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Biomedical subjects

L C Weaver

Publications and source records attributed to L C Weaver.

At least 109 records · Page 6Linked to original sources
PubMed1980

Contrasting reflexes evoked by chemical activation of cardiac afferent nerves.

Afferent neurons within cardiac sympathetic nerves can reflexly excite central sympathetic outflow. However, their contribution to cardiovascular control remains unclear because they are potentially opposed by inhibitory reflexes of cardiac vagal or arterial baroreceptor afferent origin. It was considered that sympathetically mediated, excitatory responses might be more prominent when initiated by chemical stimulation. In chloralose-anesthetized, vagotomized, sinoaortic-denervated cats, epicardial or intracoronary administration of bradykinin or potassium chloride evoked renal nerve excitation and pressor responses mediated by cardiac sympathetic afferent nerves. When upper thoracic sympathetic nerves were severed, and vagal afferent nerves remained intact, bradykinin and potassium chloride produced inhibition of renal nerve activity and depressor responses. When sympathetic and vagal components of cardiac innervation remained intact, these substances produced excitation, inhibition, or no change in sympathetic outflow. Excitation occurred as often as inhibition. A similar pattern was observed when arterial baroreceptor nerves remained intact. These data illustrate that cardiac sympathetic afferent neurons can have significant excitatory influences on the cardiovascular system in spite of opposition by inhibitory afferent groups.

Afferent Pathways↗
PubMed1977

Cardiopulmonary sympathetic afferent influences on renal nerve activity.

Cardiopulmonary sympathetic afferent nerves may affect renal control of intravascular volume by influencing renal sympathetic nerve activity. This influence was evaluated in alpha-chloralose anesthetized, vagotomized, sino-aortic denervated cats. When the afferent nerves were activated with a single electrical stimulus, the renal nerve responded with an excitatory burst of activity followed by a long period of inhibition. This response had characteristics of a supraspinal reflex. Repetitive stimulation of the sympathetic afferent nerve either inhibited or excited renal nerves and increased or decreased systemic blood pressure. The direction of these changes depended on stimulus parameters. No obligatory correlation in the direction of change of nerve activity and blood pressure was observed. Activation of cardiopulmonary sympathetic afferent nerves by intravascular volume expansion inhibited renal nerve discharge. Inhibition was elminated by sectioning the sympathetic afferent nerves. Volume expansion had no effect on lumbar sympathetic discharge monitored simultaneously with renal nerve activity. This observation suggests specificity of reflex influences of these afferent nerves on the kidney. In conclusion, cardiopulmonary sympathetic afferent nerves can reflexly alter renal nerve activity, and therefore may affect renal control of intravascular volume.

Afferent Pathways↗
PubMed1977

Digitalis toxicity: lack of marked effect on brain na+,k+-adenosine triphosphatase in the cat.

Effect of digitalis on central sympathetic neurons have been proposed to alter sympathetic influences on the heart and to contribute to the induction of arrhythmias. Recently, however, we have presented evidence which indicates that the involvement of a direct central action of digitalis is negligible in the alteration of sympathetic nerve activity after i.v. administration of the drug. Thus, a group of experiments were designed to determine if central drug concentrations or biochemical events in the brain would suggest a central action of the drug. Tritiated digoxin (20 microng/kg) was injected i.v. into cats every 15 minutes until ventricular fibrillation occurred. The concentrations of digoxin in cerebrospinal fluid and serum increased linearly with time as the cumulative dose of digoxin was increased. At the mean arrhythmic dose, 140 microng/kg, cerebrospinal fluid contained approximately 10 nM digoxin whereas free digoxin concentration in serum was approximately 30 nM and total digoxin concentration in serum was approximately 120 nM. Since inhibition of Na+,K+-adenosine triphosphatase (Na+,K+-ATPase) is often associated with the pharmacological effects of digitalis, effects of nanomolar concentrations of digoxin on Na+,K+-ATPase activity were determined in vitro. The concentration of digoxin faund in cerebrospinal fluid at arrhythmia inhibited Na+,K+-ATPase only slightly (5-10%). Activity of Na+,K+-ATP-ase was also examined in brains of cats which had died in ventricular arrhythmias due to treatment with lethal dose of digitoxin. After ventricular fibrillation, the cat brains were removed and Na+,K+-ATPase activity and ouabain binding were determined in eight areas. No reduction in Na+,K+-ATPase activity or [3H]ouabain binding was observed in any area. Thus, it appeared that toxic doses of digitalis did not cause sail to provide evidence for central effects of toxic doses of digoxin or digitoxin.

Adenosine Triphosphatases↗
PubMed1977

Enhancement of phrenic nerve activity by digoxin: an effect dependent upon intact ninth and tenth cranial nerves.

Digitalis increases phrenic nerve activity and causes hyperventilation. To determine whether this effect on respiration is caused by central drug actions on brainstem respiratory neurons or by peripheral drug actions which increase excitatory afferent drive to central respiratory neurons, digoxin was administered intravenously to cats with or without intact IXth and Xth cranial nerves. Digoxin caused marked increases in phrenic nerve activity in cats with intact afferent cranial nerves, but it had no effect in cats with severed afferent nerves. This suggested that effects of digoxin on respiration depend upon afferent input to respiratory neurons. However, digoxin may have had subliminal effects on central neurons which increased phrenic activity only in the presence of excitatory input. To test this possibility, effects of intravenously administered digoxin were observed on centrally evoked submaximal responses in the phrenic nerve. Subarrhythmic, arrhythmic or lethal doses of digoxin had no effect on excitatory phrenic responses evoked from the pons. Thus, effects of digoxin on phrenic nerve activity appeared to be due primarily to drug actions on peripheral neural sites which had excitatory influences on respiration.

Animals↗
PubMed1976

Digoxin toxicity: primary sites of drug action on the sympathetic nervous system.

Increases and decreases in sympathetic nerve activity have been reported to accompany digitalis-induced arrhythmias. These effects may result from drug action on various sites such as the central nervous system, ganglia, chemoreceptor or baroreceptor afferent fibers or peripheral efferent nerve fibers. The relative importance of each possible site of drug action has not been clarified. To define the involvement of some of these sites, digoxin was administered intravenously to cats in order to study its effects on activity of preganglionic splanchnic or postganglionic inferior cardiac nerves in the presence or absence of chemoreceptor and baroreceptor reflexes. In cats with intact reflexes, arrhythmic doses of digoxin had diverse effects on postganglionic activity. In some cats digoxin increased activity and in others it decreased activity. In contrast, digoxin consistently caused large progressive increases in postganglionic activity when baroreceptors and chemoreceptors had been denervated. Digoxin inhibited preganglionic nerve activity only in cats with intact reflexes but had no effect in those without chemoreceptor and baroreceptor reflexes. Thus, the afferent component of the baroreceptor reflex is the apparent site of digoxin-induced inhibition. Digoxin produced increases in activity above control only in postganglionic nerves. This finding suggests that digoxin acts on the ganglion to increase sympathetic activity. Digoxin had no discernible effect on preganglionic activity when baroreceptor and chemoreceptor afferent input had been eliminated. To test further for any subliminal drug effect in the brain, effects of intravenously administered digoxin were observed on centrally evoked submaximal responses in the splanchnic nerve. Lethal doses of digoxin had no effect on responses evoked from the medulla or the hypothalamus. Therefore, these data are not consistent with the hypothesis that a primary site of drug action is in the central nervous system. Instead, the data suggest that neural effects of digoxin result primarily from drug actions within the peripheral autonomic nervous system on sites such as the ganglion and peripheral afferent components of the baroreceptor reflex.

Animals↗
PubMed1975

Opposing responses in sympathetic nerve activity induced by central injections of ouabain.

Cardiac glycosides induce changes in activity of peripheral sympathetic nerves. Arrhythmic doses have been suggested to act in the central nervous system to produce these changes, but direct central effects of digitalis on sympathetic discharge have not been documented. Thus, the central action of ouabain on sympathetic outflow was examined in baroreceptor and chemoreceptor denervated cats. Ouabain was injected into 128 vasoconstrictor or cardioaccelerator sites in the medulla or hypothalamus. Electrical stimulation of 24% of these sites evoked arrhythmias and stimulation consistently caused marked increases in heart rate, blood pressure and nerve activity, but ouabain had several effects, inducing either no change or increases or decreases in spontaneous activity of vasoconstrictor and cardioaccelerator nerves. Effects of ouabain were also observed on signal-averaged potentials evoked in these nerves by electrical stimulation of the medullary or hypothalamic sites of injection. The amplitude of the evoked potentials was either increased, decreased or left unchanged. In general, spontaneous and evoked activities were inhibited by ouabain more frequently than they were enhanced. The pattern of nervous responses to ouabain did not relate to the dose of drug or to the anatomical site of injection. Medullary and hypothalamic injections of ouabain often produced large changes in blood pressure, heart rate and nerve activity, but these effects were not accompanied by alterations in cardiac rhythm. Thus, central microinjections of ouabain produced heterogeneous patterns of effects on activity of peripheral sympathetic nerves, and these microinjections were not sufficient to evoke cardiac arrhythmias in cats with sectioned cranial nerves IX and X.

Animals↗