Coronary Blood Flow Regulation During General Anesthesia

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.

Study Overview

• Status: Completed
• Conditions: Myocardial Ischemia; Healthy; Diabetes; Autonomic Neuropathy

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.

• Study Type: Observational
• Enrollment (Actual): 45

Contacts and Locations

Study Locations

• Netherlands
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1007 MB
      • VU University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

• 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.

Description

Inclusion Criteria:

• male
• age between 18-75 years
• scheduled for non-cardiac intermediate or high risk surgery
• for patient group 2: indication for thoracic epidural anesthesia

Exclusion Criteria:

• neurosurgery
• known/documented cardiac disease
• (untreated) hypertension
• abnormal ECG or echocardiogram
• peripheral vascular disease
• renal disease requiring hemo- or peritoneal dialysis
• inability to perform transthoracic echocardiography
• medication interfering with presynaptic catecholamine uptake
• for patient group 2: contra-indication for thoracic epidural anesthesia (bleeding diathesis, infection at the puncture site, patient refusal, severe stenotic valvular disease)
• previous allergic reaction to echocardiographic contrast agents
• contraindications for the use of echocardiographic contrast agents

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Healthy; Healthy subjects scheduled for general anesthesia
Healthy with thoracic epidural anelgesia; Healthy subjects scheduled for general anesthesia and thoracic epidural analgesia
Diabetes; Subjects with diabetes scheduled for general anesthesia
Diabetes with autonomic neuropathy; Subjects with diabetes and cardiovascular autonomic neuropathy scheduled for general anesthesia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Coronary flow reserve	Within the first 3 days postoperatively

Secondary Outcome Measures

Outcome Measure	Time Frame
Diabetic autonomic neuropathy	Within the first 3 days postoperatively

Collaborators and Investigators

• Sponsor: Amsterdam UMC, location VUmc
• Collaborators: Netherlands Heart Foundation
• Investigators: Principal Investigator: Carolien SE Bulte, MD, Amsterdam UMC, location VUmc; Principal Investigator: R. A. Bouwman, MD, PhD, Amsterdam UMC, location VUmc; Study Chair: C. Boer, PhD, Amsterdam UMC, location VUmc; Study Director: S. A. Loer, MD, PhD, MSC, Amsterdam UMC, location VUmc; Study Chair: O. Kamp, MD, PhD, Amsterdam UMC, location VUmc; Study Chair: M. Diamant, MD, PhD, Amsterdam UMC, location VUmc

Publications and helpful links

General Publications

• Bulte CS, van den Brom CE, Loer SA, Boer C, Bouwman RA. Myocardial blood flow under general anaesthesia with sevoflurane in type 2 diabetic patients: a pilot study. Cardiovasc Diabetol. 2014 Mar 23;13:62. doi: 10.1186/1475-2840-13-62.

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (ACTUAL): February 1, 2014
• Study Completion (ACTUAL): October 1, 2014

Study Registration Dates

• First Submitted: March 20, 2009
• First Submitted That Met QC Criteria: March 20, 2009
• First Posted (ESTIMATE): March 23, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): October 14, 2015
• Last Update Submitted That Met QC Criteria: October 12, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: general anesthesia; autonomic neuropathy; coronary flow reserve; thoracic epidural; autonomic dysfunction; coronary blood flow; cardiac sympathetic innervation
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Ischemia; Ischemia
• Other Study ID Numbers: ANES 2008-12; 2008 T003