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Biomedical subjects

D H Singer

Publications and source records attributed to D H Singer.

At least 37 records · Page 2Linked to original sources
PubMed1987

Heart rate variability and sudden death secondary to coronary artery disease during ambulatory electrocardiographic monitoring.

Data are analyzed from 5 patients who died suddenly during ambulatory electrocardiographic monitoring. Three of the patients were also assessed in terms of 2 recently developed indexes of heart rate (HR) variability. One of these, the standard deviation of RR intervals during successive 5-minute segments averaged over 24 hours, has been reported to be a putative index of vagal tone. Comparisons were made with HR variability findings in 20 normal volunteers. Sudden death was due to ventricular tachycardia degenerating into ventricular fibrillation in all cases. Both early (3 patients) and late cycle (2 patients) ventricular premature complexes initiated the terminal dysrhythmia. An increased density of ventricular ectopic activity was noted in the hour before onset of ventricular fibrillation. HR variability as measured by the standard deviation was significantly (p less than 0.01) lower in the patients who died suddenly (30 +/- 10 ms) than in the normal subjects (76 +/- 14 ms). These findings support suggestions that HR variability analysis may be useful in identifying patients at a higher risk of sudden death.

Aged↗
PubMed1987

Intra- and extracellular potassium activities and the potassium equilibrium potential in partially depolarized human atrial cells.

Under tissue bath conditions, isolated specimens of human right atrium are characterized by the presence of large numbers of partially depolarized cells. The basis for the depolarization is still not understood. To determine if reduced intracellular potassium activity (aKi) is responsible for the low levels of maximum diastolic potential (MDP), aKi was directly measured with potassium ion-selective micro-electrodes (KISE). The effects of varying bath potassium concentration ([K+]0) on aiK and on the relationship between MDP and the potassium equilibrium potential (EK) also were determined. In 4 mM [K+]0, all specimens studied were partially depolarized (MDP = -43.9 +/- 1.3 mV [mean +/- S.E.]) and beat spontaneously. aKi was 98.1 +/- 1.5 mM, and EK was -93.3 +/- 0.4 mV. Changes in [K+]0 between 2.5 and 40 mM did not change aKi significantly. MDP was relatively insensitive to [K+]0 and was always far positive to EK over the entire range of [K+]0 studied. The ability of the KISE to reliably measure aKi in the face of the spontaneous diastolic depolarization was assessed by using acetylcholine or cooling to depress automaticity. These measures did not significantly alter the calculated aKi. The results indicate that: aKi in human atrial specimens is similar to that in atria from other mammalian species, and the low level of MDP exhibited by human atrial cells subject to conventional tissue bath conditions does not primarily result from low levels of aKi.

Body Fluids↗
PubMed1987

Amiodarone-induced block of sodium current in isolated cardiac cells.

Sodium current (INa) block by amiodarone (AMI) was investigated in isolated single Purkinje and ventricular myocardial cells using the single suction-pipette voltage-clamp technique. AMI produced marked resting block that was enhanced at low holding potentials, findings consistent with a shift in the steady-state INa availability curve to more negative potentials (-16 +/- 3 mV). Resting block was not associated with any change in the time course of INa decay during a depolarizing clamp step. AMI also produced use-dependent block in conjunction with increases in rate (0.5-5.0 Hz) and pulse duration (2-200 msec). These changes are consistent with a slowing of the recovery from inactivation of the sodium channel. Brief depolarizing pulses produced little use-dependent block, suggesting that the onset of drug-induced block is slow. Thus, AMI blocks INa and shifts the availability curve in isolated myocytes, both of which contribute to the net tonic block. The results suggest that both rested state and inactivated state sodium channel block are factors in AMI's antiarrhythmic efficacy.

Amiodarone↗
PubMed1986

Characterization of a sodium pump-induced hyperpolarization in isolated human atrium.

Specimens of right atrial appendage from 106 patients were incubated in cold Tyrode solution, and transmembrane resting potentials (Em) were recorded during rewarming at selected temperatures. Rewarming caused a transient hyperpolarization to develop. The hyperpolarization had a temperature threshold between 17 and 22 degrees C and was inhibited by acetylstrophanthidin. Acetylcholine (ACh) induced a depolarization during early rewarming in 7, 10, 20, and 40 mM K+, indicating that Em hyperpolarized to a potential negative to the equilibrium potential for K+. ACh had no effect after some decline of Em, and hyperpolarization was induced by ACh when Em had reached steady state. The relationship between [K+] in the bulk phase of the superfusate [( K]b) and the "reversal potentials" for the ACh effect was log linear and had a slope of 61.7 mV per tenfold change in [K]b. The relationship between [K]b and hyperpolarization was studied in the presence of 0.5 mM Ba2+. The apparent [K]b resulting in half-maximal pump-induced hyperpolarization was 1.3 mM. The data indicate that human atrium can pump Na+ electrogenically and that the characteristics of the Na+ pump-induced hyperpolarization resemble those described for cardiac tissue from several other mammalian species.

Aged↗
PubMed1985

Inhibition of electrogenic Na-pumping attributable to binding of cardiac steroids to high-affinity pump sites in human atrium.

Binding of cardiac steroids to the Na,K-pump may occur at both high- and low-affinity sites. Binding at low-affinity sites causes pump inhibition. However, the functional significance of binding at high-affinity sites is controversial. The effects of cardiac steroids presumed bound at high-affinity sites on electrogenic Na-pumping was therefore examined in human atrial tissue. Specimens were preloaded with Na+ by cooling to 2 degrees C for 60 min and then rewarmed to 30 degrees C in 20 mM K+. In nine control experiments, the resting membrane potential hyperpolarized to -69.9 +/- 0.7 mV (mean +/- S.E.) due to enhanced Na,K-pump activity upon rewarming. Maximal hyperpolarization was less negative during exposure to 10(-9) to 10(-6) M acetylstrophanthidin in a dose-dependent manner. The differences between maximal hyperpolarization during control experiments and during exposure to acetylstrophanthidin were attributed to pump inhibition. Inhibition occurred at all acetylstrophanthidin concentrations including the low range in which binding at high-affinity sites should predominate. The relationship between acetylstrophanthidin concentration and pump inhibition was bimodal with a "shoulder" around 10(-8) M. The data were well described by a model which assumes that acetylstrophanthidin binds at both low capacity-high-affinity (half-saturation, 3.9 X 10(-9)M) and high capacity-low-affinity sites (half-saturation, 4.8-6.1 X 10(-7) M). Nonlinearity in the experimental assay of pump function did not appear to explain the bimodal concentration-inhibition relationship. Thus, cardiac steroids may cause Na,K-pump inhibition in humans by binding to high-affinity pump sites.

Acetylcholine↗
PubMed1984

Evidence for electrogenic Na+ pumping in human atrial myocardium.

The resting potential of "sodium-loaded' cardiac cells can transiently hyperpolarize to levels negative to the steady state resting potential [3,5,6]. Hyperpolarization is associated with the coupled efflux of Na+ and influx of K+ driven by an active transport process and may result from an increased K+ equilibrium potential (EK), an outward pump current or both. Using conventional microelectrode techniques, we found that Na+-loaded human atrial myocardium can also transiently hyperpolarize. Na+ loading was induced by cooling to 2 degrees to 3 degrees C. Upon rewarming to 37 degrees C in a 20 mM K+ solution, the resting potential transiently hyperpolarized to levels at least 11 mV negative to the calculated EK and 29 +/- 2 mV (mean +/- S.E.) negative to the steady state level (- 33 +/- 2 mV) recorded some 15-20 minutes later. An increase in K+ conductance induced by acetylcholine exposure [2,7,10] during the transient hyperpolarization caused a depolarization, indicating that the resting potential was indeed negative to EK. These findings cannot be explained by either conductance changes or electroneutral Na+ pumping and concomitant extracellular K+ depletion. We conclude that the Na+-loaded human atrium can generate net pump current.

Atrial Function↗
PubMed1984

Intra- and extracellular potassium activities, acetylcholine and resting potential in guinea pig atria.

Intracellular potassium activity in guinea pig left atria was measured using potassium ion-selective microelectrodes and conventional microelectrodes. The effects of extracellular potassium concentration and acetylcholine on both intracellular potassium activity and the relationship between the resting membrane potential and the potassium equilibrium potential were investigated. Intracellular potassium activity was 102.1 mM in bathing media with a potassium concentration of 5 mM. Neither increasing extracellular potassium concentration to 10 mM nor exposure to acetylcholine (2 x 10(-6) to 10(-3) M) significantly altered intracellular potassium activity. In contrast, intracellular potassium activity decreased to 92.9 mM in 2.5 mM potassium concentration solutions. Resting membrane potential was 18.6, 9.6, and 7.3 mV positive to the potassium equilibrium potential in 2.5, 5, and 10 mM potassium, respectively. Acetylcholine caused a significant hyperpolarization at each extracellular potassium activity, confirming that resting membrane potential was positive to the potassium equilibrium potential. Even after exposure to 10(-3) M acetylcholine, the resting membrane potential apparently remained positive to the potassium equilibrium potential. If potassium accumulates in extracellular clefts during acetylcholine exposure, the calculated potassium equilibrium potentials are too negative, and the resting membrane potential might closely approximate the potassium equilibrium potential under these conditions. Fading of the acetylcholine-induced hyperpolarization and overshoot of the resting membrane potential on washout of acetylcholine were observed and are consistent with an accumulation of potassium during exposure to acetylcholine. In 5.0 mM potassium bathing solution, preparation-to-preparation variability of resting membrane potential can largely be explained by variability of intracellular potassium activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1981

Autonomic nervous system and cellular injury from circumflex ligation in dogs.

The role of the autonomic nerves in the development of irreversible cellular injury (ICI) after circumflex coronary occlusion was examined in dogs with intact, acutely, or chronically decentralized cardiac nerves. Cardiac nerves were chronically decentralized 2 wk before ligation (CD) or acutely at the time of ligation (AD). In one group of AD dogs, the beta-blocker oxprenolol (0.3 mg/kg) was administered before ligation (AD + Ox). Hearts were paced at 160 beats/min to exclude any contribution of rate change secondary to autonomic intervention. The results are expressed in terms of percent of the cross-sectional area of the posterior papillary muscle (PPM) sustaining ICI after 40-min occlusion: intact 64 +/- 4% (SE), 6 +/- 4%, AD 39 +/- 10%, and AD + Ox 2 +/- 2%. Both acute and chronic denervation protect against ICI even in the absence of changes in heart rate. Furthermore, in dogs with intact cardiac nerves, reduction in pacing rate from 160 to 60 beats/min also decreased the extent of ICI from 64 +/- 4 to 34 +/- 10%. Experiments defining the time course of development of ICI in the PPM indicate that protection was only temporary, delaying the onset of injury by 25 min. These findings suggest that 1) neural activity in extrinsic cardiac sympathetic nerves activate beta-receptors, thereby influencing the development of ICI, and 2) differences in protection afforded by acute denervation with and without beta-blockade indicated that intrinsic postganglionic sympathetic nerve terminals can liberate transmitter in response to ischemia even in the absence of extrinsic neural activity.

Animals↗
PubMed1979

Pseudo atrioventricular block.

Pseudo first- and second-degree atrioventricular (AV) block can occur due to depressive effects of concealed junctional discharges on AV conduction of sinus impulses. Pseudo AV block is not indicative of a primary impairment of AV conduction and is reversible by interventions that suppress ectopy.

Electrocardiography↗
PubMed1979

Pseudodysrhythmias in ambulatory ECG monitoring.

Artifacts mimicking a variety of dysrhythmias occur relatively frequently in ambulatory ECG (Holter) monitoring records. Proper interpretation is imperative if serious therapeutic errors are to be avoided. Two-channel recording systems may facilitate recognition of some, but not all, of these artifacts. Pseudodysrhythmias may mimic paroxysmal supraventricular tachycardia and atrial fibrillation, atrial dissociation, extrasystoles, and sinus pauses. There are several causes of pseudodysrhythmias. Failure to recognize these patterns may result in serious errors in patient management.

Ambulatory Care↗
PubMed1978

Cellular electrophysiological marker of irreversible ischemic myocardial injury.

Glass microelectrode studies on posterior papillary muscle (PPM) slice preparations from 20 pentobarbital-anesthetized dogs (15 subjected to prior circumflex coronary artery ligation, 5 to sham ligation) have resulted in the definition of an electrophysiological marker of irreversible ischemic injury, namely, findings of areas composed of cells unable to generate a significant resting potential (less than -25) mV), designated "electrically inactive areas." Electrically inactive areas were essentially confined to PPM from dogs with circumflex coronary ligation; the incidence and distribution of the areas was related to duration of ischemia. Correlative phase- and light-microscopic studies demonstrated close correspondence between such areas and morphological evidence of irreversible ischemic injury. Analysis of frequency and distribution of electrically inactive areas permits quantitative assessment of the extent and spatial distribution of irreversible injury. This method has been used to quantitate injury in PPM from dogs that had been subjected to ligation for varying time periods. The potential utility of this method for evaluation of interventions designed to protect against ischemic injury and to assess electrical properties of surviving cells is considered.

Animals↗
PubMed1978

ECG diagnosis of acute myocardial infarction in patients with pacemakers.

Ventricular pacing may mimic or obscure the Q waves of myocardial infarcton. Although ST-T changes may occur for other reasons, their presence should alert the physician to the possibility of acute infarction. QRS complexes may be evaluated for infarction if supraventricular beats without left bundle-branch block occur prematurely, as part of a supraventricular tachycardia or as escape beats after inhibition of the articifial pacemaker.

Electrocardiography↗