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PubMed2001

Comparison of the effects on drug concentrations, electrophysiologic parameters, and termination of atrial fibrillation in dogs when procainamide and ibutilide are delivered into the right atrium versus intravenously.

INTRODUCTION: We tested the hypothesis that right intra-atrial (i.a.) administration of antiarrhythmic drugs resulted in higher peak serum drug concentrations, greater electrophysiologic effects, and greater efficacy for termination of atrial fibrillation (AF) than intravenous (i.v.) drug delivery. METHODS AND RESULTS: Eight dogs were treated with 9.7 mg/kg procainamide infusion and eight dogs with 0.02 mg/kg ibutilide infusion, injected over 5 minutes. Each dog had both an electrophysiologic (EP) and an AF termination study during i.a. and i.v. drug administration at > or = 2-day intervals (total four studies each). Right atrial pacing capture threshold, right atrial effective refractory period (ERP), right atrial and right ventricular monophasic action potential (MAP) durations at 70% and 90% of repolarization (MAPD70, MAPD90), AH, HV, and QT intervals, QRS width, intra-arterial systolic and diastolic blood pressures, and cardiac output were measured at different time-points. Blood samples were drawn from the coronary sinus and femoral vein for drug level determination. The right atrium was paced at 400-msec cycle length throughout the study. AF was induced by rapid right atrial pacing and maintained by methacholine infusion at 1.5 to 3 microg/kg/min. The sustained AF was allowed to persist for 10 minutes before starting the antiarrhythmic drug infusion. We found no significant difference between the procainamide concentrations in the coronary sinus and femoral vein during i.a. and i.v. drug delivery. The time course and extent of increase in right atrial ERP, MAPD70, MAPD90, and all the other measured EP parameters did not differ between the two routes of drug administration. No significant difference was found in termination of AF between i.v. (5/7 procainamide; 4/8 ibutilide) or i.a. (3/8 procainamide; 3/8 ibutilide) drug delivery or between drugs (8/15 procainamide; 7/16 ibutilide). CONCLUSION: Our data do not support any beneficial effect of i.a. versus i.v. procainamide or ibutilide delivery.

Animals↗
PubMed1984

Positive direct antiglobulin tests and immune hemolytic anemia in patients receiving procainamide.

To characterize the autoimmune phenomena in patients receiving procainamide, we studied the prevalence of positive direct antiglobulin (Coombs') tests and immune hemolytic anemia in 100 such patients and compared them with 100 age-matched and sex-matched controls. There was a significant increase in the frequency of positive direct antiglobulin tests in patients receiving procainamide (21 vs. 10 per cent, P = 0.05). The mechanism of red-cell sensitization in patients receiving procainamide was the production of red-cell autoantibody, which was serologically indistinguishable from that seen in warm autoimmune hemolytic anemia. In contrast, positive direct antiglobulin tests in control patients were due to the presence of complement components. Red-cell autoantibody production secondary to procainamide was not correlated with a higher-than-expected frequency of antinuclear antibodies or the clinical syndrome of drug-induced lupus erythematosus. In the series of 100 patients receiving procainamide, we identified three cases of immune hemolytic anemia. In two of the three cases, the anemia resolved after the medication was discontinued and did not require steroid therapy. We conclude that procainamide often results in the production of red-cell autoimmune phenomena.

Aged↗
PubMed1982

Development of Fluoroimmunoassays for the determination of individual or combined levels of procainamide and N-acetylprocainamide in serum.

A fluoroimmunoassay has been developed for the simultaneous determination of serum levels of procainamide and its active metabolite N-acetylprocainamide. It employs procainamide linked through its aromatic amino group to fluorescein isothiocyanate as tracer and an antiserum raised against procainamide conjugated to human thyroglobulin through the same position. Separation is rapidly and simply achieved by covalently linking the antiserum to magnetisable microparticles and use of a magnet. Specific magnetisable particle fluorimmunoassays were also developed for procainamide and for N-acetylprocainamide by the use of suitable immunogens and fluorescein-labelled tracers. That for procainamide uses an antiserum raised to a procainamide-enzyme conjugate and fluorescein-labelled p-aminobenzoic acid while the fluoroimmunoassay for N-acetylprocainamide employs an antiserum against a N-acetylprocainamide-enzyme conjugate and fluorescein-labelled p-acetamidobenzoic acid.

Acecainide↗
PubMedDate not supplied

Myocardial procainamide concentration in canine atria and ventricles.

The aim of this investigation was to examine the distribution of procainamide in the canine heart. Eight anesthetized open-chest dogs received intravenous infusions of 14C-labeled procainamide at 40 micrograms/kg/min for 4 hr. Just prior to the end of the infusion period, 51Cr-labeled microspheres were injected into the left atrium to measure regional myocardial blood flow. The heart was then excised and dissected into regional myocardial sections from each cardiac chamber. Samples from each section were combusted, and the liberated 14CO2 was trapped and counted to determine regional myocardial procainamide concentration. The remainder of each section was analyzed for 51Cr to determine regional myocardial blood flow. Plasma procainamide concentration (mean +/- SE) at the termination of the infusion was 2.68 +/- 0.14 micrograms/ml. Left ventricular procainamide concentration was 6.09 +/- 0.46 micrograms/g. The right ventricular drug concentration was 94% (NS), the left atrial concentration was 85% (p less than 0.005), and the right atrial concentration was 79% (p less than 0.005) of the left ventricular concentration. Within the myocardium of each cardiac chamber there was no correlation between drug concentration and blood flow. We conclude that these concentration differences are insufficient to explain differences in procainamide efficacy between ventricular and atrial arrhythmias.

Animals↗
PubMed1986

High performance liquid chromatography of procainamide and N-acetylprocainamide in human blood plasma.

Procainamide is used in antiarrhythmic therapy, and the need to monitor the drug concentration as well as its major plasma metabolite, N-acetyl-procainamide, is well established. An assay designed for the routine clinical therapeutic drug monitoring laboratory has been developed. A 0.5-ml aliquot of blood plasma is treated with 0.1 ml of internal standard solution, and the mixture is alkalinized. The drug, its metabolite, and the internal standard, N-propionyl procainamide are extracted with methylene chloride. After evaporation to dryness and addition of 0.3 ml of mobile phase, a volume of 0.1 ml is injected onto a liquid chromatograph equipped with spectrofluorimetric detection, which has a better specificity than UV absorptiometric detection. The between-day coefficient of variation was 3.5% for procainamide and 5% for N-acetylprocainamide. The sensitivity of this technique permits detection of 0.1 micrograms/ml of procainamide and 0.25 micrograms/ml of N-acetylprocainamide. Several drugs that are often present in patients receiving procainamide were shown not to interfere.

Acecainide↗
PubMed1993

Ventricular defibrillation in canines with chronic infarction, and effects of lidocaine and procainamide.

Prior studies in dogs with normal hearts have demonstrated that lidocaine increases but procainamide does not change the energy required for successful defibrillation. Because many postinfarct patients receiving implantable cardioverter defibrillator devices require adjunctive antiarrhythmic therapy, we have studied the effects of lidocaine and procainamide on the relationship between delivered voltage and defibrillation success in mongrel dogs 21 +/- 3 days following ligation of the left anterior descending and first diagonal coronary arteries. Internal defibrillation testing using a patch-patch electrode configuration was performed before and during the administration of saline controls (n = 10), lidocaine (n = 10) and procainamide (n = 10). The mean infarct size as determined by staining with tetrazolium was 13.4% +/- 8.3% of right and left ventricles, and did not differ significantly between groups. The 50% effective defibrillation (ED50) voltage increased with infusions of saline (16% +/- 15%), lidocaine (40% +/- 22%), and procainamide (13% +/- 15%) and the ED50 energy increased 41% +/- 44%, 104% +/- 62%, and 35% +/- 36%, respectively. However, the increase in ED50 voltages and energies were significantly greater in animals receiving lidocaine compared to those receiving either saline control or procainamide (P < 0.01). There were trends toward change of hemodynamic parameters in all animals following baseline defibrillation testing; stroke volume declined 21% +/- 16%; and mean pulmonary artery and aortic pressure increased by 22% +/- 25% and 11% +/- 15%, respectively. In conclusion, unlike our previous studies in dogs with normal hearts, in this model hemodynamic deterioration occurred with repeated fibrillation and defibrillation, and defibrillation voltage requirements increased in the control series. Taking into consideration the increase in defibrillation voltage requirements over the duration of the experiments, lidocaine increases and procainamide does not change ED50; thus, their effects are similar in normal and infarcted canine hearts.

Animals↗
PubMed1997

Procainamide induced change of the width of the zone of entrainment and its relation to the inducibility of reentrant ventricular tachycardia.

Procainamide depresses conduction velocity and prolongs refractoriness in myocardium responsible for reentrant VT, but the mechanism by which the induction of VT is suppressed after procainamide administration remains to be determined. In the present study, the relationship between electrophysiological parameters and the noninducibility of VT was assessed during procainamide therapy with a special reference to the change of an excitable gap. Clinically documented monomorphic sustained VT was induced in 30 patients and, utilizing the phenomenon of transient entrainment, the zone of entrainment was measured as the difference between the cycle length of VT and the longest paced cycle length interrupting VT (block cycle length) which was determined as the paced cycle length decreased in steps of 10 ms, and used as an index of the excitable gap. The effective refractory period was measured at the pacing site and the paced QRS duration was used as an index of the global conduction time in the ventricle. The cycle length of VT, the block cycle length, and the width of the zone of entrainment were determined and compared between the responders and nonresponders. In 15 patients, these parameters were determined at the intermediate dose and related to subsequent noninducibility at the final dose. At the final doses of procainamide, VT was suppressed in 8 (26.7%) of 30 patients. However, the cycle length of VT, the block cycle length, and the width of the zone of entrainment were unable to predict the drug efficacy, i.e., noninducibility. The change in the effective refractory period at the pacing site or the width of the paced QRS duration was not different between the responders and nonresponders. Among the variables, only the width of the zone of entrainment showed a significant narrowing in the responders at the intermediate dose of procainamide, and it was smaller than that of the nonresponders. The significant narrowing of the width of the zone of entrainment was associated with the subsequent noninducibility of VT at the final dose. The present study showed that the baseline cycle length of VT, the block cycle length, the drug induced change of the effective refractory period, or the paced QRS duration was not a predictor of the noninducibility after procainamide administration. However, a significant narrowing of the width of the zone of entrainment at the intermediate dose was associated with the noninducibility of VT at the final dose.

Adolescent↗
PubMed1999

The effect of procainamide on T wave alternans.

INTRODUCTION: The measurement of microvolt level T wave alternans (TWA) is a technique for detecting arrhythmia vulnerability. Previous studies demonstrated that the magnitude of TWA is dependent on heart rate. However, the effects of antiarrhythmic drugs on TWA are unknown. METHODS AND RESULTS: This was a prospective evaluation of intravenous procainamide on TWA in 24 subjects with inducible sustained ventricular tachycardia (VT). Measurements of TWA were performed at baseline in the drug-free state and after procainamide loading (1,204+/-278 mg). Recordings were made in normal sinus rhythm, and during atrial pacing at 100 beats/min and 120 beats/min. The magnitude of TWA in the vector magnitude lead was decreased by procainamide at all heart rates: 0.6+/-0.8 to 0.3+/-0.4 microV in sinus rhythm, 2.0+/-1.6 to 0.7+/-0.7 microV at 100 beats/min, and 3.0+/-2.0 to 1.7+/-1.8 microV at 120 beats/min (P<0.001 by analysis of variance). The sensitivity of TWA for the induction of VT at baseline was 5% in sinus, 60% at 100 beats/min, and 87% at 120 beats/min, while it decreased with procainamide to 5%, 19%, and 60%, respectively. Decreases in TWA in response to procainamide were independent of the antiarrhythmic effects on VT inducibility. CONCLUSIONS: These results indicate that the magnitude of TWA decreases with acute procainamide loading and this effect decreases the sensitivity of TWA for the induction of sustained VT.

Anti-Arrhythmia Agents↗
PubMed2000

Transport of procainamide via H(+)/tertiary amine antiport system in rabbit intestinal brush-border membrane.

Transport characteristics of procainamide in the brush-border membrane isolated from rabbit small intestine were studied by a rapid-filtration technique. Procainamide uptake by brush-border membrane vesicles was stimulated by an outward H(+) gradient (pH(in) = 6.0, pH(out) = 7.5) against a concentration gradient (overshoot phenomenon), and this stimulation was reduced when the H(+) gradient was subjected to rapid dissipation by the presence of a protonophore, FCCP. An outward H(+) gradient-dependent procainamide uptake was not caused by H(+) diffusion potential. The initial uptake of procainamide was inhibited by other tertiary amines with N-dimethyl or N-diethyl moieties in their structures, such as triethylamine, dimethylaminoethyl chloride, and diphenhydramine, but not by tetraethylammonium and thiamine. Furthermore, procainamide uptake was stimulated by preloading the vesicles with these tertiary amines (trans-stimulation effect), indicating the existence of a specific transport system for tertiary amines. These findings indicate that procainamide transport in the intestinal brush-border membrane is mediated by the H(+)/tertiary amine antiport system that recognizes N-dimethyl or N-diethyl moieties in the structures of tertiary amines.

Amines↗
PubMed1987

Effect of procainamide and N-acetylprocainamide on atrial flutter: studies in vivo and in vitro.

We studied the effects of procainamide and N-acetylprocainamide (NAPA) in a conscious dog preparation of atrial flutter resulting from circus movement around the tricuspid orifice. We also recorded transmembrane potentials of atrial tissues from the circus path in vitro. In 12 instrumented dogs, average flutter cycle length was 157 msec, the duration of the excitable gap was 73 msec, and conduction velocity was 0.75 m/sec. At 4 and 8 mg/kg, procainamide moderately prolonged cycle length, but did not terminate the flutter. At a cycle length of 300 msec procainamide increased effective refractory period (ERP) by 12% and 20% and conduction time by 8% and 19%. At 16 and 32 mg/kg procainamide prolonged cycle length, ERP, and conduction time by 60% to 80% and stopped the flutter in all trials. NAPA, at 16, 32, and 64 mg/kg, increased flutter cycle length by 16%, 16%, and 31%, ERP by 14%, 28%, and 41%, and conduction time by less than 15%. NAPA terminated the flutter in two of six dogs given 32 mg/kg, and three of five dogs given 64 mg/kg. The excitable gap was lengthened by both procainamide and NAPA. Transmembrane potentials showed that at a cycle length from 1000 to 300 msec procainamide (10 mg/liter) increased action potential duration and decreased the first time derivative of phase O of the action potential (Vmax), whereas NAPA (20 mg/liter) increased action potential duration without changing Vmax. These findings show the difficulty of relating drug effects on transmembrane potentials to efficacy in vivo since the former do not necessarily indicate which changes in cellular electrical activity are responsible for efficacy against a particular arrhythmogenic mechanism.

Acecainide↗
PubMed1989

The human atrial strength-interval relation. Influence of cycle length and procainamide.

We defined the atrial strength-interval relation in 23 patients at cycle lengths of 600, 450, and 300 msec before and after procainamide. The atrial diastolic threshold was similar at cycle lengths of 600 and 450 msec, but the threshold at 300 msec was significantly higher than that determined at 600 and 450 msec both before and after procainamide. Procainamide significantly increased the diastolic threshold only at a cycle length of 300 msec. The strength-interval relation was nonlinear, showing progressively decreasing decrements in the measured refractory period as the stimulating current was increased. Progressive decreases in the drive cycle length from 600 to 450 to 300 msec caused similar decreases in refractory periods. The shape of the curves was similar at cycle lengths of 600 and 450 msex. However, at low current strengths, the slope of the curve determined at 300 msex was significantly more vertical than the slopes of the curves at the longer drive cycle lengths. Procainamide caused similar increases in apparent refractory periods at each paced cycle length. Procainamide did not alter the shape of the curves at any paced cycle length. These observations confirm the importance of stimulation frequency on atrial excitability. They suggest that the effects of procainamide on the effective refractory period of the atrium are not cycle length dependent, although the drug effects on threshold are dependent on the drive cycle length.

Adult↗
PubMed1993

Differential effects of isoproterenol on sustained ventricular tachycardia before and during procainamide and quinidine antiarrhythmic drug therapy.

BACKGROUND: Autonomic modulation, especially increased sympathetic activity may play a role in the genesis of ventricular arrhythmias. The purpose of this study was to determine whether beta-sympathetic stimulation with isoproterenol would alter sustained ventricular tachycardia (VT) circuits similarly during the drug-free and antiarrhythmic drug-treated states. METHODS AND RESULTS: Twenty-five patients with repeatedly inducible, hemodynamically stable, sustained VT were evaluated by programmed ventricular stimulation. In the antiarrhythmic drug-free state, isoproterenol (0.03 microgram/kg per minute) shortened the following intervals (in milliseconds; mean +/- SEM; 25 patients; paired t test): sinus cycle length (792 +/- 37 to 568 +/- 18; (p < 0.001), ventricular paced QT interval (386 +/- 8 to 348 +/- 6; p < 0.001), ventricular paced QRS duration (185 +/- 4 to 182 +/- 4; p = 0.014), ventricular effective (238 +/- 5 to 208 +/- 4; p < 0.001) and functional (261 +/- 6 to 227 +/- 5; p < 0.001) refractory periods, and the VT cycle length (VTCL) (311 +/- 9 to 291 +/- 9; p < 0.001). Isoproterenol (0.03 microgram/kg per minute) was administered during 31 antiarrhythmic drug trials (procainamide, n = 18; quinidine, n = 13) in 22 patients. Isoproterenol shortened the sinus cycle length, QT interval during ventricular pacing, and ventricular effective and functional refractory periods before and during procainamide and quinidine therapy (ANOVA; isoproterenol effect, p < or = 0.0002 for all). The amount of decrease in these intervals with isoproterenol was the same before and during procainamide and quinidine therapy (ANOVA interaction, p = NS for all). The QRS duration during ventricular pacing and VTCL were also shortened by isoproterenol before and during procainamide (baseline, n = 17; QRS, 182 +/- 4 to 178 +/- 4 msec; VTCL, n = 18, 314 +/- 11 to 291 +/- 11 msec; during procainamide, QRS, 218 +/- 7 to 197 +/- 6 msec; VTCL, 422 +/- 15 to 359 +/- 11 msec) and quinidine (baseline, n = 13; QRS, 190 +/- 6 to 185 +/- 5 msec; VTCL, n = 12, 298 +/- 10 to 280 +/- 9 msec; during quinidine, QRS, 223 +/- 9 to 208 +/- 8 msec; VTCL, 415 +/- 14 to 355 +/- 10 msec) (isoproterenol effect p < or = 0.0003 for all). However, the amount of decrease in QRS duration and VTCL with isoproterenol was greater during procainamide and quinidine than in the drug-free state (ANOVA interaction, p < or = 0.02 for all). These changes continued to be significant when normalized for the initial QRS duration and VTCL (p < or = 0.03 for all). CONCLUSIONS: Isoproterenol affects presumed reentrant sustained VT circuits less in the absence of antiarrhythmic drugs but markedly attenuates the antiarrhythmic drug-induced slowing of sustained VT. To the extent that the change in QRS duration reflects a change in conduction within the VT circuit, these data imply that the attenuation of drug-induced slowing of VT by isoproterenol is due to a greater change in conduction rather than refractoriness.

Adult↗
PubMed1994

Prolonged thrombocytopenia associated with procainamide in an elderly patient.

OBJECTIVE: To report a case of thrombocytopenia associated with the use of extended-release procainamide hydrochloride in a geriatric patient. CASE SUMMARY: A 77-year-old man was admitted to the hospital for four-vessel coronary artery bypass surgery. He subsequently developed new onset atrial fibrillation and was started on extended-release procainamide on hospital day 7. The patient's platelet count on admission was 229 x 10(9)/L. The platelet count began to decrease on hospital day 22 and was 79 x 10(9)/L by day 30 and 13 x 10(9)/L by hospital day 37. The patient exhibited gross hematuria and lower extremity petechiae. There were no signs of splenic sequestration and other hematologic indices were normal. Procainamide was discontinued on hospital day 32. There was full recovery of the platelet count to baseline 33 days after procainamide was discontinued. DISCUSSION: Other possible medical and drug-related causes of thrombocytopenia are reviewed and ruled out. Previous reports of procainamide-associated thrombocytopenia describe an immune-mediated peripheral destruction of platelets with platelet recovery within three to eight days after drug discontinuation. However, the prolonged recovery period and the presence of antiplatelet antibodies suggest an immune-mediated process in the bone marrow of this patient. CONCLUSIONS: Clinicians should be aware of the possible adverse hematologic effects of procainamide in the elderly.

Aged↗
PubMed1999

Procainamide-induced psychosis: a case report and review of the literature.

OBJECTIVE: To describe a case of procainamide-induced psychosis in an adult treated for atrial fibrillation. CASE SUMMARY: A 45-year-old Native American woman developed acute psychosis within 72 hours of initiating procainamide for atrial fibrillation. Symptoms abated within 24 hours of discontinuing procainamide. Serum procainamide/N-acetylprocainamide concentrations were therapeutic throughout treatment. Sotalol was started without recurrence of symptoms. DISCUSSION: Psychosis is a rare complication of treatment with procainamide, but the exact mechanism for this adverse event is not fully understood. Seven cases implicating procainamide as the cause of acute psychosis are reported in the literature. Cases of psychosis involving other antiarrhythmic agents have also been reported. CONCLUSIONS: Healthcare personnel should be aware of this adverse event related to procainamide and other antiarrhythmic agents.

Adult↗
PubMed1979

Procainamide-induced sinus node dysfunction in patients with chronic renal failure.

Two patients with chronic renal failure developed transient sinus node dysfunction requiring insertion of a temporary pacemaker while receiving procainamide to control ventricular arrhythmias. Blood levels of procainamide were found to be elevated, although at these levels, sinus node dysfunction has not previously been reported. Following discontinuance of procainamide, sinus rhythm returned. A combination of factors, including elevated levels of N-acetyl procainamide, the metabolite of procainamide with anti-arrhythmic properties, are suggested as possible contributory causes for the ECG findings. Thus, procainamide may produce electrophysiologic features of "sick sinus syndrome" in patients with chronic renal failure even when blood levels of this substance are being monitored.

Acecainide↗
PubMed1992

Procainamide conversion of acute atrial fibrillation after open-heart surgery compared with digoxin treatment.

In 30 patients who developed atrial fibrillation after open-heart surgery the efficacy of intravenous procainamide was evaluated and compared with standard acute digoxin digitalisation. The patients were randomized to two groups of 15. One group received procainamide intravenously at a rate of 25 mg/min and with maximum dose 15 mg/kg. In the other group digoxin 0.75-1.0 mg was given intravenously according to renal function and body weight. Conversion to sinus rhythm occurred during or immediately after the infusion in 87% of the procainamide group, but only in 60% of the digoxin group (p < 0.05). The mean time from start of treatment to conversion was 40 min in the procainamide vs. 540 min in the digoxin group (p < 0.002). There were no serious complications of the procainamide treatment. Intravenous procainamide conversion of postoperative atrial fibrillation is concluded to be effective and safe and can be recommended as the treatment of first choice in awake and nonintubated postoperative cardiac patients.

Adolescent↗
PubMed1999

[Procainamide-induced skin eruption associated with disseminated intravascular coagulation in a patient with sustained ventricular tachycardia].

A 70-year-old man, who had sustained ventricular tachycardias following a previous anterior myocardial infarction, suffered from skin eruptions and abnormal blood tests after 10 days following the oral administration of 1500 mg/day of procainamide. These abnormalities disappeared early after the discontinuation of oral procainamide. However, similar skin eruptions exhibited again when the procainamide was resumed. These results suggest that oral procainamide therapy induces skin eruptions and serious abnormal blood tests in the patient. No reports have suggested such a serious early complication by procainamide therapy. Careful follow-up is needed after the administration of oral procainamide therapy.

Aged↗
PubMed2001

In vitro production of antibodies to histones in patients receiving chronic procainamide therapy.

OBJECTIVE: Procainamide related autoimmunity is characterized by the production of antibodies to histones and, in particular, to the H2A-2B dimer. We evaluated in vitro production of antibodies to total histones and the H2A-2B dimer by peripheral blood mononuclear cells (PBMC) from patients chronically exposed to procainamide and related this to in vivo production, and assessed possible immunostimulatory response by the postulated reactive metabolite procainamide hydroxylamine (PAHA) using PAHA conjugated autologous erythrocytes. METHODS: We evaluated in vitro spontaneous and mitogen induced production of histone antibodies by PBMC from 26 asymptomatic patients, who were chronically receiving procainamide, in the presence and absence of PAHA conjugated autologous erythrocytes. Correlations with in vivo production were sought. RESULTS: PBMC from 9 patients revealed significant spontaneous production of histone antibodies, of whom 2 developed procainamide related lupus within 2 mo of the evaluation. There was a significant increase in in vitro production of antibodies to total histones by PBMC that had been cultured in the presence of PAHA-autologous erythrocyte conjugates, but in the absence of mitogens, from 15 (65%) of 23 patients, and of antibodies to H2A-2B by cells from 10 (42%) of 24 patients. Patients' cells that were co-cultured with PAHA-erythrocyte conjugates produced significantly greater amounts of antibodies to both total histones (p = 0.03) and the H2A-2B dimer (p = 0.009) compared with those cultured alone. Co-culture with similarly pretreated erythrocytes also resulted in a significant increase in the production of antibodies to total histones (p < 0.001), but not to the H2A-H2B dimer, by cells from controls. CONCLUSION: Some patients receiving chronic procainamide therapy have spontaneous production of histone antibodies. Co-culture with PAHA-erythrocyte conjugates resulted in significantly greater production, suggesting an immunomodulating effect by this metabolite.

Adult↗