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Biomedical subjects

W C Randall

Publications and source records attributed to W C Randall.

At least 37 records · Page 2Linked to original sources
PubMed1991

Intracellular recordings from canine intracardiac ganglion cells.

Stable transmembrane potentials were recorded from 60 canine intracardiac ganglion cells taken from 10 dogs, which had intact synaptic connections: mean resting membrane potential, input resistance and time constant were 61.5 mV, 70 M omega and 3.3 ms. Action potentials could be evoked by intrasomal current injection and by orthodromic and antidromic stimulation of interganglionic nerves. Orthodromic action potentials were initiated by excitatory postsynaptic potentials and mediated by nicotinic receptors. All action potentials could be blocked by tetrodotoxin. Intracellular labeling revealed large cell bodies and long dendritic and axonal processes. Thus, the functional and anatomical properties of canine cardiac ganglion cells and their synaptic connections can be elucidated using this preparation.

Action Potentials↗
PubMed1991

Spinal mediation of thermally induced sweating.

The sweat responses of nine patients with physiologically complete lesions of the spinal cord (six cervical and three thoracic) were recorded by two different techniques while the patients were exposed to elevated environmental temperatures. Oral temperatures, heart rate and respiration were monitored throughout the observational periods. Oral temperature invariably rose during exposure to heat and both heart rate and respiration tended to increase. Sweating was detected on all of the test areas by both the iodine-starch-paper technique and the quinizarin technique, but it was of widely varying intensity in different portions of the body. In the patients with cervical lesions sweating was generally profuse on the head and neck and occurred in progressively decreasing intensity down to the level of the umbilicus. It was invariably present, but only in very low intensity, on the lower extremity. Sweating was frequently present as a result of manipulation of the patient during the initial preparations, but this generally declined or stopped before the heat was turned on. With application of heat, sweating was recruited on previously dry areas or increased in intensity on those areas in which it was previously present. After oral temperature had increased moderately, the heat was turned off and the doors of the chamber opened widely so that the heat stimulus was suddenly removed. Despite a continued rise in oral temperature, sweating stopped or decreased dramatically. These results are interpreted to indicate the direct mediation by the isolated spinal cord of reflex sweating responses to a heat stimulus applied to the skin. The general distribution of sweating was similar to that associated with distension of the urinary bladder, and careful attention was taken to avoid this complication. The distribution of sweating on the patients with lesions in the thoracic cord was quite different, being most obvious and profuse on the lower extremities and lower trunk and completely absent from the upper trunk, head and upper extremities.

Adolescent↗
PubMed1991

SA nodal parasympathectomy delineates autonomic control of heart rate power spectrum.

The purpose of this study was to quantify the relative roles of the canine cardiac parasympathetic and sympathetic nerves in controlling the distribution of power within the heart rate (HR) power spectrum using a highly selective surgical technique to parasympathectomize the SA node. DAta were recorded in awake dogs (n = 6) before and after the selective denervation; the animals were isolated from human contact and their behavior carefully monitored during the measurements. The average amplitude in the high-frequency (approximately 0.32 Hz) peak in the HR power spectrum decreased from a predenervation control of 2.68 +/- 1.54 (mean +/- SD, arbitrary units) to 0.07 +/- 0.06 (P less than 0.05). Corresponding resting HR increased from 80 +/- 9 to 106 +/- 16 beats/min (P less than 0.05). The low-frequency peak (approximately 0.02 Hz) also decreased from a control of 2.45 +/- 1.18 to a postparasympathectomy value of 1.25 +/- 0.92 (P less than 0.05). beta-Adrenergic blockade (propranolol, 1 mg/kg) further decreased the latter peak to 0.59 +/- 0.52 (P less than 0.05). These data directly demonstrate that the high-frequency peak of the HR power spectrum 1) results from parasympathetic control of SA nodal automaticity, while 2) the low-frequency peak reflects activity in both divisions of the autonomic nervous system.

Adrenergic beta-Antagonists↗
PubMed1991

Autonomic regulation of subsidiary atrial pacemakers during exercise.

Cardiac responses to graded treadmill exercise were compared in conscious dogs before and after excision of the sinoatrial node (SAN) and adjacent tissue along the sulcus terminalis. The chronotropic and dromotropic responses to dynamic exercise were compared with and without selective muscarinic (atropine) and/or beta-adrenergic (timolol) blockade. With the SAN intact, cardiac acceleration was prompt during onset of exercise and in proportion to work intensity. Immediately after SAN excision (1-7 days), pacemaker activity exhibited marked instability in rate and pacemaker location, with rapid shifts between atrial and junctional foci. Soon thereafter (1-2 wk), subsidiary atrial pacemakers (SAPs) assumed the primary pacemaker function. Although the SAP foci demonstrated stable heart rates and atrioventricular (AV) intervals at rest and during exercise, heart rates at rest and during steady-state exercise were reduced 34% from corresponding levels in the SAN-intact state, both with and without selective autonomic blockade. For control of dromotropic function, animals with SAP foci showed pronounced shortening in AV interval in conjunction with exercise that was further exacerbated by pretreatment with atropine. Eight weeks after excision of the primary SAN pacemakers, direct electrophysiological mapping localized the SAP foci to either the inferior right atrium along the sulcus terminalis or the dorsal cranial right atrium (in or near Bachmann's bundle). Animals with SAPs localized to the inferior right atrium had a more marked suppression in heart rate with a corresponding greater decrease in AV interval during exercise than dogs with SAP foci identified within the dorsal cranial right atrium.

Animals↗
PubMed1991

Surgical interruption of postganglionic innervation of the sinoatrial nodal region.

Recent experiments have revealed synapses that selectively mediate right and left vagal regulation of sinoatrial function in the fat pad overlying and surrounding the right pulmonary vein complex. However, precise vagal postganglionic pathways to the sinoatrial region have remained obscure. Such pathways, including critically important neural inputs to sinoatrial and atrioventricular nodal regions, may be vulnerable to surgical approaches to atrial or intracardiac repair. The present experiments seek to delineate specific autonomic pathways to the sinoatrial region of the canine heart. The distal ends of the cut right and left cervical vagi and the right and left ansae subclaviae were electrically stimulated (10 to 20 Hz, 1 msec, 2 to 3 V) before and after surgical incisions were placed. Cut No. 1 was made longitudinally along the ventral caval surface from the pericardial reflection caudally to the pulmonary vein fat pad, cut No. 2 was made from the caudal end of cut No. 1 transversely across the sulcus terminalis to a point midway across the anterior (ventral) surface of the right atrium. Each incision was closed with 4-0 silk, with care being taken to avoid injury to either the sinoatrial nodal or the pulmonary fat pad regions. In four of seven animals, these two incisions totally interrupted vagal input to the sinoatrial node, whereas in the remaining three dogs a residual inhibitory influence remained. These residual fibers were surgically ablated by excision of globular fat pads situated on the rostrodorsal surfaces of the right superior pulmonary vein, suggesting a dorsorostral route into the interatrial septum and thence to the sinoatrial node. There was little or no interruption of either right or left vagal input to the atrioventricular nodal region; sympathetic supplies to both sinoatrial nodal and atrioventricular nodal regions remained essentially intact after the two incisions. Thus the major parasympathetic postganglionic projections to the sinoatrial node in the dog heart are by way of the free wall of the right atrium and are vulnerable to surgical interventions in this portion of the heart.

Animals↗
PubMed1990

Hands-on laboratory experience in teaching-learning physiology.

Reactivation of several model 5 (vacuum tube) Grass polygraphs for active hands-on laboratory experiments by small student groups, in contrast to demonstrations and pretaped illustrations of physiological principles, resulted in remarkable rejuvenation of interest and excitement for learning in premed and introductory science classes at Taylor University. Accurate and perceptive observations were performed on the students themselves, each recording his own electrocardiogram, for example, as well as direct recordings from the pithed frog, the turtle heart, the anesthetized rabbit, and noninvasive recordings from students subjects during exercise. In the latter experiment, sweat recruitment patterns were recorded initially on the lower extremities, followed by successive appearances on thigh and abdomen and with final occurrence on the upper extremities and face. To our knowledge, this is the first report of such recruitment patterns during exercise. Results of actual student participation, with organized group discussions, convince us that laboratory teaching remains the premiere mechanism for teaching and learning organ-system physiology.

Animals↗
PubMed1990

Parasympathetic postganglionic pathways to the sinoatrial node.

Vagal ganglia that innervate the canine sinoatrial node (SAN) have been localized to a fat pad overlying and surrounding the right pulmonary vein complex (PVFP). The ventral epicardial surface of the right atrium was mapped in seven dogs anesthetized with alpha-chloralose after beta-blockade (timolol) and cardiac sympathetic and parasympathetic decentralization. A small, concentric bipolar exploring electrode was used to stimulate (during the atrial refractory period and using trains of five to eight stimuli per beat) systematically in the epicardial regions between the PVFP and the SAN. Changes in SAN rate with stimulation were measured, and the anatomic location was identified on a 150-point grid fitted to conform to size and shape of the atrium. Mapping was performed before and after local (PVFP) and systemic ganglionic blockade (hexamethonium). Data reveal that the primary vagal postganglionic pathways to the sinoatrial nodal region are subepicardial and adjacent to the SAN artery along the sulcus terminalis. Hexamethonium in the PVFP abolishes SAN inhibition during preganglionic vagal excitation, without interrupting vagal suppression of atrioventricular conduction. However, SAN slowing (with varying attenuation) continued to occur after hexamethonium (either PVFP or systemically) when the exploring electrode was applied directly over intramural postganglionic fibers between PVFP and sinus node. Attention is directed to existence of a very few synapses closer to SAN, probably in isolated ganglia immersed in fatty connective tissues along the sulcus terminalis.

Animals↗
PubMed1989

Selective vagal postganglionic innervation of the sinoatrial and atrioventricular nodes in the non-human primate.

The distribution of parasympathetic postganglionic nerves to the atrioventricular (AVN) and sinoatrial nodal (SAN) regions was investigated in the non-human primate heart. Eight male monkeys (Macaca fascicularis) weighing 5.5-7.0 kg. were anesthetized (alpha-chloralose, 50 mg/kg and urethane, 500 mg/kg) and instrumented to measure arterial pressure, electrocardiogram, atrial and ventricular electrograms. The cervical vagi were electrically stimulated (20 Hz, 4 V, 2 ms) before and after selective denervation (D) of the AVN and/or SAN. Vagal stimulation was repeated during atrial pacing to assess parasympathetic modulation of AVN conduction. Ablation of parasympathetic pathways to the AVN, accomplished by the disruption of the epicardial fat and surface muscle layer at the junction of the inferior vena cava and inferior left atrium eliminated (P less than 0.01) the dromotropic effects of vagal stimulation without affecting the heart rate response (right vagus, before D, paced: atrial rate 218.0 +/- 6.3, ventricular rate 67.1 +/- 23.7; after D: atrial rate 210.3 +/- 6.4, ventricular rate 210.3 +/- 6.4 beats/min, means +/- S.D.). In sharp contrast, surgical dissection of the fat pad overlying the right pulmonary vein-superior vena cava junction significantly (P greater than 0.01) attenuated negative chronotropic effects of vagal stimulation (left vagus, before D the R-R interval increased by 832.7 +/- 146.4 ms, 209.5% increase; after D 37.4 +/- 18.0 ms, 8.8% increase). These data demonstrate discrete vagal efferent pathways innervate both the SAN and AVN regions of the non-human primate heart.

Animals↗
PubMed1989

Chemical synthesis of echistatin, a potent inhibitor of platelet aggregation from Echis carinatus: synthesis and biological activity of selected analogs.

Echistatin, a polypeptide from the venom of the saw-scaled viper, Echis carinatus, containing 49 amino acids and 4 cystine bridges was synthesized by solid-phase methodology in 4% yield. In the final step, air oxidation of the octahydroderivative was found to be optimal at pH 8. The synthetic product was shown to be physically and biologically indistinguishable from native material. It inhibits fibrinogen-dependent platelet aggregation stimulated by ADP with IC50 = 3.3 x 10(-8) M and also prevents aggregation initiated by thrombin, epinephrine, collagen, or platelet-activating factor. Reduction of purified synthetic echistatin to octahydroechistatin with dithiothreitol followed by air oxidation regenerated homogeneous echistatin in quantitative yield. This highly specific refolding strongly suggests that the linear sequence of octahydroechistatin contains all of the information that is required for the proper folding of the peptide. The sequence Arg24-Gly-Asp of echistatin occurs also in adhesive glycoproteins that bind to the platelet fibrinogen receptor--a heterodimeric complex composed of glycoproteins IIb and IIIa. In an effort to evaluate the role of this putative binding site we have synthesized analogs of echistatin with substitution of Arg-24. Replacement with ornithine-24 (Orn-24) resulted in an analog having a platelet aggregation inhibitory activity with IC50 = 1.05 x 10(-7) M. Substitution with Ala-24 gave IC50 = 6.1 x 10(-7) M. The inhibitory activity of the corresponding short sequence analogs Arg-Gly-Asp-Phe (IC50 = 6 x 10(-6) M), Orn-Gly-Asp-Phe (IC50 = 1.3 x 10(-4) M), and Ala-Gly-Asp-Phe (IC50 = 5.0 x 10(-4) M) was also determined. These results suggest that arginine plays a more important role in the binding of the tetrapeptide than in that of echistatin.

Amino Acid Sequence↗
PubMed1988

[3H]L-654,284 as a probe of the central alpha 2 adrenoceptor.

L-654,284 [2R, 12bS)-N-(1,3,4,6,7,12b-hexahydro-2H-benzo[b]-furo[2,3-a] quinolizin-2-yl)-N-methyl-2-hydroxyethanesulfonamide], a potent and selective antagonist of the alpha 2 adrenoceptor, was tritiated to high specific activity. Saturation binding to cell membrane suspensions obtained from calf cerebral cortex revealed a high affinity binding site (0.63 nM). Kinetics of association and dissociation were well represented by single exponential processes, and the equilibrium dissociation constant obtained from the ratio of rate constants agreed well with that found by saturation binding. A direct comparison of saturation binding revealed that the antagonist [3H]L-654,284 had roughly the same affinity for the alpha 2 adrenoceptor as the agonist [3H]clonidine and eight times the affinity of the antagonist [3H]rauwolscine. The maximum receptor densities of these radioligands were not significantly different. Competition assays with a series of compounds of known receptor affinity revealed that [3H]L-654,284 selectively binds to a site with all of the characteristics expected of the alpha 2 adrenoceptor.

Adrenergic alpha-Antagonists↗
PubMed1988

Influence of selective parasympathectomy of the A-V nodal region on atrioventricular conduction in conscious dogs.

The maximum atrial paced rate with 1:1 atrioventricular conduction (Rmax) was compared before and after selective parasympathectomy of the atrioventricular nodal region (AVNR). Each animal was instrumented with right atrial and right ventricular bipolar electrodes. Rmax was determined (1) under quietly resting, control conditions, (2) following beta-adrenergic blockade, (3) following muscarinic blockade, and (4) following combined beta-adrenergic and muscarinic blockade. During a second surgical procedure approximately two weeks later, parasympathectomy was achieved by dissection and topical application of phenol to the fat pad and underlying epicardium at the inferior left atrial junction with the inferior vena cava; completeness of AVNR parasympathectomy was tested at surgery by supramaximal stimulation of right and left cervical vagi, with and without rapid atrial pacing. AVNR sympathetic innervation remained intact. All studies were conducted while the animals were conscious and quietly resting. Before parasympathectomy, Rmax under control conditions averaged 136 +/- b4 beats per minute (bpm). Following beta-blockade, Rmax was 126 +/- 5 bpm; while with muscarinic blockade, Rmax averaged 373 +/- 4 bpm (P less than 0.001, with control). With combined beta- and muscarinic blockade, Rmax was 300 +/- 14. After AVNR parasympathectomy, although the resting heart rate was unchanged, the Rmax under control conditions was 342 +/- 10 bpm. beta-Blockade reduced this significantly (P less than 0.001) to 278 +/- 15 bpm. With muscarinic blockade, Rmax averaged 346 +/- 11 bpm, which was not different from the control Rmax after AVNR parasympathectomy. Combined beta- and muscarinic blockade produced an Rmax of 280 +/- 14 bpm.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1988

Structure-affinity relationships of arylquinolizines at alpha-adrenoceptors.

Hexahydroaryl[a]quinolizines comprise a prominent structural element in several alpha 2-adrenoceptor antagonists. Eight hexahydroheteroarylquinolizines were prepared as minimal ligands to investigate the relationship between the nature of the aromatic ring and affinity of these molecules for alpha-adrenoceptors. Affinity for alpha 1-and alpha 2-adrenoceptors was assessed by displacement of [3H]prasozin and [3H]clonidine, respectively. Lipophilicity of the aryl portion of the molecules, reflected by their partition coefficient between octanol and pH 7.4 buffer, correlated well with affinity at both receptor subtypes. Although some compounds showed nanomolar affinity for alpha-adrenoceptors, no subtype selectivity was observed. These results suggest that the aromatic ring enhances binding at both receptors chiefly through hydrophobic interactions and contributes little to subtype selectivity.

Algorithms↗
PubMed1988

Sympathetic activation induces asynchronous contraction in awake dogs with regional denervation.

To determine effects of regional left ventricular (LV) denervation on regional contractile responses to sympathetic activation, dogs with posterior LV wall denervation (posterior wall-denervated group) and dogs with innervated posterior LV walls (intact group) were studied during excitement, exercise, bilateral sympathetic nerve stimulation, and norepinephrine infusion. In intact conscious dogs, all modes of sympathetic activation increased the magnitude and decreased the time of onset of systolic wall thickening (WT) similarly in the anterior and posterior wall. In the denervated group, excitement failed to increase posterior WT during systole but instead elicited asynchronous contraction, i.e., postsystolic WT, as well as delayed onset of contraction. Asynchronous contraction was not observed with excitement after beta-adrenergic receptor blockade. Asynchronous contraction of the posterior wall was also observed during the initial phase of exercise in conscious dogs and during bilateral stellate stimulation in anesthetized dogs in the posterior wall-denervated group. In comparison to neural activation, adrenergic receptor activation with norepinephrine (0.2 microgram/kg-1.min-1 iv) induced a supersensitive increase in systolic WT in the denervated posterior wall (36 +/- 5%) compared with the anterior wall (17 +/- 2%) and a delay in the end of contraction in the anterior region. Thus asynchronous contraction can be elicited in dogs with regional LV denervation as a result of an early and enhanced contraction in the innervated region during neural sympathetic activation. The reverse was observed with systemic administration of norepinephrine because of catecholamine supersensitivity in the denervated posterior wall.

Animals↗
PubMed1988

Responses to coronary artery occlusion in conscious dogs with selective cardiac denervation.

The extent to which cardiac denervation alters responses to myocardial ischemia remains controversial. This study compared responses to 24-h coronary artery occlusion (CAO) on measurements of wall thickness (ultrasonic crystals), regional myocardial blood flow (microspheres), and infarct size (triphenyltetrazolium chloride technique) in three groups of conscious dogs with 1) selective posterior left ventricular (LV) wall denervation, 2) selective ventricular denervation, or in 3) intact dogs. After CAO, hemodynamic changes were not different among the three groups. Wall thickening in the ischemic zone became akinetic or paradoxical early after CAO and did not recover in any group over the 24-h monitoring period. Blood flow in the area at risk fell similarly in all groups. Infarct size, as a percentage of the area at risk, was 45 +/- 7% in intact, 48 +/- 6% in posterior LV wall-denervated, and 48 +/- 8% in ventricular-denervated group. There was, however, a lower (P less than 0.05) frequency of arrhythmic beats per minute after 3 h of CAO in the ventricular-denervated group (3.2 +/- 1.4) compared with the intact (11.3 +/- 4.1) or posterior wall-denervated (12.6 +/- 3.2) group. An additional group of ventricular-denervated dogs was studied to determine the effects of sequential, brief 2-min CAO at 2, 4, and 8 wk after denervation. Responses of regional wall thickening to CAO were not affected significantly even after 8 wk following ventricular denervation. Thus, in conscious dogs, neither selective ventricular denervation nor selective denervation of the posterior LV wall improved collateral blood flow, affected regional function favorably, or reduced infarct size after CAO.

Animals↗
PubMed1988

Activity of in vivo canine cardiac plexus neurons.

The activity of 394 spontaneously active neurons located in the ganglionated plexus of the ventral epicardial fat pad overlying the right atrium and pulmonary veins was recorded. Ganglia that contained various numbers of neurons, many with two or more nucleoli, were identified adjacent to the recording sites. Spontaneous activity was correlated with the cardiac cycle in 39% and with the respiratory cycle in 8% of the identified neurons. Neuronal activity occurred in specific phases of the cardiac cycle when arterial pressure was between approximately 70 and 175 mmHg. During increases in systolic pressure induced by positive inotropic agents or aortic occlusion, responses of neurons that displayed cardiovascular-related activity were enhanced. These responses persisted after acute decentralization. The activity of 14% of all identified neurons was altered when discrete regions of the heart, great thoracic vessels, or lungs were mechanically distorted by gentle touch. Trains of stimuli, but not single stimuli, delivered to the vagosympathetic complexes, stellate ganglia, or cardiopulmonary nerves activated ganglionic neurons in intact or acutely decentralized preparations. It is concluded that the activity of some cardiac ganglion neurons is related to cardiovascular or respiratory dynamics and that some of these neurons receive inputs from sympathetic and parasympathetic efferent axons as well as from cardiac mechanoreceptors.

Adipose Tissue↗
PubMed1988

Differential sympathetic regulation of automatic, conductile, and contractile tissue in dog heart.

Sympathetic pathways mediating chronotropic, dromotropic, and inotropic responses during ansae subclavia stimulation were determined by sequential dissection around major cardiac vessels. Right sympathetic (RS) projections influencing ventricular contractile force converge at the common pulmonary artery and within the pulmonary artery nerves (PAN). RS projections influencing left atrial contractile force course within the PANs. RS pathways to pacemaker and right atrial contractile tissue were localized between the superior vena cava and ascending aorta. RS projections influencing conductile tissue converge between the common pulmonary artery and proximal right pulmonary artery. Left sympathetic (LS) projections to ventricular contractile tissue were localized at the common pulmonary artery, within the PANs, and in the ventral lateral cardiac nerve (VLCN). LS pathways influencing heart rate and conductile tissue were localized at the left pulmonary artery and coursing between the right pulmonary artery and left superior pulmonary vein. LS projections to atrial contractile tissue were localized within the PANs and coursing between the right pulmonary artery and left superior pulmonary vein. We conclude that there are parallel, yet distinct, projections of sympathetic efferents to automatic, conductile, and contractile tissue of the canine heart.

Animals↗
PubMed1988

Localization of vagal preganglionic somata controlling sinoatrial and atrioventricular nodes.

Canine cardiac vagal ganglia in the region of the inferior vena cava and inferior left atrium (IVC-ILA) and at the junction of the right pulmonary veins and left atrium (PVFP) control atrioventricular conduction and heart rate, respectively. After retrograde transport of horseradish peroxidase (HRP) injected separately into these ganglia in different dogs, the left and right and longitudinal distributions of brain stem somata terminating in these ganglia were compared with functional dominance of left and right vagal control of heart rate and atrioventricular conduction. Labeled somata innervating these ganglia had quite similar longitudinal distribution patterns. Although functional dominance of heart rate was found to be in either the right vagus or bilaterally in both vagi, a corresponding difference in somata innervating the PVFP ganglia was not found. Functional vagal dominance of atrioventricular conduction was found to be either right, bilateral, or left with correspondence between left-right distributions of somata after HRP injection into the IVC-ILA region. However, these results should be cautiously interpreted because these ganglia mediate other cardiac functions.

Animals↗