Clinical trial NCT00546390: Protection of the Heart With Remote Ischemic Preconditioning During Heart Surgery: A Pilot Study
Official title: Protection of the Heart With Remote Ischemic Preconditioning During Heart Surgery: A Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Remote Ischemic Preconditioning
Myocardial Protection
Lead sponsor: University of Alberta
Sponsor class: OTHER
First posted: 2007-10-18
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to compare a treatment called remote ischemic preconditioning (rIP) to no treatment. rIP is a simple treatment that is believed to help patients recover better after heart surgery. This treatment involves applying a large blood pressure cuff to one leg. The blood pressure cuffs will be inflated for 5 minutes and then deflated for 5 minutes. This will be done 4 times in a row.

Detailed description: Purpose:

1. Determine, in a pilot study, if surrogate markers of rIP can be detected in patients presenting for cardiac surgery. Specifically measure the effect of rIP on the expression profile of HSP-70, iNOS, PKC-E, p38 MAPK, PI3K, and sarcolemmal KATP
2. Determine if rIP influences the expression of genes known to influence substrate preference and thereby myocardial metabolism in patients undergoing heart surgery. Specifically the expression of HIF-1a, PPAR-a and AMPK

Hypothesis:

We hypothesize that rIP provides myocardial protection in patients presenting for heart surgery and that this protection is defined by a distinct gene expression profile with regards to genes involved in rIP and myocardial metabolism.

Study Design:

This proposal is for a randomized blinded pilot study on the use of rIP in patients requiring heart surgery.

Study Population:

The study will include 100 male and female patients undergoing elective heart surgery with cardiopulmonary bypass (CPB).

Randomization:

Patients will be randomized 1:1 to receive either rIP or no treatment.

Blinding Procedures:

The patient will be blinded as well as those performing the experimental analysis.

Interventions:

Remote Ischemic Preconditioning

rIP will be induced immediately following induction of anesthesia. Four 5 minute cycles of lower unilateral limb ischemia and reperfusion induced tourniquet inflation to 300 mmHg will constitute the preconditioning stimulus.

Blood sample collection/analysis

1. Two cardiac biopsies (50 - 200 mg) will be collected pre-bypass and post- bypass and will be analyzed for gene and protein expression.
2. Blood samples (4 mL) will be drawn immediately before induction of anesthesia, and at the same times as cardiac tissue samples are harvested and analyzed for gene/protein expression as well as at 1, 24, 48 and 72 hours post surgery. Troponin I and NT-ProBNP will be measured at baseline, 1, 24, 48 and 72 hours after surgery and 3 mL of blood will be collected for these tests. A total of 43 mL of blood will be collected per patient.
3. rIP induced changes in leukocyte gene expression will be measured at the aforementioned time points.

Other

ECG assessment on post-operative day 1, 2, and 3.

National Institute of Health stroke scale assessment will be conducted at screening and post operatively prior to hospital discharge.

Each patient will receive a telephone follow-up call at 30 days post operatively to collect adverse events and mortality data.

Experimental Methods:

1. qRT-PCR will be used to measure gene expression.
2. Immunoblotting will be used to measure protein expression

Eligibility criteria: Inclusion Criteria:

* Written informed consent
* Age 18 through 80 years, inclusive
* Scheduled for heart surgery with CPB

Exclusion Criteria:

* Females of childbearing potential
* Emergency surgery
* Previous sternotomy
* Myocardial infarction within 48 hours prior to surgery
* Diabetes and/or BMI \>35
* Need for Alpha2-agonists perioperatively
* Peripheral Vascular Disease

Primary outcomes:
measure: Myocardial Protection Against Ischemic Injury
timeFrame: 72 hours post operatively
Secondary outcomes:
measure: All-cause Death and Cardiovascular Long-term Outcome
timeFrame: 6-month cardiovascular outcome
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
Study officials:
affiliation: University of Alberta
name: Barry A Finegan, MB
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lucchinetti E, Bestmann L, Feng J, Freidank H, Clanachan AS, Finegan BA, Zaugg M. Remote ischemic preconditioning applied during isoflurane inhalation provides no benefit to the myocardium of patients undergoing on-pump coronary artery bypass graft surgery: lack of synergy or evidence of antagonism in cardioprotection? Anesthesiology. 2012 Feb;116(2):296-310. doi: 10.1097/ALN.0b013e318242349a.