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Biomedical subjects

W C Randall

Publications and source records attributed to W C Randall.

At least 109 records · Page 6Linked to original sources
PubMed1981

Hierarchy of supraventricular pacemakers.

Definitive subsidiary atrial pacemakers (SAPs) exist within the crista terminalis and in the atrial free wall tissue at the junction of the inferior vena cava and the inferior right atrium. These pacemakers are capable of maintaining cardiac rhythm at a rate intermediate between that of the sinoatrial (SA) nodal and atrioventricular (AV) junctional pacemakers upon default of the normal SA nodal cells. The conventional concept of a single (junctional) escape mechanism needs to be updated by recognition of these SAP sites, which are under comprehensive autonomic regulation. A great variety of clinically important cardiac syndromes require understanding of the SAPs, not only for diagnostic significance but also for therapeutic consideration. SAPs differ from the SA pacemakers in that they possess intrinsically slower spontaneous rates and are less stable. There is early competition among them for instantaneous dominance. They are more responsive to both sympathetic and parasympathetic control, and they are initially more susceptible to underdrive stimulation by another pacemaker (whether artificial or natural) than are pacemakers with the SA node.

Atrial Function↗
PubMed1980

Atrial ectopic foci in the canine heart: hierarchy of pacemaker automaticity.

The sinoatrial node (SAN) and adjacent tissue of the sulcus terminalis were surgically excised in sequential multiple sections to study the location and intrinsic rate of emerging pacemakers in the acute open-chest dog. Under chloralose anesthesia total of 17 ectopic atrial pacemakers emerged in 12 dogs ranging in location from the anterior interatrial band, midsulcus terminalis, and junction of the inferior vena cava-inferior right atrium. Four AV junctional and one idioventricular pacemakers also emerged in these experiments. Each successively inferior focus had a slower rate than the SAN. The average heart rate of the atrial ectopic pacemakers was 73 +/- 4% of the SAN but that the AV junctional pacemakers was 56 +/- 4% of the SAN (P less than 0.05). The greatest reductions in rate were achieved with total excision of the SAN and entire sulcus terminalis, but in only 50% of the animals did this result in a junctional rhythm. The location and rate of atrial ectopic foci support the notion that the AV junctional region is not the fastest pacemaker in the absence of the classically defined SAN and suggest that atrial ectopic pacemakers are intermediate in the hierarchy of cardiac pacemakers in the dog.

Action Potentials↗
PubMed1980

Cardiac arrhythmias after chronic embolization of the sinus node artery: alterations in parasympathetic pacemaker control.

Embolization of the sinus node artery was accomplished in dogs by injecting rapidly hardening vinyl latex into the sinus node artery. Embolization immediately shifted the pacemaker to a junctional focus; however, with time postoperatively, the pacemaker shifted to an atrial site. Variable episodes of pacemaker failure, sinoatrial block, junctional rhythm, wandering atrial pacemaker and idioventricular escape rhythms were commonly observed on Holter monitor in isolation but only rarely when the dog was in the laboratory. Severe bradycardia (38.9 +/- 3.7 beats/min) was the predominant rhythm by 3-6 months postoperatively. In addition, these same dogs had a greater overall increase in heart rate after atropine than normal dogs (17.5 +/- 13.5 vs 116.6 +/- 15.9 beats/min above control; p less than 0.02). Responses to vagal stimulation in this group were abnormal, as long periods of asystole and bradycardia were observed after stimulation was terminated. These data suggest an alteration in parasympathetic pacemaker control after chronic embolization of the sinus node artery.

Animals↗
PubMed1979

Quantitative structure-activity relationships involving the inhibition of glycolic acid oxidase by derivatives of glycolic and glyoxylic acids.

The enzyme glycolic acid oxidase oxidizes glycolate to glyoxylate and glyoxylate to oxalate. Three series of compounds related to the natural substrates, substituted glycolic, oxyacetic, and glyoxylic acids, have been investigated as inhibitors of this enzyme using the techniques of regression analysis and quantitative structure-activity relationships. The best overall correlation with inhibitory potencies was found with the Hansch hydrophobic parameter pi. The classical electronic parameters sigmap, sigmam, F, and R performed poorly. For the substituted glyoxylic acids, a dummy parameter relating to the presence of a nucleophilic group in close proximity to the alpha-carbonyl of the glyoxylate group was found to be highly significant. The syntheses of six novel glycolic and glyoxylic acids are described.

Acetates↗
PubMed1979

The unbalanced heart. Animal models of cardiac dysrhythmias.

The heart often appears to function independently because it can maintain regular activity even when isolated from the rest of the body. Likewise, it maintains its regularity in the midst of powerful but balanced neural and pressure influences. Experimental situations designed to unbalance these forces produce rhythm disturbances resembling those encountered clinically. Unbalancing of the sympathetic supply with the parasympathetic supply totally obliterated, leads to tachycardias of various origin which are eliminated by adrenergic blockade. Removing the sinoatrial node results in atrial brady-tachyarrhythmia, eliminated by cholinergic blockade. Unbalancing the pressure load results in premature ventricular contractions that are clearly not mediated by external neural controls. Cardiac rhythm disturbances thus result from a variety of forces that may be readily tolerated when balanced by opposing forces but cannot be controlled without that buffer.

Animals↗
PubMed1979

Supraventricular pacemaker underdrive in the absence of sinus nodal influences in the conscious dog.

The ability to reduce and maintain heart rate by electrical stimulation (underdrive) was tested in three groups of chronically instrumented dogs: sinoatrial node intact, ectopic atrial pacemaker produced by injection of rapidly hardening latex into the sinoatrial nodal artery, and idioventricular pacemaker produced by injection of formalin into the atrioventricular node. In the conscious unsedated state, underdrive of sinoatrial or idioventricular pacemakers resulted in competition between driven and intrinsic foci. However, the cycle length of ectopic atrial pacemakers could be increased by 148.4 +/- 30.7 msec (P less than 0.001) and maintained at that value. Cessation of underdrive resulted in a period of pacemaker suppression similar to that produced following overdrive. Single premature stimuli produced marked cycle length prolongations in dogs with ectopic atrial foci. Total autonomic blockade had no significant effect on the production of underdrive. Thus, the results of the present experiments provide evidence for maintained capture of cardiac pacemakers at rates significantly below intrinsic control and indicate that underdrive varies as a function of pacemaker site. Underdrive may explain the failure of junctional escape in the presence of slower atrial rhythms.

Animals↗
PubMed1978

Sinus node dysfunction. An overview with emphasis on autonomic and pharmacologic consideration.

Sinus node dysfunction is a disorder of impulse generation and impulse conduction. Previous works have emphasized that the dysfunction occurs not only within the sinus node but also within the escape pacemaker. Adrenergic and cholinergic mechanisms, as well as pulsations and pressure within the sinus node artery, play an important role in normal sinus node activity. Although perinodal fibers act as a buffer zone for sinoatrial conduction, their role in man is yet to be clarified. During normal sinus node activity, pacemaker shifts from the sinus node to the crista terminalis have been shown to occur. Following sinus node destruction, similar shifts do occur. Clinical methods of determining sinus node function, such as the sinus node recovery time and sinus atrial conduction time, are useful but have limitations. Dynamic electrocardiographic monitoring provides the best clinical method available for detecting sinus node dysfunction. Digitalis appears to improve the parameters of sinus node function by increasing the automaticity of latent atrial pacemakers. The atrial arrhythmia of sinus node dysfunction appears to be related to the characteristics of latent atrial pacemaker and "enhanced" cholinergic tone.

Arrhythmias, Cardiac↗
PubMed1978

Synthesis and antihypertensive activity of some ester progenitors of methyldopa.

A variety of esters of methyldopa was synthesized with the objective of obtaining derivatives that would be more efficiently absorbed from the gastrointestinal tract than the free amino acid and would undergo conversion to methyldopa readily in the blood or target tissues. Two of the esters, alpha-pivaloyloxyethyl (4u) and alpha-succinimidoethyl (4w), were found to be more potent antihypertensive agents than methyldopa in animal models and were selected for further study in man. The amino esters were prepared by three different methods, including direct esterification of methyldopa without the use of N- or O-protecting groups.

Animals↗
PubMed1978

Cardiac pacemakers in absence of the SA node: responses to exercise and autonomic blockade.

Surgical excision of the sinoatrial node, verified histologically, is followed by a supraventricular (atrial) rhythm in both resting and exercising dog whether anesthetized or conscious. The ECG is characterized by a definitive P wave and associated atrial electrograms. Waxing and waning in heart rate, generally referred to as sinus arrhythmia continues in the awake animal after complete excision of the SA node. This arrhythmia is responsive to both adrenergic and cholinergic interventions, thus indicating the presence of both sympathetic and parasympathetic regulation of subsidiary atrial pacemaking tissues.

Adrenergic beta-Antagonists↗