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Vasovagal syncope (VVS) is the most common cause of syncope across all age groups. Nonetheless, despite its clinical importance and considerable research effort over many years, the pathophysiology of VVS remains incompletely understood. In this regard, numerous studies have been undertaken in an attempt to improve insight into the evolution of VVS episodes and many of these studies have examined neurohormonal changes that occur during the progression of VVS events primarily using the head-up tilt table testing model. In this regard, the most consistent finding is a marked increase in epinephrine (Epi) spillover into the circulation beginning at an early stage as VVS evolves. Reported alterations of circulating norepinephrine (NE), on the other hand, have been more variable. Plasma concentrations of other vasoactive agents have been reported to exhibit more variable changes during a VVS event, and for the most part change somewhat later, but in some instances the changes are quite marked. The neurohormones that have drawn the most attention include arginine vasopressin [AVP], adrenomedullin, to a lesser extent brain and atrial natriuretic peptides (BNP, ANP), opioids, endothelin-1 (ET-1) and serotonin. However, whether some or all of these diverse agents contribute directly to VVS pathophysiology or are principally a compensatory response to an evolving hemodynamic crisis is as yet uncertain. The goal of this communication is to summarize key reported neurohumoral findings in VVS, and endeavor to ascertain how they may contribute to observed hemodynamic alterations during VVS.

Head-up tilt (HUT) has long been used to examine heart rate and blood pressure adaptation to changes in position. During such studies, incidental observations noted that some test subjects experienced total or near-total transient loss of consciousness and that, in some cases, hypotension was associated with unexpected marked bradycardia compatible with a vasovagal syncope (VVS) reaction. The first report of HUT as a clinical tool to confirm a diagnosis of suspected VVS was published in 1966, and led to the concept of using HUT as a diagnostic tool for VVS. Subsequently, HUT testing, either drug-free or, if necessary, with pharmacological provocation (usually nitroglycerin) has proven to be a useful and safe modality for identifying susceptibility to VVS. In this regard, it is recognized that VVS is best diagnosed by careful history taking. Unfortunately, the history may be non-diagnostic; HUT may be helpful in such cases. However, the interpretation of HUT requires care and experience; in particular, the outcome must be consistent with the patient's clinical presentation. The reproduction of patient symptoms may not only provide a diagnosis, but also offer some comfort to the patient and family in that the medical team has documented the basis of symptoms and are thereby positioned to address therapy.

INTRODUCTION: Diagnostic ambulatory ECG (AECG) monitoring is widely used for evaluating syncope and collapse, and practice guidelines provide recommendations regarding optimal AECG device selection. However, whether physicians utilize AECGs in accordance with the pertinent guidelines is unclear. This study assessed utilization of AECG monitoring systems for syncope and collapse diagnosis by physicians in the United States. METHODS AND RESULTS: A quantitative survey was undertaken of physicians comprising multiple specialties (Emergency Room, n = 35; Primary care, n = 35; Hospitalists, n = 30; Neurologists, n = 30; non-implanting, n = 34 and implanting-Cardiologists, n = 35). Depending on specialty, respondents reported that neural-reflex and orthostatic causes accounted for 17-23%, cardiac causes for 12-20%, and 'neurological causes' (specifically psychogenic pseudo-syncope/pseudo-seizures and acute cerebrovascular conditions) for 7-12%, of their syncope/collapse cases. The choice of AECG technology varied by specialty. Thus, despite patients having daily symptoms, 25% of respondents chose an AECG technology other than a Holter-type monitor. Conversely, when monitoring for infrequent events (e.g., less than monthly), 12-18% indicated that they would choose a 24-48 hour Holter, 20-34% would choose either a conventional event recorder or a mobile cardiac telemetry system, and only 53-65% would select an insertable cardiac monitor . CONCLUSIONS: In evaluation of syncope/collapse, most U.S. clinicians across specialties use AECG's appropriately, but in a substantial minority there remains discordance between choice of AECG technology and guideline-based recommendations. This article is protected by copyright. All rights reserved.

Syncope is a clinical syndrome defined as a relatively brief self-limited transient loss of consciousness (TLOC) caused by a period of inadequate cerebral nutrient flow. Most often the trigger is an abrupt drop of systemic blood pressure. True syncope must be distinguished from other common non-syncope conditions in which real or apparent TLOC may occur such as seizures, concussions, or accidental falls. The causes of syncope are diverse, but in most instances, are relatively benign (e.g., reflex and orthostatic faints) with the main risks being accidents and/or injury. However, in some instances, syncope may be due to more worrisome conditions (particularly those associated with cardiac structural disease or channelopathies); in such circumstances, syncope may be an indicator of increased morbidity and mortality risk, including sudden cardiac death (SCD). Establishing an accurate basis for the etiology of syncope is crucial in order to initiate effective therapy. In this review, we focus primarily on the causes of syncope that are associated with increased SCD risk (i.e., sudden arrhythmic cardiac death), and the management of these patients. In addition, we discuss the limitations of our understanding of SCD in relation to syncope, and propose future studies that may ultimately address how to improve outcomes of syncope patients and reduce SCD risk. Keywords: Syncope, Sudden cardiac death, Risk assessment

In this correspondence, the pathophysiology of reflex syncope (vasovagal syncope, carotid sinus syndrome, and situational syncope) is reviewed, including clarification of the nomenclature.

Professional cardiology organizations have compiled guidelines for advising patients if and when they may drive a car or pilot an aircraft following a diagnosis of syncope. Legal jurisdictions have compiled laws governing driving and flying, but the laws range from being very specific to very broad. For driving, medical guidelines have largely adopted a mathematical model for risk stratification such that a private individual driving a passenger car should be allowed to drive if their annual risk of sudden incapacitation is less than 22% because they pose the same risk of harm to others as a commercial truck driver in North America who has been legally allowed to drive with medical conditions that carry no more than a 1% risk of sudden incapacitation. The aviation literature has adopted a “1% rule” such that commercial airline pilots should have no more than a 1% annual chance of sudden incapacitation. All pilots must be evaluated by a designated medical examiner with specific legal guidelines by which they cannot certify a pilot to fly without referral to their specific national aviation authority.

Syncope is one of a number of conditions that result in transient loss of consciousness (TLOC). Syncope is distinguished from other causes of TLOC in that syncope results from transient global cerebral hypoperfusion. In the majority of cases, global cerebral hypoperfusion is the result of a fall in mean arterial pressure (MAP) to such a degree that cerebral blood flow autoregulatory mechanisms fail. A fall in MAP leading to syncope can result from a variety of mechanisms, which are often classified into four broad categories: (1) reflex syncope, (2) orthostatic hypotension, (3) arrhythmia, and (4) structural etiologies. Of these, reflex syncope syndromes are the most common regardless of the patient population being studied. Within a given category, more than one pathophysiologic mechanism may be involved. Initial evaluation is focused on identification of the cause of syncope. The cause of a given patient’s syncope can often be determined with a careful history and physical examination. On occasion, ancillary testing may be needed. Determining the cause of syncope is critical in order to determine an individual patient’s risk of recurrence and risk of morbidity and mortality. The cause of syncope must be established to allow for an effective treatment strategy.

Swallow syncope is usually classified among the situational reflex syncope syndromes. Although by definition associated with swallowing, the precise trigger site(s) for swallow syncope is unclear. Herein we report two patients in whom swallow syncope occurred in conjunction with carotid sinus hypersensitivity (CSH). Patient 1 was a 63-year-old man whose swallow-induced symptoms comprised repetitive syncope and near-syncope while drinking water. Patient 2 was a 62-year-old man who, in addition to syncope, also experienced chest discomfort while drinking water. Ambulatory electrocardiograms (AECG) revealed symptomatic sinus pauses and paroxysmal AV block in Patients 1 and 2 respectively. During autonomic laboratory testing, each patient exhibited abnormal responses during both carotid sinus massage (CSM) and a cold liquid swallowing test. Patient 1 revealed a primarily cardioinhibitory (CI) response to swallowing and CSM, while Patient 2 exhibited principally a CI response to swallowing and a vasodepressor (VD) reaction during CSM. In conclusion, while CSH is common in older men and consequently its association with swallow syncope could thereby be a coincidence, the presence of both in the same patients raises the possibility that in some patients there may be concordance of trigger mechanisms within the pharynx and/or neck in these forms of reflex syncope. Further, the use of a swallowing test to distinguish the relative importance of CI and VD features in individual swallow syncope patients may be helpful for selecting an appropriate treatment strategy.

Background Syncope triggered by swallowing is a well-known but uncommon condition that has been the focus of case reports but is otherwise largely unstudied. To better understand swallow syncope we examined heart rate (HR) and blood pressure (BP) changes during swallowing in clinically suspected swallow syncope patients and asymptomatic control subjects. Methods The study population comprised four individuals with a history suggesting swallow syncope (three men, 53 ± 14.9 years) and 15 (nine men, 46 ± 17.1 years, P = NS vs patients) asymptomatic volunteer control subjects. Studies in all individuals comprised noninvasive beat-to-beat HR and BP measurement during swallowing 150 mL of cold liquid while standing. Additional tests in swallow syncope patients included: active standing, Valsalva maneuver, carotid sinus massage (CSM), and head-up tilt (HUT). Results Swallowing resulted in a greater decrease of both HR (-22 ± 22.1 vs -3 ± 11.7 beats/minute [bpm]; P = 0.045) and BP (-22 ± 17.4 vs - 2 ± 11.8; P = 0.036) in swallow syncope patients than in controls. Further, in swallow syncope patients the time to lowest HR and BP differed (9 ± 5.5 vs 19 ± 7.2 seconds; P = 0.02), suggesting that both cardioinhibitory (CI) and vasodepressor (VD) mechanisms are present but operate independently. Other autonomic studies were normal in swallow syncope patients except for CSM pause more than 3 seconds in two patients. Conclusion Swallow syncope is associated with transient and temporally independent CI and VD features, consistent with reflex syncope. Potentially, a swallowing test during autonomic evaluation may be useful to unmask relative magnitudes of CI and VD responses, thereby facilitating treatment strategy decisions.

Syncope is one of several disorders that cause transient loss of consciousness. Cerebral hypoperfusion is the proximate cause of syncope. Transient or fixed autonomic nervous system dysfunction is a major contributor in many causes. A structured approach to the evaluation of syncope allows for more effective therapy.

INTRODUCTION Syncope/collapse is a common reason for emergency department visits, and approximately 30-40% of these individuals are hospitalized. We examined changes in hospitalization rates, in-hospital mortality, and cost of syncope/collapse-related hospital care in the United States from 2004 to 2013. METHODS We used the US Nationwide Inpatient Sample (NIS) from 2004 to 2013 to identify syncope/collapse-related hospitalizations using ICD-9, code 780.2, as the principal discharge diagnosis. Data are presented as mean ± SEM. RESULTS From 2004 to 2013, there was a 42% reduction in hospitalizations with a principal discharge diagnosis of syncope/collapse from 54,259 (national estimate 253,591) in 2004 to 31,427 (national estimate 156,820) in 2013 (P

In this correspondence, the pathophysiology of reflex syncope (vasovagal syncope, carotid sinus syndrome, and situational syncope) is reviewed, including clarification of the nomenclature.

Syncope is a frequent cause for presentation to emergency departments and urgent-care clinics. The physician should establish a confident causal diagnosis, assess prognostic implications, and provide appropriate advice to prevent recurrences. An organized approach is needed to the assessment of the patient with syncope, including a careful initial examination as well as application of specialized syncope evaluation units and structured questionnaires for history taking. The initial patient evaluation, particularly a detailed medical history, is the key to identifying the most likely diagnosis. Based on these findings, subsequent diagnostic tests can be chosen to confirm the clinical suspicion.

The morbidity and mortality of patients with cardiomyopathy are related to either pump failure or arrhythmia-induced death or decompensation. Cardiomyopathy can also be induced by arrhythmias. Adequate and prompt therapy of arrhythmias is an essential part in the multidisciplinary approach to these patients. We review the arrhythmias seen in patients with multiple types of cardiomyopathy and the therapeutic options available. The implantable cardioverter defibrillator has become the main therapy for sudden cardiac death prevention. We also review the different oral antiarrhythmics available. Ablation therapy has become an effective means of curing or controlling arrhythmias. Finally, we discuss arrhythmias in specific cardiomyopathies and patient with left ventricular assist devices.

This chapter focuses on the potential risk of premature death, and in particular sudden cardiac death (SCD), in patients who present with collapse and are presumed to have had syncope. However, before a clinician can attempt to assess mortality risk relative to an episode of syncope, it is first essential to determine that collapse was in fact due to syncope (i.e., transient self-limited loss of consciousness due to cerebral hypoperfusion) and not of other cause (e.g., seizure, trauma, etc.). This chapter provides an approach to establishing the accurate diagnosis of syncope. While this step may seem to be self-evident, the hectic pace of modern medicine can result in the diagnosis not being considered with sufficient care. Finally, we discuss the assessment of the risks of recurrence, mortality and sudden cardiac arrest associated with syncope of various etiologies.

When patients present with palpitations, the primary care physician can perform the initial evaluation and treatment for premature ventricular contractions (PVCs). Many patients need only reassurance and do not need to see a cardiologist.

Whether the risk factors for cardiovascular (CV) outcomes are different in primary versus secondary prevention implantable cardioverter-defibrillator (ICD) patients is unclear. We sought to identify predictors of CV outcomes in ICD recipients for primary (G1) versus secondary prevention (G2). Consecutive patients who had ICD implanted during August 2005 to December 2009 were included. The primary outcome was a composite of appropriate shock, acute coronary syndrome, ischemic stroke, coronary revascularization, heart failure exacerbation, CV hospitalization, or all-cause death. We used Cox proportional hazards model and a stepwise selection method to fit the most parsimonious model to predict the primary outcome in all patients and separately for G1 and G2 patients. We followed 223 (184 G1 and 39 G2, mean age 61 years) patients through December 31, 2012; 141 (63.2%) developed the primary outcome. In all patients, atrial fibrillation (AF; hazard ratio 6.72, 95% CI 4.20 to 10.75; p0.001), use of antiarrhythmic drug (1.55, 1.02 to 2.36; p = 0.04), and lower estimated glomerular filtration rate (0.99, 0.98 to 0.997; p = 0.01) were associated with increased risk of the primary outcome; the attributable risks were 21.6%, 16.0%, and 15.9%, respectively. In G1, AF, hypertension, and lower estimated glomerular filtration rate were associated with increased risk, whereas in G2, AF, use of antiarrhythmic drug, and nonischemic cardiomyopathy were associated with increased risk. In conclusion, although risk factors are different for primary and secondary prevention patients, AF is a strong and consistent risk factor for adverse outcomes in both populations.

Although vasovagal syncope (VVS) is preceded by a surge of circulating catecholamines (epinephrine [Epi] and norepinephrine [NE]) of adrenal/renal and synaptic origin, prevention of VVS with β-adrenergic blockade has been ineffective except in "older" VVS patients.We hypothesized that age-related differences of β-blocker effect may be due in part to differences in the relative magnitudes of Epi and NE release during an evolving faint, specifically, greater Epi/NE ratio in younger fainters compared to older patients. To assess this hypothesis, we measured changes in Epi/NE ratios in younger (40 years) vs older (≥40 years) patients during head-up tilt-table test-induced VVS.The study comprised 29 patients (12 patients ≥40 years [mean 56 ± 10.7 years] and 17 patients40 years mean 25 ± 5.7 years]) with recurrent suspected VVS in whom 70° head-up tilt testing reproduced symptoms. Arterial Epi and NE concentrations were measured at baseline (supine), 2 minutes of head-up tilt, and syncope.Baseline Epi and NE concentrations and the Epi/NE ratio did not differ in younger and older groups (Epi: 90 ± 65 pg/mL vs 70 ± 32 pg/mL; NE: 226 ± 122 pg/mL vs 244 ± 183 pg/mL). However, Epi/NE ratio increased to a greater extent in younger fainters during head-up tilt and tended to be greater in younger patients at both 2 minutes (40: 1.02 ± 1.29 vs ≥40: 0.40 ± 0.27, P = .11) and at symptoms (40: 2.6 ± 1.26 vs ≥40: 1.6 ± 0.71, P = .03). At symptoms, Epi/NE ratio ≥2.5 was observed in 9 of 17 younger patients vs 1 of 12 older patients (P = .02).Epi/NE ratios tend to be greater in younger fainters, a finding that may account in part for the observation that β-blocker therapy is less effective in reducing VVS susceptibility in younger individuals.

Ablation outcomes in 22 consecutive long-standing persistent atrial fibrillation (LPAF) patients with failed direct current cardioversion (DCCV; group 1) were compared with findings in 22 consecutive LPAF patients who had successful DCCV (control 1) and 22 consecutive patients with paroxysmal atrial fibrillation (AF; control 2). All patients underwent a stepwise progressive ablation protocol (pulmonary vein isolation, ablation of complex fractionated atrial electrogram, and repeat ablation of any induced atrial tachycardias). Over 18-month follow-up, 59 % of group 1 patients remained in sinus rhythm without recurrent AF, compared to 64 % and 77 % in controls 1 and 2, respectively. The procedure time was longer in LPAF with a higher procedure complication risk in these 44 LPAF patients (5 % vs. 0 %) than in patients with paroxysmal AF. Our data suggest that catheter ablation provides a practical treatment option with moderate efficacy for restoring sinus rhythm in LPAF patients after failed DCCV.

Syncope is one of several disorders that cause transient loss of consciousness. Cerebral hypoperfusion is the proximate cause of syncope. Transient or fixed autonomic nervous system dysfunction is a major contributor in many causes. A structured approach to the evaluation of syncope allows for more effective therapy.

Background Implantable cardioverter-defibrillators (ICDs) can terminate some ventricular tachycardias (VTs) painlessly with antitachycardia pacing (ATP). ATP has not routinely been applied for VT >188 bpm because of concerns about efficacy, risk of acceleration, and delay of definitive shock therapy. This prospective, multicenter study evaluated the efficacy of empirical ATP to terminate fast VT (FVT; >188 bpm). Methods and Results Two hundred twenty coronary artery disease patients received ICDs for standard indications. Empirical, standardized therapy was programmed so that all FVT episodes (average cycle length [CL] 240 to 320 ms, 250 to 188 bpm) were treated with 2 ATP sequences (8-pulse burst pacing train at 88% of the FVT CL) before shock delivery. A total of 1100 episodes of spontaneous ventricular tachyarrhythmias occurred during a mean of 6.9±3.6 months of follow-up. Fifty-seven percent were classified as slow VT (CL≥320 ms), 40% as FVT (240 ms≤CL Conclusions FVT (CL

Atrial fibrillation is the most common cardiac arrhythmia requiring treatment. Limitations of medical treatment have prompted development of nonpharmacologic therapies for this arrhythmia. These are aimed at ventricular rate control during atrial fibrillation, termination of the arrhythmia, and/or prevention of recurrences. Ventricular rate control can be achieved with transcatheter ablation or modification of the atrioventricular node. The MAZE operation is effective in preventing arrhythmia recurrence, but because it requires cardiac surgery, its appeal is limited. Development of the technique for direct transcatheter ablation of atrial fibrillation is eagerly anticipated and may represent the standard curative treatment of the future. In appropriately selected patients, implantable device therapy may play an important role in the treatment of paroxysmal atrial fibrillation.

Although it is essential to cardiac conduction, little is known about the biochemistry underlying postreceptor adrenergic, cholinergic and purinergic processes in the AV node. To study these mechanisms, we adapted a new and highly sensitive fluorometric assay for cyclic adenosine monophosphate (AMP) to characterize regional adenylylcyclase activity (cyclic AMP production in pmol/min/mg of protein) in membrane preparations made from 20-50 pieces of freeze-dried, 20-microm thick, microdissected samples of tissue from canine right atrium, the AV nodal region, and left ventricle. Basal and NaF-stimulated adenylylcyclase activity (mean +/- SEM, n = 6) were 7.2 +/- 0.4 and 72.4 +/- 7.5 in atrial, 15.6 +/- 1.3 and 58.8 +/- 4.7 in AV nodal, and 6.4 +/- 0.9 and 66.7 +/- 5.0 in ventricular tissues, respectively. Isoproterenol (10(-7)-10(-4) M) increased adenylylcyclase activity in a dose-dependent fashion in three different regions. The isoproterenol (10(-6) M)-stimulated adenylylcyclase activity (n = 6) was 14.4 +/- 1.3 in atrial, 21.9 +/- 1.6 in AV nodal and 13.4 +/- 1.4 in ventricular tissues. Adenosine (10(-3) M) and carbachol (10(-5) M) inhibited isoproterenol (10(-6) M)-stimulated adenylylcyclase activity to 10.1 +/- 1.1, 12.9 +/- 1.3 in atrial, 15.1 +/- 1.6, 15.5 +/- 1.2 in AV nodal, and 7.5 +/- 0.7, 11.9 +/- 1.2 in ventricular tissues, respectively. The results demonstrate that there are regional differences in adenylylcyclase activity under basal conditions and after adrenergic, purinergic, and cholinergic stimulation in the heart. Unlike adenosine, the inhibitory effects of cholinergic stimulation appear to be more specific for the AV node.

The recent identification of the sequences of the peptides derived from a number of human melanoma-associated antigens has presented opportunities for developing a specific-peptide-based vaccine in this form of cancer. Since antigen-presenting cells (APC) play a crucial role in the induction of the T-cell-mediated immune response, we examined whether or not ex vivo cultured APC, bearing the appropriate MHC restricting elements, when pulsed with a relevant melanoma-specific cytotoxic-T-lymphocyte (CTL)-determined peptide, can present the peptide to the CTL. Here we show that a population of cells, derived from the monocyte/macrophage lineage from peripheral blood and grown in granulocyte/macrophage-colony-stimulating factor, exhibit many essential characteristics of "professional" APC (dendritic-type morphology with a proportion of the population, the B7 molecule, and high levels of MHC class I and class II molecules, CD11b and CD54 molecules) and are capable of efficiently presenting the nonapeptide, EADPTGHSY, encoded by the melanoma antigen MAGE-1 gene, to the MAGE-1-specific CTL clone, 82/30. These results suggest that this type of autologous ex vivo cultured population of professional APC, when pulsed with the relevant-CTL-determined peptide, can serve as a novel type of candidate vaccine for active specific immunization against HLA-A1-positive patients with melanoma expressing the MAGE-1 antigen.

Syncope is a frequent cause for presentation to emergency departments and urgent-care clinics. The physician should establish a confident causal diagnosis, assess prognostic implications, and provide appropriate advice to prevent recurrences. An organized approach is needed to the assessment of the patient with syncope, including a careful initial examination as well as application of specialized syncope evaluation units and structured questionnaires for history taking. The initial patient evaluation, particularly a detailed medical history, is the key to identifying the most likely diagnosis. Based on these findings, subsequent diagnostic tests can be chosen to confirm the clinical suspicion.

Background: Little is known about the frequency of, risk factors predisposing to, and long-term impact of post-operative atrial fibrillation (AF) after lung transplantation.

Background— Successful antitachycardia pacing (ATP) terminates ventricular tachycardia (VT) up to 250 bpm without the need for painful shocks in implantable cardioverter-defibrillator (ICD) patients. Fast VT (FVT) >200 bpm is often treated by shock because of safety concerns, however. This prospective, randomized, multicenter trial compares the safety and utility of empirical ATP with shocks for FVT in a broad ICD population. Methods and Results— We randomized 634 ICD patients to 2 arms—standardized empirical ATP (n=313) or shock (n=321)—for initial therapy of spontaneous FVT. ICDs were programmed to detect FVT when 18 of 24 intervals were 188 to 250 bpm and 0 of the last 8 intervals were >250 bpm. Initial FVT therapy was ATP (8 pulses, 88% of FVT cycle length) or shock at 10 J above the defibrillation threshold. Syncope and arrhythmic symptoms were collected through patient diaries and interviews. In 11±3 months of follow-up, 431 episodes of FVT occurred in 98 patients, representing 32% of ventricular tachyarrhythmias and 76% of those that would be detected as ventricular fibrillation and shocked with traditional ICD programming. ATP was effective in 229 of 284 episodes in the ATP arm (81%, 72% adjusted). Acceleration, episode duration, syncope, and sudden death were similar between arms. Quality of life, measured with the SF-36, improved in patients with FVT in both arms but more so in the ATP arm. Conclusions— Compared with shocks, empirical ATP for FVT is highly effective, is equally safe, and improves quality of life. ATP may be the preferred FVT therapy in most ICD patients.

As part of a new effort to develop an implantable drug infusion/pacing system to treat atrial fibrillation, this study examined the effects of rapid intracardiac procainamide infusion in humans with pacing-induced atrial fibrillation. Twenty patients with atrial fibrillation for > 5 minutes during an EP study received 500 mg of procainamide either via a peripheral venous infusion (n = 5) or directly in the right atrium (n = 15). Peak coronary sinus and femoral vein procainamide blood levels (mean +/- SEM) during 10, 5, and 3.3 minute central infusions were 17.0 +/- 4.1, 25.1 +/- 4.5, 45.6 +/- 5.1 and 11.3 +/- 3.2, 17.1 +/- 6.4, 18.7 +/- 5.0, respectively. In contrast, peak coronary sinus and femoral procainamide levels following the 5 minute intravenous infusion were 17.7 +/- 5.1 and 9.3 +/- 2.1. Changes in QT, QTc, QRS, and RI intervals were similar at each infusion rate. Systolic blood pressures (BP) decreased more with higher procainamide infusion rates but similar when comparing intravenous versus central drug administration at the same rate. The mean +/- SEM decreases in blood pressure with the 10, 5, and 3.3 min procainamide infusions were 12f5, 20f11, and 39f14, respectively. Conversion to sinus rhythm was not a primary endpoint given the often transient nature of acute atrial fibrillation in this setting. We conclude that significantly higher femoral vein and coronary sinus procainamide levels can be achieved by central rather than peripheral drug infusion. These data support that concept that rapid central infusion of anti-arrhythmic therapy can result in high intracardiac levels of antifibrillatory agents for the treatment of paroxysmal atrial fibrillation.

Although essential to cardiac conduction, little is known about the biochemistry underlying post-receptor adrenergic, cholinergic. and purinergic processes in the AV node. To study these mechanisms, we developed a highly sensitive fluorometric assay for cAMP and used it to characterize regional adenylyl cyclase activity (ACA) (pmollmin/mg of protein) in membrane preparations made from freeze-dried 20 micron thick micro-dissected pieces of canine (n = 6) right atrium (RA), AV nodal region (AVN), and left ventricle (LV). Adjacent sections were stained for acetylcholinesterase activity to identify the AVN. Basal and NaF-stimulated ACAs (mean ± SEM) were 7.2 ± 0.4 and 72.4 ± 7.5 in RA, 15.6 ± 1.3 and 58.8 ± 4.7 in AVN. and 6.4 ± 0.9 and 66.7 ± 5.0 in LV, respectively. Isoproterenol (10 –7 –10 –4 M) increased ACA in a dose-dependent fashion and the increment of cAMP production rate was similar in three different regions. Adenosine (10 –3 M) and carbachol (10 –5 M) inhibited isoproterenol (10 –6 M)-stimulated ACA as follows: Download high-res image (64KB) Download full-size image Results of this study demonstrate for the first time that (l) there are significant regional differences in ACA under basal conditions and after adrenergic, purinergic, and cholinergic stimulation in the heart. and (2) adenosine inhibits ACA in the RA, AVN and LV, whereas the inhibitory effects of cholinergic stimulation are more specific for the AVN.