AUTONOMIC MODULATION OF ISCHEMIC ARRHYTHMIAS

  • Zipes, Douglas, (PI)

Project: Research project

Description

Many clinical and animal studies implicate the autonomic nervous
system in the genesis of some of the arrhythmias responsible for
sudden cardiac death, an event that accounts for almost 25% of all
deaths annually in the U.S. The long-term objective of our studies
is to investigate the mechanism(s) by which the autonomic nervous
system modulates cardiac excitable properties and is in turn
modulated by the ischemia/infarction, to promote, precipitate or
prevent the development of cardiac arrhythmias after coronary
occlusion. Although much is known about the physiological and
biochemical consequences of stimulating autonomic receptors, and
indeed, several of the receptors have been cloned, data integrating
and linking findings from cellular and subcellular research to the
development of cardiac arrhythmias in animal models in vivo and in
patients with cardiac arrhythmias are lacking. We plan a series
of studies based on the overall hypothesis that the myocardial
infarction and/or ischemia alters the function of nerve axons
passing through the ischemic/infarcted area, producing acute
(functional) and then chronic (anatomical) denervation, denervation
supersensitivity and reinnervation. These autonomic influences
modulate cardiac excitable properties, resulting in suppression,
facilitation or initiation of cardiac arrhythmias. The specific
aims are to investigate mechanisms responsible for the functional
denervation following acute myocardial ischemia, determine whether
preconditioning ischemia alters the subsequent degree and time
course of acute denervation, determine the concordance of afferent
and efferent ischemic denervation, determine whether some types of
myocardial infarction are more arrhythmogenic than others,
determine whether after depolarizations are responsible for some
arrhythmias, determine whether exposure to quinidine and digitalis
is more arrhythmogenic in hearts with sympathetic denervation and
supersensitivity, determine the mechanisms of adrenergic and
cholinergic supersensitivity and determine whether sympathetic or
vagal denervation occurs in patients following myocardial
infarction and is arrhythmogenic. Autonomic stimulation will be
produced by electrical stimulation of efferent vagal and
sympathetic nerves, provocation of afferent myocardial reflexes
with bradykinin and nicotine and infusion of various drugs.
Noninvasive imaging with metaiodobenzylguanidine will be done to
determine efferent myocardial sympathetic innervation in patients
with coronary artery disease.
StatusFinished
Effective start/end date4/1/893/31/95

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

Fingerprint

Cardiac Arrhythmias
Denervation
Sympathectomy
Ischemia
Infarction
Quinidine
Bradykinin
Nicotine
Adrenergic Agents
Electric Stimulation
Myocardial Ischemia
Inpatients
Coronary Artery Disease
Animal Models
Research
Pharmaceutical Preparations

ASJC

  • Medicine(all)