PubMed Health⌕ Search

Biomedical subjects

H C Strauss

Publications and source records attributed to H C Strauss.

At least 91 records · Page 5Linked to original sources
PubMed1984

Lipid solubility modulates pH potentiation of local anesthetic block of Vmax reactivation in guinea pig myocardium.

Current theories envision recovery from local anesthetic block of sodium channels via slow hydrophilic and fast hydrophobic paths. Extracellular pH reduction which increases cationic/neutral anesthetic form should especially prolong recovery kinetics of highly lipid soluble compounds that could readily exit via the hydrophobic pathway at normal extracellular pH. To test this hypothesis, we compared the effects of three related compounds with similar pKa on the time course of Vmax reactivation in guinea pig papillary muscle at pHo 7.4 and 6.95. The compounds were lidocaine and its two desethylation products, monoethylglycinexylidide and glycinexylidide. Judged from the octanol:water partition coefficient, lidocaine was the most lipid soluble (log partition coefficient 2.39 +/- 0.10), followed by monoethylglycinexylidide (log partition coefficient 1.32 +/- 0.09) and glycinexylidide was the least lipid soluble (log partition coefficient 0.41 +/- 0.09). At 30 microM and pHo 7.4, the potency order for Vmax depression at zero diastolic interval was lidocaine (53 +/- 6%), monoethylglycinexylidide (17 +/- 3%), and then glycinexylidide (7.8 +/- 1.9%). The decay of Vmax block appeared monoexponential, and the time constant of recovery was dose independent. Most important is the fact that there were significant differences in the tau r increase with extracellular pH reduction (P less than 0.05; Scheffé contrasts). The increase was greatest with lidocaine [73 +/- 28% (mean +/- SD)], less with monoethylglycinexylidide (42 +/- 15%), and least with glycinexylidide (13 +/- 17%). The simplest interpretation of the differences in extracellular pH-dependence of recovery kinetics was that recovery from block due to the neutral form of these ionizable local anesthetics depended on lipid solubility, whereas recovery from block due to the protonated form depended on molecular weight.

Action Potentials↗
PubMed1983

The measurement of sinus node refractoriness in man.

We recently described a method for measuring sinus node refractoriness in the rabbit heart. Atrial premature beats either may result in reset return responses or may become interpolated because of encroachment on sinus node refractoriness. In previous studies with rabbits we defined the effective refractory period of the sinus node (SNERP) as the longest premature interval that is interpolated. This study presents results on the extension of this technique to the measurement of sinus node refractoriness in man. Out of 30 patients (12 with and 18 without sinus node dysfunction), SNERP could be measured in 26 at one or more basic cycle lengths. At a basic pacing cycle length of 600 msec, SNERP ranged from 250 to 380 msec (mean 325 +/- 39) in patients without sinus node dysfunction and from 500 to 550 msec (mean 522 +/- 20) in patients with sinus node dysfunction. This clear differentiation of patients with and without sinus node dysfunction by SNERP is in contrast to various results obtained by assessing sinus node function from sinus node recovery time and sinoatrial conduction time. Thus this study suggests the possible use of the measurement of SNERP in the assessment of sinus node function in man and its possible value in identifying patients with sinus node dysfunction.

Adolescent↗
PubMed1983

Unitary sodium channels in isolated cardiac myocytes of rabbit.

Transmembrane ionic movements are thought to occur through special membrane areas or channels. Until recently, it has not been possible to study the properties of individual ionic channels, directly. We have used the extracellular patch clamp technique to resolve unitary sodium channels in enzyme-dissociated rabbit ventricular myocytes. Depolarizing voltage clamp steps elicited rectangular inward current fluctuations representing open-closed transition of the channels. Probability of channel opening increased with depolarization. Single channel current amplitude ranged from 0.6 to 1.9 pA. Channel open time increased with depolarization. Sodium channels could be distinguished from calcium channels by their insensitivity to cadmium and inactivation voltage range. First-event latency histograms suggest multiple-closed states. The patch clamp technique can be readily applied to the study of sodium channels in adult cardiac myocytes.

Action Potentials↗
PubMed1983

Sinus node dysfunction.

The syndrome of sinus node dysfunction has become increasingly recognized as a cause of symptoms and morbidity, particularly in the elderly population. This syndrome does not represent a homogeneous disease entity. Increased investigation has shown that many pathologic conditions and pathophysiologic mechanism may lead to one of the several clinical and electrocardiographic manifestations of the sick sinus syndrome. Attempts to improve diagnostic accuracy, identify underlying mechanisms and to predict the outcome of therapy have led to the development of various diagnostic tests. However, at present these have proven of limited clinical value and the mainstay of diagnosis remains ECG monitoring. Treatment is directed at the control of symptoms with pacemaker therapy for bradyarrhythmias and combined pacemaker and antiarrhythmic drug therapy for the bradycardiatachycardia syndrome.

Anti-Arrhythmia Agents↗
PubMed1982

Effects of reduced PO2 on rapid-drive-induced hyperpolarization of diastolic transmembrane potential in feline cardiac Purkinje strands.

Using standard microelectrode techniques, we evaluated effects of diminished oxygen tension on the magnitude and time course of frequency dependent changes in maximum diastolic transmembrane potential (MDP) and on alteration of action potential duration (APD) in feline Purkinje fibers. MDP was recorded continuously during a control period (cycle length (CL) = 1000 ms), during a 5-min period of rapid drive (CL = 400 ms) and following return to pacing CL = 1000 ms. Rapid drive resulted in hyperpolarization of MDP from control value; and after return to pacing CL = 1000 ms. MDP gradually depolarized, eventually attaining a steady state value within +/- 0.5 mV of the control value. The difference between hyperpolarized MDP value and final steady-state value was designated VH, and the decline of MDP towards steady-state value approximated an exponential function (time constant = tau VH). Exposure to reduced PO2 (75 +/- 2.1 mmHg vs. control 473 +/- 39.1 mmHg) (1 mmHg = 133.322 Pa) resulted in reduction in the magnitude of VH (6.2 +/- 3.43 mV vs. 7.8 +/- 2.73 mV, mean +/- SD, p less than 0.005) and shortening of APD within 0-24 min, while measurable prolongation of tau VH (75 +/- 18.5 vs. 54 +/- 9.0 s, p less than 0.005) began at 25-49 min following onset of reduced PO2. These observations suggest that rate-related changes of MDP in cardiac tissues are oxygen dependent, and they support previously reported analagous observations in nerve which suggested that frequency dependent potential changes may in part reflect alterations of electrogenic Na-K pump activity.

Action Potentials↗
PubMed1982

Effect of myocardium at risk on outcome after coronary artery occlusion and release.

The relationship between the probability of sustaining ventricular fibrillation during occlusion or release of a canine coronary artery and the amount of myocardium made ischemic has never been carefully assessed. We occluded the left anterior descending coronary artery above or below the septal artery for 20 min and then released the ligation. The amount of left ventricle perfused by the ligated vessel was determined by injection of different color monastral dyes above and below the ligation. Despite careful ligature placement immediately proximal or distal to the septal artery, there was wide variation in the amount of left ventricle perfused by the ligated vessel, or myocardium "at risk." Myocardium at risk ranged between 24 and 51 g for ligations placed above the septal artery and 14 and 27 g for ligations placed below the septal artery. Ventricular fibrillation during occlusion and after release correlated significantly with the amount of myocardium at risk. This relationship was well described using the logistic risk regression model. The model predicts uniformly low and uniformly high probability of ventricular fibrillation with small and large amounts of myocardium at risk, respectively, and a direct correlation for midrange values of myocardium at risk. This relationship can account for a substantial portion of non-drug related variability in outcome of antiarrhythmic trials using the canine coronary occlusion or release model.

Animals↗
PubMed1982

Intracellular potassium activity in guinea pig papillary muscle during prolonged hypoxia.

During prolonged hypoxia, intracellular potassium concentration, [K](i) has been reported to fall by 70% with a concomitant decrease in the calculated potassium equilibrium potential, E(K). Nevertheless, resting membrane potential, V(m), declined only slightly. Because V(m) depolarized very little in relation to the calculated E(K), it was hypothesized that electrogenic Na-K pumping contributed up to 40 mV to V(m) during prolonged hypoxia. To further test this hypothesis we studied what changes prolonged hypoxia makes in the thermodynamically active fraction of cellular potassium, intracellular potassium activity, alpha(K) (i), and how change in alpha(K) (i) affects the relationship between V(m), E(K) and, by inference, the Na-K pump. Using double-barrel K-selective electrodes, V(m) and alpha(K) (i) were measured in quiescent guinea pig right ventricular papillary muscles superfused for 8 h with hypoxic Tyrode's solution. Over the 8-h period both V(m) and alpha(K) (i) decreased. However, the decline in V(m) was paralleled by a decrease in the E(K) calculated from alpha(K) (i). At no time was there hyperpolarization of V(m) beyond E(K). After 8 h the Na-K pump was inhibited by exposing the muscles to 0.1 mM ouabain. The onset of an increase in extracellular potassium activity, measured with a double-barrel electrode, was used to mark the amount of depolarization of V(m) due solely to pump inhibition. After hypoxia, V(m) depolarized 8.4+/-4.4 mV before extracellular potassium activity (alpha(K) (e)) increased. Thus, the decrease in alpha(K) (i) during hypoxia is much less than that reported for [K](i). The parallel decline in V(m) and E(K) and the small depolarization of V(m) with ouabain suggest that after prolonged hypoxia the Na-K pump continues to contribute to V(m), but the amount of this contribution is substantially less than previously reported.

Action Potentials↗
PubMed1981

Effects of stimulation frequency on potassium activity and cell volume in cardiac tissue.

We examined the effects of increases in stimulation frequency on the intracellular potassium activity and cell volume of feline and canine Purkinje fibers and feline ventricular fibers. Intracellular potassium activity was measured with potassium liquid ion exchanger microelectrodes in single- and double-barrel configuration. Cell volume was measured with an electrophysiologic technique. From single-barrel electrode recordings, intracellular potassium activities (means +/- SE) in feline Purkinje fiber, feline papillary muscle, and canine Purkinje fiber are 117.1 +/- 5.4, 87.3 +/- 3.1, and 112.4 +/- 4.4 mM, respectively, with [K]o (external potassium concentration) of 5.4 mM. Thus direct evidence for a 30-mM gradient in intracellular potassium activity from Purkinje fiber to ventricular muscle is presented. Intracellular potassium activity did not change in any tissue studied during or after 3 min of 4 Hz stimulation. The lack of change is partially explained by a reversible 2% decrease in cell volume induced by the stimulation protocol. Net losses greater than 2% seen in earlier studies probably reflect either differences between perfused vs. superfused preparations or functional sequestration of cellular potassium involved in transfers during frequency changes.

Animals↗
PubMed1981

Electrophysiologic effects on combined autonomic blockade in patients with sinus node disease.

Thirty-two patients were studied before and after i.v. administration of 0.15-0.20 mg/kg of propranolol. Twenty-one of the 32 underwent combined autonomic blockade with the additional infusion of 0.04 mg of atropine. Twenty other patients with sinus node disease underwent electrophysiologic studies both before and after i.v. administration of 0.04 mg of atropine alone. Spontaneous cycle length, maximal corrected sinus node recovery time, sinoatrial conduction time, secondary pauses and intrinsic heart rate were measured. Secondary pauses were more common in those with abnormal intrinsic heart rates, and they did not correlate with changes in maximal corrected sinus node recovery time or sinoatrial conduction time. In patients with normal intrinsic heart rate, abnormal test measurements usually returned to normal after combined blockade (hypervagotonia); however, some patients showed a new abnormality after propranolol that was not reversible with atropine (catecholamine-dependent). Abnormal test responses in patients with abnormal intrinsic heart rate persisted or increased after combined blockade. We conclude that patients with sinus node disease may be categorized as (1) those with intrinsic sinus node disease; (2) those with normal intrinsic sinus node function but either relative hypervagotonia or catecholamine dependency; and (3) those with abnormal intrinsic sinus node function affected by vagal or catecholamine factors.

Adult↗
PubMed1981

Ouabain effects on intracellular potassium activity and contractile force in cat papillary muscle.

The relationship between the positive inotropic and toxic effects of cardiac glycosides and their effects on intracellular ionic composition is incompletely defined. We measured intracellular potassium activity (alpha ik), extracellular potassium activity (alpha ek), resting potential, action potential duration, and contractile force at 32 degrees C in paired papillary muscles from feline right ventricles exposed to ouabain. Muscles used for electrophysiological measurements were quiescent except for isolated stimulation to confirm impalement and record action potential duration. Muscles used for contractile force measurements were quiescent except for 4-min periods when force was measured at a cycle length of 1,400 ms. Muscle length was adjusted to achieve 50% of maximal tension at this cycle length before each experiment. In four experiments, alpha ik and contractile force were measured in the same muscle. Alpha iK was measured with single and double-barrel K-sensitive electrodes. At 10 nM ouabain, action potential duration is prolonged. Among the concentrations tested, the threshold for a clear positive inotropic effect is 0.1 microM ouabain. The threshold for decrease in alpha iK, increase in alpha eK, and decrease in membrane potential is 1 microM, at which concentration toxic signs develop, including arrhythmias, aftercontractions, and alteration in the staircase response of contractile force to repetitive stimulation. Ouabain need not change alpha iK to effect positive inotropy in ventricular muscle, a relationship different from that reported between [K]i (intracellular potassium concentration) and positive inotropy. Higher ouabain concentrations, which others have shown to clearly inhibit active Na and K transport, are shown to upset intracellular potassium activity homeostasis and to consistently produce toxicity.

Animals↗
PubMed1980

Hypersensitive carotid sinus syndrome manifested as cough syncope.

We describe a patient with cough syncope who was found to have carotid sinus hypersensitivity with mixed cardioinhibitory and vasodepressor responses. Symptoms were ameliorated by denervation of the more hypersensitive carotid sinus. Spontaneous atypical Wenckebach cycles in this patient were caused by the combined hypersensitive cardioinhibitory and vasodepressor responses. This report stresses the importance of checking blood pressure as well as heart rate in all patients in whom carotid sinus syndrome is suspected.

Blood Pressure↗