple algorithm incorporating the left ventricular ejection fraction and the response to intravenous procainamide at the initial electrophysiologic study. Early consideration of an implantable device or arrhythmia surgery may be appropriate for such patients.

Electrophysiological Observations During QRS Alternans in a Patient with Incessant Tachycardia

Electrophysiological observations during preoperative and intraoperative study of a 46-year-old patient with incessant ventricular tachycardia and QRS alternans demonstrated a potential mechanism for this electrocardiographic finding. During QRS alternans, conduction delay (or block) was recorded from the site of origin of the tachycardia, high on the anterior septum to the His bundle: After procainamide infusion, the tachycardias slowed and, concurrent with the disappearance of QRS alternans, conduction from the site of tachycardia origin to the His bundle could no longer be demonstrated.

QRS morphology-dependent pharmacodynamics in multiform ventricular ectopic activity

The effect of an infusion of intravenous procainamide on the frequency of ventricular premature complexes (VCPs) of differing QRS morphologies was studied in 20 patients with multiform ectopic activity. In 17 of 20 patients, there was differential suppression of single VPCs with different QRS morphologies. VPCs of the most frequent QRS morphology and the second most frequent QRS morphology were compared with respect to the procainamide level at the escape of VPCs from 85% suppression and the duration of suppression measured from the onset of the procainamide infusion. In 8 patients, VPCs of the most frequent QRS morphology remained suppressed at lower procainamide concentrations and for longer times than did VPCs of the second most frequent QRS morphology (escape procainamide concentration = 2.8 ± 1.7 versus 5.4 ± 2.3 μug/ml, p < 0.025; time to escape 244 ± 138 versus 98 ± 114 min; p < 0.05). In 9 other patients, VPCs of the second most frequent QRS morphology remained suppressed at lower procainamide concentrations and for longer times than did VPCs of the most frequent QRS morphology (escape procainamide concentration 2.9 ± 1.4 versus 8.3 ± 6.3 μg/ml, p < 0.025; time to escape 317 ± 114 versus 63 ± 80 min; p < 0.001). Thus, in individual patients there are specific patterns of suppression of VPCs of different QRS morphologies which are independent of the frequency of each morphology. There is apparently a differential pharmacologiceffect of procainamide on the foci or pathways responsible for the different QRS morphologies of multiform VPCs.

Pharmacodynamics of intravenous procainamide as used during acute electropharmacologic testing

No previous studies have determined the pharmacodynamics of intravenous procainamide when administered in a dose of 15 mg/kg and at a rate of 50 mg/min, as is common practice during etectropharmacologic testing. In this study, 30 patients received procainamide in this fashion; the right ventricular effective refractory period and the QRS duration at a ventricular pacing rate of 120/minute were then determined every minute for 20 minutes. Ten patients received no maintenance infusion of procainamide (group A), 10 received a 4 μg/min maintenance infusion (group B) and 10 received an 8 mg/min maintenance infusion (group C). Ten additional patients received no procainamide and served as control subjects (group D). The plasma procainamide concentration was measured at 1, 5, 10,15 and 20 minutes after the loading dose was administered. A stable plasma procainamide concentration was not present in group A, B, or C until 15 minutes after infusion of the loading dose. The effective refractory period and QRS duration increased compared with baseline at 1 minute, decreased between 1 and 10 minutes and then remained essentially unchanged between 10 and 20 minutes in all 3 treatment groups. Concentration-effect relation was linear in each treatment group. The plasma procainamide concentrations in group C were significantly greater than in group A; however, the effects on refractoriness and QRS duration were similar in both groups. These findings indicate that with a procainamide dosing method commonly used during electropharmacologic testing, the plasma procainamide concentration decreases significantly during the first 15 minutes after the loading dose is administered; the effects of procainamide on ventricular refractoriness and conduction parallel the changes in the plasma procainamide concentration; and an 8 mg/min maintenance infusion of procainamide results in higher plasma procainamide concentrations without an associated increase in ventricular refractoriness or slowing of conduction.

Rate-dependent effects of procainamide on his-purkinje conduction in man

Microelectrode studies in isolated cardiac tissues have shown that the depressant effect of several antiarrhythmic drugs on the maximal upstroke velocity of the cardiac action potential is rate-dependent. To determine whether this effect of anti-arrhythmic drugs is seen in humans, 14 patients undergoing atrial pacing at several rates were prospectively studied before and after the infusion of procainamide (15 mg/kg). The HV Interval (His Purkinje conduction rate) and the QRS duration (Intraventricular conduction rate) were measured. Before procainamide infusion, atrial pacing did not significantly prolong the maximal HV interval (from 54 ± 15 to 58 ± 13 ms). After procainamide Infusion (mean serum level 10.0 ± 3 μg/ml) atrial pacing at an average of 5 pacing rates significantly prolonged the HV interval (from 67 ± 18 to 80 ± 20 ms, p <0.001). The extent of HV prolongation with atrial pacing after procainamide infusion was independent of the HV interval at rest before procainamide. The duration of the QRS complex also tended to prolong with atrial pacing after procainamide infusion, but this prolongation was not statistically significant. Thus, procainamide produces a rate-dependent depressant effect on His-Purkinje and intraventricular conduction, confirming observations made in isolated tissue preparations.

Effects of infarction, procainamide, coupling interval, and cycle length on refractoriness of extrastimuli.

The effects of prematurity, cycle length, site of stimulation, and procainamide on ventricular refractoriness following an extrastimulus (S2) were assessed in 10 dogs with and 10 dogs without infarction. Extrastimuli were introduced at preselected coupling intervals (S1-S2) from normal right and left ventricular sites and from left ventricular sites of infarction during drive cycle lengths (S1-S1) of 350 and 250 ms. At each S1-S2 interval, the effective refractory period of S2 was determined by introducing a second extrastimulus (S3). At all stimulation sites, cycle lengths, and before and during infusion of procainamide (mean concn 18.6 +/- 3.5 micrograms/ml), shortening (greater than 10 ms change) in refractoriness was most marked over a narrow range of closely coupled S1-S2 intervals. Regardless of stimulation site, the effective refractory period of S2 was less during a cycle length of 250 ms compared with a cycle length of 350 ms. In dogs without infarction, the effective refractory periods of S2 from left ventricular sites tended to be longer than from right ventricular sites, particularly during procainamide administration. The refractory period of S2 at sites of infarction did not differ consistently from those at normal sites. Finally, at all stimulation sites and cycle lengths, procainamide prolonged refractoriness of S2 at each S1-S2 interval and blunted the total shortening in refractoriness in response to S2.

Procainamide infusion and acute atrial fibrillation.

We report the use of intravenous procainamide infusion in the treatment of fifteen patients with acute atrial fibrillation. Procainamide was infused at 50 mg/min to a maximum of 20 mg/kg, with blood pressure and electrocardiographic monitoring. Ten patients responded, with a mean dose of 8.7 (standard deviation 4.3) mg/kg, four of these reverting to sinus rhythm after a low dose of less than 5.0 mg/kg. Hypotension was a common concomitant and was seen in four cases, but required termination of the infusion only in a patient with cardiomyopathy. An increase in ventricular rate or conversion to atrial flutter was not seen. Intravenous infusion of procainamide is a safe and moderately effective method of cardioversion in acute atrial fibrillation.

Conversion of atrial fibrillation to sinus rhythm by acute intravenous procainamide infusion

We evaluated the efficacy of an intravenous infusion of procainamide in 26 consecutive candidates for cardioversion of atrial fibrillation. Procainamide was administered at a rate of 15 to 20 mg/min up to a maximum of 1000 mg. The treatment was considered effective only if cardioversion occurred during the procainamide infusion. Conversion to sinus rhythm occurred in 15 patients. Converters had a significantly shorter mean duration of atrial fibrillation (6 ± 7 days, mean ± S.D.) compared to nonconverters (79 ± 88 days) ( p < 0.01). The mean left atrial size of converters (4.3 ± 0.6 cm) did not differ significantly from that of nonconverters (4.7 ± 0.9 cm). The dose of procainamide required for cardioversion ranged from 3.6 to 16.4 mg/kg. Two patients developed nonsustained ventricular tachycardia, and there was one episode of bifascicular block during the infusion. Intravenous procainamide is an effective form of therapy for conversion of atrial fibrillation of new onset.

Effects of procainamide on strength-interval relations in normal and chronically infarcted canine myocardium

The effects of procainamide on strength-interval relations in normal and chronically infarcted canine myocardium were determined in nine adult mongrel dogs susceptible to sustained ventricular tachyarrhythmias. The dogs were studied at 3 to 30 days after two stage occlusion and reperfusion of the mid left anterior descending coronary artery. Unipolar cathodal stimulation (pulse duration 2 ms, drive cycle length 300 ms) was used to evaluate excitability and refractoriness at a total of 19 normal and 22 infarct sites both before and 15 to 30 minutes after intravenous infusion of procainamide, 20 to 25 mg/kg body weight. The electrophysiologic effects of procainamide were evaluated at the time of the plateau phase of procainamide's antiarrhythmic activity in this model. At normal sites, procainamide had only a minimal effect on the mean diastolic excitability threshold (increased from a mean [± standard deviation]of 0.07 ± 0.02 to 0.08 ± 0.02 mA [probability (p) = not significant (NS)], the mean effective refractory period (increased from 137 ± 10 to 139 ± 11 ms [p = NS]) and the mean ventricular refractory period at twice diastolic threshold (increased from 156 ± 12 to 163 ± 16 ms [p <0.01]). At infarct sites, the mean diastolic excitability threshold was similarly unchanged after procainamide (from 0.57 ± 1.13 to 0.57 ± 1.09 mA [p = NS]), but both the mean effective refractory period (from 142 ± 17 to 159 ± 27 ms [p <0.001]) and the mean ventricular refractory period at twice diastolic threshold (from 166 ± 25 to 187 ± 33 ms [p <0.001]) were moderately prolonged. In addition, dispersion of refractoriness between normal and infarct sites as well as within areas of infarcted myocardium was often either unchanged or increased rather than decreased by procainamide. Thus, the antiarrhythmic activity of procainamide in this canine model of chronic myocardial infarction was not explained by an effect on the excitability or refractoriness of normal myocardium, by changes in the diastolic excitability of infarcted tissue or by an effect on the dispersion of refractoriness. The most prominent effect of procainamide was to decrease the excitability of abnormal myocardium during the relative refractory period and to prolong the refractoriness of abnormal myocardium.

Modification of ventricular tachycardia by procainamide in patients with coronary artery disease

Fifteen consecutive patients with coronary artery disease had rapid (158 to 272 beats/min) and sustained ventricular tachycardia induced by the extrastimulus technique, and received procainamide infusion. Before the study, all but one patient had severe symptoms with tachycardia, and six had survived apparent sudden death. Procainamide consistently slowed ventricular tachycardia. However, in traditional doses (1 g infusion, plasma concentration greater than 4 μg/ml), it prevented induction of ventricular tachycardia in only 2 of the 15 patients. Induction of ventricular tachycardia was facilitated by procainamide in 10 patients. Larger doses of procainamide (plasma concentration 20.2 μg/ ml ± 9.7 [mean ± standard deviation]) prevented induction of ventricular tachycardia in one of eight patients. Rapid ventricular rates (more than 210 beats/min) that were not slowed (by 50 percent or more) after a 1 g infusion of the drug predicted failure of procainamide to prevent ventricular tachycardia. Therefore, procainamide slowed but did not prevent induced ventricular tachycardia in most of these patients with coronary artery disease at risk of sudden death.

Efficacy of intravenous procainamide infusion in converting atrial fibrillation to sinus rhythm. Relation to left atrial size.

The efficacy of intravenous procainamide, infused at 30 mg/min to a maximum dose of 20 mg/kg, in converting atrial fibrillation was evaluated under electrocardiographic and blood pressure control in 21 patients. Nine patients had atherosclerotic heart disease, seven had valvular lesions, five had hypertension, and six had no apparent heart disease. Nine patients (converters), who reverted to sinus rhythm at a mean dose of procainamide of 13.3 +/- 3.6 mg/kg (mean plasma concentration, 7.4 +/- 3.9 micrograms/ml) had normal echocardiographic left atrial diameters. All but one of the remainder, the 12 non-converters, who received a mean drug dose of 13.1 +/- 3.5 mg/kg (mean plasma concentration 13.9 +/- 7.6 micrograms/ml), had atrial diameters exceeding 4.0 cm. QRS and QTc intervals were not altered significantly in converters, but were prolonged significantly in non-converters. No serious side effects from the infusion were encountered. Intravenous procainamide infusion appears to be a safe and rapidly effective method of converting recent-onset atrial fibrillation to sinus rhythm in patients with normal left atrial dimensions.

Clinical pharmacokinetics of procainamide infusions in relation to acetylator phenotype

The pharmacokinetics of procainamide was determined in 21 lidocaine-resistant patients who received the drug according to a pharmacokinetically designed double-infusion technique. Thirteen patients were phenotyped as slow acetylators, seven as fast, and one as intermediate. The total body clearances (ClT) of PA in slow and fast acetylators were 22.6 and 34.8 liters/hr, respectively. The fraction of PA cleared by the formation of NAPA in the corresponding acetylator group was 0.2 and 0.4. Renal impairment affected the pharmacokinetics of PA more profoundly as the ClT's of PA in patients with and without renal impairment were 17.9 and 31.2 liters/hr, respectively. None of the calculated volumes of distribution was affected by acetylator phenotype or renal impairment. These data identify the contribution of at least two of the major factors accounting for variability in PA disposition in patients undergoing therapy.

Safety and efficacy of procainamide infusions

Thirty-four patients who were resistant to conventional doses of lidocaine received procainamide intravenously according to a pharmacokinetically designed two infusion technique. A mean peak serum concentration of 7.1 mg/liter was achieved with an average loading dose of 989 mg administered over 1 hour. A mean steady state serum concentration of procainamide of 6.5 mg/liter was achieved with a mean dose of 64.4 mg/kg body weight for the first 24 hours of treatment. Dose, renal impairment, the degree of congestive heart failure and acetylator status influenced the steady state serum concentration of procainamide. Dangerous ventricular arrhythmias were abolished in 74 percent of the patients at a steady state level of 6.9 ± 3.7 mg/liter (mean ± standard deviation). Nonresponders to procainamide had a mean steady state serum concentration of procainamide of 4.2 ± 2.1 mg/liter (P < 0.05). Systolic and diastolic blood pressures decreased moderately (10 and 8 percent, respectively), and heart rate decreased 11 percent. The infusion was interrupted in one patient because of hypotension. The duration of electrocardiographic conduction intervals was increased slightly in some patients. It is concluded that procainamide administered by this two infusion method is effective and well tolerated by most patients.

Abolition and modification of reentry within the His-Purkinje system by procainamide in man.

The effects of intravenous procainamide infusion of 10--14 mg/kg body weight (i.e., 750 mg) of procainamide (PA) on reentry within the His-Purkinje system (HPS) were studied in 13 patients using His bundle electrograms and ventricular extrastimulus method. PA abolished reentry in eight patients (group 1) and decreased the width of reentry zone in the remaining five (group 2). At comparable S1S2 intervals, the S2H2 intervals after PA were longer than control in all patients. In group 1 patients, after PA, reentry did not occur even at S2H2 intervals that were significantly longer than control critical S2H2 intervals. In two of eight patients in group 1, PA abolished reentry by converting unidirectional block into bidirectional block in the antegrade limb (right bundle) of the reentry circuit. In the remaining six patients reentry was abolished because of consistent retrograde block of S2 impulse at some point between the site of stimulation and the His bundle recording site. In group 2, reentry was initiated after PA at approximately the same S1S2 intervals as in control, but required significantly longer S2H2 intervals; in these patients the zone of reentry was shortened due to increase in effective refractory period of the ventricular muscle. PA significantly increased the functional refractory period of HPS and the effective refractory period of ventricular muscle. The results of this study differ from the previously reported effects of lower concentrations of PA which facilitated reentry within the same circuit. We conclude that the effects of PA on reentry are dose-related and can both facilitate and suppress reentry, depending on critical changes in conduction and refractoriness of the HPS.