Myocardial IschemiaNCT00866801
Coronary Blood Flow Regulation During General Anesthesia
An observational study of Myocardial Ischemia and Autonomic Neuropathy, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Myocardial Ischemia, Autonomic Neuropathy, Healthy
- How many people
- 45 participants
- Where
- 1 siteNetherlands
- Study dates
- Apr 2009to Oct 2014
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- male
- age between 18-75 years
- scheduled for non-cardiac intermediate or high risk surgery
- for patient group 2: indication for thoracic epidural anesthesia
Who cannot join
- neurosurgery
- known/documented cardiac disease
- (untreated) hypertension
- abnormal ECG or echocardiogram
- peripheral vascular disease
- renal disease requiring hemo- or peritoneal dialysis
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
VU University Medical Center
Amsterdam, North Holland, 1007 MB
About this study
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.
Read the 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.
- Conditions
- Myocardial Ischemia, Autonomic Neuropathy, Healthy, Diabetes
- Keywords
- coronary blood flow, coronary flow reserve, cardiac sympathetic innervation, general anesthesia, thoracic epidural, autonomic dysfunction, autonomic neuropathy
- Medical subject headings
- Myocardial Ischemia, Diabetes Mellitus, Primary Dysautonomias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 being measured
The primary outcome is the main question the study is designed to answer.
Coronary flow reserve
Measured: Within the first 3 days postoperatively
Secondary outcomes (1)
Diabetic autonomic neuropathy
Measured: Within the first 3 days postoperatively
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2009 (estimated)
- Study startApr 2009
- Primary completionFeb 2014
- Study completionOct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Myocardial IschemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Time perspective
- Prospective
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Collaborators
- Netherlands Heart Foundation
- Responsible party
- Principal investigator, C.S.E. Bulte, Amsterdam UMC, location VUmc
- Investigators
- Carolien SE Bulte, MD, Principal investigator, Amsterdam UMC, location VUmcR. A. Bouwman, MD, PhD, Principal investigator, Amsterdam UMC, location VUmcC. Boer, PhD, Study chair, Amsterdam UMC, location VUmcS. A. Loer, MD, PhD, MSC, Study director, Amsterdam UMC, location VUmcO. Kamp, MD, PhD, Study chair, Amsterdam UMC, location VUmcM. Diamant, MD, PhD, Study chair, Amsterdam UMC, location VUmc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00866801
- Sponsor's protocol ID
- ANES 2008-12
- Other IDs
- 2008 T003
- Status last verified
- Oct 2015
- First submitted
- 20 Mar 2009
- Last updated
- 14 Oct 2015
- Results posted
- No
- Data monitoring committee
- No
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.
PubMed 24656118
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cardiac Sympathetic Innervation and Coronary Blood Flow Regulation During General Anesthesia
- ClinicalTrials.gov ID
- NCT00866801
- Acronym / sponsor ID
- ANES 2008-12
- Conditions
- Myocardial Ischemia, Autonomic Neuropathy, Healthy, Diabetes
- Keywords
- coronary blood flow, coronary flow reserve, cardiac sympathetic innervation, general anesthesia, thoracic epidural, autonomic dysfunction, autonomic neuropathy
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Amsterdam UMC, location VUmcUniversity, hospital or other
- Collaborators
- Netherlands Heart Foundation
- Study start
- Apr 2009
- Primary completion
- Feb 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 23 Mar 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (4 listed)
- male
- age between 18-75 years
- scheduled for non-cardiac intermediate or high risk surgery
- for patient group 2: indication for thoracic epidural anesthesia
Key exclusion criteria (11 listed)
- neurosurgery
- known/documented cardiac disease
- (untreated) hypertension
- abnormal ECG or echocardiogram
- peripheral vascular disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Coronary flow reserve
Time frame: Within the first 3 days postoperatively
1 secondary outcome
Diabetic autonomic neuropathy
Time frame: Within the first 3 days postoperatively
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2015.
- Derived from this study: PubMed 24656118Bulte 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Carolien SE Bulte, MD principal investigator
Amsterdam UMC, location VUmc
R. A. Bouwman, MD, PhD principal investigator
Amsterdam UMC, location VUmc
C. Boer, PhD study chair
Amsterdam UMC, location VUmc
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Myocardial Ischemia and Autonomic Neuropathy, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Coronary flow reserve (time frame: Within the first 3 days postoperatively). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00866801, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2015.