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Biomedical subjects

F Urthaler

Publications and source records attributed to F Urthaler.

At least 73 records · Page 4Linked to original sources
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

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↗
PubMed1978

Progressive postnatal changes in sinus node response to atropine and propranolol.

Postnatal development of autonomic control of heart rate was evaluated in the sinus nodes of isolated, perfused right atria obtained from 21 sibling puppies in three different litters between 3 and 11 wk postpartum. Age-related changes in response to autonomic blockade indicated that propranolol administered after atropine had its most profound direct depressive effect on less mature atrial cells. In the youngest sinus nodes the familial antimuscarinic action (increase in sinus rate) of atropine was regularly preceded by a brief period of cholinomimetic action (a marked slowing of sinus rate) in the youngest sinus nodes. These two opposing effects of atropine underwent a developmental change during the 2-mo study. The cholinomimetic action diminished, whereas the antimuscarinic action increased as a function of age.

Aging↗
PubMed1978

Neural pathways of a cardiogenic hypertensive chemoreflex.

Excitation of a cardiac chemoreceptor with 5-hydroxytryptamine (serotonin) produces a complex autonomic reflex which includes hypertension, changes in heart rate and contractile force, and disturbances of AV conduction. This study examines the afferent and efferent neural pathways of this autonomic reflex in 60 anesthetized dogs. We used cooling and sectioning techniques in 40 of these, and in 20 others recorded afferent neurograms. The most common afferent pathways for the reflex were found in the left and right recurrent cardiac nerves. No preferential efferent routes to the heart were found, although the nature of the reflex cardiac response could be altered by specific nerve interruption. Cyproheptadine (1 mg/kg iv) regularly abolished both the reflex and the chemoreceptor afferent neural traffic, but injection of a 10 times higher concentration of serotonin (1 mg/ml) readily surmounted the blockade and restored the chemoreceptor neural traffic. Thus cyproheptadine interdicts the reflex at the site of its initiation.

Afferent Pathways↗
PubMed1978

Hemodynamic components of a cardiogenic hypertensive chemoreflex in dogs.

The mechanical and hemodynamic components of a cardiogenic hypertensive chemoreflex were studied in 50 dogs. Within 6 seconds after a single injection of serotonin (100 microgram/ml) into the left atrium, mean pressure (mm Hg) rose in the aorta from 103 to 197 and in the pulmonary artery from 21 to 34. Left ventricular dp/dt virtually doubled. There was an increase (75%) in peripheral vascular resistance that returned to control within 10 seconds. There was no significant change in pulmonary vascular resistance. Aortic and pulmonary arterial hypertension were associated with a profound depression (82%) in atrial force. Atropine transformed this negative inotropic effect on the atria into a positive inotropic action that averaged 65%. In contrast, ventricular force was always sharply increased, more in the right (95%) than in the left ventricle (50%). Bilateral stellectomy did not eliminate the reflex but it completely abolished the initial increase of cardiac contractility; a delayed increase in contractility persisted and was due exclusively to release of catecholamines from the adrenal glands. This cardiogenic hypertensive chemoreflex uses the vagus for its afferent neural traffic and both the sympathetic and the vagus nerves for its efferent route. The brief and intense systemic vasoconstriction concomitant with an increase in cardiac contractility might represent a kind of "aortic cough." Some possible clinical implications are discussed.

Adrenal Medulla↗
PubMed1977

Differential sensitivity to neurotransmitters in denervated canine sinus node.

This investigation determined the chronotropic effects of norepinephrine and acetylcholine (ACh) administered selectively into the canine sinus node artery after cardiac denervation. In 42 dogs the cervical vagi were isolated, the heart was exposed, and vagal stimulations were performed before and after sham procedure or extrinsic cardiac parasympathectomy. Four additional dogs underwent bilateral stellectomy. The dogs were reanesthetized 4-23 days later, and blood pressure, heart rate, ECG, and local cardiac electrograms were recorded. The vagi were again stimulated and the effectiveness of the parasympathectomy was verified in 11 of the dogs. On selective perfusion of the sinus node with 0.001- to 1-microgram doses of ACh, the sinus bradycardias of the parasympathectomized and the sham-operated dogs were not significantly different. The responses to norepinephrine (0.01 and 0.1 microgram/ml) administered via the same route in the stellectomized dogs were significantly greater than those in the sham-operated dogs, thus verifying this technique for the assessment of sinus node sensitivity to neurotrasmitters. We conclude that extrinsic denervation of the canine sinus node leads to development of a differential response between adrenergic and cholinergic neurotransmitters. These differential sensitivities may be important when considering the pharmacological responses and electrical stability of the denervated and/or transplanted heart.

Acetylcholine↗
PubMed1976

Spontaneous action potentials of cells in the canine sinus node.

Right atria were excised from the hearts of 20 young dogs (15 +/- 5 weeks old) and maintained in vitro in order to perform microelectrode impalements. The atria contracted spontaneously for at least 6 hours at a stable rate of 127/min when they were perfused with Krebs-Ringer bicarbonate solution through the sinus node artery. Cells within a small area near the sinus node artery and between the superior vena cava and right atrium consistently yielded transmembrane potentials typical of pacemaker cells. This area was verified histologically to be the midportion of the sinus node. Electrical characteristics of these sinus node pacemaker cells were: maximum diastolic potential, -56 +/- 7 mV (mean +/- 1 SD); action potential amplitude, 56 +/- 8 mV; overshoot, 0 +/- 2 mV. Smooth transitions from phase 4 to phase 0 were always present. From these experiments we conclude that the excised perfused canine right atrium provides a useful new experimental cardiac preparation because it maintains stable spontaneous activity for many hours in vitro and the sinus node within it is readily accessible for study by intracellular microelectrodes.

Action Potentials↗
PubMed1976

Both direct and neurally mediated components of the chronotropic actions of aminophylline.

Aminophylline was selectively perfused through either the sinus node or through the AV (atrioventricular) junction of 35 intact canine hearts in situ. The positive chronotropic action observed was equally powerful in accelerating either sinus rhythm (50 +/- 8 percent increment) or AV junctional rhythm (55 +/- 10 percent increment). This positive chronotropic effect has at least three distinct components: a major direct action on autonomic centers, a lesser effect due to local catecholamine release, and a part due to peripheral vagolytic action.

Acetylcholine↗
PubMed1976

Comparison of the inotropic action of morphine and ketamine studied in canine cardiac muscle.

This study compares the inotropic action of morphine sulfate and ketamine hydrochloride on isolated canine right ventricular trabeculae. The heart was removed from 19 mongrel puppies weighing 5 to 9 kilograms and placed in Krebs-Ringer bicarbonate solution. The bathing solution contained 1.3 mM. of Ca2+ and was bubbled with a gas mixture of 95 per cent oxygen and 5 per cent carbon dioxide. At Lmax (i.e., the peak of isometric force-length curve) morphine even in large concentrations (up to 1 mg. per milliter) produced no significant direct inotropic effect. At the lower concentrations tested there was a minor but not significant increase in contractile performance, whereas at the highest concentration used there was a minor but not significant depression in contractility. In these same muscles lower concentrations of ketamine had a significant positive inotropic action, but a concentration of 200 mug per milliliter, which is approximately equimolecular to 1 mg. per milliliter of morphine sulfate, caused a profound depression in contractile performance. In the presence of a beta-blocking agent and in reserpine-pretreated muscles, low concentrations of ketamine, which had only a positive inotropic action in the normal muscles, now caused depression of contractile performance. The positive inotropic action of ketamine is thus indirect and mediated via adrenergic influences. At each concentration studied the direct inotropic action of ketamine was exclusively negative. Because of this bimodal inotropic action seen when adrenergic mechanisms are intact, we conclude that caution must be exercised when ketamine is given to patients previously treated or still under the influence of drugs having adrenolytic properties. Caution is also necessary when ketamine is used in patients having diminished cardiac adrenergic reserves as in congestive heart failure.

Animals↗