Healthy Clinical Trial
Official title:
Cardiac Sympathetic Innervation and Coronary Blood Flow Regulation During General Anesthesia
The central hypothesis in the present project is that general anesthesia may alter autonomic
control such that perioperative coronary blood flow (CBF) is significantly disturbed.
These disturbances in coronary blood flow may contribute to the development of myocardial
ischemia in the perioperative period. Furthermore, patients with an intrinsically altered
autonomic sympathetic innervation, like diabetics, are even more prone to develop
perioperative disturbances in coronary blood flow.
Here the researchers will investigate what the direct effects are of general and
locoregional anesthesia on the CBF. Furthermore, the researchers aim to evaluate whether
diabetic subjects show more disturbed CBF responses to anesthesia as compared to
non-diabetics.
In response to intraoperative stress, increased autonomic sympathetic activity may alter
myocardial oxygen demand. Under normal physiological circumstances, sympathetic stimulation
increases myocardial blood flow via adrenergic coronary vasodilation. However, coronary
vessels contain both α- and β-adrenoreceptors, and if the coronary circulation is impaired
due to cardiovascular disease, unopposed adrenergic coronary vasoconstriction may contribute
to ischemia. Anesthetics reduce both coronary blood flow (CBF) regulation and the
sympathetic autonomic nervous activity. However, it is unclear whether anesthetic-related
reductions in CBF are a result of inhibited autonomic sympathetic innervation. Data
regarding alterations in myocardial blood flow in response to sympathetic stimulation during
anesthesia provide conflicting results. Moffitt and Sethna showed in patients undergoing
cardiac surgery that CBF decreased during sternotomy-induced sympathetic stimulation,
whereas Kirno et al. showed an increase in coronary blood flow after sternotomy. To our best
knowledge, coronary vascular responses to sympathetic stimulation in anesthetized healthy
humans are lacking because of absence of reliable non-invasive measurement of myocardial
blood flow. The introduction of non-invasive contrast-echocardiographic techniques that
allow evaluation of regional myocardial blood flow enable evaluation of the relation between
autonomic control and CBF during anesthesia.
Cardiac complications like myocardial ischemia remain one of the main causes of
perioperative morbidity and mortality. Interestingly, the presence of cardiovascular
autonomic neuropathy (CAN) strongly predicts abnormalities in myocardial perfusion and
impaired coronary vasodilator responses to stress. This implies that symptoms of CAN, like
resting tachycardia, orthostasis and alterations in heart rate variability may predict the
degree of impairment of CBF regulation. Indeed, autonomic neuropathy as determined by heart
rate variability predicted mortality in patients with coronary artery disease undergoing
non-cardiac surgery, but the contribution of impaired coronary vasodilatory responses to
these results has not been established. Clarification of the relation between autonomic
control and CBF during anesthesia may not only contribute to our insight in pro-ischemic
processes in the heart, but may lead to changes in preoperative assessment of patients at
risk for perioperative ischemia, thereby reducing perioperative complications.
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Time Perspective: Prospective
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