Ignite Creation Date:
2024-05-05 @ 9:58 PM
Last Modification Date:
2024-10-26 @ 10:11 AM
Study NCT ID:
NCT00995670
Status:
COMPLETED
Last Update Posted:
2015-03-17
First Post:
2009-10-13
Brief Title:
IschemiaReperfusion Injury of Human Endothelium Role of Glucose and Statins
Sponsor:
US Department of Veterans Affairs
Organization:
VA Office of Research and Development
Study Overview
Official Title:
IschemiaReperfusion Injury of Human Endothelium Role of Glucose and Statins
Status:
COMPLETED
Status Verified Date:
2015-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Anesthetic preconditioning APC a brief exposure to an anesthetic gas has become an area of intense research interest because of its ability to protect tissue and organs from injury resulting from a cessation of blood flow and then a re-establishment of flow The blood vessel lining plays a key role in this injury This research will examine in human volunteers several important modifiers of APC in human blood vessels high blood sugar vitamin C and statin drugs Thus the proposed studies will advance the investigators understanding of mechanisms of this injury in humans and explore important modifiers of APC protection from injury
Detailed Description:
Injury to vital organs and tissue can occur when blood flow is stopped and then re-established This happens in a variety of clinical situations and contributes to poor outcomes A newer concept of protection from this injury by an anesthetic drug might occur because of the effect of the volatile anesthetics on the tissue that lines blood vessels Thus a brief exposure to a volatile anesthetic before a cessation of blood flow called anesthetic preconditioning APC can substantially reduce the resulting injury to the lining of the blood vessels In animal models high levels of blood sugar block this protection while cholesterol lowering drugs statins restore the protection and may independently protect blood vessel lining from injury The interactions of high blood sugar and statin drugs on the blood vessel reaction to APC and a subsequent 20-min cessation of blood flow to the forearm will be studied in humans In addition the involvement of reactive oxygen species ROS in the harmful effects of high blood sugar and the beneficial effects of statins will be explored The following four hypotheses will be studied 1 high blood sugar blocks the anesthetic protection of blood vessels from injury in a dose and time dependent manner 2 reactive oxygen species are involved in the inhibition of APC by high blood sugar 3 statins modulate injury in a dose related manner and 4 statins reduce high blood sugar inhibition of APC
A standard model to evaluate forearm blood vessel function will be used Thin rubber-band-like strain gauges will be strapped around each forearm and the change in their stretch during a variety of interventions on the experimental arm the other arm will not receive any interventions and will be the control arm will be measured These interventions will allow the investigator to determine whether the hypotheses listed above are true During all studies there will be a 20-min arrest of the forearm circulation Additional effects of injury APC high blood sugar and statins will be determined by evaluating blood vessel inflammatory responses from markers in blood samples taken before and after IR injury Several studies will involve varying the forearm blood glucose concentration for brief 30 min to longer 2 hours periods prior to APC and injury The ROS scavenger vitamin C will be used to evaluate the role of ROS in adverse effects of high blood sugar There are several other studies that will continue to seek the mechanism of action of this effect via the use of other drug interactions
A standard model to evaluate forearm blood vessel function will be used Thin rubber-band-like strain gauges will be strapped around each forearm and the change in their stretch during a variety of interventions on the experimental arm the other arm will not receive any interventions and will be the control arm will be measured These interventions will allow the investigator to determine whether the hypotheses listed above are true During all studies there will be a 20-min arrest of the forearm circulation Additional effects of injury APC high blood sugar and statins will be determined by evaluating blood vessel inflammatory responses from markers in blood samples taken before and after IR injury Several studies will involve varying the forearm blood glucose concentration for brief 30 min to longer 2 hours periods prior to APC and injury The ROS scavenger vitamin C will be used to evaluate the role of ROS in adverse effects of high blood sugar There are several other studies that will continue to seek the mechanism of action of this effect via the use of other drug interactions
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None