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PubMed1997

Effect of verapamil and procainamide on atrial fibrillation-induced electrical remodeling in humans.

BACKGROUND: Atrial fibrillation (AF) shortens the atrial effective refractory period (ERP) and predisposes to further episodes of AF. The purpose of this study was to determine the effect of verapamil and procainamide on these manifestations of AF-induced electrical remodeling. METHODS AND RESULTS: In adult patients without structural heart disease, the atrial ERP was measured before and after AF after pharmacological autonomic blockade and administration of verapamil (17 patients), procainamide (10 patients), or saline (20 patients). AF was then induced by rapid pacing. Immediately on AF conversion, the post-AF ERP was measured at alternating drive cycle lengths of 350 and 500 ms. In the saline group, the pre-AF and first post-AF ERPs at the 350-ms drive cycle length were 206+/-19 and 179+/-27 ms (P<.0001), respectively, and at the 500-ms drive cycle length, the values were 217+/-16 and 183+/-23 ms, respectively (P<.0001). There was a similar significant shortening of the first post-AF ERP in the procainamide group. In the verapamil group, however, there was no difference between the pre-AF and the first post-AF ERP at the 350-ms (226+/-15 versus 227+/-22 ms, P=.8) or 500-ms (230+/-17 versus 232+/-20 ms, P=.6) drive cycle length. During determinations of the post-AF ERP, 105 secondary episodes of AF were unintentionally induced in 12% of verapamil patients compared with 90% and 80% of saline and procainamide patients (P<.01 versus verapamil). CONCLUSIONS: Pretreatment with the calcium channel antagonist verapamil, but not the sodium channel antagonist procainamide, markedly attenuates acute, AF-induced changes in atrial electrophysiological properties. These data suggest that calcium loading during AF may be at least partially responsible for AF-induced electrical remodeling.

Adult↗
PubMed1989

Anti-cholinergic effects of quinidine, disopyramide, and procainamide in isolated atrial myocytes: mediation by different molecular mechanisms.

Effects of quinidine, disopyramide, and procainamide on the acetylcholine (ACh)-induced K+ channel current were examined in single atrial cells, using the tight-seal, whole-cell clamp technique. The pipette solution contained guanosine-5'-triphosphate (GTP) or guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma S, a nonhydrolysable GTP analogue). In GTP-loaded cells, not only ACh but also adenosine induced a specific K+ channel current via GTP-binding proteins (G) by activating muscarinic ACh or adenosine receptors. Quinidine and disopyramide depressed the ACh-induced K+ current quite effectively. Procainamide had a weak inhibitory effect. Quinidine also depressed adenosine-induced K+ current, while the effect of disopyramide on adenosine-induced current was much smaller than that on ACh-induced current. In GTP-gamma S-loaded cells, the K+ channel was uncoupled from the receptors and was activated irreversibly, probably due to direct activation of G proteins by GTP-gamma S. Quinidine depressed the GTP-gamma S-induced K+ current just as in the cases of ACh- and adenosine-induced currents of GTP-loaded cells. Disopyramide had only a weak inhibitory effect and procainamide showed no effect. From these results, it is strongly suggested that the major mechanisms underlying the anti-cholinergic effects of quinidine, disopyramide, and procainamide are different; quinidine may inhibit the muscarinic K+ channel itself and/or G proteins, while disopyramide and high doses of procainamide may mainly block functions of muscarinic ACh receptors in atrial myocytes.

Animals↗
PubMed1988

Transport of procainamide and N-acetylprocainamide from blood into the intestinal lumen and intestinal dialysis by oral activated charcoal in rats with acute renal failure.

The characteristics of exsorption and/or excretion of procainamide and its metabolite, N-acetylprocainamide (NAPA), into the small intestinal lumen in both normal rats and rats with acute renal failure (ARF rats) induced by uranyl nitrate were investigated by an in situ single-pass perfusion technique. The exsorption of procainamide and NAPA from blood into the intestinal lumen was increased in ARF rats compared with normal rats. The mean apparent renal, biliary and intestinal clearance values of procainamide were 186, 1.83 and 73.9 ml/h/kg in normal rats, respectively, and were 2.02, 1.37 and 55.8 ml/h/kg in ARF rats respectively. Furthermore, the mean renal, biliary and intestinal clearance values of NAPA were 35.2, 19.4 and 21.1 ml/h/kg in normal rats, respectively, and were 1.12, 21.0 and 26.0 ml/h/kg in ARF rats, respectively. There was little difference in the intestinal clearance values of procainamide and NAPA between normal and ARF rats. The ratio of nonrenal clearance/total body clearance was greater in ARF rats than in normal rats. Treatment with oral activated charcoal reduced the serum NAPA levels in both normal and ARF rats, and had little effect on the serum procainamide levels in normal rats, while it reduced the serum drug levels in ARF rats. Consequently, the increase in both drugs transported into the intestinal lumen induced by renal failure may enhance the intestinal clearance of the drug by oral administration of activated charcoal.

Acecainide↗
PubMed1990

Comparison of transport of procainamide and N-acetylprocainamide from blood into the intestinal lumen with that into the peritoneal cavity in rats.

Transfer of procainamide and its active metabolite, N-acetylprocainamide (NAPA) from the blood into the intestinal lumen was compared with that into the peritoneal cavity after i.v. administration of procainamide at the dose of 10 mg/kg to rats. The amounts of both drugs transferred from the blood into the intestinal lumen were much greater than those into the peritoneal cavity. The average amounts of procainamide transferred in 2 h into the intestinal lumen and the peritoneal cavity were 12.7% and 1.7% of dose (10 mg/kg), respectively, while those of NAPA were 3.5% and 1.4% of dose. The intestinal and peritoneal clearance values of procainamide were 143.5 and 59.4 ml/h, respectively, and those of NAPA were 32.6 and 13.5 ml/h. The difference in transfer rates across the intestinal and peritoneal membranes may be due to difference in the area of permeative surface and the extent of ionization in the dialysate. Consequently, it is expected that the gastrointestinal dialysis by oral administration of activated charcoal may serve as one of the more useful hemopurification methods than the peritoneal dialysis in procainamide and NAPA intoxication.

Acecainide↗
PubMed1999

Dynamic effects of intravenous procainamide infusion on the electrophysiological properties during atrial fibrillation.

Although the mechanism of atrial fibrillation (AF) is still controversial, multiple wandering reentry is considered the primary mechanism in most AF. It has been suggested that prolongation of the wavelength would make it impossible for the reentry to continue and would lead to the termination of the AF. In the present study a dynamic fluctuation in the electrophysiological properties was observed with procainamide infusion during AF. In 12 patients, both the local electrogram and monophasic action potentials (MAP) during AF were recorded from the right atrium before, during and after infusion of procainamide (10 mg/kg). The minimum AF cyclelength (CLmin), MAP duration at 90% repolarization (MAPD90) and widths of the intraatrial potentials (WAP) were measured with custom-made computer software. The conduction velocity index (CVI) was determined from the WAP. The wavelength index (WLI=CVIxCLmin) and postrepolarization refractoriness (PRR= CLmin-MAPD90) were calculated. In 6 patients, AF was terminated by procainamide infusion (group A), but not in the other 6 patients (group B). Group A patients showed a biphasic change in the parameters following procainamide infusion. In phase I, the CLmin, MAPD90 and PRR increased, while the CVI decreased, and the WLI remained unchanged. In phase II, the PRR, CVI and WLI increased and the AF was terminated. No restoration of the CVI nor increase in the WLI were observed in group B. The biphasic fluctuation in the CVI and the remarkable increase of the PRR and WLI were observed before termination of AF by procainamide infusion.

Adult↗
PubMed1994

Procainamide-induced changes in reentrant ventricular tachycardia with special reference to the tachycardia-interrupting critical paced cycle length during transient entrainment with rapid pacing.

With rapid ventricular pacing, sustained ventricular tachycardia (VT) is often entrained and interrupted at a critical paced cycle length. In this paper, the possible mechanism and determinant of the critical cycle length interrupting VT are addressed. Sixteen consecutive patients underwent rapid ventricular pacing in 18 morphologically distinct sustained VTs before and after procainamide. The VT morphology was identical before and after the drug. The VT origin was determined by endocardial mapping as the earliest site of activation of VT and an electrode catheter was located at the site. Rapid pacing was performed to entrain VT and repeated in 10 msec decrements of cycle length until VT was interrupted at a critical paced cycle length which was defined as the block cycle length. The effective refractory period was measured at the pacing site. The paced QRS duration and the local conduction time were measured and used as indices of conduction time in the normal myocardium. VT was entrained and interrupted in all patients. At the block cycle length, initial constant fusion was replaced abruptly by the fully paced QRS complex. At the same time, the local electrogram at the site of VT origin showed changes in the morphology and the timing of activation which were identical to those of the fully paced beat. This loss of fusion and the changes in the local electrogram were considered to be a result of orthodromic block and the block cycle length was assumed to represent the cycle length at which 1:1 conduction fails in the area of slow conduction. After procainamide, both the VT cycle length and the block cycle length were prolonged to a similar degree (p < 0.001) but the relative degree of change varied from patient to patient. The paced QRS duration and the conduction time were prolonged by procainamide but in smaller degrees than the cycle length of VT or the block cycle length (p < 0.02-01). The effective refractory period at the pacing site and the QT interval showed small changes after procainamide. The postrepolarization refractoriness rather than the duration of action potential can be responsible for the procainamide-induced prolongation of the block cycle length, and the block cycle length might be used as a new index to characterize the electrophysiologic property of the VT circuit and also the action of antiarrhythmic drugs.

Adolescent↗
PubMed1995

Sustained-release procainamide-induced reversible granulocytopenia after myocardial infarction.

A 71-year-old man with paroxysmal atrial fibrillation who had a previous anterior myocardial infarction exhibited granulocytopenia 8 days following the administration of oral sustained-release procainamide (750 mg/day). The plasma concentrations of procainamide and N-acetyl procainamide were at subtherapeutic levels. Discontinuation of procainamide led to complete recovery. A bone marrow aspiration showed slight hypoplasia with normocellular marrow. Lupus erythematosus (LE) and antinuclear antibody (ANA) tests were negative. The frequency and relationship of granulocytopenia caused by sustained-release procainamide in patients with tachyarrhythmias are briefly discussed, and prior reported cases are reviewed. Precautionary measures for the early recognition of this grave hazard in exposed patients are advocated. The physician should be aware of this complication before in initiating treatment with this drug.

Aged↗
PubMedDate not supplied

Poisoning due to class IA antiarrhythmic drugs. Quinidine, procainamide and disopyramide.

Quinidine, procainamide and disopyramide are antiarrhythmic drugs in the class 1A category. These drugs have a low toxic to therapeutic ratio, and their use is associated with a number of serious adverse effects during long term therapy and life-threatening sequelae following acute overdose. Class 1A agents inhibit the fast inward sodium current and decrease the maximum rate of rise and amplitude of the cardiac action potential. Prolonged Q-T interval and, to a lesser extent, QRS duration may be observed at therapeutic concentrations of quinidine. With increasing plasma concentrations, progressive depression of automaticity and conduction velocity occur. 'Quinidine syncope' (a transient loss of consciousness due to paroxysmal ventricular tachycardia, frequently of the torsade de pointes type) occurs with therapeutic dosing, often in the first few days of therapy. Extracardiac adverse effects of quinidine include potentially intolerable gastrointestinal effects and hypersensitivity reactions such as fever, rash, blood dyscrasias and hepatitis. Procainamide produces electrophysiological changes that are similar to those of quinidine, although Q-T interval prolongation with the former is less pronounced at therapeutic concentrations. Hypersensitivity reactions including fever, rash and (more seriously) agranulocytosis are associated with procainamide, and a frequent adverse effect requiring cessation of therapy is the development of systemic lupus erythematosus. Of the 3 drugs, disopyramide has the most pronounced negative inotropic effects, which are especially significant in patients with pre-existing left ventricular dysfunction. As with quinidine, unexpected 'disopyramide syncope' at therapeutic concentrations has been described. Anticholinergic side effects are common with this drug and may require cessation of therapy. Disopyramide therapy may unpredictably induce severe hypoglycaemia. Severe intoxication with the class 1A agents may result from acute accidental or intentional overdose, or from accumulation of the drugs during long term therapy. Acute overdose can result in severe disturbances of cardiac conduction and hypotension, frequently accompanied by central nervous system toxicity. Decreased renal function can cause significant accumulation of procainamide and its active metabolite acecainide (N-acetyl-procainamide), resulting in severe intoxication. Mild to moderate renal dysfunction is less likely to lead to quinidine or disopyramide intoxication, unless renal failure is severe or concurrent hepatic dysfunction is present. Management of acute intoxication with class 1A drugs includes gut decontamination with provision of respiratory support and treatment of seizures as needed. Hypertonic sodium bicarbonate, by antagonising the inhibitory effect of quinidine on sodium conductance, may reverse many or all manifestations of cardiovascular toxicity.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMedDate not supplied

Clinical pharmacokinetics of procainamide.

Procainamide is almost completely absorbed after oral administration and peak plasma concentrations are generally reached within 1 to 2 hours. Upon intravenous administration there is a rapid initial distribution phase, which is completed after about 30 minutes. The pharmacokinetics can be described by a 2-compartment open model. The plasma half-life during the beta-phase averages 3 hours. The apparent volume of distribution is about 2L/kg body weight. At therapeutic plasma levels about 15% is bound to plasma proteins. Approximately 50% of administered procainamide is eliminated as unchanged drug via the kidneys. N-Acetylprocainamide is the main metabolite and is the main metabolite and is pharmacologically active, with a recovery in urine of about 15% (range 7 to 34% in healthy subjects). The acetylation of procainamide seems to be under the same monogenic control as that of isoniazid. At least 2 more metabolites have been found but are not yet identified. The renal clearance of procainamide ranges from 179 to 660ml/min. Glomerular filtration and active tubular secretion seem to be the most important mechanisms. In patients with low-output cardiac and/or renal impairment, the absorption, distribution and elimination of the drug may be significantly altered. Determination of plasma levels is of particular value in these cases and will contribute to more safe and effective therapy in the majority of patients. As N-acetylprocainamide seems to have pharmacological effects comparable with those of procainamide, both agents should be monitored simultaneously in order to optimise therapy.

Acute Kidney Injury↗
PubMedDate not supplied

Population pharmacokinetics of procainamide from routine clinical data.

Routine clinical pharmacokinetic data collected from patients receiving procainamide were analysed to estimate population pharmacokinetic parameters. 116 plasma concentration determinations for procainamide and 14 timed urine collections for the drug and its major metabolite N-acetylprocainamide (NAPA) were obtained from 39 patients, mostly males. The data were analysed using NONMEM, a computer program designed for population pharmacokinetic analysis that allows pooling of data from many individuals. Estimates of the influence of weight, height, renal function, and the presence of congestive heart failure (CHF) on the renal clearance (CLR), acetylation clearance (CLA), miscellaneous metabolic clearance (CLO), and volume of distribution (Vd) of procainamide were obtained. The mean (SE) CLR, CLA, CLO and Vd for procainamide in a 70kg patient with normal renal function were estimated to be 14.4 (2.3) L/h, 10.1 (1.7) L/h, 1.2 (1.3) L/h, and 136.0 (20.0) L, respectively. These pharmacokinetic parameters vary linearly with bodyweight; height adds no information if weight is known. The presence of CHF has no significant effect on either CLO or Vd, but reduces CLA and CLR by 11% (p less than 0.01). Even after adjustments for CHF, renal function and weight, the total clearance and Vd of procainamide vary unpredictably among individuals, with a coefficient of variation between 30 and 40%, and less than 50%, respectively.

Arrhythmias, Cardiac↗
PubMed1982

Inhibition of Con A mitogenesis by serum from procainamide-treated patients and patients with systemic lupus erythematosus.

Serum obtained from patients with spontaneous systemic lupus erythematosus or from patients treated at least 3 months with procainamide could specifically inhibit Con A mitogenesis of cultured peripheral blood mononuclear cells obtained from procainamide-treated patients or from normal donors. Transfer of procainamide treated patients to N-acetylprocainamide eliminated the blocking factor from their serum. The blocking factor is not procainamide itself since adding the drug to normal serum and only slight effects on mitogenesis of normal peripheral blood mononuclear cells. These data suggest that systemic lupus erythematosus and procainamide-induced lupus may differ in the relative reversibility of a regulatory defect associated with a Con A responsive population of peripheral blood mononuclear (PBM) cells.

Acecainide↗
PubMed1975

Hemodynamic effects of procainamide and quinidine and the influence of beta-blockade before and after experimental myocardial infarction.

The use of antiarrhythmie drugs in combination has been limited because of possible side effects secondary to myocardial depression in the acute myocardial infarction patient. Therefore, we investigated in intact dogs (group I) the hemodynamic interaction of propranolol plus procainamide (subgroup A) or quinidine (subgroup B) and in dogs after experimental myocardial infarction produced by coronary artery ligation (group II). Infusion of procainamide (30 mg/kg over 5 min) in animals of group IA produced a significant (P less than 0.05) decrease of 30% in mean aortic pressure, a decrease of 40% in left ventricular dp/dt and 29% in cardiac output. When procainamide was reinfuse after propranolol (1 mg/kg), its hemodynamic effects were not significantly different from those observed before propranolol in both groups IA and IIA. Infusion of quinidine (10 mg/kg over 5 min) in animals of group IB (intact dogs) also produced significant decreases of 24% in mean aortic pressure and 38% in dp/dt while cardiac output was unchanged. However, these hemodynamic changes were seen only after beta-blockade and were significantly different from those obtained before propranolol, where heart rate increased by 14%, dp/dt by 30%, and cardiac output by 35%. These changes occurred despite a similar reduction in mean aortic pressure. This drug combination produced similar response in animals after coronary artery ligation (group IIB). In conclusion, we feel that the administration of propranolol does not prevent the depressive circulatory effects of procainamide. The combined use of quinidine and propranolol also has a negative circulatory effect although not as marked as the effects observed after procainamide with propranolol.

Adrenergic beta-Antagonists↗
PubMed1981

Acetylprocainamide therapy in patients with previous procainamide-induced lupus syndrome.

Acetylprocainamide was used to treat 11 patients with previous procainamide-induced lupus syndrome for their cardiac arrhythmias. Three patients from whom procainamide had been withdrawn and whose lupus was in remission did not have a recurrence during a course of acetylprocainamide therapy of a longer average duration than their prior procainamide therapy. Lupus symptoms subsided during treatment in two patients who had symptoms when acetylprocainamide was started. Drug fever developed in one patient, and another had a mild recurrence of lupus symptoms during high-dose acetylprocainamide therapy that regressed with dosage reduction. All patients had small amounts of circulating procainamide from in-vivo deacetylation of acetylprocainamide. These observations strongly support the hypothesis that the aromatic amino group on procainamide is important for induction of the lupus syndrome and that acetylating this amino group blocks the lupus-inducing effect.

Acecainide↗
PubMed2005

[Anticholinergic effect of procainamide and its sulfonylcarbamide derivatives on electromechanical activity in guinea pig atrium].

The aim of the study was to investigate the effect of class IA antiarrhythmic drug procainamide and its new derivatives PA20, PA23, PA28 and PA53 on carbachol-induced action potential duration and contraction force in guinea pig atrial muscles. Experiments were carried out using standard method of registration of myocardium electromechanical activity. Under control conditions (perfusion of atrial strips with Tyrode solution), mean action potential duration measured at 90% (AP90) and 50% (AP50) of repolarization were 92.5+/-4.5 ms and 44.4+/-2.9 ms (n=18), respectively, and contraction force was of 2.7+/-0.5 mN (n=12). Carbachol (10(-6) M), an agonist of muscarinic acetylcholine receptor and activator of K(Ach) channels, markedly decreased AP90 to 32.4+/-2.4%, AP50 - to 25.4+/-2.2% (n=18) (p<0.001) and contraction force - to 24.2+/-5.8% (n=16) (p<0.05), vs. control. Procainamide and its new sulfonylcarbamide derivatives PA20, PA23, PA28 (10(-5)-3x10(-3) M), and PA53 (10(-5)-10(-3) M) reversed the carbachol-induced action potential duration shortening at different extent: procainamide derivative PA20 (N-cyclohexylsulfonylcarbamide fragment is linked up to benzene ring) had the most potent anticholinergic effect on action potential duration and contraction force of guinea pig atrial muscles. N-ethylsulfonylcarbamide fragment in PA23 or permanent positive charge of aliphatic nitrogen in PA28 had a weaker anticholinergic effect (similar to procainamide action) on action potential duration and contraction force than PA20. The weakest anticholinergic effect was induced by procainamide derivative PA53 with isosteric form of sulfonylcarbamide.

Action Potentials↗
PubMedDate not supplied

Determination of metabolically derived nitroprocainamide in the urine of procainamide-dosed humans and rats by liquid chromatography with electrochemical detection.

The N-oxidized metabolites of the antiarrhythmic procainamide have previously been implicated as inciting agents in the autoimmune condition drug-related lupus. Although much data have been collected with respect to the in vitro behavior of these metabolites, relatively little has been accomplished in vivo because of their extreme reactivity. The determination of nitroprocainamide (NPA), a stable decomposition product of the reactive hydroxylamine and nitroso species, in the urine of rats dosed with procainamide is reported here using the sensitive and selective method of HPLC with electrochemical detection. For orally and i.v.-dosed animals, up to microgram amounts of NPA were excreted over 24 hr from an initial dose of 66-100 mg procainamide/kg body weight. Also, the apparent elimination of microgram quantities of NPA in the urine specimens of 9 of 11 patients undergoing treatment with procainamide was observed. This suggests that N-oxidation of the aromatic ring of procainamide is occurring at sufficient levels to result in the formation of significant amounts of the reactive hydroxylamine and nitroso metabolites in vivo, and may have direct implications in the diverse and widespread symptomatology associated with procainamide-induced drug-related lupus.

Animals↗
PubMedDate not supplied

Procainamide induced sustained monomorphic ventricular tachycardia in a patient with benign premature ventricular complexes.

A 59-year old female with history of benign ventricular ectopy who developed sustained monomorphic ventricular tachycardia (VT) during therapy with procainamide is reported. The tachycardia occurred 24 hours after institution of procainamide without any other evidence of drug toxicity or QT prolongation. When procainamide was withheld, VT resolved completely and no arrhythmia could be induced by programmed ventricular stimulation. When the patient was rechallenged with procainamide at therapeutic level, sustained monomorphic VT was initiated reproducibly by programmed ventricular stimulation. Without antiarrhythmic therapy, patient has been asymptomatic and free of recurrent VT after a follow-up of 9 months. This case: Demonstrates that procainamide may cause the first emergence of sustained monomorphic VT in a patient with no previous history of VT; and Emphasizes the utility of programmed ventricular stimulation in providing direct evidence for drug mediated exacerbation of the ventricular arrhythmia.

Bundle-Branch Block↗
PubMed1989

Influence of age, renal function and heart failure on procainamide clearance and n-acetylprocainamide serum concentrations.

Twenty Caucasian adult patients with ventricular tachycardia were treated with intravenous procainamide. Seven patients also had moderate congestive heart failure. Steady-state procainamide (PA) and n-acetylprocainamide (NAPA) concentrations were used to compute procainamide clearance and NAPA/PA concentration ratio. Using stepwise multiple linear regression age, creatinine clearance and congestive heart failure were found to influence procainamide clearance significantly (p less than 0.05). Age and creatinine clearance effected the NAPA/PA concentration ratio (p less than 0.05). Based on this data, age appears to have an independent effect on both procainamide clearance and the NAPA/PA ratio that is separate from the decline in renal function that occurs in elderly patients.

Acecainide↗
PubMed1989

Immunomodulatory effects of procainamide metabolites: their implications in drug-related lupus.

Evidence suggests that N-oxidized metabolites of procainamide may be responsible for the development of lupus-like symptoms associated with procainamide therapy. The human hepatic microsomal metabolism of procainamide has been previously reported to result in formation of the N-hydroxylamine derivative of procainamide (procainamide hydroxylamine [PAHA]). The objective of this study was to examine the effects of PAHA on human lymphocytes and adherent cells (monocytes and macrophages). When incubated with lymphocytes in whole blood, PAHA enhanced the response to mitogen and immunoglobulin secretion at lower concentrations (less than or equal to 4 mumol/L) but suppressed these functions at higher concentrations. The cytotoxic effects were nonselective for T lymphocytes and B lymphocytes and appeared to involve an interaction between PAHA and hemoglobin. When erythrocytes were removed or when hemoglobin was converted to carboxyhemoglobin, the suppressive effects of PAHA on lymphocytes were reduced. PAHA stimulated interleukin-1 production by adherent cells at 25 mumol/L but had no effect at lower concentrations. Superoxide anion release was unaffected by PAHA in "resting" adherent cells. Pretreatment with PAHA (2 mumol/L) diminished superoxide release in response to stimulation by phorbol myristate acetate (PMA) or latex bead phagocytosis but augmented superoxide release when coincubated with PMA or latex. These observations indicate that PAHA produces complex, concentration-dependent interactions with human immunoregulatory cells, and they suggest that the effects of PAHA on lymphocyte function may result from the further oxidation of PAHA by hemoglobin, perhaps to the nitroso form.

Adult↗