Administration Of Procainamide Research Articles

The “Better” Answer

The “Better” Answer

Sinus Standstill in a Patient after Intracoronary Papaverine Administration for a Coronary Fractional Flow Reserve

A 78-year-old woman had paroxysmal atrial fibrillation and effort angina. Two months before she was admitted for a coronary angiography, she had been feeling dizzy. A Holter 24-hour electrocardiography monitor exhibited an asymptomatic episode of 2.9 seconds of RR interval. She underwent a coronary angiography, which showed intermediate stenosis in the left descending artery. Fractional flow reserve (FFR) measurement using intracoronary papaverine administration was performed. After intracoronary papaverine (12 mg) administration, pause of 4 seconds led to polymorphic ventricular tachycardia (VT), although the VT terminated spontaneously. Premature ventricular beat occurred and led to sustained polymorphic VT. In cardiac electrophysiology study, pacing from the right atrium showed that the maximum sinus node recovery time (SRT) was 910 ms. After procainamide (10 mg/kg) administration, the maximum SRT was 16.3 seconds with some junctional escapes. After intravenous papaverine administration, there was a slight change. Intracoronary papaverine administration induced about 9-seconds pause with some junctional escapes. We conclude that intracoronary papaverine administration reveals potential sinus node dysfunction. The patient has been asymptomatic since the implantation of the pacemaker. Patients with suspicious sinus dysfunction should be careful.

Procainamide Inhibits DNA Methylation and Alleviates Multiple Organ Dysfunction in Rats with Endotoxic Shock

Excessive inflammatory and oxidative stress lead to circulatory failure, multiple organ dysfunction, and high mortality in patients with sepsis. Microbial infection-induced DNA hypermethylation is associated with the augmentation of inflammation and oxidative stress. In our previous study, the antiarrhythmic drug procainamide inhibits the expression of DNA methyltransferase 1 (DNMT1) and diminishes IL-6 levels in rats with rhabdomyolysis. Thus, we further evaluated the effects of procainamide on the development of circulatory failure and multiple organ dysfunction in rats with endotoxic shock. Male Wistar rats were intravenously infused with saline or lipopolysaccharide (LPS) followed by procainamide administration. The changes of hemodynamics, blood glucose, biochemical variables, and plasma nitric oxide (NO) levels were analyzed during the experimental period. At the end of experiments, animal organs were also obtained for examining superoxide production, neutrophil infiltration, and DNA methylation status. Our results showed that LPS induced circulatory failure, multiple organ dysfunction, and high mortality rate in endotoxemic rats. Overt neutrophil infiltration and superoxide production, accompanied by the elevations of DNMT1 and 5-methylcytosine levels in the lung of endotoxemic rats were also observed. Treatment of endotoxemic animals with procainamide not only inhibited the increased levels of DNMT1 and 5-methylcytosine but also ameliorated neutrophil infiltration and superoxide production in the lung. In addition, the anti-inflammatory gene, IL27RA, was down-regulated in the LPS group and up-regulated in the LPS + Procainamide group. Procainamide also diminished IL27RA methylation in the lung of endotoxemic rat. Moreover, both DNMT inhibitors procainamide and hydralazine improved hypotension, hypoglycemia, and multiple organ dysfunction of LPS-treated rats. Thus, we suggest that the beneficial effects of procainamide could be attributed to the suppression of DNA methylation, neutrophil infiltration, superoxide production, and NO formation. It seems that this old drug may have new potential uses in infectious diseases, in particular, associated with endotoxemia.

Long QT syndrome caused by N-acetyl procainamide in a patient on hemodialysis

A 65-year-old male on hemodialysis three times a week due to end-stage renal failure underwent cardiac surgery one year previously, and complained of breathlessness on exertion after surgery. Echocardiograms evidenced a significant obstruction in the left ventricular outflow with intraventricular pressure gradient of 62mmHg, and the patient was started on beta-blocker. After a maximal dose of carvedilol was given, a class 1A antiarrhythmic drug of Na channel blocker, procainamide, was added because of insufficient relief of symptoms. Electrocardiogram (ECG) showed prolonged QT intervals (523ms) on a regular visit one month after the administration of procainamide, and the dose of procainamide was decreased. On the next day, he was brought to our hospital due to cardiac pulmonary arrest. Initial rhythm was ventricular fibrillation and the corrected QT intervals (QTc) were prolonged (531ms). Blood examination revealed that N-acetyl procainamide (NAPA), metabolite of procainamide, was significantly higher than the recommended threshold. NAPA was identified as the cause of prolonged QTc and procainamide was stopped. NAPA decreased under the recommended threshold on the seventh day and the QT intervals were normalized. This case report outlines the first case of long QT syndrome caused by NAPA in a hemodialysis patient.<Learning objective: Administration of procainamide could be dangerous even in patients undergoing hemodialysis whose serum procainamide level is within normal limits. We should pay careful attention to it and must not forget to measure the concentrations of procainamide and NAPA. The measurement of QT intervals could help to avoid a fatal side effect.>

Possible protective effect of procainamide as an epigenetic modifying agent in experimentally induced type 2 diabetes mellitus in rats

BackgroundDiabetes mellitus (DM) is a metabolic disease that is associated with disturbed carbohydrates, lipids and protein metabolism due to insulin deficiency and/or impaired insulin action. Recently epigenetic mechanisms were shown to be involved in endocrine cell differentiation and islets function. Procainamide which is a cardiac antiarrhythmic drug has been recently classified as one of the epigenetic drugs targeting DNA methylation. AimThe present study was designed to evaluate the effect of procainamide as a demethylating epigenetic agent on streptozotocin-induced type 2 diabetes mellitus in rats. MethodsFifty adult male albino rats of weight ranging from 150 to 200g were included in this study. Rats were divided into five groups (each of 10 rats) as follows: group I: served as a normal control group, group II: diabetic rats that received 1ml gum acacia 2% orally, daily for 4weeks, group III: diabetic rats that received procainamide (20mg/kgbodyweight)/day, orally for 4weeks, group IV: diabetic rats that received metformin (300mg/kg/day), orally for 4weeks, group V: diabetic rats that received both procainamide and metformin in the same previous doses for 4weeks.The following parameters were assessed in rats of all studied groups: fasting blood glucose level, serum insulin level, serum tumor necrosis factor alpha (TNF-α) (as a proinflammatory cytokine as well as an indirect biomarker of DNA methylation) and DNA methyltransferase enzyme (DNMT) activity in pancreatic tissues (as a direct marker of DNA methylation). ResultsThe present study revealed that combined administration of both procainamide and metformin produced a statistically significant reduction of fasting blood glucose levels as compared to untreated diabetic rats as well as diabetic rats treated by either procainamide or metformin alone. In addition, procainamide administration either alone or in combination with metformin resulted in a statistically significant rise of serum insulin levels. TNF-α levels were statistically elevated in diabetic untreated rats as well as those treated with metformin only while procainamide intake led to its statistical decrease. Also, procainamide administration produced a statistically significant reduction in the activity of DNA methyltransferase in pancreatic tissues reflecting its possible role as a demethylating agent that increases insulin expression and release by pancreatic cells. ConclusionThe present work could provide a proof of concept that procainamide could be used as a possible therapeutic potential in type 2 diabetics as an epigenetic demethylating agent to increase insulin levels and it is better to be used in combination with oral hypoglycemic agent e.g. metformin to decrease insulin resistance.

Management of Patients With Atrial Fibrillation (Compilation of 2006 ACCF/AHA/ESC and 2011 ACCF/AHA/HRS Recommendations)

This document is a compilation of the current American College of Cardiology Foundation/American Heart Association (ACCF/AHA) practice guideline recommendations for atrial fibrillation (AF) from the “ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation),”* the “2011 ACCF/AHA/HRS Focused Update on the Management of Patients With Atrial Fibrillation (Updating the 2006 Guideline)”† and the “2011 ACCF/AHA/HRS Focused Update on the Management of Patients With Atrial Fibrillation (Update on Dabigatran).”‡ Updated and new recommendations from 2011 are noted and outdated recommendations have been removed. No new evidence was reviewed, and no recommendations included herein are original to this document. The ACCF/AHA Task Force on Practice Guidelines chooses to republish the recommendations in this format to provide the complete set of practice guideline recommendations in a single resource. ### 1.1. Pharmacological and Nonpharmacological Therapeutic Options #### 1.1.1. Rate Control During AF Class I 1. Measurement of the heart rate at rest and control of the rate using …

Impact of Emergency Department Management of Atrial Fibrillation on Hospital Charges

IntroductionEmergency department (ED) cardioversion (EDCV) and discharge of patients with recent onset atrial fibrillation or atrial flutter (AF) has been shown to be a safe and effective management strategy. This study examines the impact of such aggressive ED management on hospital charges.Methods:A random sample of 300 AF patients were identified from an ED electronic data base and screened for timing of onset of their symptoms. Patients were considered eligible for EDCV if either nursing or physician notes documented an onset of symptoms less than 48 hours prior to ED presentation and the patient was less than 85 years of age. An explicit chart review was then performed to determine patient management and disposition. Cardioversion attempts were defined as ED administration of procainamide, flecainide, propafenone, ibutilide, amiodarone or direct current cardioversion (DCCV). Total hospital charges for each patient were obtained from the hospital billing office. Differences across medians were analyzed utilizing through Wilcoxon rank sum tests and chi square.Results:A total of 51 patients were included in the study. EDCV was attempted on 24 (47%) patients, 22 (92%) were successfully cardioverted to normal sinus rhythm (NSR). An additional 12 (23%) spontaneously converted to NSR. Twenty (91%) of those successfully cardioverted were discharged from the ED along with 4 (33%) of those spontaneously converting. Pharmacologic cardioverson was attempted in six patients and was successful in three (50%), one after failed DCCV attempt. Direct current cardioversion was attempted in 21 (88%) and was successful in 19 (90%), two after failed pharmacologic attempts. Median charges for patients cardioverted and discharged from the ED were $5,460 (IQR $4,677–$6,190). Median charges for admitted patients with no attempt at cardioversion were $23,202 (IQR $19,663–$46,877). Median charges for patients whose final ED rhythm was NSR were $5,641 (IQR $4,638–$12,339) while for those remaining inAF median charges were $30,299 (IQR $20,655 – $69,759).Conclusion:ED cardioversion of recent onset AF patients results in significant hospital savings.

Mandibular and parotid salivary excretion of procainamide and N-acetylprocainamide after intravenous administration of procainamide to rats

Flow rate, protein level and pH of mandibular and parotid saliva samples in rats were almost stabilized 2 h after induction of salivation with pilocarpine (9.0 mg h-1 kg-1). Salivary excretion profiles of procainamide, 50 mg kg-1 i.v., and its metabolite N-acetylprocainamide (NAPA) were then investigated. Plasma and salivary procainamide levels declined bi-exponentially with time almost in parallel. Salivary procainamide levels (Y) from both types of gland were correlated with the plasma level (X) over a wide concentration range [Y = 0.108X + 1.96 (r = 0.795) for mandibular and Y = 0.917X (r = 0.974) for parotid glands]. The mean saliva to plasma concentration ratio (S/P ratio) was significantly higher in parotid (0.974 +/- 0.243) than in mandibular (0.284 +/- 0.119) saliva samples. Similar correlations and S/P ratios were observed for NAPA. Procainamide and NAPA mean S/P ratios for saliva from both glands were fairly consistent with the calculated value according to the pH-partition hypothesis.

A Young Case of IntraFascicular Ventricular Tachycardia with Narrow QRS Complex

Introduction: Some previous reports demonstrated that ventricular tachycardia may rarely show narrow QRS complex. We experienced a young boy who had past history of Kawasaki disease with such a pattern of ventricular tachycardia. Case Presentation: A 14 year-old boy was transferred to our emergency department in a hemodynamically collapsed state. On 12-lead electrocardiograms, narrow QRS tachycardia with left posterior hemiblock morphology was recorded. We tried to terminate the tachycardia by intravenous infusion of medicine. At first, ATP was injected rapidly, the tachycardia was not terminated. We subsequently injected procainamide. The tachycardia was terminated. QRS complexes during sinus rhythm were similar to those during the tachycardia. Imaging examinations did not reveal structural heart disease on him. We performed electrophysiological study for diagnosis of the tachycardia. The tachycardia was easily induced by atrial extra stimulus and terminated by atrial burst pacing. The interval of His-right fascicular potentials was shorter than that of normal sinus rhythm. Therefore, the mechanism of the tachycardia was assumed to be microreentry rotating around proximal site of purkinje network, which means intrafascicular ventricular tachycardia. In other day, we tried catheter ablation, but the tachycardia was no more induced by any stimuli, so we could not have the procedure. The young patient was treated with oral administration of procainamide and remained asymptomatic.

Accelerated AV Nodal Conduction with Use of Procainamide in Atrial Fibrillation

Background: Atrial fibrillation is a common dysrhythmia seen in the emergency department (ED). Chemical or electrical cardioversion may be performed on patients who have had atrial fibrillation for < 48 h duration and who are at low risk for thromboembolic events. Multiple studies suggest that intravenous procainamide is an appropriate agent in the treatment of acute atrial fibrillation due to its relatively low risk profile and high conversion rate. Objectives: A case is presented that demonstrates an adverse reaction to the use of intravenous procainamide for chemical cardioversion of atrial fibrillation in an otherwise hemodynamically stable patient. Case Report: We report a case of lone paroxysmal atrial fibrillation in a patient with a structurally normal heart who suffered paradoxical accelerated atrioventricular nodal conduction and secondary hypotension in response to procainamide administration. Conclusion: When administering procainamide for chemical cardioversion of atrial fibrillation, a low threshold should be maintained for administration of a complementary rate-controlling agent, and facilities for immediate electrical cardioversion always must be available.

Effects of Verapamil and Procainamide on Acute Atrial Electrical Remodeling Induced by Short-term Rapid Atrial Pacing in Humans

Atrial electrical remodeling (ER) after spontaneous or pacing-induced atrial fibrillation has been previously described in humans. We investigated atrial ER induced by a 5-minute period of rapid atrial pacing and the pharmacologic effects of verapamil and procainamide on this atrial ER phenomenon. The atrial effective refractory periods (ERPs) at drive cycle lengths of 400 (ERP 400 ) and 600 (ERP 600 ) ms, at five representative atrial sites (high right atrium [HRA]; proximal, middle and distal coronary sinus; interatrial septum), were determined in 20 patients at baseline and immediately after cessation of a 5-minute period of rapid pacing from the HRA at a rate of 150 bpm. The degrees of atrial ERP 400 and ERP 600 shortening after pacing were calculated as acute atrial ER. The same protocol was repeated in another 15 patients after intravenous administration of verapamil (0.15 mg/kg) and in another 15 patients after intravenous administration of procainamide (15 mg/kg). The results demonstrated that, in the control state acute atrial ER can be significantly demonstrated at each atrial representative site ( p < 0.001). The mean ERP 400 and ERP 600 shortenings were 9 +/- 4% and 8 +/- 4%, respectively. After procainamide infusion, but not after verapamil, baseline ERP 400 and ERP 600 values were significantly prolonged at the five representative atrial sites ( p < 0.01). Acute atrial ER could still be demonstrated at each atrial site after procainamide or verapamil infusion ( p < 0.001). In conclusion, acute atrial ER can be demonstrated after only a 5-minute period of rapid atrial pacing in humans. Intravenous verapamil or procainamide does not abolish this ER process.

Drug-Herb Interaction: Effect of St John's Wort on Bioavailability and Metabolism of Procainamide in Mice

St John's wort induces the activity of the cytochrome P450 enzyme system causing treatment failure because of increased metabolism of many drugs. Procainamide is metabolized by a different pathway to N-acetyl procainamide. To study St John's wort-procainamide interaction using a mouse (Swiss Webster) model. One group of mice (group A, 4 mice in each group) was fed St John's wort each day for 2 weeks (last dose 1 day before administration of procainamide); another group (group B) received the same dose of St John's wort for 1 week. The third group (group C) received only a single dose 1 hour before administration of procainamide, and the control group (group D) received no St John's wort. All groups later received a single oral dose of procainamide. Blood was drawn 1, 4, and 24 hours after administration of procainamide and concentrations in serum of procainamide as well as N-acetyl procainamide were measured using immunoassays. The procainamide concentrations 1 hour after administration was highest in group C (mean, 11.59 microg/mL) followed by group A (9.92 microg/mL), whereas group B (7.44 microg/mL) and control group D (7.36 microg/mL) showed comparable values. The concentration in group C was significantly greater than the control group D (P = .03, 2-tailed independent t test). N-Acetyl procainamide concentrations and estimated half-life of procainamide among groups were comparable. In a separate experiment when mice were fed purified hypericin, the active component of St John's wort, a significant increase in bioavailability (53%) of procainamide was observed compared with the control group. St John's wort has an acute effect to increase bioavailability of procainamide but has no effect on its metabolism.

Magnitude of prestretch during ventricular activation is proportional to the amount of late activated tissue in the canine heart

Ventricular pacing alters the pattern of electrical activation of the heart, resulting in a region of late activated tissue far from the pacing site. In late activated tissue, previous studies have described an area of mechanical stretch termed ‘prestretch’. We hypothesized that the magnitude of prestretch is related to the amount of late activated tissue. To test this hypothesis, an array of radiopaque markers was inserted into the anterior and lateral walls of the LV in 2 open chest dogs, forming a 5 by 5 cm grid. The animals underwent ventricular pacing at a remote site before and after administration of procainamide. Finite strains were determined from biplane cineradiography of the markers. Maximum prestretch was defined as the largest circumferential strain at the time of peak +dP/dt. Conduction time was defined as the time for a posterior wall stimulus to reach the anterior wall. Conduction time was an average of 81 ms before and 92 ms after procainamide, reflecting a reduced conduction velocity and an increase in late activated tissue. As the amount of late activated tissue increased from an average of 68% to 80% of the array, maximum prestretch (circumferential strain) increased from 0.28 to 0.58. In areas of prestretch, circumferential strains were, on average, 3.5 times larger than longitudinal strains, similar to previous data for passive inflation of the dog heart. Thus the magnitude of prestretch is determined by the amount of late activated tissue, and prestretch may be a continuation of passive filling mechanics in those areas of tissue not yet activated. Supported by NIH grant HL32583.

Idiopathic Premature Ventricular Contraction Originating from Left Epicardial Outflow Tract —Effects of Antiarrhythmic Drugs, Autonomic Provocation and Radiofrequency Catheter Ablation—

We present a patient with frequent episodes of palpitation who had idiopathic premature ventricular contraction (PVC. with QRS morphology exhibiting a right bundle branch block pattern with an inferior axis. Neither administration of procainamide, propranolol, lidocaine or verapamil could inhibit PVC, whereas administration of adenosine triphosphate, carotid sinus massage and Valsalva maneuver could effectively eliminate PVC. The earliest activation preceding the QRS complex by 25 msec at occurrence of the PVC was recorded at the distal site of the coronary sinus and within the left coronary cusp. Pacemapping in the supravalvular site during sinus rhythm produced a QRS complex more similar to PVC than that produced in the infravalvular site of the left ventricular outflow tract (LVOT). Radiofrequency catheter ablation was performed at the supravalvular site close to the epicardial LVOT, which resulted in successful elimination of PVCs.

Intrapericardial drug delivery: pharmacologic properties and long-term safety in swine

Background: Intrapericardial drug delivery is a promising new technique, but the pharmacologic properties of various agents delivered via this route are not known. Furthermore, the long-term safety of intrapericardial catheters has not been previously examined. Methods: Using a pericardial access device, a catheter connected to a drug-delivery system was implanted in five pigs. Plasma levels and electrocardiographic measurements were obtained after intravenous and intrapericardial administration of digoxin and procainamide. Histological examination was performed after the device had been implanted for a total of 6 months. Results: The QTc interval did not change significantly after digoxin or procainamide intravenous administration. QTc decreased by 47±23 ms ( p=0.046) 8 h after digoxin intrapericardial administration and increased by 128±60 ms ( p=0.002) 1 h after procainamide intrapericardial administration. The QRS duration did not change significantly after intravenous administration of either agent, but it increased by 17±9 ms ( p=0.004) 1 h and by 15±4 ms ( p=0.01) 8 h after procainamide intrapericardial administration. After intravenous procainamide the RR interval decreased, but it did not change significantly after intrapericardial administration of either agent. Histology showed moderate inflammatory infiltration and fibrosis adjacent to the catheter. Conclusions: Intrapericardial delivery of digitalis and procainamide produces unique electrophysiological properties. In contrast to satisfactory success of the implantation technique, long-term dwell of the catheter in the pericardium induces moderate, albeit probably clinically significant, fibrosis.

Autosomal Dominant Polycystic Kidney Disease Showing Rupture of a Lateral Ventral Hernia Following Paralytic Ileus

We report an 83-year-old Japanese male with autosomal dominant polycystic kidney disease (ADPKD), which was marked by unusually enlarged kidneys, and in whom ileus occurred after administration of procainamide. The bowels became swollen and ruptured the skin and appeared on the outside of the skin. Even after the ileus state was resolved, the projected intestinal tract was not restored due to a large defect of the skin, and ostomy was performed. Abdominal hernia including lateral ventral hernia due to enlarged kidneys may result in perforation of the abdominal wall as well as intestinal wall.

Usefulness of procainamide challenge for electrophysiologic arrhythmia risk stratification

Among 58 consecutive patients who underwent electrophysiologic testing for risk assessment and who subsequently received a third-generation implantable cardioverter-defibrillator, 39 had ventricular tachycardia induced in the baseline state and 19 had ventricular tachycardia induced only after administration of intravenous procainamide, increasing the yield of electrophysiologic risk assessment by 49%. At follow-up, ventricular arrhythmias requiring implantable cardioverter-defibrillator termination occurred in 14 of 39 patients inducible in the baseline state and in 7 of 19 patients inducible only with intravenous procainamide. The provocative use of intravenous procainamide during electrophysiologic risk assessment increases the detection rate for risk of sustained ventricular arrhythmias with no loss of positive predictive value.

N-acetyltransferase 2 genotyping: an accurate and feasible approach for simultaneous detection of the most common NAT2 alleles.

N -Acetyltransferase 2 (NAT2; EC 2.3.1.5) is involved in the detoxification of numerous xenobiotics. The human NAT2 gene is highly polymorphic and represents one of the best studied examples of the large interindividual variability of genetic control of drug or xenobiotic metabolism. In addition to the antituberculosis agent isoniazid (1), the first NAT2 substrate discovered, numerous other chemicals possessing a primary aromatic amine or hydrazine group, such as sulfamethazine, procainamide, hydralazine (2), dapsone, nitrazepam, and caffeine, are metabolized by this enzyme. Arylamine chemicals such as benzidine, β-naphthylamine, and 2-aminofluorene can also be acetylated by NAT2. As early as 1970, Reidenberg et al.(3) reported clinical problems associated with polymorphic acetylation of procainamide. The determination of NAT2 genotype or NAT2 phenotype has been proposed as a way to predict adverse reactions in patients with tuberculosis and before the concomitant administration of procainamide and phenytoin (4). The proportions of rapid and slow phenotypes vary in different ethnic groups. In Caucasians, 40–70% of individuals have the slow acetylator phenotype, whereas Asian populations have only 10–30% slow acetylators (5). Several single-nucleotide polymorphisms have been identified in the human NAT2 coding region, which are responsible for the observed phenotypes [see Ref. (6); accession no. X14672]. The presence of the NAT2 * 4 (wild-type) allele defines the NAT2 genotype as rapid, and combinations of the frequently occurring mutant alleles NAT2 * 5B , * 5C , * 6A , * 7B , and * 14 cluster as slow. Allele frequencies in Caucasians are 23% for NAT2 * 4 (wild type), 1.3% for * 5A , 35% for * 5B , 5.0% for * 5C , 30.5% for * 6A , 4.5% for * 7B , and 0.2% for …

Effects of class I antiarrhythmic drugs on the digitalis-induced triggered activity arrhythmia model: a rationale for the short-term use of class I drugs against triggered arrhythmias.

Delayed afterdepolarization (DAD)-induced triggered activity has been considered to be one of the generation mechanisms of ventricular arrhythmias in the presence of intracellular Ca2+ overload. In this study, we analyzed the antiarrhythmic effects of class I antiarrhythmic drugs, namely, disopyramide, procainamide, mexiletine, and flecainide, on a recently developed DAD-induced triggered arrhythmia model, which consists of a canine ventricular septum preparation cross-circulated with a blood-donor dog. After intravenous administration of ouabain to the donor dog, triggered arrhythmias were consistently induced in the cross-circulated preparation by train stimulation (cycle length: 300 ms; train number: 15). Intracoronary administration of disopyramide, procainamide, mexiletine, and flecainide as well as lidocaine suppressed the triggered arrhythmias at clinically relevant doses. Similar doses have been demonstrated to suppress intraventricular conduction in the same experimental model. These results suggest that the Na+ channel inhibition by class I drugs is an effective pharmacological intervention for suppressing Ca2+ overload, which may provide a rationale for the short-term use of class I drugs against the triggered arrhythmias in clinical practice.

Effect of losartan microinjections into the NTS on the cardiovascular components of chemically evoked reflexes in a rabbit model of acute heart ischemia.

In the acute phase of myocardial infarction (MI) there are modifications of the autonomic outflow with an increase in the sympathetic tone and changes in cardiovascular reflexes. Activation of angiotensin AT1 receptors in the nucleus tractus solitarii (NTS) inhibits the baroreceptor and enhances the carotid chemoreflex. In this study, we investigated the role of NTS-AT1 receptors on the cardiovascular reflex responses evoked on stimulation of carotid chemoreflex and cardiac chemosensitive fibres in the acute phase of MI. We also test the hypothesis that changes in cardiovascular responses to activation of carotid chemo and cardiac chemosensitive reflexes are secondary to changes in haemodynamic conditions due to infarction or to the activation of nociceptors of the heart. Rabbits were anaesthetised, paralysed and artificially ventilated. Carotid chemoreceptors and cardiac chemosensitive fibres were stimulated with lobeline and ATP, respectively. Arterial blood pressure, electrocardiogram and heart rate were monitored. A craniotomy was made to expose the caudal portions of the medulla and a multibarreled glass microelectrode was inserted in order to allow the identification of NTS and the microinjection of losartan (an angiotensin AT1 receptor antagonist). The heart was exposed by a midline thoracotomy and cardiac ischemia was produced by ligating the left descending coronary artery. The carotid chemoreflex and cardiac chemosensitive reflexes were evoked before and following the coronary ligation. The effect of losartan injection into the NTS on these reflexes was also assessed. In control experiments reflexes were assessed before and after the administration of capsaicin and procainamide. Results show that the activation of carotid chemoreflex elicited a greater increase of blood pressure and bradycardia after MI and that this was partially reversed by losartan microinjection after MI. Also the stimulation of cardiac chemosensitive fibres evoked a larger decrease on blood pressure and heart rate after MI and these were also partially reversed by losartan. The same enhancement of cardiovascular carotid chemo and cardiac chemosensitive receptors was observed after administration of capsaicin on the ventricular surface but not after procainamide. In conclusion, this study strongly suggests that, at NTS level, angiotensin AT1 receptors are involved in the modifications of autonomic outflow observed in the acute phase of MI.