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Biomedical subjects

T N James

Publications and source records attributed to T N James.

At least 19 recordsLinked to original sources
PubMed1979

Experimental studies on the pathogenesis of asystole after verapamil in the dog.

The effect of verapamil on automaticity and conduction in the atrioventricular (A-V) junctional region was studied in anesthetized dogs. In five normal dogs verapamil, 10 microgram/ml, was selectively perfused into the A-V nodal artery and caused first degree heart block, which progressed to second degree heart block in three of the five. Higher concentrations of verapamil, 25 microgram/ml, caused complete heart block in three of five other dogs, but no episodes of asystole (defined as a ventricular pause of 10 or more seconds). In six other dogs after beta receptor blockade with propranolol, 20 microgram/ml, perfused into the A-V nodal artery, verapamil, 10 microgram/ml, regularly caused second degree heart block; in four of the six dogs there was a transient episode of third degree A-V block, and in two of these there was a period of asystole. In each of the 10 dogs pretreated with reserpine, verapamil, 10 microgram/ml, caused third degree A-V block; in seven of these there was a period of asystole with ventricular standstill up to 30 seconds. Concentrations of verapamil that do not produce high grade heart block in the normal heart thus readily cause both high grade block and prolonged ventricular standstill after elimination of adrenergic influences in the A-V junction.

Adrenergic beta-Antagonists↗
PubMed1979

Fine structure of cells and their histologic organization within internodal pathways of the heart: clinical and electrocardiographic implications.

The fine structure of the normal internodal pathways was studied in 1 human and 2 canine hearts and correlated with histologic observations on more than 100 human and 10 canine hearts. From the electron microscopic studies six different kinds of myocardial cells were classified from two locations: the Eustachian ridge (posterior internodal pathway) and the Bachmann bundle (anterior internodal pathway). Five of the six kinds of cells (working myocardial cells, Purkinje-like cells, either broad or slender transitional cells and P cells, all previously described) were present in both locations. A sixth cell, pleomorphic and dark in appearance, with a special intertwined relation to P cells, is newly designated as an ameboid cell. It was found solely in the Eustachian ridge. In the same area a rare direct contact between a nerve and a myocardial cell was observed. The importance of these different kinds of cells, their respective cell connections, and their topographic locations inside the internodal pathways are discussed relative to certain functions such as rapid conduction and subsidiary pacemaking. The possible influence of these factors on clinical electrocardiographic changes is considered.

Animals↗
PubMed1979

Dysautonomia in mitral valve prolapse.

Many of the clinical features of patients with mitral valve prolapse can logically be attributed to abnormal autonomic neural function. Accordingly, we have studied heart rate and blood pressure response to a standardized Valsalva maneuver and postural test in 44 untreated patients with demonstrated mitral valve prolapse. Fifteen healthy subjects of similar age served as controls. The directional changes of blood pressure and heart rate were similar in control subjects and patients in both tests, but patients differed from control subjects by their widely oscillating heart rate during the upright posture, and their exaggerated and prolonged bradycardia during the recovery phase of the Valsalva maneuver and following their return to recumbency in the postural test. This bradycardia persisted for 30 to 90 seconds after blood pressure returned to control values. Patients also showed a greater respiratory variation of R-R interval, which became especially marked during the adjustment to changes of posture. We postulate an abnormal central modulation of baroreflexes as the best explanation for the dysautonomic responses of symptomatic patients with prolapsed mitral valves.

Adolescent↗
PubMed1979

Correlative electrophysiological and anatomical studies concerning the site of origin of escape rhythm during complete atrioventricular block in the dog.

Complete heart block was produced in eight dogs by the selective perfusion of physostigmine or neostigm into the atrioventricular (AV) node artery. A characteristic escape AV junctional rhythm emerged in each dog. After reversal of the cholinesterase paralysis with atropine, in each dog partial heart block was produced by an incision into the AV nodal region. In three of these eight dogs, a second incision placed slightly more anteriorly produced complete AV block which was followed by the emergence of an escape AV junctional rhythm similar to the one produced pharmacologically. Hearts of these three dogs were examined histologically with serial sections to determine the exact location of the incisions and their relationship to the AV node and His bundle. In each dog the incision that produced complete heart block passed directly through the junction of AV node with His bundle. In this region previous studies had demonstrated numerous P cells, which are thought to be the site of origin of normal cardiac automaticity. In each of the three hearts there were abundant P cells in continuity with the His bundle distal to the cut producing heart block. Significance of these findings is discussed relative to the locus of action of acetylcholine within the AV junction, the site of origin of AV junctional rhythm, and sme aspects of the experimental and therapeutic production of heart block.

Animals↗
PubMed1979

Mechanism of postarrhythmic renal vasoconstriction in the anesthetized dog.

The mechanism of postarrhythmic renal vasoconstriction was studied in 28 dogs anesthetized with pentobarbital sodium (30 mg/kg i.v.). Rapid atrial or ventricular pacing or induction of atrial fibrilation were used to produce at least 20% prompt decrease in cardiac output and mean arterial blood pressure. Return to control cardiac output and blood pressure occurred within 3 minutes after cessation of the arrhythmia, but renal blood flow remained significantly decreased (26%) with gradual recovery by 17.7 +/- 6.6 min. Infusion of phentolamine (0.25 mg/min) into the renal artery, intravenous hexamethonium (l mg/kg), adrenal demedullation, or cooling the cervical vagi prevented postarrhythmic renal vasoconstriction. In contrast, renal denervation, intravenous bretylium (10 mg/kg), intravenous atropine (0.5 mg/kg) or intrarenal SQ 20881 (0.20 mg/min) has no effect on postarrhythmic renal vasoconstriction. Intravenous propranolol (0.5 mg/kg) intensified postarrhythmic renal vasoconstriction. These data suggested that the postarrhythmic renal vasoconstrictive response required intact vagi and was due to alpha adrenergic stimulation by adrenal catecholamines. However, femoral arterial catecholamine levels were not elevated above control during postarrhythmic renal vasoconstriction. We therefore sought local vascular pathways by which catecholamines might reach the kidneys. An adrenorenal vascular network was found in each dog. Collection of catecholamines from these vessels during postarrhythmic renal vasoconstriction in six dogs revealed catecholamine concentrations threefold higher than simultaneously collected femoral arterial catecholamines levels. Because ligation of these vessels abolished postarrhythmic renal vasoconstriction in each dog, we conclude that postarrhythmic renal vasconstriction is due to adrenal catecholamines reaching the kidneys through an adreno-renal vascular network and that the response requires intact vagi.

Adrenal Glands↗
PubMed1979

Chronotropic and dromotropic effects of histamine on the canine heart.

The actions of 2-methylhistamine (H1 agonists), 4-methylhistamine (H2 agonist), and histamine were studied by selective perfusion of the sinus node artery and atrioventricular node artery in 75 dogs anesthetized with pentobarbital sodium. 2-Methylhistamine and histamine had variable and inconsistent effects on the sinus rate. 4-Methylhistamine (100 microgram/ml) produced acceleration of the sinus rate from 158 +/- 4 to 173 +/- 5 beats per minute (P less than 0.05) when perfused via the sinus node artery. The effects of the histamine agonists on atrioventricular junctional rhythms were similar to the effects on sinus rhythm. The response of the sinus node to vagal stimulation was attenuated by selective perfusion with histamine; however, the direct negatively chronotropic action of acetylcholine was not affected by histamine. Neither 2-methylhistamine nor 4-methylhistamine affected the response of the sinus node to vagal stimulations. Both 4-methylhistamine and histamine (but not 2-methylhistamine) attenuated (P less than 0.05) the response of the sinus node to stimulation of the right stellate ganglion. The positively chronotropic effects of directly perfused norepinephrine were unaffected by histamine or 4-methylhistamine. These results suggest a neural depressing action of histamine on autonomic efferent fibers. In the atrioventricular junction, both histamine and 2-methylhistamine (but not 4-methylhistamine) had negatively dromotropic effects. Cimetidine (an H2 antagonist) had no significant direct effects on the sinus rate or atrioventricular conduction and failed to prevent the acceleration of the sinus rate produced by local perfusion with 4-methylhistamine.

Acetylcholine↗
PubMed1979

Cardiac ganglionitis associated with sudden unexpected death.

In a postmortem study of the hearts of two young women who died suddenly and unexpectedly, we found a remarkably similar and distinctive ganglionitis, predominantly in the region of the sinus node. Both women had ventricular fibrillation at the time of collapse. Vesicular neuritis and older neural degeneration were present in other regions of the heart. Except for focal fibromuscular dysplasia of the sinus node artery and atrioventricular node artery of one heart, there was no other significant anatomic abnormality in either heart. The functional significance of this cardiac ganglionitis is unclear, but its location in and around the conduction system makes it a possible cause of the fatal electrical instability. Recognition that ganglionitis of the heart may be associated with sudden death should stimulate a number of additionally useful studies.

Adult↗
PubMed1979

Effects of verapamil on automaticity and conduction with particular reference to tachyphylaxis.

Verapamil delivered via the sinus node artery exerted a dose-related, exclusively negative chronotropic action at all concentrations studied. Perfusion through the AV node artery during AV junctional rhythm also caused a dose-related negative chronotropic response, but the concentrations required to depress this pacemaker were ten times higher than those required to depress sinus node automaticity. Verapamil administered into the AV node artery during sinus rhythm impaired AV conduction. His bundle electrograms demonstrated that depressed A-V conduction was exclusively located at the A-H level. In 5 out of 10 dogs verapamil (5 to 10 mg) delivered into the septal artery caused an abrupt onset of ventricular fibrillation without premonitory dysrhythmias. Verapamil (except at very high concentrations) did not alter the responsiveness of the sinus node and the AV junction to acetylcholine or norepinephrine, whether administered selectively into the sinus node artery or the AV node artery or released by neural stimulation. Serial injections of verapamil were associated with tachyphylaxis for the direct chronotropic and dromotropic properties of the drug.

Acetylcholine↗
PubMed1979

Termination of "ventricular" arrhythmias from digoxin by selective production of complete atrioventricular block with physostigmine in the dog.

In previous studies we have come to doubt that ventricular rhythms of an automatic nature will arise spontaneously from the peripheral Purkinje system. In 20 anesthetized dogs, digoxin was administered i.v. (0.1-1.0 mg/kg) and in 12 dogs by selectively perfusing the atrioventricular (AV) node artery (2 ml; 40 microgram/ml). We obtained the following results. First, selective pharmacological production of complete AV block (acetylcholine or physostigmine) interrupts the "ventricular" arrhythmias considered characteristic of digitalis intoxication.Second, digitalis arrhythmias are difficult to produce when this type of complete heart block had been previously established. Third, abolition of ventricular arrhythmias by selective pharmacological production of heart block can be reversed (i.e., the arrhythmia restored) with atropine. Fourth, rapid pacing of the ventricles during complete heart block in dogs poisoned with digitalis can eventually induce ventricular arrhythmias, but not quickly. We interpret that these digitalis arrhythmias originated within the acetylcholine-sensitive portion of the AV node-His bundle region.

Acetylcholine↗
PubMed1979

Morphological changes in the right ventricular septomarginal trabecula (false tendon) during maturation and ageing in the dog heart.

Right ventricular septomarginal trabeculae ('false-tendons') from puppies, young adult, and older adult dogs were examined by light and electron microscopy. The connective tissue of the trabeculae obtained from the puppies and the young adult dogs had few elastic fibres, but this component was well developed in the connective tissue of the adult dogs. The trabeculae of older dogs also showed scattered foci of extracellular fat droplets, and their junctional regions nearest to the ventricular wall were often heavily laden with fat. The Purkinje cells were uniform in each group, but differed from one group to another: in the puppies they resembled typical conducting cells, being predominantly cuboidal with few, poorly developed myofibrils, whilst in the adults the Purkinje cells resembled working myocytes, being elongated with a well developed complement of longitudinally arranged myofibrils. The cells of all age groups showed a complete absence of T-tubules, simply arranged interculated discs, and frequent dilatations of the sarcoplasmic reticulum. The cells of older dogs showed separations of the undifferentiated regions of most discs. Membrane degenerations and the presence of numerous fat droplets also were common. The fine structural cytology of Purkinje cells therefore appears to change considerable with age in the right ventricular septomarginal trabeculae ('false-tendons') of the dog heart.

Aging↗
PubMed1978

The effect of aging on ventricular contractile performance.

The effects of aging on mechanical performance of isolated canine right ventricular trabeculae were studied in two age groups. The first group was comprised of nine dogs, about 9 months of age. The second group was composed of seven dogs over 8 years of age. Aging had no significant effect on developed force. Extent of shortening tended to decrease. There was a significant decrease in both the rate of rise of tension and the velocity of shortening (20%). THis reduction was primarily due to an increased duration of contraction. Twitch duration increased by as much as 40% during aging but most of this prolongation was due to a profound slowing of relaxation. Aging caused a significant increase in passive stiffness since equivalent changes in muscle length brought about twice as much increase in resting tension in the aged muscle as in the young muscle. On the other hand, aging caused a significant shift of Lo to the right. Taken collectively, these results indicate that aging is associated with increased passive stiffness and decreased speed of contraction without changes in strength.

Aging↗