Evaluation of environmental impacts for future influent scenarios using a model-based approach.

Changes in dilution of wastewater to a treatment plant due to infiltration or surface runoff can have a great impact on treatment process performance. This paper presents a model-based approach in which realistic influent scenarios are generated and used as inputs to a dynamic plant-wide process model of the wastewater treatment plant. The simulated operation is subsequently evaluated using life-cycle assessment (LCA) to quantify the environmental impacts of the future influent scenarios. The results show that increased infiltration led to higher environmental impact per kg nitrogen removed. The increase in surface runoff had a minor impact.

The effect of hydraulic retention time in onsite wastewater treatment and removal of pharmaceuticals, hormones and phenolic utility substances.

Micropollutants such as pharmaceuticals, hormones and phenolic utility chemicals in sewage water are considered to be an emerging problem because of increased use and observed adverse effects in the environment. The study provides knowledge on the removal efficiency of micropollutants with a range of physical and chemical properties in three commercially available onsite wastewater treatment facilities (OWTFs), tested on influent wastewater collected from 2500 person equivalents in Bildchen, Germany. A longer hydraulic retention time would in theory be expected to have a positive effect, and this study presents results for three different OWTFs in full-scale comparable tests under natural conditions. A range of 24 different pharmaceuticals, five phenols and three hormones were analyzed. Flow-proportional consecutive sampling was performed in order to determine the removal efficiency. Twenty-eight substances were detected in the effluent wastewater out of 32 substances included. Average effluent concentrations of Simvastatin, Estrone, Estradiol and Ethinylestradiol were above the indicative critical-effect concentration of pharmacological effect on fish in all facilities. Average effluent concentrations of both Diclofenac and Estradiol were higher than the Environmental Quality Standards applied in Sweden (190-240 times and 9-35 times respectively). The removal efficiency of micropollutants was high for substances with high logKow, which enhance the adsorption and removal with sludge. Low removal was observed for substances with low logKow and acidic characteristics, and for substances with stabilizing elements of the chemical structure. Facilities that use activated sludge processes removed hormones more efficiently than facilities using trickling filter treatment technique. Moreover, longer hydraulic retention time increased the removal of pharmaceuticals, hormones, turbidity and total nitrogen. Removal of Caffeine, Ibuprofen, Estrone, Naproxen and Estradiol, was strongly correlated to the sludge and particles removal. Thus, the efficiency of the tested OWTFs could be improved by adjusting the technical methods and increasing the hydraulic retention time.

Permanent jejunal fistula: promising method for obtaining small intestinal chyme without disturbing intestinal function.

Accurate information on changes in small intestinal microflora in dogs is rather limited because of difficulties in obtaining samples of small intestinal chyme. In the study reported here, intussuscepted nipple valves were surgically placed into the jejunum of seven laboratory beagles to obtain intestinal juice samples. The influence of the fistula on intestinal motility was determined by use of barium-impregnated polyethylene spheres (BIPS) and on microflora by use of bacterial culturing. The BIPS were fed two weeks before surgery and again five weeks after surgery. Bacterial samples were collected before (fecal samples), during (small intestinal samples) and 11 weeks after surgery. There were no surgical complications, and the animals tolerated the fistula well. Mean orocolic transit percentage was 93% before and 83% after surgery, and notable changes in gastrointestinal motility were not seen, except in one dog. The surgery did not markedly alter the bacterial flora in feces. Microflora did change in small intestinal samples; however, methodologic factors may explain most of these differences. In conclusion, the nipple valve is a promising method that creates easy and safe long-term access to the jejunum and appears not to have an influence on intestinal function.

Method for long-term cerebrospinal fluid collection in the conscious dog.

In medical research there is often a need for cerebrospinal fluid (CSF) collection from conscious animals. A number of models have been published, but long-term use is often limited by factors such as damage to implant or loss of patency. When part of an implant is exteriorized, group housing is often not possible; even when singly housed, the instrumented animals might have to be fitted with protective devices such as collars, vests, or helmets. Over the last 10 years we have, through the use of this technique, managed to perform repeated CSF collections in 12 beagles. Time of implant duration has ranged from 2.3 to 6.8 years. The method uses two permanent stainless steel guide cannulas screwed into the parietal bone, positioned above but not penetrating the lateral ventricles of the brain. At the time of collection, one of the subcutaneous stainless steel cannulas is used to serve as a guide for a 20-gauge collection needle. The collection is performed under local analgesia and with minimal discomfort to the dog. With its long-term use, we feel that this model is very useful and of high ethical and welfare standards due to the virtual lack of postoperative complications, maintenance requirements, and housing restrictions.

Method for long-term intestinal access in the dog.

A variety of devices have been used to establish long-term intestinal access in laboratory animals. Their use is complicated by infection, tissue reaction, and a frequent need for single housing to prevent implant damage. Intussuscepted nipple valves have long been used in the human field of surgery for various applications where there is a need to create a reservoir without leakage. With the use of the nipple valve it was possible to establish long-term intestinal access in dogs with minimal post-operative complications, no leakage and, because no foreign material was used, no complications due to tissue rejection. The advantages of a nipple valve over the similar technique of a straight stoma is less postoperative complications in the form of leakage as well as enhanced access due to the design of the nipple valve. Encouraging results prompted us to widen the use of nipple valves to 14 dogs in which it has been possible to establish long-term colonic or duodenal/ileal access at one or two sites. Nine of the dogs are still in use with duration of instrumentation for some animals exceeding 60 weeks. This method requires minimal maintenance, does not prevent group housing of instrumented dogs or outdoor activities nor does it compromise the quality of life for the animals.

Antiarrhythmic activity of amiloride: mechanisms.

We have previously shown that amiloride suppresses the induction of sustained ventricular tachycardia both in dogs late following myocardial infarction and in patients. In those studies the only electrophysiologic correlate of amiloride's antiarrhythmic activity observed was prolongation of ventricular effective refractory period at the zone bordering the infarct. The purpose of this study was to assess the pharmacologic effects of amiloride associated with antiarrhythmic efficacy. However, amiloride has multiple pharmacologic effects, including inhibition of the slow inward calcium current (ICa), inhibition of the sodium-calcium and sodium-hydronium ion exchangers, acidification of intracellular pH resulting in partial inhibition of the inwardly rectifying potassium current (IK1), and increase in serum potassium and magnesium. The approach used in this study was to use selective pharmacologic probes to produce the known components of amiloride's pharmacologic effects. The selective agents consisted of verapamil (partial blockade of ICa), 3',4'-dichlorobenzamil (partial inhibition of the Na-Ca exchanger), 5-(N-ethyl-N-isopropyl) amiloride (partial inhibition of the Na-H exchanger), the combination of these congeners, KCl infusions to increase serum potassium, MgSO4 infusions to increase serum magnesium, the combination of KCl and MgSO4 infusions, barium (partial block of IK1), ryanodine (partial blockade of sarcoplasmic reticulum calcium release), and placebo. In this study only barium produced antiarrhythmic and electrophysiologic effects similar to those of amiloride. However, amiloride prolongs border zone refractoriness selectively, whereas barium prolongs refractoriness diffusely throughout the myocardium. Blockade of ICa by verapamil, increases in serum magnesium and potassium alone or in combination, and partial blockade of sarcoplasmic reticulum by ryanodine were not antiarrhythmic in this model. Monotherapies that produced partial blockade of the Na-Ca and Na-H exchangers separately did not produce antiarrhythmic activity. However, the combination of these amiloride congeners reproduced the antiarrhythmic activity of amiloride but did not prolong border zone refractoriness. From these studies we conclude that the antiarrhythmic activity of amiloride relates to (a) selective blockade of IK1 in the border zone and/or (b) combined inhibition of sodium-calcium and sodium-hydronium ion exchangers.

Role of quinidine in the mexiletine-quinidine interaction: electrophysiologic correlates of enhanced antiarrhythmic efficacy.

Quinidine has multiple electrophysiologic effects, including prolongation of ventricular conduction time, repolarization, and refractoriness. The purpose of this study was to address the relative contributions of these electrophysiologic effects to the enhanced anti-arrhythmic activity observed when quinidine is combined with mexiletine. We compared antiarrhythmic and electrophysiologic effects observed when quinidine or its stereoisomer quinine were combined with mexiletine. Quinine and quinidine both prolong conduction time; however, these agents have divergent effects on ventricular repolarization time and refractoriness. The modest prolongation of conduction time observed with quinine and mexiletine-quinine in the absence of change of ventricular refractoriness was not associated with antiarrhythmic efficacy. The antiarrhythmic efficacy of mexiletine-quinidine exceeds that of mexiletine-quinine, suggesting that the ability of quinidine to prolong refractoriness and repolarization contributes to the antiarrhythmic efficacy of mexiletine-quinidine. Although, both the mexiletine-quinidine combination and quinidine monotherapy prolonged refractoriness to a similar extent, the mexiletine-quinidine combination produced greater antiarrhythmic efficacy and prolonged interventricular conduction within the periinfarct zone to an extent greater than did quinidine alone. We concluded that the role of quinidine in producing enhanced antiarrhythmic activity when combined with mexiletine includes both prolongation of refractoriness and conduction time in the periinfarct zone.

Quinidine/quinine: stereospecific electrophysiologic and antiarrhythmic effects in a canine model of ventricular tachycardia.

The two major electrophysiologic effects of quinidine are prolongation of refractoriness and prolongation of conduction time. To determine which of these effects contributes to its antiarrhythmic effect, we compared the electrophysiologic effects of quinidine and its stereoisomer quinine (which was expected to prolong conduction time but not refractoriness) in 24 dogs with inducible sustained ventricular tachyarrhythmia late after ischemic injury. Conscious but sedated animals were randomly assigned to receive infusions of saline, quinidine, or quinine. Serum concentrations of quinidine and quinine were 18 +/- 9 and 23 +/- 8 microM, respectively. Both drugs prolonged conduction times to a similar extent, but quinidine prolonged local repolarization times and refractoriness much more than quinine. Sustained ventricular tachyarrhythmia was consistently inducible during placebo (saline) studies. Antiarrhythmic efficacy was observed with quinidine (3 of 12) but not quinine (0 of 15) or saline (0 of 13) (p less than 0.05, Chi-square test). Quinidine also significantly prolonged monomorphic ventricular tachycardia (VT) cycle length (157 +/- 33 ms on quinidine vs. 129 +/- 26 ms at baseline, p less than 0.001) whereas quinine had no significant effect. Thus, prolonging refractoriness is important in preventing the induction of ventricular tachyarrhythmias and in prolonging VT cycle length.

Amiloride. Antiarrhythmic and electrophysiological activity in the dog.

Amiloride, a widely used diuretic, has multiple pharmacological actions, including inhibition of the sodium-hydronium ion and the sodium-calcium exchanger in heart. In terms of cardiac electrophysiology, amiloride prolongs action potential duration without alteration in upstroke velocity of phase 0 in Purkinje fibers. The antiarrhythmic efficacy of amiloride was assessed in a model of inducible sustained ventricular tachyarrhythmias in 16 dogs late after 2-hour occlusion-reperfusion of the left anterior descending coronary artery. Sixteen animals were studied: Four were randomly assigned to placebo, and 12 were assigned to amiloride treatment. Prolonged loading and maintenance infusions were designed to produce amiloride concentrations over the range achievable in humans. Animals were chronically instrumented to allow electrophysiological measures of conduction and refractoriness in the left ventricular infarct and border zones. Of the 12 animals treated with amiloride, six responded with inability to induce ventricular tachyarrhythmias, whereas of the four animals treated with placebo, none responded. The mean infarct size of the six animals responding to amiloride (12 +/- 5%) was significantly less than that of the six animals not responding to amiloride (20 +/- 8%). Overall, the only electrophysiological effect of amiloride observed in this study was prolongation of border zone ventricular refractoriness. This electrophysiological effect was accentuated in animals responding to amiloride. In addition, when animals were subdivided into responders, partial responders, or nonresponders, the border zone repolarization time was prolonged in responders and partial responders, whereas this measure shortened in nonresponding animals. Amiloride has antiarrhythmic activity in the suppression of sustained ventricular tachyarrhythmias in this postinfarction model.

Time-dependent change in electrophysiologic milieu after myocardial infarction in conscious dogs.

This study was designed to assess the time-dependent change in propensity to induction of malignant ventricular tachyarrhythmia after myocardial infarction. Instrumented conscious dogs were assessed during serial drug-free electrophysiologic studies over 26 +/- 9 days (range 17 to 35 days) after 2 hr occlusion-reperfusion of the left anterior descending coronary artery. Of the 19 animals studied, 11 continued to have sustained ventricular tachyarrhythmias inducible (group I) over this time period. In the eight remaining animals, spontaneous loss in the ability to induce sustained ventricular tachycardia occurred (group II). Myocardial infarct size in group I animals (18 +/- 8%) was significantly greater than that in group II dogs (12.5 +/- 5%; p less than .05). Even in group I animals, time-dependent changes occurred in the number of extrastimuli required to induce ventricular tachycardia and the frequency with which left ventricular stimulation was necessary. A differential pattern of time-dependent changes in electrophysiologic variables was observed when comparing group I and II animals. The conduction time to the infarct zone was prolonged during follow-up in group I animals, while in group II animals this variable was unchanged. Repolarization time recorded in the border zone remained unchanged in group I animals, but it was significantly shortened in group II animals. In addition, ventricular effective refractory period in the infarct zone shortened over time in group I animals but did not change in group II animals. In conclusion, time-dependent changes occur in electrophysiologic variables that are associated with a progressive decrease in propensity to induction of ventricular tachycardia after myocardial infarction. A critical determinant of whether propensity to ventricular tachycardia resolves over time is size of myocardial infarction.