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H C Strauss

Publications and source records attributed to H C Strauss.

At least 55 records · Page 3Linked to original sources
PubMed1991

Reconstitution of the solubilized cardiac sarcoplasmic reticulum potassium channel. Identification of a putative Mr approximately 80 kDa polypeptide constituent.

Recent evidence has indicated that potassium ion movement through sarcoplasmic reticulum (SR) K+ channels is an important countercurrent for Ca2+ release from SR. We used Chaps-solubilized SR vesicles and sucrose density gradient centrifugation to identify components of the canine cardiac SR K+ channel. To overcome the difficulty of the absence of a high-affinity specific ligand, we have successfully applied the planar lipid bilayer reconstitution technique to identify and functionally assay for the solubilized SR K+ channel. We found that Chaps solubilization of the channel did not change the protein's functional properties. The cardiac SR K+ channel sediments as a 15-20S protein complex. A polypeptide of Mr approximately 80 kDa was found to specifically comigrate with the 15-20S gradient fractions and might be a major constituent of the cardiac SR K+ channel.

Animals↗
PubMed1991

Digoxin Immune Fab therapy in the management of digitalis intoxication: safety and efficacy results of an observational surveillance study.

An observational surveillance study was conducted to monitor the safety and effectiveness of treatment with Digoxin Immune Fab (Ovine) (Digibind) in patients with digitalis intoxication. Before April 1986, a relatively limited number of patients received treatment with digoxin-specific Fab fragments through a multicenter clinical trial. Beginning with commercial availability in July 1986, this study sought additional, voluntarily reported clinical data pertaining to treatment through a 3 week follow-up. The study included 717 adults who received Digoxin Immune Fab (Ovine). Most patients were greater than or equal to 70 years old and developed toxicity during maintenance dosing with digoxin. Fifty percent of patients were reported to have a complete response to treatment, 24% a partial response and 12% no response. The response for 14% of patients was not reported or reported as uncertain. Six patients (0.8%, 95% confidence interval 0.3% to 1.8%) had an allergic reaction to digoxin-specific antibody fragments. Three of the six had a history of allergy to antibiotic drugs. Twenty patients (2.8%, 95% confidence interval 1.7% to 4.3%) developed recrudescent toxicity. Risk of recrudescent toxicity increased sixfold when less than 50% of the estimated dose of antibody was administered. A total of 215 patients experienced posttreatment adverse events. The events for 163 patients (76%) were judged to result from manifestations of underlying disease and thus considered unrelated to Fab treatment. Digoxin-specific antibody fragments were generally well tolerated and clinically effective in patients judged by treating physicians to have potentially life-threatening digitalis intoxication.

Adolescent↗
PubMed1991

Voltage dependence of bovine pulmonary artery endothelial cell function.

Vascular mediator synthesis in endothelial cells is Ca2+ sensitive. Bradykinin increases [Ca2+]i by releasing it from intracellular stores and by increasing influx across the plasmalemma. The latter is believed to occur through receptor-operated channels. Although gating of these plasmalemmal channels is voltage-insensitive, we hypothesized that Ca2+ influx would still be dependent on the Ca2+ electrochemical gradient and relative cation permeability. Using cultured bovine pulmonary endothelial cells we therefore measured: membrane voltage (Em) in single cells using the "tight seal" whole cell recording technique, Ca2+i in endothelial cell monolayers using fura-2, and arachidonic acid (AA) release using 3H-AA prior to and following exposure to bradykinin at different [K+]0. Our data indicate that the resting membrane potential of these cells is at least -67 mV in physiological saline and that the background resting membrane properties can be described with a (PNa/PK) ratio of approximately 0.027-0.040. Varying [K+]0 is shown to be an effective means for altering and controlling membrane potential and thus the calcium electrochemical gradient. Increases in [K+]0 lead to a concentration-dependent decrease in the magnitude of the Ca2+ transient and in the relative amount of arachidonic acid released following exposure to bradykinin suggesting that Ca2+ influx through the plasmalemma and AA release are regulated by the Ca2+ electrochemical gradient. In addition, a simple theoretical membrane conductance model is presented which is able to reconcile the wide range in apparent resting membrane potentials which have been reported for endothelial cells.

Animals↗
PubMed1991

Blockade of cardiac sarcoplasmic reticulum K+ channel by Ca2+: two-binding-site model of blockade.

Potassium countercurrent through the SR K+ channel plays an important role in Ca2+ release from the SR. To see if Ca2+ regulates the channel, we incorporated canine cardiac SR K+ channel into lipid bilayers. Calcium ions present in either the SR lumenal (trans) or cytoplasmic (cis) side blocked the cardiac SR K+ channel in a voltage-dependent manner. When Ca2+ was present on both sides, however, the block appeared to be voltage independent. A two-binding site model of blockade by an impermeant divalent cation (Ca2+) can explain this apparent contradiction. Estimates of SR Ca2+ concentration suggest that under physiological conditions the cardiac SR K+ channel is partially blocked by Ca2+ ions present in the lumen of the SR. The reduction in lumenal [Ca2+] during Ca2+ release could increase K+ conductance.

Animals↗
PubMed1990

Open-channel subconductance state of K+ channel from cardiac sarcoplasmic reticulum.

We have characterized the K+ channel of canine cardiac sarcoplasmic reticulum in terms of its gating kinetics and conductance states. We demonstrate that the open channel dwells in two states, O1 and O2, where O1 is a true subconductance state of O2. The two open states are linked with a closed state by a cyclic gating scheme. Under certain circumstances, however, important information can be derived using a binary model. Each open state separately exhibited an ohmic current-voltage relation with unitary conductance values of 105 (O1) and 189 (O2) pS in 0.1 M K+. Gating between closed and open states was weakly voltage dependent, and we derive reaction rate constants for the state transitions. Finally, we postulate three models to explain the existence of a subconductance state (blockade, stenosis, flutter). We argue that a flutter model best accounts for our observations of O1.

Animals↗
PubMed1990

Cocaine-mediated impairment of cardiac conduction in the dog: a potential mechanism for sudden death after cocaine.

Deaths from cocaine abuse continue to increase, while the mechanism of lethality remains unclear. Previous investigations have focused on potential ventricular dysrhythmias and myocardial ischemic events from enhanced autonomic tone or seizure activity from central stimulation. However, cocaine is a local anesthetic and may impair cardiac conduction. To evaluate this, 16 conscious dogs received i.v. cocaine over 30 sec to mimic "recreational" use in doses of 3 mg/kg (n = 6), 5 mg/kg (n = 6) or 7 mg/kg (n = 4). Another group of anesthetized dogs (n = 6) received two infusions of cocaine (5 mg/kg) 1 hr apart. Plasma cocaine levels and His bundle electrograms were obtained at control and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 10 and 15 min after cocaine administration. At 0.5 min, plasma cocaine reached peak levels of 30.0, 45.0 and 59.6 micrograms/ml with increasing dose. Cocaine rapidly produced severe prolongation of His to ventricle interval and widening of the R wave. Slowing of conduction was dose-dependent, with maximal increases in His to venticle interval of 37 to 56% (P = .0299) and R wave duration of 34 to 77% (P less than .025). Furthermore, significant conduction impairment developed at cocaine levels that did not produce seizures. Conduction effects were equally pronounced during repeated administration of cocaine. These data indicate that cocaine causes marked conduction slowing, which could play an important role in cocaine death.

Animals↗
PubMed1990

Effects of amiloride on pH regulation in canine cardiac Purkinje fibers.

Myocardial cells utilize membrane transport systems for proton extrusion as well as internal buffers to preserve pH homeostasis. Our laboratory had shown previously that amiloride (0.01-1.0 mM) causes a time- and dose-dependent increase in action potential duration, early after depolarizations and enhanced automaticity. Ion-selective microelectrode technique was used to evaluate whether the observed electrophysiologic effects of amiloride are linked to inhibition of Na/H exchange and subsequent inability of the myocardial cell to maintain steady-state intracellular pH (pHi), either under normal physiological conditions or in the presence of an imposed acid load. We analyzed different components of intracellular pH transients that occur in response to NH4Cl exposure and washout, which allowed us to quantitatively describe the effects of Na/H exchange inhibition in a multicellular preparation. Amiloride (0.01-1.0 mM) did not change the steady-state pHi, but did cause a dose-dependent increase in both the time for the pHi to reach a minimum value (time-to-peak) during washout of NH4Cl as well as in the absolute minimum value of pHi (peak acid). The effects of amiloride on pHi transients are rapidly reversible and antagonized by physiologic values of extracellular sodium activity. We conclude that Na/H exchange inhibition by amiloride does not cause intracellular acidosis under normal physiologic conditions, despite the dramatic changes in action potential characteristics. However, amiloride affected the time-to-peak and the peak acid value of the pHi transient during NH4Cl washout at concentrations that had no discernible effect on the overall time course of pHi recovery.

Acid-Base Equilibrium↗
PubMed1989

Reconstitution of ionic channels from human heart.

This report is the first description of single ion channels from human myocardium. Using explanted human left ventricular tissue, we have studied three K-conducting and two anion-conducting channels. We report our observations of gating and ionic selectivity properties of these channels which, we argue, derive from both sarcolemmal and sarcoplasmic reticulum membranes. We postulate that one channel is the K-conducting channel (SR K channel) from human cardiac sarcoplasmic reticulum. Another channel is similar to a dimeric Cl- channel from Torpedo electroplax, displaying two equally spaced levels of open state conductance.

Animals↗
PubMed1989

Potassium channel of cardiac sarcoplasmic reticulum is a multi-ion channel.

We have characterized mechanisms of ionic permeation in the K channel of canine cardiac sarcoplasmic reticulum (SR K channel). Ionic selectivity, as measured by relative permeabilities, followed Eisenman sequence l, a low field strength sequence. Slope conductance measured in symmetrical solutions across the bilayer followed Eisenman sequence V. In all cases, the selectivity characteristics of the prominent subconductance state (O1) were similar to those of the main-state (O2). Further, our studies have revealed that this channel differs in three significant ways from the highly characterized SR K channel of skeletal muscle. First, the ratio of permeabilities Cs+ to K+ was a complex function of ion concentration. Second, the concentration dependence of conductance was not well described by the Michaelis-Menten formalism. Instead, we modeled the observed relations using a more general approach based on classical rate theory. Third, mole fraction experiments (Cs+ with K+) demonstrated a prominent anomalous effect. Certain of our Cs+ data required the Eyring rate theory approach for adequate interpretation. We adopted a symmetrical energy profile incorporating ion-ion interaction and thereby accounted for much of the data. We conclude that the canine cardiac SR K channel is significantly different from that of skeletal muscle, and it may accommodate more than one ion at a time.

Animals↗
PubMed1989

Characterization of concentration- and use-dependent effects of quinidine from conduction delay and declining conduction velocity in canine Purkinje fibers.

The dynamic response of squared conduction velocity, theta 2, to repetitive stimulation in canine Purkinje fibers with quinidine was studied using a double-microelectrode technique. With stimulation, a frequency-dependent monoexponential increase in conduction delay (CD) and a decline in theta 2 were observed. The exponential rates and changes in steady-state CD and theta 2 were frequency- and concentration-dependent. The overall drug uptake rates describing blockade and the interpulse recovery interval were linearly related and steady-state values of theta 2 were linearly related to an exponential function of the stimulus intervals. Based on first-order binding, the frequency- and concentration-dependent properties of quinidine were characterized by the apparent binding and unbinding rates of 14.2 +/- 5.7 X 10(6) mol-1.s-1 and 63 +/- 12 s-1 for activated and 14.8 +/- 1.0 X 10(2) mol-1.s-1 and 0.16 +/- 0.03 s-1 for resting states. The recovery time constant extracted from the pulse train interpulse interval was 5.8 +/- 1.5 s compared with 5.1 +/- 0.6 s determined from a posttrain test pulse protocol. This study demonstrates that the kinetics of drug action can be derived from measures of impulse propagation. This provides a basis for characterizing frequency-dependent properties of antiarrhythmic agents in vivo and suggests the plausibility of a quantitative assessment of drug binding and recovery rates in man.

Action Potentials↗
PubMed1989

Effects of flecainide on occlusion and reperfusion arrhythmias in dogs.

To assess flecainide's ability to suppress ventricular fibrillation during reperfusion, we compared flecainide acetate (2 mg/kg i.v.) with saline placebo in 50 pentobarbital-anesthetized dogs undergoing proximal anterior descending coronary artery occlusion for 20 min followed by sudden release. Treatment selection was blinded and randomized. Flecainide (1 mg/kg) was given for 5 min before ligation and 1 mg/kg over the 20 min occlusion period. Heart rate, blood pressure, myocardium at risk, and QRS duration before drug infusion were similar between treatment groups. Flecainide prolonged the QRS duration 12% with no effect on heart rate or blood pressure. Dogs successfully cardioverted from ventricular fibrillation during occlusion were subjected to reperfusion. One of the 25 dogs treated with placebo fibrillated during occlusion, whereas 13 of the 25 dogs treated with flecainide fibrillated during occlusion and 10 of these 13 could not be resuscitated. Thirteen of the 25 dogs in the placebo group fibrillated during reperfusion, whereas 3 of the remaining 15 dogs in the flecainide treatment group fibrillated during reperfusion. The proarrhythmic effects of flecainide during occlusion confound interpretation of its antiarrhythmic activity during reperfusion. Thus, although flecainide may have prevented ventricular fibrillation during reperfusion, it clearly caused ventricular fibrillation during occlusion in this preparation of acute myocardial ischemia.

Animals↗
PubMed1989

Physician utilization of laboratory procedures to monitor outpatients with congestive heart failure.

Little is known about how different types of physicians use laboratory procedures in the management of outpatients with congestive heart failure. We therefore analyzed data from a national survey of randomly selected general practitioners, internists, and cardiologists to assess their management of outpatients with New York Heart Association class II congestive heart failure. Most of the 2704 respondents (90%) scheduled office visits between two and four months apart. Body weight, serum electrolytes, and chest roentgenograms were followed regularly by 98% or more of respondents, at median intervals of one to two months, three to five months, and 12 to 17 months, respectively. Serum digoxin levels in patients taking digoxin were followed by 90% of respondents at a median interval of 12 months. Echocardiography, radionuclide ventriculography, and exercise testing were used by fewer respondents (81%, 61%, and 61%, respectively), each at a median interval of 18 months or longer. Cardiologists were significantly more likely to follow patients using either echocardiography, radionuclide ventriculography, or exercise testing. The estimated yearly cost of following a class II congestive heart failure outpatient varied nearly fourfold from the lowest quartile of physicians ($303) to the highest ($1167). Cardiologists were disproportionately represented among the high-cost users. In addition, physicians who were younger or who practiced in an urban setting were significantly more likely to be high-cost users. Thus, simple laboratory tests were used most frequently to follow patients with heart failure, but differences in use of more expensive tests led to large differences in cost. Test use for similar patients is affected by characteristics of both the physician and practice setting.

Ambulatory Care↗
PubMed1988

Theoretical study of the voltage and concentration dependence of the anomalous mole fraction effect in single calcium channels. New insights into the characterization of multi-ion channels.

Several recent independent studies on macroscopic Ca currents have demonstrated the anomalous mole fraction effect in mixtures of Ca and Ba at concentrations of 10 mM or less. Recently, Hess and Tsien (1984; Nature 309) proposed a dual binding site model, based upon Eyring rate theory, to account for this effect in L-type cardiac Ca channels. This model predicts that the anomalous mole fraction effect can be accounted for solely in terms of open single channel permeation properties; it was able to adequately reproduce the effect for macroscopic Ca currents recorded in 10 mM solutions. However, the electrochemical gradients under which single Ca channel current recordings are routinely made with the patch clamp technique vary dramatically from those used for macroscopic Ca currents. To properly assess the general validity of the Hess and Tsien model at the single Ca channel level, the effects of both large electrical potentials and elevated divalent concentrations must be understood. Computer simulations were therefore carried out using the original parameters used by Hess and Tsien under conditions designed to mimic those used in patch clamp studies. The permeation behavior generated by this model is quite complex. In particular, hyperpolarization and increased divalent concentration combine to reduce and ultimately abolish the anomalous mole fraction effect. It may therefore be very difficult to observe the anomalous mole fraction effect at the single Ca channel level; the dual-site model displays a relationship between current and mole fraction generally associated with a single-site model under the conditions frequently employed to resolve single Ca channel activity. Nonetheless, analysis of such monotonic mole fraction behavior can still be used as a test for the general validity of the dual-site model. Apparent Kms for Ca and Ba can be extracted from such monotonic behavior, and may not only be functions of membrane potential but may also depend upon the total divalent cation concentration. This is a unique prediction which is incompatible with the simple single-site model. Our analysis provides (a) a possible resolution for the apparent discrepancies presently existing in the experimental literature regarding the existence of the anomalous mole fraction effect at the single Ca channel level, (b) a mechanistic description of previously unexplained observations on the voltage-dependence of the anomalous mole fraction effect, and (c) a useful theoretical framework for future experimentation designed to test the general validity of the dual binding site model of the Ca channel.

Animals↗
PubMed1988

Comparison of time domain and frequency domain variables from the signal-averaged electrocardiogram: a multivariable analysis.

The relative values of the unprocessed signal-averaged electrocardiogram (ECG) and time domain analysis and frequency domain analysis of the signal-averaged ECG were compared in 36 patients with sustained monomorphic ventricular tachycardia and a remote myocardial infarction, in 29 asymptomatic patients with a remote myocardial infarction and in 23 normal subjects. Area ratios of the energy spectra derived from fast Fourier transform analysis were calculated using six separate 140 ms intervals starting at 0, 40, 50 and 60 ms after QRS onset; 40 and 50 ms before QRS end and a variable length interval starting 40 ms before QRS end and extending to the T wave. Total filtered QRS duration, late potential duration and root mean square voltage of the terminal QRS complex were measured from the filtered vector magnitude signal-averaged ECG. The total QRS duration was also measured from the X, Y, Z leads of the unfiltered signal-averaged ECG. Seven variables were significantly different in univariate tests between myocardial infarction patients with and without ventricular tachycardia: three fast Fourier transform area ratios with the sampling interval starting at 1) QRS onset (p = 0.007), 2) 40 ms after QRS onset (p = 0.02), and 3) 60 ms after QRS onset (p less than 0.0001); and all four time domain variables at 1) total filtered QRS duration (p less than 0.0001), 2) late potential duration (p = 0.0001), 3) root mean square terminal QRS voltage (p = 0.0001), and 4) QRS duration from the unprocessed signal-averaged ECG (p less than 0.0001). Of these seven variables, only the fast Fourier transform area ratio starting at QRS onset was significantly different between patients with myocardial infarction without ventricular tachycardia and normal subjects. In multi-variable analysis, the total filtered vector magnitude QRS duration, a time domain variable that includes the late potential, was the only independent factor that separated patients with myocardial infarction with and without associated ventricular tachycardia.

Analysis of Variance↗