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A mass balance is formulated to evaluate the mobilization of chlorinated ethene compounds (CE) from the rock matrix of a fractured mudstone aquifer under pre- and postbioremediation conditions. The analysis relies on a sparse number of monitoring locations and is constrained by a detailed description of the groundwater flow regime. Groundwater flow modeling developed under the site characterization identified groundwater fluxes to formulate the CE mass balance in the rock volume exposed to the injected remediation amendments. Differences in the CE fluxes into and out of the rock volume identify the total CE mobilized from diffusion, desorption, and nonaqueous phase liquid dissolution under pre- and postinjection conditions. The initial CE mass in the rock matrix prior to remediation is estimated using analyses of CE in rock core. The CE mass mobilized per year under preinjection conditions is small relative to the total CE mass in the rock, indicating that current pump-and-treat and natural attenuation conditions are likely to require hundreds of years to achieve groundwater concentrations that meet regulatory guidelines. The postinjection CE mobilization rate increased by approximately an order of magnitude over the 5 years of monitoring after the amendment injection. This rate is likely to decrease and additional remediation applications over several decades would still be needed to reduce CE mass in the rock matrix to levels where groundwater concentrations in fractures achieve regulatory standards., (© 2017, National Ground Water Association.)

Field characterization of a trichloroethene (TCE) source area in fractured mudstones produced a detailed understanding of the geology, contaminant distribution in fractures and the rock matrix, and hydraulic and transport properties. Groundwater flow and chemical transport modeling that synthesized the field characterization information proved critical for designing bioremediation of the source area. The planned bioremediation involved injecting emulsified vegetable oil and bacteria to enhance the naturally occurring biodegradation of TCE. The flow and transport modeling showed that injection will spread amendments widely over a zone of lower-permeability fractures, with long residence times expected because of small velocities after injection and sorption of emulsified vegetable oil onto solids. Amendments transported out of this zone will be diluted by groundwater flux from other areas, limiting bioremediation effectiveness downgradient. At nearby pumping wells, further dilution is expected to make bioremediation effects undetectable in the pumped water. The results emphasize that in fracture-dominated flow regimes, the extent of injected amendments cannot be conceptualized using simple homogeneous models of groundwater flow commonly adopted to design injections in unconsolidated porous media (e.g., radial diverging or dipole flow regimes). Instead, it is important to synthesize site characterization information using a groundwater flow model that includes discrete features representing high- and low-permeability fractures. This type of model accounts for the highly heterogeneous hydraulic conductivity and groundwater fluxes in fractured-rock aquifers, and facilitates designing injection strategies that target specific volumes of the aquifer and maximize the distribution of amendments over these volumes., (© 2017, National Ground Water Association.)

Background: Biventricular epicardial (Epi) pacing can augment left ventricular (LV) function in heart failure. We postulated that these effects might involve catecholamine release from local autonomic nerve activation. To evaluate this hypothesis we applied low intensity Epi electrical stimuli during the absolute refractory period (ARP), thus avoiding altered activation sequence., Methods: Anesthetized pigs (n = 6) were instrumented with an LV pressure (LVP) transducer, left atrial (LA) and LV Epi pacing electrodes, and sonomicrometer segment length (SL) gauges placed proximal and remote to the LV stimulation site. A catheter was placed into the great cardiac vein adjacent to the LV pacing site for norepinephrine (NE) analysis. During LA pacing at constant rate, 3 pulses (0.8 milliseconds, 2-3x threshold) were applied to the LV Epi electrodes during the ARP. An experimental run consisted of baseline, stimulation (10 minutes), and recovery (5 minutes), repeated 3 times before and after β1 - receptor blockade (BB, metoprolol)., Results: ARP stimulation produced significant increases in cardiac function reflected by elevated LVP, LV, dP/dtmax , and reduced time to LV dP/dtmax . This was accompanied by increased coronary NE levels and increases in LVP versus SL loop area in the remote myocardial segment. In contrast, the proximal segment exhibited early shortening and decreased loop area. BB abolished the changes in SL and LV function despite continued NE release., Conclusion: These results demonstrate that ARP EPI stimulation induces NE release mediating augmented global LV function. This effect may contribute to the beneficial effect of biventricular Epi pacing in heart failure in some patients., (© 2016 Wiley Periodicals, Inc.)

Production of elemental mercury, Hg(0), via Hg(II) reduction is an important pathway that should be considered when studying Hg fate in environment. We conducted a kinetic study of abiotic homogeneous and surface-catalyzed Hg(0) production by Fe(II) under dark anoxic conditions. Hg(0) production rate, from initial 50 pM Hg(II) concentration, increased with increasing pH (5.5-8.1) and aqueous Fe(II) concentration (0.1-1 mM). The homogeneous rate was best described by the expression, r(hom) = k(hom) [FeOH(+)] [Hg(OH)2]; k(hom) = 7.19 × 10(+3) L (mol min)(-1). Compared to the homogeneous case, goethite (α-FeOOH) and hematite (α-Fe2O3) increased and γ-alumina (γ-Al2O3) decreased the Hg(0) production rate. Heterogeneous Hg(0) production rates were well described by a model incorporating equilibrium Fe(II) adsorption, rate-limited Hg(II) reduction by dissolved and adsorbed Fe(II), and rate-limited Hg(II) adsorption. Equilibrium Fe(II) adsorption was described using a surface complexation model calibrated with previously published experimental data. The Hg(0) production rate was well described by the expression r(het) = k(het) [>SOFe((II))] [Hg(OH)2], where >SOFe((II)) is the total adsorbed Fe(II) concentration; k(het) values were 5.36 × 10(+3), 4.69 × 10(+3), and 1.08 × 10(+2) L (mol min)(-1) for hematite, goethite, and γ-alumina, respectively. Hg(0) production coupled to reduction by Fe(II) may be an important process to consider in ecosystem Hg studies.

Background: There have been no studies of atrial diastolic function after catheter ablation of atrial fibrillation (AF). We encountered a few patients with symptomatic left atrial (LA) diastolic dysfunction and associated pulmonary hypertension (PH) that developed after catheter ablation for atrial fibrillation. Similar findings were described in patients after cardiac surgery and were referred to as the "stiff left atrial syndrome.", Objective: The purpose of this study was to prospectively quantify the incidence of patients developing PH associated with diastolic hemodynamic abnormalities of the LA after radiofrequency ablation of AF and to identify the possible predictors., Methods: Between January 2009 and July 2010, data on 1,380 consecutive patients were prospectively collected. Before ablation and at follow-up, all patients had an echocardiogram to assess for the presence of PH. Patients with no echocardiographic evidence of PH but complaining of unexplained dyspnea with LA diastolic abnormalities were evaluated with right heart catheterization (RHC). Patients were included in the analysis if they developed new or worsening PH postablation with evidence of LA diastolic dysfunction by RHC or direct LA pressure measurement. All patients were evaluated for pulmonary vein stenosis and excluded if this condition was identified., Results: The mean age was 62 ± 11 (75% male), and nonparoxysmal AF was the predominant arrhythmia (71%). New or worsening PH with associated LA diastolic abnormalities was detected in 19 (1.4%) patients after ablation. The prevalence of PH did not differ between AF types (P = .612). Compared with patients who did not develop PH, LA scarring (P <.001), diabetes (P = .026), and obstructive sleep apnea (OSA; P = .006) were more frequently observed among those who developed PH. In a multivariable logistic model, preprocedure LA size ≤45 mm (odds ratio [OR] = 6.13; P = .033), mean LA pressure (OR 1.14; P = .025), severe LA scarring (OR = 4.4; P = .046), diabetes mellitus (OR = 9.5; P = .004), and OSA (OR = 6.2; P = .009) were independently associated with the development of PH postablation., Conclusions: After radiofrequency catheter ablation of atrial fibrillation (RFCAF), PH with LA diastolic dysfunction or the so-called stiff LA syndrome is a rare but potentially significant complication of AF ablation. Severe LA scarring, LA ≤45 mm, diabetes mellitus, OSA, and high LA pressure are clinical variables that predict the development of this syndrome. The main clinical findings include dyspnea, congestive heart failure, PH, and large V waves on pulmonary capillary wedge pressure (PCWP) or LA pressure tracings in the absence of mitral regurgitation., (Copyright © 2011 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Thin patients with thoracic pacemakers and automatic implantable cardioverter-defibrillators often have minimal tissue over the devices, with erosion through the surface a major concern. This erosion can lead to device infection and need for removal, or primary device infection can, in turn, lead to erosion. Even worse is exposure and infection of the leads to the heart, with fatalities having occurred. Pressure symptoms, as with shoulder seatbelt straps, can occur, and the visible deformity may be objectionable., Methods: To correct these problems without device removal, we used a novel surgical approach. Thirteen patients had 15 grafts, of either the acellular dermal graft AlloDerm (LifeCell Corp, Branchburg, NJ [n = 13 for threatened exposure or pressure symptoms, including two repeats]) or autogenous dermis (n = 2 for existing open wounds with chronic drainage) placed over the devices., Results: After all graft procedures, there was no skin breakdown; exposure and extrusion were completely prevented. Follow-up was 3 to 68 months (mean 36.8). The 2 open wound patients treated with dermis autografts had no recurrence of wound breakdown. Most patients with pressure symptoms had reduction in tenderness and pain. Patients liked the visible softening of the device contour, but not the subtly increased forward projection. The only immediate complication was one rapidly expanding hematoma leading to graft removal. One late complication was a mild infection, treated successfully., Conclusions: Acellular human dermal allografts, or live dermis autografts, provided significant protection over cardiac pacing devices in 13 patients with 15 grafts, with no subsequent surface exposures or extrusions., (Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Adsorption of Ni and Pb on aquifer sediments from Cape Cod, Massachusetts, USA increased with increasing pH and metal-ion concentration. Adsorption could be described quantitatively using a semi-mechanistic surface complexation model (SCM), in which adsorption is described using chemical reactions between metal ions and adsorption sites. Equilibrium reactive transport simulations incorporating the SCMs, formation of metal-ion-EDTA complexes, and either Fe(III)-oxyhydroxide solubility or Zn desorption from sediments identified important factors responsible for trends observed during transport experiments conducted with EDTA complexes of Ni, Zn, and Pb in the Cape Cod aquifer. Dissociation of Pb-EDTA by Fe(III) is more favorable than Ni-EDTA because of differences in Ni- and Pb-adsorption to the sediments. Dissociation of Ni-EDTA becomes more favorable with decreasing Ni-EDTA concentration and decreasing pH. In contrast to Ni, Pb-EDTA can be dissociated by Zn desorbed from the aquifer sediments. Variability in adsorbed Zn concentrations has a large impact on Pb-EDTA dissociation.

Consumption of aquifer Fe(III) during biodegradation of ground water contaminants may result in expansion of a contaminant plume, changing the outlook for monitored natural attenuation. Data from two research sites contaminated with petroleum hydrocarbons show that toluene and xylenes degrade under methanogenic conditions, but the benzene and ethylbenzene plumes grow as aquifer Fe(III) supplies are depleted. By considering a one-dimensional reaction front in a constant unidirectional flow field, it is possible to derive a simple expression for the growth rate of a benzene plume. The method balances the mass flux of benzene with the Fe(III) content of the aquifer, assuming that the biodegradation reaction is instantaneous. The resulting expression shows that the benzene front migration is retarded relative to the ground water velocity by a factor that depends on the concentrations of hydrocarbon and bioavailable Fe(III). The method provides good agreement with benzene plumes at a crude oil study site in Minnesota and a gasoline site in South Carolina. Compared to the South Carolina site, the Minnesota site has 25% higher benzene flux but eight times the Fe(III), leading to about one-sixth the expansion rate. Although it was developed for benzene, toluene, ethylbenzene, and xylenes, the growth-rate estimation method may have applications to contaminant plumes from other persistent contaminant sources.

Assessing the quantity of U(VI) that participates in sorption/desorption processes in a contaminated aquifer is an important task when investigating U migration behavior. U-contaminated aquifer sediments were obtained from 16 different locations at a former U mill tailings site at Naturita, CO (U.S.A.) and were extracted with an artificial groundwater, a high pH sodium bicarbonate solution, hydroxylamine hydrochloride solution, and concentrated nitric acid. With an isotopic exchange method, both a KD value for the specific experimental conditions as well as the total exchangeable mass of U(VI) was determined. Except for one sample, KD values determined by isotopic exchange with U-contaminated sediments that were in equilibrium with atmospheric CO2 agreed within a factor of 2 with KD values predicted from a nonelectrostatic surface complexation model (NEM) developed from U(VI) adsorption experiments with uncontaminated sediments. The labile fraction of U(VI) and U extracted by the bicarbonate solution were highly correlated (r2 = 0.997), with a slope of 0.96 +/- 0.01. The proximity of the slope to one suggests that both methods likely access the same reservoir of U(VI) associated with the sediments. The results indicate that the bicarbonate extraction method is useful for estimating the mass of labile U(VI) in sediments that do not contain U(IV). In-situ KD values calculated from the measured labile U(VI) and the dissolved U(VI) in the Naturita alluvial aquifer agreed within a factor of 3 with in-situ KD values predicted with the NEM and groundwater chemistry at each well.

This study was designed to determine the safety and efficacy of extended, continuous infusion of urokinase plus stent deployment to treat older saphenous vein bypass grafts obstructed by both thrombus and atheromatous material. Thirty patients with angiographic evidence of thrombus and atheromatous material obstructing older vein grafts (mean age 8.3 years) underwent the combined interventions of urokinase infusion and stent deployment. The continuous infusion of urokinase was administered directly into each obstructed vein graft over a mean of 20.5 +/- 8.1 hours (median dose 2.2 +/- 0.7 million units). Stents were deployed at the sites of atheromatous obstruction either before (5 patients) or after (25 patients) infusion of urokinase. Twenty-eight of the 30 patients were successfully treated with the combined interventions (success rate 93.3%). In these 28 patients, percent diameter stenosis at the site of obstruction decreased from 86.0% to -0.2% and Thrombolysis in Myocardial Infarction trial flow increased from 1.0 to 2.5. Two patients (6.7%) developed stent thrombosis followed by myocardial infarction (1 with Q-wave infarction, 3.3%) and congestive heart failure. Minor complications included non-Q-wave myocardial infarction (5 patients, 16.7%) and access-site hemorrhage (5 patients, 16.7%). At 2-week follow-up, anginal symptoms were decreased in all 28 successfully treated patients. At 7.2 +/- 3.7-month follow-up, 5 of the 28 successfully treated patients (17.9%) had reacceleration of angina and angiographically documented restenosis at the site of stent deployment.(ABSTRACT TRUNCATED AT 250 WORDS)

Recent clinical studies have suggested an association of tolbutamide therapy with an increased incidence of cardiovascular deaths. Due to the paucity of information concerning the acute cardiac actions of tolbutamide, the effects of this agent upon cardiac contractility and automaticity were examined under in vivo and in vitro conditions in rabbit, cat and dog heart muscle preparations. Tolbutamide (10(-6) to 3 x 10(-3) M) produced a biphasic inotropic response with a peak positive inotropic response at 3 X 10(-3) M which was 13.7 +/- 5.1% of the maximal obtainable increase in tension. Similar studies in cat papillary muscle resulted in a response that averaged 19% of the maximal increase in contractile force. In contrast, canine papillary muscles as well as the intact canine heart failed to develop a positive inotropic response to tolbutamide. Responses of rabbit atrial strips to isoproterenol were not potentiated by previous exposure to tolbutamide. Exposure of rabbit atria to theophylline, 2.5 X 10(-4) M, did not potentiate the inotropic effects of tolbutamide. Stidies in spontaneously beating rabbit right atria and cat papillary muscle-Purkinje fiber preparations demonstrated that tolbutamide does not have the potential to augment automaticity in these tissues. In intact dog heart, the intracoronary administration of tolbutamide did not lead to disturbances in cardiac rhythm, providing additional evidence that tolbutamide does not increase ventricular automaticity. It is concluded that tolbutamide possess a species-specific positive inotropic effect in rabbit and cat but not in the dog. The inotropic effect is small when compared to the maximum inotropic response and is observed only in vitro. Tolbutamide lacks the ability to enhance cardiac pacemaker activity. These data do not support the conclusions of previous investigatirs concerning the possible deleterious cardiac effects of tolbutamide.

Nadolol, a recently developed noncardioselective beta-adrenergic blocker, has the potential advantages of a longer oral half-life (t 1/2) than propranolol and, in animal studies, markedly fewer direct myocardial depressant effects. Neither the relative intravenous potency of nadolol and propranolol nor the comparative effects of the 2 drugs on left ventricular performance has been studied in man. We compared equiblocking intravenous doses of nadolol and propranolol in 10 subjects with ischemic wall-motion disorders. Nadolol was on the average 6.2 times as potent on a milligram-for-milligram basis. Both drugs decreased resting heart rate (p less than 0.02) and produced small rises in both mean pulmonary artery (p less than 0.03) and mean pulmonary artery wedge (p less than 0.03) pressures without significantly reducing the cardiac output. Both drugs also produced depression of the radionuclide ejection fraction (p less than 0.002). There were no significant differences between the effects of the 2 drugs on any of the aforementioned variables. Thus, the effects of nadolol on left ventricular performances are similar to those of propranolol. Because of its long oral t 1/2, nadolol may prove to be a clinically useful drug.

P wave triggered pacemakers can produce complicated arrhythmias during normal function. A ventricular, R wave inhibited pacemaker and an atrial sensing pacemaker were both present and functioning normally in the patient reported here. A premature paced beat was observed every 12th beat which resulted from discharge of the atrial sensing pacemaker. This arrhythmia appeared because a "P" wave occurred during the noise sampling period of the atrial sensing pacemaker, disabling the demand function and resulting in generator discharge on or near the T wave of a preceding unsensed beat while the pacemaker was in the asynchronous mode.

A total of 52 syngeneic heterotopic heart transplants were performed using 9-0 Dexon microsutures to see if these anastomoses could be tolerable when challenged by the burden of transplanted heart and lung. Eighteen long-term surviving transplants were verified by reliable ECG, Doppler tracings, and direct palpation of the heart grafts. Animals sacrificed at monthly intervals beginning 3 to 6 months posttransplantation were free of thrombus, lung abscesses, and separation at the anastomoses. Even though foreign body reaction was still present up to 5 months posttransplantation, no actual sutures were present after 3 months. From these observations, Dexon microsuture is acceptable in organ transplantation procedures.

After ingestion of 12 g of theophylline caused severe toxicity in a young woman, we developed an experimental canine model to study human theophylline toxicity. Our study involved four anesthetized dogs given theophylline in a continuous intravenous drip for 180 minutes in one of four protocols. The protocols included a low-dose infusion (400 mg/h), a high-dose infusion (1000 mg/h), a high-dose infusion with beta-blockade induced by propranolol at 125 minutes after infusion, and a high-dose infusion while maintaining beta-blockade with propranolol throughout the experiment. Toxic levels of theophylline were associated with hypokalemia, hypophosphatemia, hyperglycemia, metabolic acidosis, and hypotension in both the patient and the experimental series. These effects were either prevented or partially reversed after induction of beta-blockade with propranolol. Very high levels of theophylline were associated with elevated levels of norepinephrine and epinephrine in the animals.

Prior studies have suggested that physostigmine may be useful in reversing QRS prolongation due to amitriptyline toxicity. To investigate this question, we devised a pharmacologic model in rabbits utilizing an initial intravenous bolus of amitriptyline (4-6 mg) followed by a constant amitriptyline infusion (0.2-0.4 mg/min) empirically titered to maintain the QRS at 50% or more of control value for at least 5 min. Intravenous physostigmine (2 mg) sufficient to produce muscle fasciculations and significant (P less than 0.01) slowing of sinus rate was then administered to six animals. No significant change in QRS duration was noted at 1, 3, and 5 min intervals following physostigmine. Although no immediate antidotal effect of physostigmine on amitriptyline-induced QRS prolongation could be demonstrated, these results do not exclude a possible interaction between the membrane effects of the tricyclic antidepressants (and related agents) and the vagal branch of the autonomic nervous system.

To determine whether nontoxic doses of digoxin increase the risk of serious ventricular arrhythmias after d.c. cardioversion, studies were made of the effects of different doses of digoxin on the incidence and severity of ventricular arrhythmias after graded, external d.c. shocks in 14 closed-chest dogs. Electrocardiograms were recorded continuously for 20 min before and 10 min immediately after sequential QRS-synchronized shocks of 10, 100 and 150 joules. Ventricular premature beats were counted and their severity was graded. Digoxin (0.01--0.05 mg/kg) was then given i.v. to 12 dogs. Despite a wide range of serum digoxin concentrations (1.3--12.5 ng/ml), electrocardiographic signs of digitalis toxicity did not develop in any of these animals. The same sequence of d.c. shocks was repeated after 2 hr in nine dogs and after more than 24 hr in three dogs. Neither the total number of ventricular ectopic beats nor the arrhythmia grade postshock differed significantly before and after digoxin. Furthermore, more dogs developed ventricular ectopy at each energy level after control shocks than following shocks after digoxin administration. Two additional dogs were given repeated digoxin doses until electrocardiographic evidence of digitalis toxicity was apparent. Both developed sustained ventricular tachycardia after electrical shocks at all energy levels. Whereas overt digitalis toxicity predisposes to serious ventricular arrhythmias after d.c. shocks, we conclude that the risk of postshock ventricular ectopy is not increased by pretreatment with apparently nontoxic digoxin doses.

Ventricular pacing has been used to prevent or convert ventricular tachycardia. We report the use of patient-activated asynchronous mode ventricular pacing at normal rates for conversion of ventricular tachycardia by competitive pacing impulses. Following electrophysiologic studies, a specially constructed pacemaker was inserted. Routine function mode resulted in no output but activation of the reed switch resulted in V00 (asynchronous) pacing at 80/min. Patient-initiated conversion of ventricular tachycardia was documented by ambulatory electrocardiographic monitoring. The patient reports an average of two episodes per month converted over a four year period.

Amiodarone hydrochloride is currently being investigated in the United States as a cardiac antiarrhythmic agent. Previous reports from Europe indicate that amiodarone occasionally causes a cutaneous photosensitivity reaction that may be associated with a peculiar blue-gray discoloration of the skin. In addition, corneal microdeposits of yellow-brown granules may occur. We report observations on a case of amiodarone photosensitivity and corneal deposits developing in a patient shortly after amiodarone therapy was begun. Symptoms included burning and stinging of the skin, with redness and swelling that developed immediately after sun exposure. Phototesting showed that the photoactivating wavelengths were primarily in the long-wave UV-A spectrum between 350 and 380 nm. Prior application of a 10% dioxybenzone sunscreen greatly reduced the phototest reaction. Four weeks after the patient stopped taking amiodarone, the UV-A sensitivity was still present but diminished, and by ten weeks it had disappeared. During this time, the corneal deposits were reduced in number. All ten patients we have treated so far with amiodarone for cardiac arrhythmias have shown a similar photosensitivity, indicating that this is probably a phototoxic reaction.

A technique for simplified heterotopic rat heart transplantation having only aorto-aortic anastomosis is presented. The heterotopic rt heart survives and functions well when one lung lobe is attached t the transplantation and functions as a reservoir. Iso- and allotransplants are compared by electrocardiogram (ECG) determination and histological examination. Isotransplants exhibited normal heart and lung throughout the 6-month observation period. allotransplants ceased to function by the 16th postoperative day, with the cessation of palpable heart beat over the abdominal wall by the 10th postoperative day. This simplified heterotopic rat heart transplantation model can be operated by nonsurgeons in an unhurried manner with minimal training in microvascular surgery, and can be applied to various transplantation immunological studies.

An alternative classification schema for antiarrhythmic drugs is proposed based primarily on the autonomic "side effects" of these drugs in addition to their electrophysiologic actions. In this new schema, Class I (local anesthetics) is subdivided into 1A (quinidine-like agents with cholinergic blocking actions) and 1B (agents such as lidocaine without autonomic activity). Class II comprises the digitalis glycosides which have vagotonic effects. Class III contains drugs with antiadrenergic activity, subdivided into IIIA (beta-blockers such as propranolol), IIIB (norepinephrine-release inhibitors such as bretylium) and IIIC (non-specific adrenergic blockers such as amiodarone). Class IV includes the calcium channel blockers. Thus, with the exception of Classes IB and IV, all antiarrhythmics possess important autonomic properties. A possible link between autonomic and electrophysiologic effects is suggested by this schema. Classical pharmacologic theory separates the anticholinergic and membrane-active effects of quinidine-like (1A) drugs. An alternative theory is that the anticholinergic effects of 1A agents are germane to the antiarrhythmic actions of drugs in this class. A unifying hypothesis is that the acetylcholine receptor or a site with similar structure may participate directly in the binding of 1A drugs to the ventricular conduction system. This hypothesis is supported by: 1) the anti-muscarinic effects of all Class 1A agents; 2) previous data showing binding of these agents to atrial cholinergic receptors; 3) prominent His-Purkinje cholinergic innervation; 4) striking structural similarity between cocaine, the prototypical membrane anesthetic, and atropine; and 5) quinidine-like effects of tricyclic antidepressants and phenothiazines which have cholinergic properties. Additional ramifications of this autonomic classification are discussed.