Cardiopulmonary Bypass, Coronary Artery Bypass Grafting, Reperfusion Injury
Conditions
Keywords
Doxycycline, coronary artery bypass grafting
Brief summary
The purpose of this study is to determine whether doxycycline (Periostat) at a sub-antimicrobial dose will decrease reperfusion injury after coronary artery bypass grafting (CABG) surgery with cardiopulmonary bypass (CPB).
Detailed description
This proposal is for a randomized, placebo-controlled, double-blinded study of the use of doxycycline in patients requiring CABG surgery. Patients will be randomized 1:1 to receive either doxycycline or placebo. This study will be conducted in a blinded manner. The pharmacy will randomize patients and will have the randomization code. The code will only be broken in the case of an emergency and the event will be fully documented. In addition to standard care, patients will receive oral administration of 20 mg of doxycycline or placebo twice a day at least 2 days prior to surgery, on the day of surgery, and on postoperative days 1, 2, and 3. Myocardial atrial biopsies will be taken at 2 time points during the CABG procedure: during cannulation of the right atrium and 10 minutes after cross-clamp release. Tissue will be analyzed for MMP-2 and -9 activity and TnI and MLC-1 levels. A Swan-Ganz-Catheter will be placed in the pulmonary artery over 24 hours to measure hemodynamics (LVSWI). A coronary sinus catheter will be placed under echocardiographic guidance prior to initiation of CPB (will be removed 20 minutes after cross-clamp release). Patients will have an additional ECG on post-operative days 1 and 3. Additional blood will be drawn to determine doxycycline plasma levels, MMP-2 and -9 activity, total gelatinolytic activity, and levels of troponin I and T products at the following time points: pre-induction, prior to initiation of CPB, 10 and 20 minutes following the release of the aortic cross clamp (arterial and venous) and 3, 6, 24 and 72 hours post aortic cross clamp removal (venous). Each of the above samples will require 6 mL of blood for a study total of 72 mL. At the time of each blood draw we will measure and record the hematocrit value.
Interventions
DRUGPeriostat
In addition to standard care, patients received oral administration of 20 mg of doxycycline twice a day at least 2 days prior to surgery, on the day of surgery, and on postoperative days 1, 2, and 3.
DRUGPlacebo Oral Tablet
In addition to standard care, patients received oral administration of placebo twice a day at least 2 days prior to surgery, on the day of surgery, and on postoperative days 1, 2, and 3.
Sponsors
University of Alberta
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Written informed consent * Aged 18 through 80 years, inclusive * Scheduled for primary CABG surgery with CPB
Exclusion criteria
* Females of childbearing potential * Emergency CABG * Previous sternotomy * Planned simultaneous surgery (i.e. valve repair or carotid endarterectomy) * Myocardial infarction within 48 hours * Pre-operative atrial fibrillation * Pre-operative ventricular pacing or left bundle branch block (LBBB) * Known hypersensitivity to tetracycline class antibiotics * Renal failure requiring dialysis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Left Ventricular Stroke Work Index (LVSWI) | Before surgery up to 24h of reperfusion | Measure of global left ventricular function. The formula used for calculation is: LVSWI= SI x MAP x 0.0144 LVSWI = Left Ventricular Stroke Work Index (g\*m/m2) SI = Stroke Index (mL/beat/m2) MAP = Mean Arterial Pressure (mmHg) 0.0144 is a conversion term to equalize units. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cardiac Matrix Metalloproteinase-2 Activity in Right Atrial Biopsies at 10 Minutes Reperfusion | Before surgery and 10 minutes reperfusion after surgery | Biochemical activity of MMP-2 activity in right atrial biopsies, measured at 10 minutes of reperfusion after surgery. |
| Venous Plasma Cardiac Matrix Metalloproteinase-9 Activity Before and After Reperfusion | Before surgery and up to 72 h reperfusion after surgery | Biochemical activity of MMP-9 activity in venous plasma, measured before surgery and up to 72h of reperfusion after surgery. |
| Venous Plasma Cardiac Matrix Metalloproteinase-2 Activity Before and After Reperfusion | Before surgery and up to 72 h reperfusion after surgery | Biochemical activity of MMP-2 activity in venous plasma, measured before surgery and up to 72h of reperfusion after surgery. |
| Cardiac Matrix Metalloproteinase-9 Activity in Right Atrial Biopsies at 10 Minutes Reperfusion | Before surgery and 10 minutes reperfusion after surgery | Biochemical activity of MMP-9 activity in right atrial biopsies, measured at 10 minutes of reperfusion after surgery. To determine MMP-9 activity, 20 μg of total protein from both myocardial extracts and plasma were analyzed by gelatin zymography. For detailed methodology consult Cheung PY, Sawicki G, Wozniak M, et al: Matrix metalloproteinase-2 contributes to ischemia-reperfusion injury in the heart. Circulation 2000; 101:1833-1839 |
| Cleaved TroponinI/GAPDH Ratios in Right Atrial Biopsy | Before surgery and 10 minutes reperfusion after surgery | Measurement of the ratios of cleaved TnI (troponin-I) versus GAPDH in biopsies collected from right atria. Measure is the ratio TnI/GAPDH |
| Venous Plasma Concentration of C-reactive Protein | Before surgery and up to 72 h reperfusion after surgery | Measurement of inflammation marker C-reactive protein in plasma |
| Venous Plasma Concentration of IL-6 | Before surgery and up to 72 h reperfusion after surgery | Measurement of inflammation marker interleukin-6 in plasma |
| Venous Plasma Concentration of Troponin-I | Before surgery and 10 minutes reperfusion after surgery | Measurement of levels of TnI (troponin-I), a marker of cardiac cell damage |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Oral Tablet Patients received oral administration of matching placebo pills, twice a day at least 2 days prior to surgery, on the day of surgery, and for the first 3 postoperative days (via a nasogastric tube or orally when patients tolerated it).
Placebo Oral Tablet: In addition to standard care, patients received oral administration of placebo twice a day at least 2 days prior to surgery, on the day of surgery, and on postoperative days 1, 2, and 3. | 22 |
| Periostat Patients received oral administration of 20 mg of doxycycline, twice a day at least 2 days prior to surgery, on the day of surgery, and for the first 3 postoperative days (via a nasogastric tube or orally when patients tolerated it).
Periostat: In addition to standard care, patients received oral administration of 20 mg of doxycycline twice a day at least 2 days prior to surgery, on the day of surgery, and on postoperative days 1, 2, and 3. | 20 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Initial Enrollment | Additional surgery scheduled | 0 | 2 |
| Initial Enrollment | Death | 1 | 0 |
| Initial Enrollment | Other | 1 | 2 |
| Initial Enrollment | Surgery schedule change | 4 | 4 |
Baseline characteristics
| Characteristic | Placebo Oral Tablet | Periostat | Total |
|---|---|---|---|
| Age, Continuous | 64.6 years STANDARD_DEVIATION 1.5 | 63.1 years STANDARD_DEVIATION 2 | 63.9 years STANDARD_DEVIATION 1.2 |
| Region of Enrollment Canada | 22 Participants | 20 Participants | 42 Participants |
| Sex: Female, Male Female | 6 Participants | 3 Participants | 9 Participants |
| Sex: Female, Male Male | 16 Participants | 17 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 20 |
| other Total, other adverse events | 0 / 22 | 0 / 20 |
| serious Total, serious adverse events | 0 / 22 | 0 / 20 |
Outcome results
Primary
Left Ventricular Stroke Work Index (LVSWI)
Measure of global left ventricular function. The formula used for calculation is: LVSWI= SI x MAP x 0.0144 LVSWI = Left Ventricular Stroke Work Index (g\*m/m2) SI = Stroke Index (mL/beat/m2) MAP = Mean Arterial Pressure (mmHg) 0.0144 is a conversion term to equalize units.
Time frame: Before surgery up to 24h of reperfusion
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Oral Tablet | Left Ventricular Stroke Work Index (LVSWI) | 1h reperfusion | 30 g*m/m2 | Standard Error 1.8 |
| Placebo Oral Tablet | Left Ventricular Stroke Work Index (LVSWI) | 6h reperfusion | 28 g*m/m2 | Standard Error 1.4 |
| Placebo Oral Tablet | Left Ventricular Stroke Work Index (LVSWI) | Post surgery | 29 g*m/m2 | Standard Error 1.7 |
| Placebo Oral Tablet | Left Ventricular Stroke Work Index (LVSWI) | 12h reperfusion | 30 g*m/m2 | Standard Error 1.6 |
| Placebo Oral Tablet | Left Ventricular Stroke Work Index (LVSWI) | 3h reperfusion | 31 g*m/m2 | Standard Error 1.9 |
| Placebo Oral Tablet | Left Ventricular Stroke Work Index (LVSWI) | 24h reperfusion | 32 g*m/m2 | Standard Error 1.8 |
| Placebo Oral Tablet | Left Ventricular Stroke Work Index (LVSWI) | Before surgery | 42 g*m/m2 | Standard Error 2.6 |
| Periostat | Left Ventricular Stroke Work Index (LVSWI) | 24h reperfusion | 33 g*m/m2 | Standard Error 1.9 |
| Periostat | Left Ventricular Stroke Work Index (LVSWI) | Before surgery | 43 g*m/m2 | Standard Error 2.5 |
| Periostat | Left Ventricular Stroke Work Index (LVSWI) | Post surgery | 28 g*m/m2 | Standard Error 1.7 |
| Periostat | Left Ventricular Stroke Work Index (LVSWI) | 1h reperfusion | 29 g*m/m2 | Standard Error 1.9 |
| Periostat | Left Ventricular Stroke Work Index (LVSWI) | 3h reperfusion | 29 g*m/m2 | Standard Error 2 |
| Periostat | Left Ventricular Stroke Work Index (LVSWI) | 6h reperfusion | 25 g*m/m2 | Standard Error 1.4 |
| Periostat | Left Ventricular Stroke Work Index (LVSWI) | 12h reperfusion | 30 g*m/m2 | Standard Error 1.7 |
Secondary
Cardiac Matrix Metalloproteinase-2 Activity in Right Atrial Biopsies at 10 Minutes Reperfusion
Biochemical activity of MMP-2 activity in right atrial biopsies, measured at 10 minutes of reperfusion after surgery.
Time frame: Before surgery and 10 minutes reperfusion after surgery
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Oral Tablet | Cardiac Matrix Metalloproteinase-2 Activity in Right Atrial Biopsies at 10 Minutes Reperfusion | Before surgery | .36 Arbitrary units | Standard Error 0.04 |
| Placebo Oral Tablet | Cardiac Matrix Metalloproteinase-2 Activity in Right Atrial Biopsies at 10 Minutes Reperfusion | 10 min reperfusion | .42 Arbitrary units | Standard Error 0.04 |
| Periostat | Cardiac Matrix Metalloproteinase-2 Activity in Right Atrial Biopsies at 10 Minutes Reperfusion | Before surgery | .24 Arbitrary units | Standard Error 0.04 |
| Periostat | Cardiac Matrix Metalloproteinase-2 Activity in Right Atrial Biopsies at 10 Minutes Reperfusion | 10 min reperfusion | .25 Arbitrary units | Standard Error 0.04 |
Secondary
Cardiac Matrix Metalloproteinase-9 Activity in Right Atrial Biopsies at 10 Minutes Reperfusion
Biochemical activity of MMP-9 activity in right atrial biopsies, measured at 10 minutes of reperfusion after surgery. To determine MMP-9 activity, 20 μg of total protein from both myocardial extracts and plasma were analyzed by gelatin zymography. For detailed methodology consult Cheung PY, Sawicki G, Wozniak M, et al: Matrix metalloproteinase-2 contributes to ischemia-reperfusion injury in the heart. Circulation 2000; 101:1833-1839
Time frame: Before surgery and 10 minutes reperfusion after surgery
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Oral Tablet | Cardiac Matrix Metalloproteinase-9 Activity in Right Atrial Biopsies at 10 Minutes Reperfusion | Before surgery | .75 Arbitrary units | Standard Error 0.25 |
| Placebo Oral Tablet | Cardiac Matrix Metalloproteinase-9 Activity in Right Atrial Biopsies at 10 Minutes Reperfusion | 10 min reperfusion | .44 Arbitrary units | Standard Error 0.28 |
| Periostat | Cardiac Matrix Metalloproteinase-9 Activity in Right Atrial Biopsies at 10 Minutes Reperfusion | Before surgery | 1.56 Arbitrary units | Standard Error 0.26 |
| Periostat | Cardiac Matrix Metalloproteinase-9 Activity in Right Atrial Biopsies at 10 Minutes Reperfusion | 10 min reperfusion | 1.63 Arbitrary units | Standard Error 0.29 |
Secondary
Cleaved TroponinI/GAPDH Ratios in Right Atrial Biopsy
Measurement of the ratios of cleaved TnI (troponin-I) versus GAPDH in biopsies collected from right atria. Measure is the ratio TnI/GAPDH
Time frame: Before surgery and 10 minutes reperfusion after surgery
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Oral Tablet | Cleaved TroponinI/GAPDH Ratios in Right Atrial Biopsy | Before surgery | 1.1318 Arbitrary units-Cleaved TnI/GAPDH | Standard Error 0.3852 |
| Placebo Oral Tablet | Cleaved TroponinI/GAPDH Ratios in Right Atrial Biopsy | Post surgery | 1.5195 Arbitrary units-Cleaved TnI/GAPDH | Standard Error 0.3745 |
| Periostat | Cleaved TroponinI/GAPDH Ratios in Right Atrial Biopsy | Before surgery | 2.3454 Arbitrary units-Cleaved TnI/GAPDH | Standard Error 0.3978 |
| Periostat | Cleaved TroponinI/GAPDH Ratios in Right Atrial Biopsy | Post surgery | 2.1893 Arbitrary units-Cleaved TnI/GAPDH | Standard Error 0.3868 |
Secondary
Venous Plasma Cardiac Matrix Metalloproteinase-2 Activity Before and After Reperfusion
Biochemical activity of MMP-2 activity in venous plasma, measured before surgery and up to 72h of reperfusion after surgery.
Time frame: Before surgery and up to 72 h reperfusion after surgery
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Oral Tablet | Venous Plasma Cardiac Matrix Metalloproteinase-2 Activity Before and After Reperfusion | Before anesthesia | .99 Arbitrary units | Standard Error 0.05 |
| Placebo Oral Tablet | Venous Plasma Cardiac Matrix Metalloproteinase-2 Activity Before and After Reperfusion | After anesthesia | .93 Arbitrary units | Standard Error 0.04 |
| Placebo Oral Tablet | Venous Plasma Cardiac Matrix Metalloproteinase-2 Activity Before and After Reperfusion | 10 min reperfusion | 1.01 Arbitrary units | Standard Error 0.06 |
| Placebo Oral Tablet | Venous Plasma Cardiac Matrix Metalloproteinase-2 Activity Before and After Reperfusion | 20 min reperfusion | .87 Arbitrary units | Standard Error 0.04 |
| Placebo Oral Tablet | Venous Plasma Cardiac Matrix Metalloproteinase-2 Activity Before and After Reperfusion | 3 h reperfusion | .99 Arbitrary units | Standard Error 0.05 |
| Placebo Oral Tablet | Venous Plasma Cardiac Matrix Metalloproteinase-2 Activity Before and After Reperfusion | 6 h reperfusion | .92 Arbitrary units | Standard Error 0.07 |
| Placebo Oral Tablet | Venous Plasma Cardiac Matrix Metalloproteinase-2 Activity Before and After Reperfusion | 24 h reperfusion | .78 Arbitrary units | Standard Error 0.05 |
| Placebo Oral Tablet | Venous Plasma Cardiac Matrix Metalloproteinase-2 Activity Before and After Reperfusion | 72 h reperfusion | .78 Arbitrary units | Standard Error 0.04 |
| Periostat | Venous Plasma Cardiac Matrix Metalloproteinase-2 Activity Before and After Reperfusion | 72 h reperfusion | .9 Arbitrary units | Standard Error 0.04 |
| Periostat | Venous Plasma Cardiac Matrix Metalloproteinase-2 Activity Before and After Reperfusion | Before anesthesia | 1.06 Arbitrary units | Standard Error 0.05 |
| Periostat | Venous Plasma Cardiac Matrix Metalloproteinase-2 Activity Before and After Reperfusion | 3 h reperfusion | 1.06 Arbitrary units | Standard Error 0.05 |
| Periostat | Venous Plasma Cardiac Matrix Metalloproteinase-2 Activity Before and After Reperfusion | After anesthesia | .96 Arbitrary units | Standard Error 0.04 |
| Periostat | Venous Plasma Cardiac Matrix Metalloproteinase-2 Activity Before and After Reperfusion | 24 h reperfusion | .9 Arbitrary units | Standard Error 0.05 |
| Periostat | Venous Plasma Cardiac Matrix Metalloproteinase-2 Activity Before and After Reperfusion | 10 min reperfusion | 1.05 Arbitrary units | Standard Error 0.06 |
| Periostat | Venous Plasma Cardiac Matrix Metalloproteinase-2 Activity Before and After Reperfusion | 6 h reperfusion | 1.07 Arbitrary units | Standard Error 0.07 |
| Periostat | Venous Plasma Cardiac Matrix Metalloproteinase-2 Activity Before and After Reperfusion | 20 min reperfusion | 1 Arbitrary units | Standard Error 0.04 |
Secondary
Venous Plasma Cardiac Matrix Metalloproteinase-9 Activity Before and After Reperfusion
Biochemical activity of MMP-9 activity in venous plasma, measured before surgery and up to 72h of reperfusion after surgery.
Time frame: Before surgery and up to 72 h reperfusion after surgery
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Oral Tablet | Venous Plasma Cardiac Matrix Metalloproteinase-9 Activity Before and After Reperfusion | Before anesthesia | .07 Arbitrary units | Standard Error 0.04 |
| Placebo Oral Tablet | Venous Plasma Cardiac Matrix Metalloproteinase-9 Activity Before and After Reperfusion | After anesthesia | .06 Arbitrary units | Standard Error 0.04 |
| Placebo Oral Tablet | Venous Plasma Cardiac Matrix Metalloproteinase-9 Activity Before and After Reperfusion | 10 min reperfusion | 1.22 Arbitrary units | Standard Error 0.08 |
| Placebo Oral Tablet | Venous Plasma Cardiac Matrix Metalloproteinase-9 Activity Before and After Reperfusion | 20 min reperfusion | 1.14 Arbitrary units | Standard Error 0.09 |
| Placebo Oral Tablet | Venous Plasma Cardiac Matrix Metalloproteinase-9 Activity Before and After Reperfusion | 3 h reperfusion | .52 Arbitrary units | Standard Error 0.08 |
| Placebo Oral Tablet | Venous Plasma Cardiac Matrix Metalloproteinase-9 Activity Before and After Reperfusion | 6 h reperfusion | .21 Arbitrary units | Standard Error 0.04 |
| Placebo Oral Tablet | Venous Plasma Cardiac Matrix Metalloproteinase-9 Activity Before and After Reperfusion | 24 h reperfusion | .05 Arbitrary units | Standard Error 0.03 |
| Placebo Oral Tablet | Venous Plasma Cardiac Matrix Metalloproteinase-9 Activity Before and After Reperfusion | 72 h reperfusion | .03 Arbitrary units | Standard Error 0.01 |
| Periostat | Venous Plasma Cardiac Matrix Metalloproteinase-9 Activity Before and After Reperfusion | 72 h reperfusion | .03 Arbitrary units | Standard Error 0.01 |
| Periostat | Venous Plasma Cardiac Matrix Metalloproteinase-9 Activity Before and After Reperfusion | Before anesthesia | .11 Arbitrary units | Standard Error 0.04 |
| Periostat | Venous Plasma Cardiac Matrix Metalloproteinase-9 Activity Before and After Reperfusion | 3 h reperfusion | .53 Arbitrary units | Standard Error 0.08 |
| Periostat | Venous Plasma Cardiac Matrix Metalloproteinase-9 Activity Before and After Reperfusion | After anesthesia | .12 Arbitrary units | Standard Error 0.04 |
| Periostat | Venous Plasma Cardiac Matrix Metalloproteinase-9 Activity Before and After Reperfusion | 24 h reperfusion | .09 Arbitrary units | Standard Error 0.01 |
| Periostat | Venous Plasma Cardiac Matrix Metalloproteinase-9 Activity Before and After Reperfusion | 10 min reperfusion | 1.37 Arbitrary units | Standard Error 0.08 |
| Periostat | Venous Plasma Cardiac Matrix Metalloproteinase-9 Activity Before and After Reperfusion | 6 h reperfusion | .22 Arbitrary units | Standard Error 0.04 |
| Periostat | Venous Plasma Cardiac Matrix Metalloproteinase-9 Activity Before and After Reperfusion | 20 min reperfusion | 1.3 Arbitrary units | Standard Error 0.09 |
Secondary
Venous Plasma Concentration of C-reactive Protein
Measurement of inflammation marker C-reactive protein in plasma
Time frame: Before surgery and up to 72 h reperfusion after surgery
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Oral Tablet | Venous Plasma Concentration of C-reactive Protein | Before anesthesia | 5.7 ng/ml | Standard Error 2 |
| Placebo Oral Tablet | Venous Plasma Concentration of C-reactive Protein | After anesthesia | 5.7 ng/ml | Standard Error 1.8 |
| Placebo Oral Tablet | Venous Plasma Concentration of C-reactive Protein | 10 min reperfusion | 4 ng/ml | Standard Error 1.3 |
| Placebo Oral Tablet | Venous Plasma Concentration of C-reactive Protein | 20 min reperfusion | 4 ng/ml | Standard Error 1.5 |
| Placebo Oral Tablet | Venous Plasma Concentration of C-reactive Protein | 3 h reperfusion | 5.2 ng/ml | Standard Error 1.7 |
| Placebo Oral Tablet | Venous Plasma Concentration of C-reactive Protein | 6 h reperfusion | 12.9 ng/ml | Standard Error 2 |
| Placebo Oral Tablet | Venous Plasma Concentration of C-reactive Protein | 24 h reperfusion | 51 ng/ml | Standard Error 1.9 |
| Placebo Oral Tablet | Venous Plasma Concentration of C-reactive Protein | 72 h reperfusion | 51.1 ng/ml | Standard Error 1.2 |
| Periostat | Venous Plasma Concentration of C-reactive Protein | 72 h reperfusion | 51.2 ng/ml | Standard Error 1.2 |
| Periostat | Venous Plasma Concentration of C-reactive Protein | Before anesthesia | 10 ng/ml | Standard Error 2 |
| Periostat | Venous Plasma Concentration of C-reactive Protein | 3 h reperfusion | 9.4 ng/ml | Standard Error 1.8 |
| Periostat | Venous Plasma Concentration of C-reactive Protein | After anesthesia | 9.9 ng/ml | Standard Error 2 |
| Periostat | Venous Plasma Concentration of C-reactive Protein | 24 h reperfusion | 48.8 ng/ml | Standard Error 1.9 |
| Periostat | Venous Plasma Concentration of C-reactive Protein | 10 min reperfusion | 7.5 ng/ml | Standard Error 1.5 |
| Periostat | Venous Plasma Concentration of C-reactive Protein | 6 h reperfusion | 16.3 ng/ml | Standard Error 2.1 |
| Periostat | Venous Plasma Concentration of C-reactive Protein | 20 min reperfusion | 7.2 ng/ml | Standard Error 1.3 |
Secondary
Venous Plasma Concentration of IL-6
Measurement of inflammation marker interleukin-6 in plasma
Time frame: Before surgery and up to 72 h reperfusion after surgery
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Oral Tablet | Venous Plasma Concentration of IL-6 | 3 h reperfusion | 72.9 pg/ml | Standard Error 6.6 |
| Placebo Oral Tablet | Venous Plasma Concentration of IL-6 | Before anesthesia | 5.7 pg/ml | Standard Error 2 |
| Placebo Oral Tablet | Venous Plasma Concentration of IL-6 | 6 h reperfusion | 75.6 pg/ml | Standard Error 5.9 |
| Placebo Oral Tablet | Venous Plasma Concentration of IL-6 | 10 min reperfusion | 15.4 pg/ml | Standard Error 2.7 |
| Placebo Oral Tablet | Venous Plasma Concentration of IL-6 | 24 h reperfusion | 66.4 pg/ml | Standard Error 6.4 |
| Placebo Oral Tablet | Venous Plasma Concentration of IL-6 | 20 min reperfusion | 24.4 pg/ml | Standard Error 3.3 |
| Placebo Oral Tablet | Venous Plasma Concentration of IL-6 | 72 h reperfusion | 39 pg/ml | Standard Error 5.7 |
| Placebo Oral Tablet | Venous Plasma Concentration of IL-6 | After anesthesia | 5.6 pg/ml | Standard Error 1.9 |
| Periostat | Venous Plasma Concentration of IL-6 | 72 h reperfusion | 28.1 pg/ml | Standard Error 5.8 |
| Periostat | Venous Plasma Concentration of IL-6 | Before anesthesia | 1.9 pg/ml | Standard Error 2 |
| Periostat | Venous Plasma Concentration of IL-6 | After anesthesia | 2.8 pg/ml | Standard Error 1.9 |
| Periostat | Venous Plasma Concentration of IL-6 | 20 min reperfusion | 15.1 pg/ml | Standard Error 3.4 |
| Periostat | Venous Plasma Concentration of IL-6 | 3 h reperfusion | 76.1 pg/ml | Standard Error 6.7 |
| Periostat | Venous Plasma Concentration of IL-6 | 6 h reperfusion | 83.4 pg/ml | Standard Error 6 |
| Periostat | Venous Plasma Concentration of IL-6 | 24 h reperfusion | 71.8 pg/ml | Standard Error 6.5 |
| Periostat | Venous Plasma Concentration of IL-6 | 10 min reperfusion | 7.3 pg/ml | Standard Error 2.7 |
Secondary
Venous Plasma Concentration of Troponin-I
Measurement of levels of TnI (troponin-I), a marker of cardiac cell damage
Time frame: Before surgery and 10 minutes reperfusion after surgery
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Oral Tablet | Venous Plasma Concentration of Troponin-I | Before surgery | 1.23 pg/ml | Standard Error 0.33 |
| Placebo Oral Tablet | Venous Plasma Concentration of Troponin-I | Post surgery | 1.39 pg/ml | Standard Error 0.46 |
| Periostat | Venous Plasma Concentration of Troponin-I | Before surgery | 1.07 pg/ml | Standard Error 0.34 |
| Periostat | Venous Plasma Concentration of Troponin-I | Post surgery | 1.78 pg/ml | Standard Error 0.47 |