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

Purpose:

• 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
• 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

• Two cardiac biopsies (50 - 200 mg) will be collected pre-bypass and post- bypass and will be analyzed for gene and protein expression.
• 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.
• 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:

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

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