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Biomedical subjects

W C Randall

Publications and source records attributed to W C Randall.

At least 91 records · Page 5Linked to original sources
PubMed1983

alpha-Adrenergic activities of some substituted 2-(aminomethyl)imidazolines.

A series of 2-(aminomethyl)imidazolines related to the alpha-adrenergic antagonist phentolamine was prepared and evaluated for alpha-adrenergic agonist and antagonist activities in the isolated, field-stimulated rat vas deferens. Affinities for alpha-adrenergic receptors were determined by displacement of [3H]clonidine and [3H]prazosin from membrane binding sites of calf cerebral cortex. This series provided a variety of alpha-adrenergic profiles, with some of the (aminomethyl)imidazolines being nonselective alpha 1- and alpha 2-adrenergic antagonists like phentolamine, while others were either nonselective alpha 1- and alpha 2-agonists or mixed alpha 1-agonists/alpha 2-antagonists.

Adrenergic alpha-Agonists↗
PubMed1983

Autonomic influences on atrioventricular conduction in conscious dogs.

Autonomic innervation of the atrioventricular (AV) junction modulates conduction of the cardiac impulse, the sympathetic nerves facilitating and parasympathetic nerves impeding conduction. Experiments assessed the relative importance of parasympathetic vs. sympathetic control by pharmacologic blockade with atropine (0.2 mg/kg) or propranolol (1.0 mg/kg) while pacing the right atrium (100-400 beats/min) in normal, conscious resting dogs and in dogs that had undergone chronic, intrapericardial cardiac denervation. Maximum pacing rate with 1:1 atrioventricular conduction was termed Rmax. Control Rmax at rest was 125.69 +/- 9.49 beats/min and was slightly reduced after propranolol to 118.28 +/- 10.98 (P = 0.043). After atropine, Rmax was significantly increased to 344 beats/min. Propranolol and atropine together resulted in an Rmax of 308 beats/min, which was significantly less than after atropine alone. Rmax in cardiac-denervated dogs was 301 beats/min, which was not significantly different from that following total pharmacologic blockade. In conscious, resting, unsedated dogs, the upper limit of AV nodal conduction is associated with the level of parasympathetic rather than sympathetic tone; during exercise the sympathetics assume greater importance.

Animals↗
PubMed1983

Selective denervation of the heart.

Total denervation of the canine heart consisted of intrapericardial neural dissection of the left atrium, left superior pulmonary vein, and main pulmonary artery and cutting of the ventrolateral cardiac nerve (stage I). The fat pad and all nerves were removed from between the pulmonary artery and aorta (stage II). Dissection proceeded from the pericardial reflection along the superior vena cava to the azygos vein, which was cleared, double tied, and cut. The right pulmonary artery was cleaned, and the superior right atrium was dissected to its intersection with the left atrium (stage III). Denervation was tested by electrical stimulation of both vagi and stellate ganglia, while recording inotropic, chronotropic, and dromotropic events, before and after each stage. Stage I deleted most left autonomic input to the heart without interrupting right sympathetics. Stage II completed left autonomic denervation but preserved much of the right sympathetic input. Large nerves along the dorsal surface of the pulmonary artery carried inputs from both left and right sympathetics. Stage III completed the denervation of atrioventricular and sinoatrial nodal structures and removed all remaining ventricular inotropic influences. Selective denervation of atrioventricular and sinoatrial nodal regions appears feasible for preparation of chronic canine models.

Animals↗
PubMed1983

Functional characteristics of sinoatrial and subsidiary pacemaker activity in the canine right atrium.

A canine in vitro right atrial preparation was developed to study the functional characteristics of subsidiary atrial pacemaker (SAP) activity and to compare them with those of sinoatrial node (SAN) activity. Extracellular bipolar electrodes were used to estimate the site of earliest activation and monitor spontaneous rate. Ligation of the SAN artery at the midportion of the sulcus terminalis suppressed SAN activity and usually (73.5%) elicited SAP activity in a well-defined region of the inferior atrium. SAP activity in this region required a "threshold" concentration of norepinephrine (10(-8) M) in the Tyrode's perfusate. In response to all concentrations of norepinephrine tested, SAN activity attained a greater maximum spontaneous rate than SAP activity. Cholinergic stimulation with acetylcholine or eserine elicited a greater negative chronotropic response from SAP than SAN activity. Overdrive pacing suppressed SAP activity to a significantly greater extent than SAN activity. We conclude that this in vitro preparation can be useful for studying the pharmacology and electrophysiology of subsidiary atrial pacemakers that emerge after suppression of SAN activity. In contrast to SAN activity, SAP activity requires norepinephrine and is more sensitive than SAN activity to acetylcholine and overdrive pacing. Consequently, after loss of SAN function, autonomic modulation of SAP activity may result in atrial dysrhythmias and prolonged periods of overdrive suppression.

Acetylcholine↗
PubMed1982

Effects of individual cardiac nerve stimulation on atrioventricular conduction.

This study investigated the effects of individual canine cardiac nerve stimulation on atrioventricular conductions as measured by His bundle electrograms. A-H and H-V intervals were measured before and during stimulation of each nerve in paced hearts (200 beats/min) and before and after blocking doses of either atropine or propranolol. Increases in A-H or H-V intervals were evidence of parasympathetic innervation; decreases in intervals were evidence of sympathetic innervation. Separation by autonomic composition produced 3 categories: sympathetic, parasympathetic, and mixed input to the atrioventricular junction. The sympathetic nerves were the left and right ansae subclavia, the ventrolateral cardiac nerve, and the right stellate cardiac nerve. The parasympathetic nerve was the right thoracic vagus, and the mixed nerves were the left thoracic vagus, and the innominate, ventromedial, craniovagal, caudovagal, and right recurrent cardiac nerves. The cardiac nerves eliciting a major response were the left and right ansae subclavia, the ventrolateral, right recurrent, craniovagal, and caudovagal cardiac nerves, and the left and right thoracic vagi. In theory, the nerves of the right side, because of their innervation of both sinoatrial and atrioventricular nodes, may be expected to elicit a balanced heart rate-atrioventricular conduction response when stimulated, thus matching atrial and ventricular rates. On the other hand, stimulation of the ventrolateral cardiac nerve regularly produces dysrhythmia, due to increased automaticity at the atrioventricular junction. Production of such arrhythmias indicates the possible implication of imbalanced autonomic activity in arrhythmogenesis. Three cardiac nerves produced little or no effect on atrioventricular conduction. These were the innominate, ventromedial, and right stellate cardiac nerves. Because of its limited distribution and marked sinus rate effects, the right stellate cardiac nerve can be considered almost a purely positive chronotropic nerve. Its possible role in heart rate-atrioventricular conduction mismatching has not been delineated but, because of its nearly exclusive action at the sinoatrial node, may be of considerable importance.

Animals↗
PubMed1982

Regional coronary vasoconstriction in response to stimulation of stellate ganglia.

Recent experiments have demonstrated that direct and reflex sympathetic stimulation elicit coronary vasoconstriction when the inotropic and chronotropic effects are blocked with beta-adrenergic blocking agents. This vasoconstriction can be blocked with alpha-adrenergic blocking agents. Regional variations in the flow reduction produced by right (RSS) vs. left (LSS) stellate stimulation were delineated in this study. Open-chest pentobarbital-anesthetized dogs were given propranolol (1 mg/kg iv). Hearts were neurally decentralized and paced just above the spontaneous heart rate. Radiolabeled microspheres (15 +/- 2 micrometers) were injected into the left atrium before and during RSS (n = 11) or LSS (n = 11). RSS produced relatively little vasoconstriction confined to anterior left ventricle. In contrast, LSS produced significant vasoconstriction in all areas of the right and left ventricles. In the endocardial half of the left ventricle the flow decrease was uniformly distributed among the regions studied. In the epicardial half of the flow decrease was more pronounced in posterior than in anterior regions. No significant change occurred in the endo-epi ratios with RSS, but with LSS there was a significant change in three areas. The changes were related to regional variations in the degree of epicardial constriction. Thus RSS and LSS have differential effects (quantitatively) on regional coronary blood flow.

Animals↗
PubMed1981

Protective effect of chronic versus acute cardiac denervation on contractile force during coronary occlusion.

The effects of acute coronary artery (CA) occlusion on myocardial contractile force were studied in mongrel dogs with (1) chronically denervated hearts (n = 10), (2) acutely denervated hearts (n = 5), and (3) normally innervated hearts (n = 6). Contractile force was measured in ischemic and nonischemic areas using Walton-Brodie strain gauge arches sutured to the epicardium. Coronary occlusion was accomplished by ligating several small branches of the left anterior descending and the circumflex arteries supplying the apical region on the left ventricle. Following occlusion, contractile force in the ischemic area decreased by 66.8% in the control group, by 73.6% in the acutely denervated group, but only by 21.6% (P less than 0.001) in the chronically denervated group. These results demonstrate that chronic cardiac denervation protects from the severe loss of contractile force in the ischemic area. This salutary effect is not seen with acute cardiac denervation.

Animals↗
PubMed1981

Weekly interdisciplinary colloquy on cardiology: a decade of experiment.

An experimental, continuing, regularly scheduled weekly interdisciplinary colloquy on cardiology was organized a decade ago between the departments of medicine and physiology to promote vigorous interaction between basic scientists and practicing physicians in the medical school. This colloquy has had a significant impact upon the education of fellows in clinical cardiology and candidates for the Ph.D. degree in physiology. It has fostered attitudes of academic excellence, appreciation for the opportunities offered by cooperative problem-solving, the stimulation of research, and practical teaching experience. It also provides an ongoing opportunity for updating information based upon a three month, in-depth review of three to four important advances in cardiovascular medicine each year. The faculty shares in the yield of this experimental program, which provides a forum for the investigator to present his ideas and contemplated experimental protocols, his experimental data, and his tentative interpretations to a critical, broadly experienced audience. The program contributes to the development of ability to evaluate published research critically and has led to better understanding of experimental method and design.

Cardiology↗
PubMed1981

Sinoatrial node artery distribution and its relation to hierarchy of cardiac automaticity.

The sinoatrial node (SAN) artery (SANA) was cannulated in dogs anesthetized with chloralose (7 dogs) or pentobarbital (1 dog). Intra-SANA injection of acetylcholine (ACh) with edrophonium (EPh) produced a transient junctional rhythm (JR) when the cannula tip lay near SANA origin. However, when ACh-EPh was injected while the cannula tip lay within SAN region, a slower P wave rhythm, rather than a JR, developed. To determine visually the injected ACh-EPh distribution, an equal volume of dye was injected under similar conditions. Dye-distribution patterns were consistent in all atria. These averaged 44 +/- 2% of the total endocardial surface, indicating that SANA distribution is not discrete, but widespread. Dye extended cranially, caudally, and laterally and included documented subsidiary pacemaker sites. Dye approached, but never trespassed, the coronary sinus ostium. Results suggest that cholinergic drug injection into the proximal SANA may suppress not only the SAN, but subsidiary atrial pacemakers as well. In this situation, junctional pacemakers probably emerge, not because of inherently greater automaticity, but after default of subsidiary atrial pacemakers.

Acetylcholine↗