Biomedical Sciences ETDs

Publication Date

5-16-1973

Abstract

The peripheral mechanisms involved in the cardioacceleration produced by stimulation of the canine vagosympathetic trunk have not been clearly defined. These studies were undertaken to elucidate these mechanisms.

The capacity of vagal-accelerator pathways to alter heart rate was revealed under different experimental conditions. Stimulation of the right vagosympathetic trunk resulted in bradycardia. After the stimulus was terminated, the rate transiently increased above the prestimulation value. This positive rebound was designated post vagal tachycardia (PVT). Admin­istration of atropine eliminated the initial bradycardia and revealed a tachycardia which had an onset during the stimulation. This response was designated as vagally induced tachycardia (VIT).

The mechanisms involved in the two types of cardioacceleration (PVT and VIT) were evaluated using various pharmacoloaic agents. In the first study, it was found that bretylium (Smg/kg) eliminated the positive chronotropic response to cardiac sympathetic nerve stimulation and also reduced the magnitude of VIT. Along with the reduction in magnitude, the waveform of VIT was noticeably altered. Control VIT responses consisted of two components. The first or "fast" component accounted for the short latency (2 to 3 sec) and fast rate of rise in heart rate. This fast comoonent of VIT was eliminated by bretylium. Based on these results, it was Gbncluded that this component of VIT was mediated by cardiac sympathetic nerves present in the vagosympathetic trunk. The onset of the second or "slow" component of VIT was only obvious after sympathetic blockade by bretylium. The slow component was characterized by a relatively long latency (25+-3 sec) and slow rate of rise. This accounted for the long recovery time of VIT before (123+-16 sec) and after (118+-7 sec) sympathetic blockade. It was concluded that vagal fibers mediated the slow component VIT.

To further evaluate the possible involvement of cardiac sympathetic nerves in V IT, a group of dogs was sympathectomized by treatment with 50mg/ kg of 6-hydroxydopamine (6-OHDA). This eliminated all evidence of cardiac sympathetic nerve activity. Norepinephrine levels in the sinoatrial node area were reduced 96 percent. The VIT responses in the 6-OHDA treated dogs had a waveform similar to the previously described slow component VIT. This VIT was affected by neither bretylium nor adrenal ligation. Based on these results, it was concluded that the vagal-accelerator pathway is independent of neuronal and adrenal catecholamine stores.

The slow component VIT was not inhibited by the adrenergic blocking agents, phentolamine (2mq/kg), phenoxybenzamine (15mg/kg) or practolol (Smg/kg), and it was concluded that the vagal cardioaccelerator fibers do not activate adrenergic receptor$.

To assess the possibility that the slow component VIT may involve direct effects of transmitter on pacemaker cell membrane, chronotropic responses were recorded after intracoronary injection of the local anesthetic agent, lidocaine. The vaqal-decelerator and sympathetic-accelerator pathways were not significantly affected by lidocaine. In contrast, lidocaine significantly depressed the second or slow component VIT. Based on these results, it was concluded that the vagal-accelerator pathway is mediated by more diffuse effects of a transrmitter on cell membranes. At this time the best hypothesis is that this transmitter may exert its influence on heart rate by decreasing potassium conductance.

In summary, it is concluded that the canine vaqosympathetic trunk contains at least two cardioaccelerator pathways. The first involves cardiac sympathetic nerves which release catecholamines and activate beta adrenergic receptors. The second pathway involves vagal fibers which initiate carioacceleration by a transmitter-mediated alternation of pacemaker cell potentials.

Document Type

Dissertation

Language

English

Degree Name

Biomedical Sciences

Level of Degree

Doctoral

Department Name

Biomedical Sciences Graduate Program

First Committee Member (Chair)

Joann Reinhartsen Weiss

Second Committee Member

Donald Victor Priola

Third Committee Member

Kenneth George Kastella

Fourth Committee Member

Marvin LeRoy Riedesel

Download

Share

COinS