The implementation of a hepatitis C testing service in community pharmacies: I-COPTIC consensus statement.

OBJECTIVES: This aimed to develop a blueprint for an effective community pharmacy Hepatitis C virus (HCV) testing service by producing a consensus statement. STUDY DESIGN: This was a modified Delphi process. METHODS: We recruited a heterogenous panel of experts (who had been involved in the setup or delivery of a community pharmacy HCV testing service) by purposive and chain referral methods. We had three rounds of a modified Delphi process. The first was a series of questions with free text responses and was analysed using thematic analysis, and the second and third were statements for the respondents to rate using a 7-point Likert scale. Consensus was predefined in a published protocol, and the results were reviewed by a public and patient involvement panel before the statement was finalised. RESULTS: We had 24 participants, including community and hospital-based pharmacists, local pharmaceutical committee members, charity representatives (Hepatitis C Trust), local clinical service lead, nurse specialists and doctors. The response rate of the first, second and third rounds were 100%, 96% and 88%, respectively. After the third round, we had 60 statements that reached consensus. We discussed the accepted statements with a patient and public involvement group. We used these statements to produce the I-COPTIC statement and a graphical summary. CONCLUSIONS: We developed a blueprint for the design of a gold standard community pharmacy HCV testing service. We believe this will support the successful implementation of community pharmacy testing for HCV. Community pharmacy testing is an important service to help achieve and maintain HCV elimination.

Microbialite response to an anthropogenic salinity gradient in Great Salt Lake, Utah.

A railroad causeway across Great Salt Lake, Utah (GSL), has restricted water flow since its construction in 1959, resulting in a more saline North Arm (NA; 24%-31% salinity) and a less saline South Arm (SA; 11%-14% salinity). Here, we characterized microbial carbonates collected from the SA and the NA to evaluate the effect of increased salinity on community composition and abundance and to determine whether the communities present in the NA are still actively precipitating carbonate or if they are remnant features from prior to causeway construction. SSU rRNA gene abundances associated with the NA microbialite were three orders of magnitude lower than those associated with the SA microbialite, indicating that the latter community is more productive. SSU rRNA gene sequencing and functional gene microarray analyses indicated that SA and NA microbialite communities are distinct. In particular, abundant sequences affiliated with photoautotrophic taxa including cyanobacteria and diatoms that may drive carbonate precipitation and thus still actively form microbialites were identified in the SA microbialite; sequences affiliated with photoautotrophic taxa were in low abundance in the NA microbialite. SA and NA microbialites comprise smooth prismatic aragonite crystals. However, the SA microbialite also contained micritic aragonite, which can be formed as a result of biological activity. Collectively, these observations suggest that NA microbialites are likely to be remnant features from prior to causeway construction and indicate a strong decrease in the ability of NA microbialite communities to actively precipitate carbonate minerals. Moreover, the results suggest a role for cyanobacteria and diatoms in carbonate precipitation and microbialite formation in the SA of GSL.

The monitoring of activity at home after total hip arthroplasty.

AIMS: Total hip arthroplasty (THA) has well known subjective benefits, but little is known objectively about the recovery of mobility in the early post-operative period. PATIENTS AND METHODS: A total of 33 patients aged > 60 years who underwent elective primary THA had their activity monitored for 30 days post-operatively using an at-home (Fitbit) ankle accelerometer. Their mean age was 70.7 years (61 to 86); 15 (45.5%) were female. The rate of compliance and the mean level of activity were determined. Comparisons between subgroups based on age, body mass index (BMI), surgical approach, and the destination of the patients when discharged were also performed. RESULTS: The mean compliance over the 30 days was 26.7 days (16 to 30; 89%) of use. The mean number of steps increased from 235 (5 to 1152) to 2563 (87 to 7280) (p < 0.001) between the first and the 30th post-operative day. Age < 70 years and an anterior surgical approach were significantly associated with higher levels of activity (1600 to 2400 (p = 0.016 to 0.031) and 1000 to 1800 (p = 0.017 to 0.037) more steps per day, respectively) between the second and the fourth week post-operatively. There was also a trend towards higher levels of activity in those who were discharged to their home rather than to a nursing facility (a mean of 1500 more steps per day, p = 0.02). BMI greater or less than 30 kg/m2 was not predictive of activity (p = 0.45 to 0.98). CONCLUSION: At-home remote mobility monitoring using existing commercially available technology is feasible in patients who have undergone THA. It showed a clear trend towards increased activity with the passage of time. Additionally, the remote device was able to detect differences in levels of activity clearly between patients in relation to variables of interest including age, BMI, surgical approach, and the destination of the patient at the time of discharge from hospital. Such monitoring may allow for the early identification and targeted intervention in patients who recover slowly. Cite this article: Bone Joint J 2016;98-B:1450-4.

Antimicrobial activity and biologic potential of silver-substituted calcium phosphate constructs produced with self-propagating high-temperature synthesis.

There is significant demand for synthetic bone substitute materials that can decrease the incidence of implant-based bacterial infections. The intent of this research was to evaluate the antimicrobial activity and biologic potential of calcium phosphate (CaP) constructs substituted with silver (Ag) that were produced via self-propagating high-temperature synthesis (SHS). SHS is a combustion synthesis technique that has successfully generated porous CaP bioceramics intended for use in bone repair. SHS reactions are highly versatile; dopants can be added to the reactant powders to alter product chemistry and morphology. In this research, Ag powder was added to the reactants generating porous CaP constructs containing 0.5, 1, or 2 wt% Ag. Antibacterial performance of the constructs was assessed against Escherichia coli, a representative model for Gram-negative bacteria. Liquid solutions (1 µg/mL) of CaP-Ag particles to phosphate buffered saline were incubated with 10(5) cells/mL. After 24 h, 10 µL of solution were spread on an LB agar plate and cultured for 24 h at 37 °C. Samples cultured with CaP-Ag showed complete bacterial inhibition while the controls (E. coli only and CaP without Ag) exhibited significant colony formation. The effects of Ag concentration on cytotoxicity and biocompatibility were tested in vitro. At 7 days, osteoblasts uniformly enveloped the CaP-Ag particles and displayed a healthy flattened morphology suggesting the concentrations of Ag incorporated into constructs were not cytotoxic. CaP-Ag constructs produced via SHS represent a source of synthetic bone substitute materials that could potentially inhibit, or reduce the incidence of post-operative bacterial infections.

Effects of Ni(2+) on aluminum hydroxide scale formation and transformation on a simulated drinking water distribution system.

Observations of aluminum containing sediments/scales formed within the distribution pipes have been reported for several decades. In this study, the effect of Ni(2+) on the formation and transformation processes of aluminum hydroxide sediment in a simulated drinking water distribution system were investigated using X-ray diffraction spectrum (XRD), Fourier transform infrared spectrum (FT-IR), scanning electron microscope (SEM), and thermodynamic calculation methods. It was determined that the existence of Ni(2+) had notable effects on the formation of bayerite. In the system without Ni(2+) addition, there was no X-ray diffraction signal observed after 400 d of aging. The presence of Ni(2+), however, even when present in small amounts (Ni/Al=1:100) the formation of bayerite would occur in as little as 3d at pH 8.5. As the molar ratio of Ni/Al increase from 1:100 to 1:10, the amount of bayerite formed on the pipeline increased further; meanwhile, the specific area of the pipe scale decreased from 160 to 122 m(2)g(-1). In the system with Ni/Al molar ratio at 1:3, the diffraction spectrum strength of bayerite became weaker, and disappeared when Ni/Al molar ratios increased above 1:1. At these highs Ni/Al molar ratios, Ni5Al4O11⋅18H2O was determined to be the major component of the pipe scale. Further study indicated that the presence of Ni(2+) promoted the formation of bayerite and Ni5Al4O11⋅18H2O under basic conditions. At lower pH (6.5) however, the existence of Ni(2+) had little effect on the formation of bayerite and Ni5Al4O11⋅18H2O, rather the adsorption of amorphous Al(OH)3 for Ni(2+) promoted the formation of crystal Ni(OH)2.

Bacterial abundance and composition in marine sediments beneath the Ross Ice Shelf, Antarctica.

Marine sediments of the Ross Sea, Antarctica, harbor microbial communities that play a significant role in the decomposition, mineralization, and recycling of organic carbon (OC). In this study, the cell densities within a 153-cm sediment core from the Ross Sea were estimated based on microbial phospholipid fatty acid (PLFA) concentrations and acridine orange direct cell counts. The resulting densities were as high as 1.7 × 107 cells mL⁻¹ in the top ten centimeters of sediments. These densities are lower than those calculated for most near-shore sites but consistent with deep-sea locations with comparable sedimentation rates. The δ¹³C measurements of PLFAs and sedimentary and dissolved carbon sources, in combination with ribosomal RNA (SSU rRNA) gene pyrosequencing, were used to infer microbial metabolic pathways. The δ¹³C values of dissolved inorganic carbon (DIC) in porewaters ranged downcore from -2.5‰ to -3.7‰, while δ¹³C values for the corresponding sedimentary particulate OC (POC) varied from -26.2‰ to -23.1‰. The δ¹³C values of PLFAs ranged between -29‰ and -35‰ throughout the sediment core, consistent with a microbial community dominated by heterotrophs. The SSU rRNA gene pyrosequencing revealed that members of this microbial community were dominated by ß-, δ-, and γ-Proteobacteria, Actinobacteria, Chloroflexi and Bacteroidetes. Among the sequenced organisms, many appear to be related to known heterotrophs that utilize OC sources such as amino acids, oligosaccharides, and lactose, consistent with our interpretation from δ¹³CPLFA analysis. Integrating phospholipids analyses with porewater chemistry, δ¹³CDIC and δ¹³CPOC values and SSU rRNA gene sequences provides a more comprehensive understanding of microbial communities and carbon cycling in marine sediments, including those of this unique ice shelf environment.

Hot spring siliceous stromatolites from Yellowstone National Park: assessing growth rate and laminae formation.

Stromatolites are commonly interpreted as evidence of ancient microbial life, yet stromatolite morphogenesis is poorly understood. We apply radiometric tracer and dating techniques, molecular analyses and growth experiments to investigate siliceous stromatolite morphogenesis in Obsidian Pool Prime (OPP), a hot spring in Yellowstone National Park. We examine rates of stromatolite growth and the environmental and/or biologic conditions that affect lamination formation and preservation, both difficult features to constrain in ancient examples. The "main body" of the stromatolite is composed of finely laminated, porous, light-dark couplets of erect (surface normal) and reclining (surface parallel) silicified filamentous bacteria, interrupted by a less-distinct, well-cemented "drape" lamination. Results from dating studies indicate a growth rate of 1-5 cm year(-1) ; however, growth is punctuated. (14)C as a tracer demonstrates that stromatolite cyanobacterial communities fix CO(2) derived from two sources, vent water (radiocarbon dead) and the atmosphere (modern (14)C). The drape facies contained a greater proportion of atmospheric CO(2) and more robust silica cementation (vs. the main body facies), which we interpret as formation when spring level was lower. Systematic changes in lamination style are likely related to environmental forcing and larger scale features (tectonic, climatic). Although the OPP stromatolites are composed of silica and most ancient forms are carbonate, their fine lamination texture requires early lithification. Without early lithification, whether silica or carbonate, it is unlikely that a finely laminated structure representing an ancient microbial mat would be preserved. In OPP, lithification on the nearly diurnal time scale is likely related to temperature control on silica solubility.

Low temperature S(0) biomineralization at a supraglacial spring system in the Canadian High Arctic.

Elemental sulfur (S(0) ) is deposited each summer onto surface ice at Borup Fiord pass on Ellesmere Island, Canada, when high concentrations of aqueous H(2) S are discharged from a supraglacial spring system. 16S rRNA gene clone libraries generated from sulfur deposits were dominated by ß-Proteobacteria, particularly Ralstonia sp. Sulfur-cycling micro-organisms such as Thiomicrospira sp., and ε-Proteobacteria such as Sulfuricurvales and Sulfurovumales spp. were also abundant. Concurrent cultivation experiments isolated psychrophilic, sulfide-oxidizing consortia, which produce S(0) in opposing gradients of Na(2) S and oxygen. 16S rRNA gene analyses of sulfur precipitated in gradient tubes show stable sulfur-biomineralizing consortia dominated by Marinobacter sp. in association with Shewanella, Loktanella, Rubrobacter, Flavobacterium, and Sphingomonas spp. Organisms closely related to cultivars appear in environmental 16S rRNA clone libraries; none currently known to oxidize sulfide. Once consortia were simplified to Marinobacter and Flavobacteria spp. through dilution-to-extinction and agar removal, sulfur biomineralization continued. Shewanella, Loktanella, Sphingomonas, and Devosia spp. were also isolated on heterotrophic media, but none produced S(0) alone when reintroduced to Na(2) S gradient tubes. Tubes inoculated with a Marinobacter and Shewanella spp. co-culture did show sulfur biomineralization, suggesting that Marinobacter may be the key sulfide oxidizer in laboratory experiments. Light, florescence and scanning electron microscopy of mineral aggregates produced in Marinobacter experiments revealed abundant cells, with filaments and sheaths variably mineralized with extracellular submicron sulfur grains; similar biomineralization was not observed in abiotic controls. Detailed characterization of mineral products associated with low temperature microbial sulfur-cycling may provide biosignatures relevant to future exploration of Europa and Mars.

Effect of time of admission on compliance with deep vein thrombosis prophylaxis in a tertiary medical intensive care unit.

OBJECTIVE: We sought to evaluate deep vein thrombosis (DVT) prophylaxis compliance according to time of admission in a medical intensive care unit (MICU). METHODS: This was a retrospective cohort study at a closed tertiary MICU. We classified patients into three groups (week days, weekends, and week nights), according to time of admission. An unweighted risk factor score (RFS) was calculated from 20 known risk factors. We defined DVT prophylaxis compliance as any type of prophylaxis (mechanical or pharmacologic) for RFS 3. Non-compliance was defined as no prophylaxis or single-type prophylaxis for RFS > 3. RESULTS: We analyzed 105 admissions. Eighty (76.19%) patients received compliant DVT prophylaxis, and 25 (23.81%) patients received non-compliant regimens of whom 11 (10.48%) were not on any prophylaxis. DVT prophylaxis compliance was not different across the three admission groups. The non-compliant DVT prophylaxis group had a higher RFS (3.48 +/- 2.1 vs. 2.25 +/- 1.5; P = 0.011), a trend towards fewer female patients (40% vs. 60%; P = 0.079), and a higher percentage of admissions by interns at the first postgraduate year (PGY) level (28% vs. 5.4%; P = 0.01). Logistic regression revealed that only RFS and PGY level were independent predictors for compliance (P = 0.015 and 0.005 respectively). Time of admission was not a significant factor. CONCLUSIONS: Time of admission did not influence DVT prophylaxis compliance. Compliance improved with higher PGY level and lower RFS. A higher level of knowledge probably explains the association with PGY level; however, we cannot explain the inverse relationship between RFS and compliance.

Effects of acute global low-flow ischemia on triggered arrhythmias in d-sotalol-induced long Q-T intervals in perfused rabbit hearts.

Little information is available on how acute ischemia modifies the electrophysiologic substrate associated with long Q-T interval conditions. We studied the effects of low-flow ischemia (10 min at 5.0 ml/min followed by 10 min of 2.5 ml/min) in Langendorff perfused rabbit hearts during control and in hearts 20 min after the addition to the perfusate of 92 microM d-sotalol, which reliably produced triggered activity. Epicardial electrograms, a left ventricular endocardial monophasic action potential (MAP), and simulated X and Y lead electrocardiograms were used to characterize myocardial activation and recovery during ventricular pacing. In the control hearts, conduction velocity as indicated by the mean epicardial activation time accelerated for most of the period of ischemia (maximum decrease of -9.4 +/- 7.9%). The mean activation-recovery interval, MAP duration, and Q-T interval were moderately decreased (-4.9 +/- 8.6%, -7.5 +/- 4.4%, and -4.6 +/- 2.3%, respectively). The mean standard deviation of the activation-recovery interval (epicardial heterogeneity of recovery) was increased by 34.6 +/- 23.4%. d-Sotalol had no effect on conduction but prolonged myocardial recovery time, increased heterogeneity, and produced triggered arrhythmias in all hearts. Within 2 min of ischemia triggered activity was eliminated. With d-sotalol, ischemia slowed conduction and produced relatively larger decreases in the activation-recovery interval, MAP duration, and Q-T interval (-11.8 +/- 10.3%, -13.9 +/- 12.0%, and -15.8 +/- 11.2%). The increased epicardial heterogeneity seen with d-sotalol was attenuated by ischemia. Thus ischemia superimposed on long Q-T conditions had antiarrhythmic as well as arrhythmogenic effects.

Gender and seasonally related differences in myocardial recovery and susceptibility to sotalol-induced arrhythmias in isolated rabbit hearts.

INTRODUCTION: Gender differences and seasonal variations in cardiac electrophysiology and susceptibility to arrhythmias have been described clinically. The present study was undertaken to determine if there are similar gender and seasonally related differences in the electrophysiology of the rabbit heart. METHODS AND RESULTS: We analyzed epicardial electrograms, left ventricular endocardial monophasic action potentials (MAPs), and simulated X and Y lead ECGs from 145 isolated rabbit hearts studied over a period of 41 months. Hearts from males had seasonal increases in the duration of myocardial recovery. During the months of June to September compared with October to January and February to May, epicardial activation-recovery intervals (231.6+/-23.4 vs 215.6+/-19.2 and 213.5+/-18.8 msec, P = 0.003), MAP durations (256.5+/-25.4 vs 237.0+/-19.6 and 230.7+/-26.4 msec, P < 0.001), and QT intervals (278.3+/-25.6 vs 267.3+/-11.8 and 261.3+/-13.0 msec, P = 0.037) were longer. Overall, hearts from females had shorter QT intervals than males (257.7+/-15.7 vs 270.1+/-20.3 msec, P < 0.001), and this difference was reflected in their shorter epicardial activation-recovery intervals and MAP durations. However, hearts from females showed a greater prolongation of epicardial recovery (P = 0.007) and greater incidence of arrhythmias (P < 0.001) with sotalol than males. Also, the incidence of arrhythmias was greater in the winter months October to May (P < 0.001). CONCLUSION: The isolated rabbit heart provides a spontaneous model of gender and seasonally related differences in cardiac electrophysiology and arrhythmia susceptibility. These differences may be related to variation in the expression of or regulation of the membrane ion channels mediating repolarization.

Modeling reduction of uranium U(VI) under variable sulfate concentrations by sulfate-reducing bacteria.

The kinetics for the reduction of sulfate alone and for concurrent uranium [U(VI)] and sulfate reduction, by mixed and pure cultures of sulfate-reducing bacteria (SRB) at 21 +/- 3 degrees C were studied. The mixed culture contained the SRB Desulfovibrio vulgaris along with a Clostridium sp. determined via 16S ribosomal DNA analysis. The pure culture was Desulfovibrio desulfuricans (ATCC 7757). A zero-order model best fit the data for the reduction of sulfate from 0.1 to 10 mM. A lag time occurred below cell concentrations of 0.1 mg (dry weight) of cells/ml. For the mixed culture, average values for the maximum specific reaction rate, V(max), ranged from 2.4 +/- 0.2 micromol of sulfate/mg (dry weight) of SRB. h(-1)) at 0.25 mM sulfate to 5.0 +/- 1.1 micromol of sulfate/mg (dry weight) of SRB. h(-1) at 10 mM sulfate (average cell concentration, 0.52 mg [dry weight]/ml). For the pure culture, V(max) was 1.6 +/- 0.2 micromol of sulfate/mg (dry weight) of SRB. h(-1) at 1 mM sulfate (0.29 mg [dry weight] of cells/ml). When both electron acceptors were present, sulfate reduction remained zero order for both cultures, while uranium reduction was first order, with rate constants of 0.071 +/- 0.003 mg (dry weight) of cells/ml. min(-1) for the mixed culture and 0.137 +/- 0.016 mg (dry weight) of cells/ml. min(-1) (U(0) = 1 mM) for the D. desulfuricans culture. Both cultures exhibited a faster rate of uranium reduction in the presence of sulfate and no lag time until the onset of U reduction in contrast to U alone. This kinetics information can be used to design an SRB-dominated biotreatment scheme for the removal of U(VI) from an aqueous source.

Modulation of arrhythmias by isoproterenol in a rabbit heart model of d-sotalol-induced long Q-T intervals.

Sympathetic influences have been implicated in arrhythmias associated with both congenital and acquired long Q-T intervals. We recorded epicardial electrograms, a left ventricular endocardial monophasic action potential (MAP), and a bipolar electrocardiogram in 23 isolated rabbit hearts. Spontaneous focal arrhythmias appeared within 8-18 min following 92 microM d-sotalol in 15 of 23 hearts. The epicardial activation-recovery interval was shorter at baseline and increased to a significantly greater degree after d-sotalol administration in the hearts that developed focal activity. The standard deviation of the activation-recovery interval of the epicardial sites also increased. With the addition of 0.01 microM isoproterenol, the incidence of focal activity increased, and its mean cycle length was shortened by 7%. Also, myocardial recovery time in the epicardium was shortened to a greater degree than the endocardial MAP duration. It did not alter local epicardial heterogeneity of recovery but did increase the regional dispersion between epicardial recovery times, and the endocardial MAP duration. Therefore, beta-adrenergic stimulation in the presence of d-sotalol favors the appearance of arrhythmias by increasing the propensity for closely coupled focal activity and the temporal dispersion of recovery.

Modulation of quinidine-induced arrhythmias by temperature in perfused rabbit heart.

We used low temperature to slow ion channel kinetics and studied the electrophysiological effects of quinidine at different pacing rates in isolated rabbit hearts. Fifteen epicardial electrograms together with an endocardial monophasic action potential were recorded. Epicardial activation and local recovery times were measured. Arrhythmias together with the characteristics of their mode of induction and rate were analyzed by epicardial activation sequence mapping. In the presence of quinidine, arrhythmias consistent with both triggered activity and reentry were observed. At baseline, triggered activity was not inducible, even though at 25 degrees C the recovery time was greater than that in the presence of quinidine at 36 degrees C. Also, with quinidine, the incidence of triggered activity decreased at 30 and 25 degrees C. Therefore prolongation of the recovery time per se does not cause triggered activity. Quinidine's use-dependent effects on conduction and reverse use-dependent effects on recovery time were amplified by low temperatures. These findings can be understood in terms of the known temperature sensitivities of the kinetics of the membrane ion channels responsible for activation and recovery. The results demonstrate that temperature can be used as a tool to elucidate mechanisms of drug action.

Transient isotachophoretic-electrophoretic separations of lanthanides with indirect laser-induced fluorescence detection.

Indirect laser-induced fluorescence was used for the detection of several lanthanide species separated by capillary electrophoresis. Quinine sulfate was the fluorescent component of the background electrolyte, and α-hydroxyisobutyric acid was added as a complexing agent to enable the separation of analyte ions that have similar mobilities. The UV lines (333-364 nm) of an argon ion laser were used as the excitation source with a diode array detector for monitoring the fluorescent emission at 442 nm. Electrokinetic injections and transient isotachophoresis were implemented to stack the analyte ions into more concentrated zones. On-line preconcentration factors were determined to be ∼700 and resulted in limits of detection for La(3+), Ce(3+), Pr(3+), Nd(3+), Sm(3+), and Eu(3+) in the low-ppb range (6-11 nM).

The treatment of stupor associated with MRI evidence of cerebrovascular disease.

OBJECTIVE: To describe the treatment and outcome of organic stupor associated with MRI evidence of cerebrovascular disease. DESIGN: A case series of three patients. SETTING: An urban mental health of the elderly service in southeast London. PATIENTS: Aged 69 years, 72 years and 78 years. Two had organic catatonic disorder and the third organic depressive disorder. INTERVENTIONS: Diazepam, carbamazepine, antidepressants or electroconvulsive therapy (ECT). MAIN OUTCOME MEASURES: Resolution of symptoms and discharge from hospital. RESULTS: Symptoms resolved between 1 and 10 days. All patients were able to return home but relapsed over the following 12 months. One relapse occurred when a patient stopped diazepam and moclobemide. CONCLUSIONS: It is proposed that the initial treatment of organic stupor associated with cerebrovascular disease should include a benzodiazepine or carbamazepine. If patients fail to respond then ECT should be considered. The safety of ECT is not known, when treating patients with depressive disorder associated with cerebrovascular disease.

Modulation of procainamide's effect on conduction by cellular uncoupling in perfused rabbit hearts.

INTRODUCTION: How cell-to-cell electrical coupling influences an antiarrhythmic agent's effect on conduction is largely unknown. To investigate this, we evaluated the effects of procainamide on myocardial conduction at decreasing degrees of cell-to-cell electrical coupling induced by graded doses of heptanol. METHODS AND RESULTS: Electrograms were recorded from 50 ventricular epicardial sites in a 1 cm x 0.5 cm area during pacing to produce conduction longitudinal or transverse to myocardial fiber orientation in Langendorff-perfused rabbit hearts. The effects of procainamide (15 mg/L) on conduction velocity were determined in the presence of increasing doses of heptanol (0.2, 0.5, and 1.0 mM). In addition, using standard microelectrode techniques in isolated superfused rabbit myocardium, intracellular potentials were recorded in the presence of 15 mg/L procainamide and heptanol (1.0 mM). In the absence of heptanol, procainamide slowed conduction velocity. In the presence of increasing doses of heptanol, procainamide's contribution to the depressant effect on conduction velocity was attenuated and reversed at the highest dose. The latter effect was preferentially seen for conduction longitudinal to myocardial fiber orientation. Heptanol had no effect on action potential amplitude or maximum rate of depolarization in the presence of procainamide. CONCLUSIONS: Procainamide's effect on conduction velocity is influenced by the underlying degree of cell-to-cell electrical coupling. The present model should be useful in evaluating the relative ability of other pharmacologic agents to modulate conduction under conditions of changing cell coupling.

Effect of coronary perfusion of heptanol on conduction and ventricular arrhythmias in infarcted canine myocardium.

INTRODUCTION: Abnormal cellular coupling is a major constituent of the slow, dissociated conduction that supports ventricular tachycardia (VT) following myocardial infarction. Agents that modulate cellular coupling may exert either proarrhythmic or antiarrhythmic effects. METHODS AND RESULTS: The effects of modulating cellular coupling on conduction and susceptibility to inducible VT were studied in 11 dogs with healed left anterior descending (LAD) infarction. The LAD circulation was isolated and supplied with arterial blood via a constant-flow bypass system. Localized intracoronary infusion of heptanol, an agent with relatively specific effects on intracellular coupling, was performed using this bypass system. Heptanol produced dose-dependent changes in cardiac conduction, assessed by delayed local activation times in sinus rhythm (0.5 mM: 11.9% +/- 11.0% change, P = 0.005; 1.0 mM: 45.8% +/- 25.5% change, P = 0.0004) and slowed conduction velocity both transverse and longitudinal to fiber orientation. Sustained VT was not induced in any of the control animals. During infusion of 0.5 mM heptanol, uniform sustained VT was inducible in 4 of 11 animals (P = 0.027). During infusion of 1.0 mM heptanol, sustained VT was induced in only 1 of 9 animals. CONCLUSIONS: In the canine model of healed myocardial infarction, heptanol had a bimodal effect on susceptibility to inducible VT. Low-dose heptanol facilitated the induction of sustained VT, and high-dose heptanol had an antiarrhythmic effect. This suggests that agents that modulate coupling may significantly modify susceptibility to VT following myocardial infarction.

Identification of conduction block in cardiac muscle: in vitro observations in canine epicardium.

OBJECTIVE: The aim was to examine the ability of several previously proposed criteria and of "vector mapping" to distinguish slow conduction from conduction block in canine myocardium. METHODS: Two different in vitro preparations of canine epicardium were used. In 10 tissues, an anatomical barrier was simulated by a cut (five longitudinal and five transverse to fibre orientation). Eleven tissues removed two weeks after occlusion-reperfusion infarction were also studied. Isochronal activation maps were constructed from extracellular and intracellular recordings and vector loops formed by summing two orthogonally recorded bipolar electrograms were used to indicate the direction of cardiac activation. RESULTS: In the cut model, electrograms recorded from over the anatomical barrier were usually normal or showed double potentials but could occasionally be fractionated. Isochronal activation maps obtained from extracellular recordings were able to identify five of five anatomical barriers transverse to, but only one of five barriers longitudinal to, fibre orientation. The direction of cardiac activation indicated by vector loops identified conduction block in all 10 preparations. In 11 tissues removed from canine ventricles with experimental myocardial infarction, microelectrode recordings were used to characterise regions as either slow conduction or conduction block. Isochronal activation patterns obtained from extracellular recordings generally showed impulses proceeding through zones of conduction and around zones of conduction block but disagreed with the results of microelectrode impalements in two of 11 cases. Electrogram morphology was also not always able to distinguish slow conduction from block. The direction of cardiac activation determined by vector mapping accurately characterised all regions of tissue as showing either slow conduction or conduction block. CONCLUSIONS: Limited regions of conduction block or slow conduction are frequently present in epicardial tissues removed from experimental myocardial infarction. The morphology of extracellular electrograms and isochronal activation mapping performed from extracellular recordings is often but not always able to distinguish slow conduction from conduction block. Vector mapping is useful in distinguishing slow conduction from conduction block in these situations and may help evaluate myocardial conduction patterns.

"Supernormal" conduction and excitability.

Electrocardiographic manifestation of "supernormal" conduction is defined as conduction that is more rapid than expected or presence of conduction when block is anticipated. It is not supernormal in the sense or being more rapid than normal. Therefore, the term relative supernormality or "supernormality" is more appropriate. The mechanism of "supernormal" conduction is conduction during a period of supernormal excitability and conduction associated with altered membrane potential. Some of the more common phenomena that are not dependent on conduction during the supernormal period but manifest better than expected conduction, thus simulating "supernormal" conduction, include dual AV nodal conduction, the "gap" phenomenon, "peeling back" of the refractory period, summation of subthreshold responses, diastolic phase 4 depolarization, and phasic autonomic influences.