Stroke volume equation for impedance cardiography

The study's goal was to determine if cardiac output (CO), obtained by impedance cardiography (ICG), would be improved by a new equation N, implementing a square root transformation for dZ/dt_max/Z₀, and a variable magnitude, mass-based volume conductor V_c. Pulmonary artery catheterisation was performed on 106 cardiac surgery patients pre-operatively. Post-operatively, thermodilution cardiac output (TDCO) was simultaneously compared with ICG CO. dZ/dt_max/Z₀ and Z₀ were obtained from a proprietary bioimpedance device. The impedance variables, in addition to left ventricular ejection time T_LVE and patient height and weight, were input using four stroke volume (SV) equations: Kubicek (K), Sramek (S), Sramek-Bernstein (SB), and a new equation N. CO was calculated as SV × heart rate. Data are presented as mean ± SD. One way repeated measures of ANOVA followed by the Tukey test were used for inter-group comparisons. Bland-Altman methods were used to assess bias, precision and limits of agreement. P<0.05 was considered statistically significant. CO implementing N (6.06±1.48 l min⁻¹) was not different from TDCO (5.97±1.41 l min⁻¹). By contrast, CO calculated using K (3.70±1.53 l min⁻¹), S (4.16±1.83 l min⁻¹) and SB (4.37±1.82 l min⁻¹) was significantly less than TDCO. Bland-Altman analysis showed poor agreement between TDCO and K, S and SB, but not between TDCO and N. Compared with TDCO, equation N, using a square-root transformation for dZ/dt_max/Z₀, and a mass-based V_C was superior to existing transthoracic impedance techniques for SV and CO determination.     

Analysis of the O-wave in acute right ventricular apex impedance measurements with a standard pacing lead in animals

Modern pacemakers (implantable devices used for maintaining an appropriate heart rate in patients) can use an intracardiac ventricular impedance signal for physiological cardiac stimulation control. Intracardiac ventricular impedance from nine animal subjects is analysed and presented (seven sheep: 49.0±6.5 kg, sinus rhythm 100.3±16.5 beats min⁻¹, average impedance 629.8±72.6Ω; and two dogs: 30 kg each, sinus rhythm 86.0 beats min⁻¹, 862.1Ω and 134.0 beats min⁻¹, 1114.6Ω, respectively). The averaged curve and standard deviation curve of the impedance in sinus rhythm were analysed in MATLAB to clarify and study consistent impedance shape over one heart cycle. In eight of nine (89%) animal subjects, a consistent impedance slope change (notch) was observed in the early stage of the cardiac filling phase. This result was reproduced in an additional subject with simultaneous echocardiographical measurements of mitral valve blood flow. The notch occured soon after rapid early filling (E-wave in mitral flow) but prior to ventricular filling caused by atrial contraction, indicating that the impedance notch was caused by rapid ventricular filling and that it might be a sensed feature of diagnostic value. The intracardiac impedance notch in the present study had similar features to the non-invasive transthoracic impedance O-wave reported by others, and it is shown here that an O-wave is found in intracardiac impedance signals, strongly suggesting that the non-invasive O-wave is caused by cardiac events.     

Design and evaluation of a handheld impedance plethysmograph for measuring heart rate variability

Heart rate variability (HRV) analysis from 10s ECGs has been shown to be reliable. However, the short examination time warrants a user-friendly system that can be used forad-hoc examinations without normal preparation, unlike ECG. A handheld device has been developed that can measure ultra-short HRV from impedance plethysmographic recordings of the pulse wave in distal superficial arteries. The prototype device was made user-friendly through a compact, pen-like design and the use of integrated metal electrodes that were especially designed for dry operation. The main signal processing was performed by a digital signal processor, where the discrete heart beats were detected using a correlation algorithm that could adapt to individual pulse wave shapes to account for biological variation. The novel device was evaluated in 20 mainly young volunteers, using 10 s time-correlated ECG recordings as the reference method. Agreement between the two methods in measuring heart rate and root mean square of successive differences in the heart beat interval (RMSSD) was analysed using correlation coefficients (Pearson's R²), mean differences with 95% confidence intervals and 95% limits of agreement, and Bland-Altman plots. The correlation between the two methods was R²=1.00 and R²=0.99 when heart rate and RMSSD were measured, respectively. The Bland-Altman plots showed suitable agreement between the novel device and standard 10 s ECGs, which was substantiated by 95% limits of agreement of the difference of ± 0.1 beats min⁻¹ and ∼ ± 10 ms for heart rate and RMSSD, respectively. Therefore the evaluation showed no significant systematic error of the novel device compared with ECG.     

cAMP-dependent inward rectifier current in neurons of the rat suprachiasmatic nucleus

Electrophysiological properties of the inward rectification of neurons in the rat suprachiasmatic nucleus (SCN) were examined by using the single-electrode voltage-clamp method, in vitro. Inward rectifier current (I _H) was produced by hyperpolarizing step command potentials to membrane potentials negative to approximately −60 mV in nominally zero-Ca²⁺ Krebs solution containing tetrodotoxin (1 μM), tetraethylammonium (40 mM), Cd²⁺ (500 μM) and 4-aminopyridine (1 mM).I _H developed during the hyperpolarizing step command potential with a duration of up to 5 s showing no inactivation with time.I _H was selectively blocked by extracellular Cs⁺ (1 mM). The activation of the H-channel conductance (G _H) ranged between −55 and −120 mV. TheG _H was 80–150 pS (n=4) at the half-activation voltage of −84±7 mV (n=4). The reversal potential ofI _H obtained by instantaneous current voltage (I/V) relations was −41±6mV (n=4); it shifted to −51±8mV (n=3) in low-Na⁺ (20 mM) solution and to −24±4 mV (n=4) in high-K⁺ (20 mM) solution. Forskolin (1–10 μM) produced an inward current and increased the amplitude ofI _H. Forskolin did not change the half-activation voltage ofG _H. 8-Bromo-adenosine 3′,5′-cyclic monophosphate (8-Br-cAMP, 0.1–1 mM) and dibutyryl-cAMP (0.1–1 mM) enhancedI _H. 3-Isobutyl-1-methylxanthine (IBMX, 1 mM) also enhancedI _H. The results suggest that the inward rectifier cation current is regulated by the basal activity of adenylate cyclase in neurons of the rat SCN.     

Signal source impedance of implanted pacemaker electrodes estimated from the spectral ratio between loaded and unloaded electrograms in man

The signal source impedance Z of implanted pacemaker electrodes plays an important role for adequate sensing of electrogram signals and has so far been little explored. A frequency-domain method for thein vivo calculation of Z is described. Electrogram signals picked up between two electrodes were recorded unloaded, and loaded with resistors and capacitors, then amplified, and stored on magnetic tape. After time sampling and a.d. conversion, the signals were read into a digital computer as discrete time vectors with 2^P samples. Each vector was subjected to a fast Fourier transform (f.f.t.), and the ratio H(jω_i) between the transformed loaded and unloaded vectors was calculated. For the electrode impedance Z a linear model was chosen that consisted of the tissue and electrode resistance R_T, in series with a parallel coupling between Faraday resistance R_F, and Helmholtz capacitance C_H. By nonlinear regression analysis the parameters (∧) in this model were estimated from the ratios H(jjω_i) obtained in patients with permanent pacemaker electrodes, and in patients with temporary multicore wire electrodes after open heart surgery. As an estimate for R_T was also used the voltage/current ratio R′_T, 90 μs into the stimulation pulse from an external variable parameter pulse generator. The 3-component impedance model described the essential features of the electrode impedance in the frequency range up to 100 Hz. It was found that Ĉ_H, decreased slightly with increasing frequency, and that Ř_T in general was larger than R′_T. A modified model with frequency dependent parameters was found to obtain a better approach to the experimental data.     

Evidence for electrogenic sodium-bicarbonate cotransport in cultured rat cerebellar astrocytes

We have studied the regulation of intracellular pH (pH_i), and HCO ₃ ⁻ -dependent membrane currents in cultured astrocytes from neonatal rat cerebellum, using the fluorescent pH-sensitive dye 2,7′-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF) and the whole-cell patch-clamp technique. The steady-state pH_i was 6.96 in both nominally CO₂/HCO ₃ ⁻ -free, HEPES-buffered saline (6.96 ±0.14;n=48) and in a saline containing 5% CO₂/24 mM HCO ₃ ⁻ (6.96±0.18;n=48) (at pH 7.4). Inhibition of the Na⁺/H⁺ exchange by amiloride (2 mM) caused a significant decrease of pH_i in nominally CO₂/HCO ₃ ⁻ -free saline. Addition of CO₂/HCO ₃ ⁻ in the continuous presence of amiloride induced a large and fast intracellular alkalinization. Removal of external Na⁺ also caused a fall of pH_i, and addition of CO₂/HCO ₃ ⁻ in Na⁺-free saline evoked a further fall of pH_i, while the outward current was reduced or even reversed. The stilbene 4,4′-diisothiocyanatostilbene-2,2′-disulphonic acid (DIDS, 0.3 mM) reduced the pH_i recovery from the CO₂/HCO ₃ ⁻ -evoked acidification, and blocked the prominent intracellular acidification upon removal of CO₂/HCO ₃ ⁻ . Removal of external Cl⁻ had little effect on these pH_i changes. Lowering the external pH from 7.4 to 6.6 in CO₂/HCO ₃ ⁻ -containing saline produced a large and rapid intracellular acidification and inward current, which were both greatly reduced by DIDS and in the absence of CO₂/HCO ₃ ⁻ . The results suggest that the CO₂/HCO ₃ ⁻ -dependent current is partly due to a reversible bidirectional, electrogenic Na⁺-HCO ₃ ⁻ cotransporter, which helps to regulate pH_i in these cells. In addition, a prominent Na⁺/H⁺ exchanger contributes to extrude acid equivalents from these astrocytes to maintain the steadystate pH_i.     

In vitro measurements of optical properties of porcine brain using a novel compact device

Knowledge of the optical properties of tissues can be applied in numerous medical and scientific fields, including cancer diagnostics and therapy. There are many different ways of determining the optical properties of turbid media. The paper describes measurements of the optical properties of porcine brain tissue using novel instrumentation for simultaneous absorption and scattering characterisation of small turbid samples. Integrating sphere measurements are widely used as a reference method for determination of the optical properties of relatively thin turbid samples. However, this technique is associated with bulky equipment, complicated measuring techniques, interference compensation techniques and inconvenient sample handling. It is believed that the sphere for some applications can be replaced by a new, compact device, called the combined angular and spatially resolved head sensor, to measure the optical properties of thin turbid samples. The results compare very well with data obtained with an integrating sphere for well-defined samples. The instrument was shown to be accurate to within 12% for μ_a and 1% for μ _s ^′ in measurements of intralipid-ink samples. The corresponding variations of data were 17% and 2%, respectively. The reduced scattering coefficient for porcine white matter was measured to be 100 cm⁻¹ at 633 nm, and the value for coagulated brain tissue was 65 cm⁻¹. The corresponding absorption coefficients were 2 and 3 cm⁻¹, respectively.     

Validity of the two-parameter model in estimating the anaerobic work capacity

The curvature of the power–time (P–t) relationship (W′) has been suggested to be constant when exercising above critical power (CP) and to represent the anaerobic work capacity (AWC). The aim of this study was to compare W′ to (1) the total amount of work performed above CP (W _90s′) and (2) the AWC, both determined from a 90s all-out fixed cadence test. Fourteen participants (age 30.5±6.5 years; body mass 67.8±10.3 kg), following an incremental VO_2max ramp protocol, performed three constant load exhaustion tests set at 103±3, 97±3 and 90±2% P-VO_2max to calculate W′ from the P–t relationship. Two 90s all-out efforts were also undertaken to determine W _90s′ (power output—time integral above CP) and AWC (power output—time integral above the power output expected from the measured VO₂). W′ (13.6±1.3 kJ) and W _90s′ (13.9±1.1 kJ; P=0.96) were not significantly different but were lower than AWC (15.9±1.2 kJ) by 24% (P=0.03) and 17%, respectively (P=0.04). All these variables were correlated (P<0.001) but great extents of disagreement were reported (0.2±6.4 kJ between W′ and W _90s′, 2.3±7.2 kJ between W′ and AWC, and 2.1±4.3 kJ between W _90s′ and AWC). The underestimation of AWC from both W′ and W _90s′ can be explained by the aerobic inertia not taking into consideration when determining the two latter variables. The low extents of agreement between W′, W _90s′ and AWC mean the terms should not be used interchangeably.     

Inhibition of platelet aggregation by monoclonal antibodies against glycoprotein IIb–IIIa complex

Monoclonal antibodies CRC64 are obtained against Ca²⁺-dependent glycoprotein IIb–IIIa complex of the platelet membrane which possess the ability to inhibit completely fibrinogen-dependent platelet aggregation. CRC64 is directed against the epitope formed by the glycoprotein IIb–IIIa complex and does not interact with proteins isolated after platelets are treated with ethylenediamine tetraacetate. Complete, reproducible blockade of platelet aggregation caused by 5 μM adenosine diphosphate is noted in an MCA concentration of 3 μg/ml, while in the case of a stronger inductor, namely 1 U/ml thrombin, platelet aggregation is inhibited in a concentration of 5 μg/ml. F(ab′)₂ fragments are also able to inhibit platelet aggregation completely and are usually effective in concentrations lower than native monoclonal antibodies. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 10, pp. 402–405, October, 1994 Presented by V. N. Smirnov, Member of the Russian Academy of Medical Sciences     

New intelligent polymer gels: a self-oscillating gel with pacemaking and actuating functions

We report an “intelligent” gel that undergoes autonomous swelling-deswelling oscillations without reliance on alterations in external conditions; this aspect reminds us of the heartbeat. The mechanical oscillation in our gel system was produced via an oscillating chemical reaction similar to a metabolic reaction, called the Belousov-Zhabotinsky (BZ) reaction. We have succeeded in synthesizing an ionic gel consisting of the cross-linkedN-isopropylacrylamide (NIPAAm) chain to which ruthenium tris(2,2′-bipyridine) [Ru(bpy)₃] was covalently bonded. This Ru(bpy)₃ complex acts as a catalyst for the BZ reaction; thus, the BZ reaction occurring within the gel matrix generates periodic redox changes of the catalyst moiety: Ru(bpy)₃ ²⁺⇆Ru(bpy)₃ ³⁺. This chemical oscillation is converted into the mechanical oscillation of the polymer network. As a result, the gel exhibits a periodic swelling-deswelling change. When the gel size is smaller than the chemical wavelength, the redox change occurs homogeneously in the gel. In this case, the volume change is isotropic and the gel beats as a whole, like a heart muscle cell. In the case of a large rectangular gel, the total length of the gel periodically changes with the propagation of chemical waves. The dynamic behavior that locally shrunken (or swollen) parts propagate is similar to the peristaltic motion observed in worms. This is the first study to achieve spontaneous volume oscillation of gels without external stimuli. Self-oscillation may be useful in a number of important applications to biomaterials, such as pulse generators or chemical pacemakers, self-walking actuators or micropumps with peristaltic motion, and devices for signal transmission.     

Expression of rat ileal Na+-sulphate cotransport in Xenopus laevis oocytes: functional characterization

Small-intestinal sulphate absorption is a Na⁺-dependent process having its highest rate in the ileum; it involves brush-border membrane Na⁺-sulphate cotransport. Injection of rat ileal mRNA into Xenopus laevis oocytes induced Na⁺-dependent sulphate uptake in a dose-dependent manner, with no apparent effect on Na⁺-independent sulphate uptake. For mRNA-induced transport, the apparent K _m value for sulphate interaction was 0.6±0.2 mM and that for sodium interaction was 25±2 mM (Hill coefficient: 2.3±0.3). mRNA-induced transport, was inhibited by thiosulphate, but not by phosphate or 4,4,′-diisothiocyanatostilbene-2,2′-disulphonic acid (DIDS). Using a rat renal Na⁺-sulphate cotransporter cDNA as a probe [NaSi-1; Markovich et al. (1993) Proc Natl Acad Sci USA 90:8073–8077], the highest hybridization signals (2.3 kb and 2.9 kb) were obtained in size fractions showing the highest expression of Na⁺-dependent sulphate transport in oocytes. Hybrid depletion experiments using antisense oligonucleotides (from the NaSi-1 cDNA sequence), provided further evidence that rat small-intestinal (ileal) Na⁺-sulphate cotransport is closely related to rat proximal-tubular brushborder membrane Na⁺-sulphate cotransport.     

Validity of bioelectrical impedance and ultrasonographic methods for estimating the muscle volume of the upper arm

The present study aimed to investigate the validity of bioelectrical impedance and ultrasonographic methods for predicting the muscle volume of the upper arm. Bioelectrical impedance of the right upper arm and the thickness of elbow flexor and extensor muscles were measured from 26 healthy young adult men using a specially designed bioelectrical impedance data acquisition system and brightness-mode ultrasound apparatus, respectively. As reference data, the muscle volume (MV_MRI) of the right upper arm was determined using a magnetic resonance imaging method. The impedance index was calculated as L ²/Z, where L is the upper arm length and Z is the impedance of the shoulder to the elbow. The muscle volume (MV_ULT) was calculated as π·(d/2)²·L, where d is muscle thickness. L ²/Z and MV_ULT were significantly correlated with MV_MRI with correlation coefficients of 0.971 and 0.962, respectively. In these relationships, the standard errors of estimation were 44.2 cm³ (6.3%) for L ²/Z and 50.7 cm³ (7.2%) for MV_ULT. There was no significant difference between the absolute errors of muscle volumes estimated by L ²/Z and MV_ULT: 36.2 (4.8, SEM) cm³ for L ²/Z versus 40.3 (5.8) cm³ for MV_ULT. The present results suggest that both bioelectrical impedance and ultrasonographic methods may be useful for predicting the muscle volume of the upper arm. Accepted: 7 March 2000     

Signaling pathways involved with the stimulatory effect of Angiotensin II on vacuolar H+-ATPase in proximal tubule cells

It has been documented that angiotensin II (ANG II) (10⁻⁹ M) stimulates proton extrusion via H⁺-adenosine triphosphatase (ATPase) in proximal tubule cells. In the present study, we investigated the signaling pathways involved in the effects of ANG II on H⁺-ATPase activity and on the cytosolic free calcium concentration in immortalized rat proximal tubule cells, a permanent cell line derived from rat proximal tubules. The effects of ANG on pH_i and [Ca⁺²]_i were assessed by the fluorescent probes, 2′,7-bis (2-carboxyethyl)-5(6)-carboxyfluorescein-acetoxy-methyl ester and fluo-4-acetoxy-methyl ester, in the absence of Na⁺ to block the Na⁺/H⁺ exchanger. In the control situation, the pH recovery rate following intracellular acidification with NH₄Cl was 0.073±0.011 pH units/min (n=12). This recovery was significantly increased with ANG II (10⁻⁹ M), to 0.12±0.015 pH units/min, n=10. This last effect was also followed by a significant increase of Ca⁺² _i, from 99.72±1.704 nM (n=21) to 401.23±33.91 nM (n=39). The stimulatory effect of ANG II was blocked in the presence of losartan, an angiotensin II subtype 1 (AT₁) receptor antagonist. H89 [protein kinase A (PKA) inhibitor] plus ANG II had no effect on the pH recovery. Staurosporine [protein kinase C (PKC) inhibitor] impaired the effect of ANG II. Phorbol myristate acetate (PKC activator) mimicked in part the stimulatory effect of ANG II, but reduced Ca⁺² _i. 1,2-Bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (intracellular calcium chelator) alone reduced the pH_i recovery rate below control levels and impaired the effect of ANG II, in a way similar to that of trimethoxy benzoate (a blocker of Ca⁺² _i mobilization). We conclude that ANG II regulates rat proximal tubule vacuolar H⁺-ATPase by a PKA-independent mechanism and that PKC and intracellular calcium play a critical role in this regulation.     

Heterophilic antibodies to connective tissue antigens in the blood sera of rheumatic patients do not cross-react with group AStreptococcus antigens

Heterophilic antibodies reacting with antigens of interstitial connective tissue of bovine myocardium were found in the sera of patients with rheumatic fever. These antibodies were referred to class IgG. Immunologic specificity of the reaction with these antigens was confirmed in experiments with F(ab′)₂ fragments from IgG isolated from the sera of rheumatic patients. Heterophilic antibodies were not adsorbed by various antigens of group AStreptococcus, nor were they isolated in a column with immunosorbent prepared on the basis of nontype-specific streptococcal antigens. The reaction of patients' sera was not inhibited by monoclonal antibodies to nontype-specific antigens cross-reacting with antigens of myocardial interstitial connective tisSue. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 117, N ^o 6, pp. 642–644, June, 1994 Presented by S. V. Prozorovskii, Member of the Russian Academy of Medical Sciences     

pH-regulatory mechanisms in in vitro perfused rectal gland tubules of Squalus acanthias

 Isolated in vitro perfused rectal gland tubules (RGT) were preincubated with the pH-sensitive dye 2′,7′-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF) and pH-regulatory mechanisms were studied. A reduction of bath Cl^– concentration from 269 to 6 mmol/l increased the fluorescence ratio 488/436 [corresponding to cytosolic pH (pH_i)] slightly but significantly (n=10). Depolarization by Ba²⁺ (1 mmol/l) or a bath solution containing 30 mmol/l K⁺ (n=4–6) increased the fluorescence ratio (pH_i). These data suggest that HCO₃ ^– uptake and/or H⁺ extrusion is dependent on Cl^– and/or voltage. A reduction of bath Na⁺ from 278 to 5 mmol/l reduced the ratio significantly (n=3). Addition of trimethylamine (Trima⁺, 20 mmol/l) alkalinized cytosolic pH (n=7). Similarly, addition of NH₄ ⁺ (20 mmol/l) led to an initial alkalinization and a strong acidification when NH₄ ⁺ was removed (n=59). The initial pH_i-recovery rates after NH₄ ⁺ removal were quantified and the responsible H⁺ extrusion and/or HCO₃ ^– import systems were examined. The recovery was almost completely abolished when the extracellular Na⁺ concentration was reduced to 5 mmol/l. In the presence of normal Na⁺, recovery was slower in the absence as compared to the presence of HCO₃ ^– (n=5). It was inhibited by 4,4′-diisothiocyanatostilbene-2,2′-disulphonic acid (DIDS) (0.5 mmol/l, n=11) in the presence of HCO₃ ^– and in the absence of HCO₃ ^– by the Na⁺/H⁺-exchange blocker HOE694 (0.5 mmol/l, n=6). These data suggest that acid extrusion probably occurs by basolateral Na⁺-2HCO₃ ^–/Cl^– exchange in the presence of HCO₃ ^– and by basolateral Na⁺/H⁺ exchange in the absence of HCO₃ ^–. Luminal perfusion with a solution containing a low Cl^– concentration (6 mmol/l) increased the fluorescence ratio (pH_i) (n=5). The ratio (pH_i) was further increased and pH recovery further delayed by basolateral addition of Trima⁺ (20 mmol/l, n=3). These data suggest that the HCO₃ ^–/Cl^– exchanger is present in the luminal membrane. Luminal HCO₃ ^–/Cl^– exchange and basolateral Na⁺-2HCO₃ ^–/Cl^– exchange may work in tandem to secrete HCO₃ ^– and exchange it for luminal Cl^–. Received: 7 January 1998 / Received after revision and accepted: 5 March 1998     

Thoracic Artificial Lung Impedance Studies Using Computational Fluid Dynamics and <Emphasis Type="Italic">In Vitro</Emphasis> Models

Current thoracic artificial lungs (TALs) possess blood flow impedances greater than the natural lungs, resulting in abnormal pulmonary hemodynamics when implanted. This study sought to reduce TAL impedance using computational fluid dynamics (CFD). CFD was performed on TAL models with inlet and outlet expansion and contraction angles, θ, of 15°, 45°, and 90°. Pulsatile blood flow was simulated for flow rates of 2–6 L/min, heart rates of 80 and 100 beats/min, and inlet pulsatilities of 3.75 and 2. Pressure and flow data were used to calculate the zeroth and first harmonic impedance moduli, Z ₀ and Z ₁, respectively. The 45° and 90° models were also tested in vitro under similar conditions. CFD results indicate Z ₀ increases as stroke volume and θ increase. At 4 L/min, 100 beats/min, and a pulsatility of 3.75, Z ₀ was 0.47, 0.61, and 0.79 mmHg/(L/min) for the 15°, 45°, and 90° devices, respectively. Velocity band and vector plots also indicate better flow patterns in the 45° device. At the same conditions, in vitro Z ₀ were 0.69 ± 0.13 and 0.79 ± 0.10 mmHg/(L/min), respectively, for the 45° and 90° models. These Z ₀ are 65% smaller than previous TAL designs. In vitro, Z ₁ increased with flow rate but was small and unlikely to significantly affect hemodynamics. The optimal design for flow patterns and low impedance was the 45° model.     

Effect of vinpocetine on various types of high-threshold potassium currents in snail neurons

A high-threshold (−20 mV) K⁺ current was recorded from isolated edible snail neurons by a two-microelectrode voltage clamp technique. This current consisted of three components: fast-inactivating K⁺ currents (I_A), noninactivating K⁺ current (I_KD), and Ca²⁺-dependent K⁺ current (I_K(Ca)). Different cells had one to three components of K⁺ current. Vinpocetine increased I_A, moderately inhibited I_KD (by 30–50%) and strongly suppressed I_K(Ca) (by 60–90%). Inhibition of I_K(Ca) was not related to the effect of vinpocetine on the inward Ca²⁺ current. When K⁺ current consisted of all three components, the effect of vinpocetine on the ionic current amplitude was opposite at different potentials. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 10, pp. 408–411, October, 1998     

Feasibility of using the automatic generating system for quartz watches as a leadless pacemaker power source

An automatic power-generating system (AGS) which converts kinetic energy into electric energy for quartz watches was tested as a power source for implantable cardiac pacemakers. An automatic power-generating mechanism and a capacitor (0.33 F) were removed from a quartz watch (SEIKO) and encapsulated in a polyvinyl case. Characteristics of the AGS were investigated by acceleration equipment. The capacitor in the AGS was charged to 2.0 V (0.66 J) by placing it on the equipment for about 30 minutes. The equipment has a 2 Hz cycle and generates ±1.7 G at the end of each half cycle. The AGS (fully charged to 2.0 V) was used as the power source for a pulse generator circuit built using commercially available CMOS IC. The circuit generated pulses of 0.5 ms width at 1 Hz (60 pulses min⁻¹). The voltage of the AGS was maintained at 1.6 V while it was being charged by the accelerations. The generator supplied pulses of 0.75V, 1.47 mA through a 510Ω load. With fully charged AGS, the generator was also used to pace a mongrel dog's heart at 140 beats min⁻¹ for 60 minutes. During pacing, the AGS supplied 420 mJ to the circuit and the cardiac muscle. The AGS was placed on the right ventricular wall of the mongrel dog under anaesthesia. Energy of 80 mJ is stored in a capacitor by the heart beating at about 200 beats/min for 30 minutes. Thus the AGS generated 13 μJ per heart beat. This result suggests that the AGS may supply enough energy for use in a cardiac pacemaker.     

Role of nonconserved charged residues of the AE2 transmembrane domain in regulation of anion exchange by pH

The ubiquitous AE2/SLC4A2 anion exchanger is acutely and independently regulated by intracellular (pH_i) and extracellular pH (pH_o), whereas the closely related AE1/SLC4A1 of the red cell and renal intercalated cell is relatively pH-insensitive. We have investigated the contribution of nonconserved charged residues within the C-terminal transmembrane domain (TMD) of AE2 to regulation by pH through mutation to the corresponding AE1 residues. AE2-mediated Cl⁻/Cl⁻ exchange was measured as 4,4′-di-isothiocyanatostilbene-2,2′-disulfonic acid-sensitive ³⁶Cl⁻ efflux from Xenopus oocytes by varying pH_i at constant pH_o, and by varying pH_o at near-constant pH_i. All mutations of nonconserved charged residues of the AE2 TMD yielded functional protein, but mutations of some conserved charged residues (R789E, R1056A, R1134C) reduced or abolished function. Individual mutation of AE2 TMD residues R921, F922, P1077, and R1107 exhibited reduced pH_i sensitivity compared to wt AE2, whereas TMD mutants K1153R, R1155K, R1202L displayed enhanced sensitivity to acidic pH_i. In addition, pH_o sensitivity was significantly acid- shifted when nonconserved AE2 TMD residues E981, K982, and D1075 were individually converted to the corresponding AE1 residues. These results demonstrate that multiple conserved charged residues are important for basal transport function of AE2 and that certain nonconserved charged residues of the AE2 TMD are essential for wild-type regulation of anion exchange by pH_i and pH_o. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. A. K. Stewart and C. E. Kurschat have contributed equally to this work.     

Influence of pacing parameters on pacemaker longevity

 This study retrospectively assessed the parameters that affect pulse generator longevity in 78 patients implanted with dual-chamber pacemakers. Longevity was studied in 52 generators: 14 Cosmos II, 17 Relay, 11 Ellite II, and 10 Thera DR. The lifetimes of Cosmos II and Ellite II were significantly prolonged compared to those of Relay and Thera DR. The comparative study was conducted to evaluate the effect of low-impedance leads (ThinLine I, n = 10) on generator longevity compared with a standard lead (Irox, n = 16). No significant variation in pacing threshold was found between the groups. However, the low-impedance group provided significantly lower cell voltage and higher cell impedance during all follow-up periods compared with the standard lead impedance group. The internal current of the pacemaker with rate response and sophisticated diagnostic memory function (Relay, n = 5, and Marathon DR, n = 5) increased significantly compared with the conventional pacemaker (Cosmos II, n = 5). In conclusion, the selection of unnecessary pacing parameters and the selection of low-impedance leads should be avoided in order to extend generator longevity. Received: November 5, 2001 / Accepted: May 30, 2002 Correspondence to:N. Mizutani