Influence of variable chemical conditions on EDTA-enhanced transport of metal ions in mildly acidic groundwater.

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.

Effects of equiblocking doses of nadolol and propranolol on left ventricular performance.

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.

A simplified model for heterotopic rat heart transplantation.

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.

Safety and efficacy of extended urokinase infusion plus stent deployment for treatment of obstructed, older saphenous vein grafts.

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)

Amiodarone photosensitivity.

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.

Immediate effects of physostigmine on amitryptyline-induced QRS prolongation.

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.

Arrhythmia resulting from sensing malfunction in a P wave triggered pacemaker.

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.

An "autonomic" classification of antiarrhythmic drugs.

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.

Patient activated asynchronous ventricular pacing at normal rates for termination of ventricular tachycardia.

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.

Effects of apparently nontoxic doses of digoxin on ventricular ectopy after direct-current electrical shocks in dogs.

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.

Efficacy of Dexon microsutures in rat major abdominal vessel anastomosis. I: Application to heterotopic heart transplant.

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.

The cardiac pharmacology of tolbutamide.

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.

Theophylline toxicity and the beta-adrenergic system.

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.