Coronary Blood Flow Regulation During General Anesthesia
Condition: Myocardial Ischemia; Autonomic Neuropathy; Healthy; Diabetes
MeSH terms: Myocardial Ischemia; Ischemia
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        The study population consists patients scheduled for surgery and general anesthesia.
        Patients will be recruited from the preoperative screening clinic in the four,
        aforementioned, groups of patients.
      
Biospecimen description: 
      Frozen plasma will be retained
    
Keywords: coronary blood flow; coronary flow reserve; cardiac sympathetic innervation; general anesthesia; thoracic epidural; autonomic dysfunction; autonomic neuropathy