Biomedical subjects

C M Lathers

Publications and source records attributed to C M Lathers.

76 records · Page 5Linked to original sources

PubMedDate not supplied

Are the sympathetic neural effects of digoxin and quinidine involved in their action on cardiac rhythm?

This study was initiated to determine if ventricular arrhythmia induced by digoxin was associated with a nonuniform neural discharge in the cardiac sympathetic postganglionic fibers. In addition, splanchnic neural discharge was monitored to explore the role of adrenal medullary catecholamines in digoxin-induced arrhythmia. Experiments were performed to ascertain whether the antiarrhythmic effects of quinidine in digoxin-induced arrhythmias were related to an action on cardiac sympathetic neural discharge induced by digoxin. All cats were anesthetized with alpha-chloralose and given atropine; some were pretreated with quinidine (10 or 20 mg/kg i.v. 15 min before digoxin). Digoxin was given every 15 min until death; the first three doses were 50 micrograms/kg i.v., and all subsequent doses were 25 micrograms/kg. The mean +/- SE time to arrhythmia was 32 +/- 4 min (n = 16) and was significantly increased only after 20 mg/kg quinidine (64 +/- 7 min; p less than 0.001). Mean +/- SE time to death was also increased from 74 +/- 4 to 98 +/- 7 min (p less than 0.001). Postganglionic cardiac sympathetic neural discharge before digoxin-induced arrhythmia was depressed. Of the 28 nerves monitored in 16 animals receiving digoxin, in the minute before development of arrhythmia, 22 nerves were depressed, 3 were increased, and 3 showed no change when compared with the predigoxin control. Following this depression of neural discharge, arrhythmia developed, and the neural discharge began to rise, eventually increasing above control levels. During this time the variability of the neural discharge increased greatly, as evidenced by large SE values, so that the mean values were not significantly different from control levels. Splanchnic neural discharge (n = 9) progressively decreased, reaching 66% of control values after the third injection of digoxin; the discharge then began to increase gradually toward control levels in the next 10 min and arrhythmia developed. The data indicate that the arrhythmias caused by digoxin are not associated with the development of nonuniform discharge patterns in the cardiac sympathetic nerves. Furthermore, action on the splanchnic nerve discharge is not involved in the arrhythmogenic effects of digoxin. Pretreatment with quinidine, 20 mg/kg, decreased both splanchnic and post-ganglionic cardiac sympathetic neural discharge, arterial blood pressure, and heart rate. Although quinidine, 20 mg/kg, increased the time to arrhythmia induced by digoxin, the depression of postganglionic cardiac or splanchnic neural discharge did not seem to be a major component of the antiarrhythmic effect of quinidine.

Animals↗

PubMedDate not supplied

A comparison of intraosseous and intravenous routes of administration for antiseizure agents.

Intravenous (i.v.) access for administration of antiepileptic drugs can be time-consuming and difficult in an infant during a seizure. This study examined the intraosseous (i.o.) route as an alternative means of vascular access for drug administration in an animal-seizure model. Domestic swine (13-20 kg) were anesthetized with ketamine (20 mg/kg i.m.) and alpha-chloralose (80 mg/kg i.v.) and given gallamine (4 mg/kg i.v.) to prevent muscle fasciculations. Tracheosotomies were performed and the animals were ventilated with a Harvard respirator. The left femoral vein was cannulated and pentylenetetrazol (PTZ) (100 mg/kg) was given to elicit epileptogenic activity. Sixty seconds after onset of epileptogenic activity, the animals received saline or diazepam (DZP) (0.1 mg/kg) or propranolol (2.5 mg/kg) i.v. or via the i.o. route (18-gauge spinal needle placed in the right proximal tibia). Both DZP and propranolol were effective in suppressing epileptogenic activity via the i.v. or i.o. routes. Thus, the i.o. route is a rapid and effective alternative route for the administration of antiepileptic drugs when an i.v. route cannot be readily established.

Animals↗

PubMedDate not supplied

Suppression of pentylenetetrazol-elicited seizure activity by intraosseous lorazepam in pigs.

Use of the intraosseous (i.o.) route as an alternative venous access for drug administration has increased. This study examined the efficacy of i.o. lorazepam (LZP) in suppressing pentylenetetrazol (PTZ)-induced seizure activity in pigs. Domestic swine (13-20 kg) were prepared for recordings of arterial blood pressure, EEG, and electrocortical activity. Seizure activity was induced by PTZ (100 mg/kg i.v.). Sixty seconds after onset of seizure activity, animals either received no drug (control) or LZP (1.0 mg/kg) administered i.v. or i.o. via an 18- or 13-gauge spinal needle inserted in the right proximal tibia. Both i.o. and i.v. LZP significantly suppressed the duration of seizure activity (DSA) (s/min interval) within 1 min following drug administration: DSA control, 46.2 +/- 3.6; i.v. LZP, 25.0 +/- 5.1; i.o. (18-gauge) LZP, 27.6 +/- 6.0; i.o. (13-gauge) LZP, 24.0 +/- 2.4. Seizure activity was essentially abolished at 1 min following LZP infusion. In addition, both i.v. and i.o. LZP did not have significant effects on the basal heart rate and mean arterial blood pressure. The data demonstrate that in swine (1) the i.o. route is an effective alternative venous access for LZP administration, and (2) the size of spinal needles does not affect the antiepileptic efficacy of i.o. infusion of LZP.

Animals↗

PubMedDate not supplied

Digitalis glycosides: a discussion of the similarities and differences in actions and existing controversies.

The writing of this review was initiated to answer the question of whether differences in the actions of the various digitalis glycosides exist and to discuss current controversies in the research area of the digitalis glycosides. Data obtained in our laboratory indicated that the effect of digoxin on postganglionic cardiac sympathetic neural discharge in the minute prior to the occurrence of arrhythmia differed from that of ouabain. This raised the question of whether data published in other laboratories would support the contention that differences in glycosides do exist. To answer this question, a review of the literature was begun. Our survey of these studies are cited in the tables of this review. These tables summarize the actions of glycosides in vivo and in vitro in different animal models. The reader should bear in mind that the data included within the tables do not represent an inclusive summary of all studies in the literature. For detailed review articles, the reader is referred to the following references: Gillis et al; Gillis and Quest; Roberts et al; Lathers and Roberts; Farah and Alousi; Benthe; Levitt et al; Smith and Haber; Somberg; Lee and Klaus; Mason; Schwartz. Furthermore the summary of the results for each particular study cited in the table may not, in all cases, include each finding of the published data. Nevertheless, the tables do provide a summary of data obtained in various species with different glycosides in several different areas of research, and as such, represent an abridged compendium for the research working in the field of digitalis glycosides. This review has been organized firstly to consider glycoside-induced alterations in the autonomic nervous system and, secondly, to examine their direct actions on the heart.

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