Protection of the Heart With Remote Ischemic Preconditioning During Heart Surgery: A Pilot Study

Not Applicable

Completed

Conditions: Myocardial Protection
Remote Ischemic Preconditioning

Interventions: Device: Blood Pressure Cuff

Registration Number: NCT00546390

Lead Sponsor: University of Alberta

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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 57

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ischemic Preconditioned Group (rIP)	Blood Pressure Cuff	A 15-cm sterile blood pressure cuff was placed around the right thigh and connected to the inflating device, and the patient was draped obscuring the visibility of the cuff. Subsequently, the patient was randomly allocated (by opening of an envelope) to RIPC consisting of four 5-min cycles of lower limb ischemia-reperfusion induced by a tourniquet inflated to 300 mmHg

Primary Outcome Measures

Name	Time	Method
Myocardial Protection Against Ischemic Injury	72 hours post operatively	High-sensitivity cardiac troponin T release as measured by peak hscTnT values and area-under-the-curve.

Secondary Outcome Measures

Name	Time	Method
All-cause Death and Cardiovascular Long-term Outcome	6-month cardiovascular outcome	Death and re-hospitalization due to any cause including heart and renal failure and new atrial fibrillation